Clinical Management Research Articles

Retrospective characterization of seizure semiology and treatment using continuous video‐EEG monitoring in neonatal encephalopathy in Uganda

AbstractObjectiveNeonatal encephalopathy (NE) is a leading cause of childhood death and disability, particularly in sub‐Saharan Africa. Detection of NE‐related seizures is challenging. We explored NE seizure semiology and management in Uganda.MethodsVideo‐EEG was recorded (days 1–5), seizure semiology reviewed according to ILAE classification and administration of antiseizure medication (ASM) evaluated. Clinicians treated seizures based on the clinical presentation alone.ResultsAmong 50 participants, 52% (26) had EEG‐confirmed seizures; 70% (18) combined electroclinical/electrographic; 4% (1) exclusively electroclinical; 22% (6) electrographic. Of those with electroclinical seizures (19), 42% displayed >1 semiology. Distribution of seizure semiology was; clonic 34% (11); autonomic 24% (8, of which 6 had prolonged ictal apnea); automatisms 18% (6); behavioral arrest 12% (4); and sequential 12% (4). ASM was administered to 64% (32