Therapeutic Guidelines Research Articles

Primitive neuroectodermal tumors of the ovary: a multidecade review of the scientific literature.

Primitive neuroectodermal tumor (PNET) is a general term used in scientific literature for a heterogeneous group of small round-cell malignant tumors primarily arising from neural crest cells. These are extremely aggressive neoplasms which usually occur within soft tissue or bone of young adults. Ovarian tumors composed of primitive neuroectodermal elements are extremely rare, with only few case reports in scientific literature. Due to being so exceedingly rare, PNETs are frequently misdiagnosed and there are no standard therapeutic guidelines. Young patients seem to have better prognoses and individualized strategy is recommended. Limited data suggests that various gene deletions as well as amplifications may be crucial factors for tumorigenesis and the aggressive behavior of PNET. In this paper, we performed a brief review of all cases of primary ovarian PNETs published in the scientific literature to date, in regard to their clinical, histopathological, and therapeutic aspects, with the aim to provide a more comprehensive understanding of this exceedingly rare pathology.

Clinical Characteristics and Treatment of Ophthalmic Sequelae of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at a Tertiary Eyecare Centre in Hungary.

This study analysed the causative factors and clinical characteristics of acute and chronic ocular sequelae of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) treated at a large third-referral centre in a developed country (Hungary) over a 15-year period. This was a retrospective review of patients with acute and/or chronic SJS/TEN who were managed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University in Budapest, Hungary. For each subject, clinical data, including patient demographics, clinical history, causative agents of SJS/TEN, and conservative and surgical treatment details, were reviewed. Ninety-six eyes of 48 patients were included (28 female; 58.3%); the age at disease onset was 32.1 ± 22.4years. The most common causative factors were medicines (n = 36; 75.0%). Among these drugs, 29.2% were nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 14), 20.8% were antibiotics (n = 10) and 14.6% were antiepileptic drugs (n = 7). In patients with chronic SJS/TEN, the most commonly found ocular sequelae were conjunctival hyperaemia in 45 (56.3%) eyes, symblepharon in 38 (47.5%) eyes, trichiasis/distichiasis in 37 (46.3%) eyes, corneal neovascularization in 31 (38.8%) eyes and corneal scarring in 29 (36.3%) eyes. In patients with chronic SJS/TEN, the most frequently used topical conservative treatment included antibiotics in 53 (66.3%) eyes, preservative-free artificial tears in 50 (62.5%) eyes and topical corticosteroids in 42 (52.5%) eyes of 40 patients. The most frequently performed ocular surgeries for managing chronic ocular sequelae in patients with SJS/TEN were epilation for trichiasis (n = 27; 33.8%), cataract surgery (n = 14; 17.5%), entropion surgery (n = 12; 15.0%), penetrating keratoplasty (PK) (n = 11; 13.8%) and amniotic membrane transplantation (n = 4; 5.0%). Our results suggest that NSAIDs, antibiotics and antiepileptic drugs are the most common causative factors for SJS/TEN in Hungary. Like in other countries, in Hungary, the ocular management of patients with acute and chronic SJS/TEN is heterogeneous, and most cases do not follow modern therapeutic guidelines.

Evaluation of Rational Medicines Use Based on World Health Organization Core Indicators: A Cross-Sectional Study in Five Health Districts in Mauritania.

The rational use of medicines is essential for preventing adverse medicine reactions, achieving therapeutic outcomes, and optimizing treatment costs. While the irrational use of medicines is frequently reported in sub-Saharan Africa, to the best of our knowledge no formal studies have taken place in Mauritania thus far. The main objective of this study was therefore to analyze the rational use of medicines in public and private not-for-profit health facilities, in five health districts in Mauritania. We conducted a cross-sectional study to assess the rational use of medicines. We used the standard indicators derived from the methodologies of the World Health Organization (WHO) and International Network for Rational Use of Drugs (INRUD). Data were prospectively collected from 1050 prescriptions/patients, in thirty-one public and private not-for-profit health posts/centers in 5 health districts. The data were analyzed using the Statistical Package for the Social Sciences. P value less than 0.05 at 95% confidence interval considered for significance of relationships for associations in statistical test. The average number of medicines per prescription was 2.21; 83.1% (1931/2325) of medicines were prescribed by generic name, but only 54% (1253/2325) were on the National Essential Medicine List (NEML). Antibiotics were prescribed in 62.4% (655/1050) of the consultations, and injectable medicines were prescribed in 15.6% (164/1050) of the consultations. The average consultation time was 16.32 minutes, and the average dispensing time was 97 seconds. Dispensed medicines were correctly labeled, and 83% (871/1050) of patients met the correct administration schedule. The NEML, and the "restricted NEML" for 76 commonly-used medicines, were available in all surveyed health facilities, but the National Therapeutic Guidelines were available in only 60.26% of them. Our findings indicate a possible excess of antibiotics prescriptions, and a likely lack of knowledge of the National Therapeutic Guidelines. There is a need to investigate in more detail the prescription patterns versus disease-specific therapeutic guidelines, and to qualitatively investigate the factors that contribute to the observed irrational prescribing. Moreover, training local staff in the rational use of medicines seems important.

Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match

BackgroundThe COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines.MethodsMinistries of Health or accessed...

Multidrug resistance in pathogenic Escherichia coli isolates from urinary tract infections in dogs, Spain.

Escherichia coli (E. coli) is a pathogen frequently isolated in cases of urinary tract infections (UTIs) in both humans and dogs and evidence exists that dogs are reservoirs for human infections. In addition, E. coli is associated to increasing antimicrobial resistance rates. This study focuses on the analysis of antimicrobial resistance and the presence of selected virulence genes in E. coli isolates from a Spanish dog population suffering from UTI. This collection of isolates showed an extremely high level of phenotypic resistance to 1st-3rd generation cephalosporins, followed by penicillins, fluoroquinolones and amphenicols. Apart from that, 13.46% of them were considered extended-spectrum beta-lactamase producers. An alarmingly high percentage (71.15%) of multidrug resistant isolates were also detected. There was a good correlation between the antimicrobial resistance genes found and the phenotypic resistance expressed. Most of the isolates were classified as extraintestinal pathogenic E. coli, and two others harbored virulence factors related to diarrheagenic pathotypes. A significant relationship between low antibiotic resistance and high virulence factor carriage was found, but the mechanisms behind it are still poorly understood. The detection of high antimicrobial resistance rates to first-choice treatments highlights the need of constant antimicrobial resistance surveillance, as well as continuous revision of therapeutic guidelines for canine UTI to adapt them to changes in antimicrobial resistance patterns.

The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives.

Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs and small molecules administered for coexisting diseases, resulting in ulcer healing. In this review, we summarize the discoveries regarding the pathophysiology of PG and present treatment options to raise awareness and improve the management of this rare entity.

Improving the antibiotic duration of therapy with the implementation of antimicrobial lanyard cards and education in a regional hospital

AbstractBackgroundThere is increasing evidence to support reducing antibiotic duration of therapy (DoT). The Therapeutic Guidelines: Antibiotic (version 16 [TG]) have been updated accordingly. However, these recommendations are not consistently followed.AimThe project aimed to reduce antibiotic DoT for common infections using antimicrobial lanyard cards and education.MethodA retrospective pre‐ and post‐implementation audit was undertaken to examine whether antimicrobial stewardship education and lanyard cards defined DoT per infection and severity in accordance with the TG improved antibiotic DoT for common respiratory, urinary, abdominal, and skin infections. Cards were distributed to doctors and pharmacists, with education delivered by an antimicrobial stewardship (AMS) pharmacist. This project was exempt due to the local policy requirements that constitute research by the Darling Downs Hospital and Health Service Human Research Ethics Committee (Reference no: EX/2022/QTDD/86644). The justification for this ethics exemption was as follows: the study conformed with the National Health and Medical Research Council (NHMRC) Ethical considerations in quality assurance and evaluation activities; education was incorporated as part of routine, scheduled sessions ran at Toowoomba hospital and staff were provided with information on the project as part of the education; consent was not required from staff to attend the education nor for using the lanyard cards; the research did not include any assessment of the education program, use of lanyard cards, or involvement of staff.ResultsFor all patients an improvement was found in the percentage of antibiotics prescribed per the TG (55–72%, p = 0.0095). This included statistically significant differences for respiratory (42–89%, p = 0.0002), but not for urinary (87–91%, p = 0.99), skin (58–77%, p = 0.3039), or abdominal infections (48–44%, p = 0.6990). The mean total excess treatment days decreased across all infections from 1.86 to 0.95 days (p = 0.0036, 95% confidence interval = −1.52 to −0.30).ConclusionThe introduction of antibiotic DoT cards, with AMS education, can improve antimicrobial prescribing in line with the TG in a regional hospital.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study

BackgroundOvarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP.MethodsPatients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed.ResultsFifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively).ConclusionThese results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.

Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature.

Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0.1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.

Simultaneous Parkinsonism and Dementia as Initial Presentation of Intracranial Dural Arteriovenous Fistulas: A Systematic Review

Intracranial dural arteriovenous fistulas (IDAVFs) are abnormal vascular connections between dural arteries and various venous structures within the brain. IDAVFs, rarely present with parkinsonism and dementia concurrently, making this a unique and underexplored clinical scenario. To the best of our knowledge, this is the first systematic review to comprehensively analyze cases of IDAVFs manifesting as both parkinsonism and dementia. We assessed databases from inception to September 18, 2023. We identified studies describing patients with IDAVFs initially presenting with dementia or parkinsonism. Inclusion criteria encompassed case reports and case series, while excluding review articles, guidelines, technical notes, comments, conference abstracts, and editorials. The systematic search resulted in the initial screening of 383 studies, with 33 articles meeting the inclusion criteria. Among these, 29 were case reports, often describing 3 or fewer patients. From the remaining 4 case series, data pertinent to patients presenting both parkinsonism and dementia were selectively extracted, yielding a total study population of 43 patients. The anatomical distribution of IDAVFs within this cohort was diverse, with the transverse and sigmoid sinuses being the most common locations. Although most of these patients received endovascular therapy, a few underwent microsurgical occlusion or combined surgical and endovascular treatment. IDAVFs presenting with both parkinsonism and dementia represent a rare clinical entity. This systematic review provides valuable insights into the clinical characteristics, treatment options, and outcomes for such cases. However, additional research involving larger cohorts is essential to better comprehend the underlying mechanisms and establish standardized therapeutic guidelines.

Assessing Pharmacokinetic Correlates of Escitalopram-Related Adverse Drug Reactions.

To assess the pharmacokinetic correlates of reported adverse drug reactions (ADRs) under antidepressant treatment with escitalopram (ESC) using a large therapeutic drug monitoring database. A large naturalistic sample of inpatients and outpatients prescribed ESC was analyzed. ADRs were classified using the Udvalg for Kliniske Undersogelser side effect rating scale. We compared ESC-treated patients with (n = 35) and without ADRs (n = 273) using ESC plasma concentrations as the primary outcome. We also compared ADR rates in the 2 groups based on 2 cut-off ESC levels reflecting the recommended upper thresholds of the therapeutic reference range of 80 ng/mL, suggested by the consensus therapeutic drug monitoring guidelines, and 40 ng/mL, based on recent meta-analysis data. The effects of age, sex, smoking, daily ESC dose, plasma concentrations, and concentrations corrected for daily dose were included in a binary logistic regression model to predict ADRs. No differences in clinical, demographic, or pharmacokinetic parameters were observed between patients with and without ADRs ( P > 0.05). Patients with ESC-related ADRs were more frequently diagnosed with psychotic disorders than those without (25% vs. 7.1%, P = 0.004). None of the variables was associated with ADR risk. Overall, ADR rates were not significantly different in patients above versus below thresholds of ESC concentrations (ESC concentrations >40 [n = 59] vs. ≤40 ng/mL [n = 249] and >80 [n = 8] vs. ≤80 ng/mL [n = 300]; P = 0.56 and P = 1.0, respectively). No distinct pharmacokinetic patterns underlying ESC-associated ADRs were observed. Further studies with more specific assessments of ADRs in larger cohorts are required to better identify potential underlying patterns.

Treatment of non-systemic juvenile idiopathic arthritis.

In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis.

Adecuación de las prescripciones médicas en faringitis estreptocócicas y otitis media aguda a las guías terapéuticas

Background and objective: to analyze the degree of adequacy to consensus therapeutic guidelines in acute pharyngotonsillitis and acute otitis media of primary care pediatricians. Material and Methods: retrospective observational study with data collection from electronic medical records of patients with suppurative AOM and streptococcal AAF in patients from 0 to 14 years of age residing in Araba, in an 18-month period study. Results: in the group of patients with suppurative AOM, 238 episodes have been evaluated, with a degree of therapeutic adequacy of 56.7%, being underdosing the main cause of inadequacy. In the group of patients with streptococcal AAF, 1721 episodes have been evaluated, with a degree of therapeutic adequacy of 57%, being the main causes of inadequacy overdose and short-duration regimens. Conclusion: in both suppurative AOM and streptococcal AAF, the degree of therapeutic adequacy is somewhat lower than in other analysed studies. To achieve a correct treatment in these processes in primary care settings is of vital importance due to its high frequency of diagnosis. It is also important to improve the quality of registered data in medical records of all patients.

Approaching the Sarcopenic Patient with Nonalcoholic Steatohepatitis-related Cirrhosis.

Sarcopenia is a well-known complication of chronic liver disease (CLD), and it is almost always observed in patients with cirrhosis, at least in those with decompensated disease. Since nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is becoming the leading cause of end-stage liver disease, a new scenario characterized by the frequent coexistence of NAFLD, obesity, and sarcopenia is emerging. Although it is not yet resolved whether the bidirectional relationship between sarcopenia and NAFLD subtends causal determinants, it is clear that the interaction of these two conditions is associated with an increased risk of poor outcomes. Notably, during the course of CLD, deregulation of the liver-muscle-adipose tissue axis has been described. Unfortunately, owing to the lack of properly designed studies, specific therapeutic guidelines for patients with sarcopenia in the context of NAFLD-related CLD have not yet been defined. Strategies aimed to induce the loss of fat mass together with the maintenance of lean body mass seem most appropriate. This can be achieved by properly designed diets integrated with specific nutritional supplementations and accompanied by adequate physical exercise. Future studies aiming to add to the knowledge of the correct assessment and approach to sarcopenia in the context of NAFLD-related CLD are eagerly awaited.

Why Is Surgery Still Done after Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer in Romania?

The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85-90 Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemoradiotherapy (total dose 60-65 Gy at point A), followed by surgery, which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated-on patients compared to 62% for non-operated-on patients receiving suboptimal concurrent chemotherapy alone. In conclusion, in Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control.

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.

Desmoplastic Small Round Cell Tumors: Clinical Presentation, Molecular Characterization, and Therapeutic Approach of Seven Patients

Desmoplastic small round blue cell tumor (DSRCT) is a highly aggressive fatal sarcoma without evidence‐based therapeutic guidelines. We present here seven patients with DSRCT including immunohistochemistry combined with fluorescence in situ hybridization (FISH), next generation sequencing (NGS, n = 6) as well as OncoScan array (n = 3) analyses and show consecutive therapeutic approaches. All seven DSRCT patients presented with an extended abdominal mass; median age at diagnosis was 24.8 years. NGS analyses revealed five class 4 or 5 sequence variants. Remarkably, OncoScan and targeted analyses by FISH identified genomic gains of CCND1 in two cases. Cyclin D1 expression was present in all seven tumors as shown by immunohistochemical staining. Multimodal therapeutic concepts included systemic therapies, resection, and radiation. Six patients were treated as first‐line therapy with conventional chemotherapy. All except one patient had a dismal therapy response. Subsequent therapy lines consisted of chemotherapeutic combinations followed by targeted therapies. Due to Cyclin D1 expression, the CDK4/6 inhibitor palbociclib was applied to four patients. The median therapy duration until disease progression in these patients was 4.5 months (range, 1.5–5 months). So, CCND1 genomic gain and Cyclin D1 expression are common features pointing to cell‐cycle deregulation as a possible therapeutic target.

Key differences between chronic inducible and spontaneous urticaria.

The latest international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for urticaria recommends limited laboratory testing for chronic spontaneous urticaria (CSU) and selective testing for only certain chronic inducible urticaria (CIndU) subtypes, though the rationale for these recommendations is poorly explained. This study aimed to improve the understanding of CIndU subtypes by comprehensively comparing their demographic, clinical, and laboratory characteristics with those of the better-characterized CSU. We conducted a retrospective analysis of 567 patients (median age 41 years, 67% female) diagnosed with CSU, symptomatic dermographism (SD), cold urticaria (ColdU), cholinergic urticaria (CholU), and delayed pressure urticaria (DPU). Our findings revealed that patients with SD, ColdU, and CholU had lower levels of C-reactive protein (CRP), higher total serum immunoglobulin E (IgE) levels, and higher basophil counts compared to CSU patients. These subtypes also had distinct demographic and clinical features, such as a younger age of onset and a longer disease duration. In contrast, patients with DPU had significantly higher CRP levels and neutrophil counts compared to those with CSU. These findings highlight the heterogeneity among chronic urticaria subtypes, suggesting that a tailored approach to laboratory testing may be more effective. The distinct immunological and clinical features observed in CIndU subtypes suggest a need for subtype-specific diagnostic and therapeutic guidelines.

Unraveling the H19/GAS1 axis in recurrent implantation failure: A potential biomarker for diagnosis and insight into immune microenvironment alteration.

Recurrent implantation failure (RIF) presents a significant clinical challenge due to the lack of established diagnostic and therapeutic guidelines. Emerging evidence underscores the crucial role of competitive endogenous RNA (ceRNA) regulatory networks in non-cancerous female reproductive disorders, yet the intricacies and operational characteristics of these networks in RIF are not fully understood. This study aims to demystify the ceRNA regulatory network and identify potential biomarkers for its diagnosis. We analyzed expression profiles of three RNA types (long noncoding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) sourced from the GEO database, leading to the identification of the H19-hsa-miR-301a-3p-GAS1 ceRNA network. This network demonstrates significant diagnostic relevance for RIF. Notably, the H19/GAS1 axis within this ceRNA network, identified through correlation analysis, emerged as a promising diagnostic marker, as evidenced by operating receiver operator characteristic (ROC) curve analysis. Further investigation into the binding potential of miR-301a-3p with H19 and GAS1 revealed a close association of these genes with endometrial disorders and embryo loss, as per the Comparative Toxicogenomics Database. Additionally, our immune infiltration analysis revealed a lower proportion of T cells gamma delta (γδ) in RIF, along with distinct differences in the expression of immune cell type-specific markers between fertile patients and those with RIF. We also observed a correlation between aberrant expression of H19/GAS1 and these immune markers, suggesting that the H19/GAS1 axis might play a role in modifying the immune microenvironment, contributing to the pathogenesis of RIF. In conclusion, the ceRNA-based H19/GAS1 axis holds promise as a novel diagnostic biomarker for RIF, potentially enhancing our understanding of its underlying mechanisms and improving the success rates of implantation.

Impaction of Primary Molars in Indian Children – A Retrospective Radiographic Study and Upgraded New Classification System

Aim: To evaluate the prevalence of impacted primary molars including both first and second molars in children of Indian ethnicity. Materials and Methods: The present study included children with age ranging from 3 to 15 years who reported to Dental Outpatient wing, Karnataka ENT Hospital and Research centre, Chitradurga, Karnataka, India for their dental problems during the period from 2020 to 2022. Orthopantomograph radiographs of children were investigated for the prevalence, unilateral or bilateral occurrence and ratio between two genders found with impacted primary mandibular molars were recorded and the data obtained was subjected to statistical analysis using descriptive statistics. Results: The present study recorded a total of five cases of impacted primary mandibular molars among Indian children. In one case, first primary molar was involved (20%) and remaining four cases were associated with second molars (80%). No bilateral occurrences of impaction were observed. Four cases occurred on the left side (80%) and one on the right side (20%). Three cases were noticed in males (60%) and remaining two cases in girls (40%). Regarding the level of the impaction, two cases were classified as extremely severe (Type III) (40%), two as severe (Type II) (40%), and one as moderate (Type I) (20%). Pertaining to treatment, none of the cases received treatment. When assessing the condition of the succedaneous premolars, two patients exhibited distal drifting of the second premolar tooth bud towards the second primary molar. In one case malformed second premolar was erupted clinically and in another case odontoma formation was noticed, and in one case, second premolar was erupted buccally. Conclusion: Occurrence of ankylosed and impacted primary molars does exist and hence all clinicians should be aware of its occurrence as treatment of this condition requires early diagnosis followed by meticulous management including a multidisplinary approach. More research including large number of epidemiological studies are highly warranted on this domain to formulate new diagnostic and therapeutic guidelines.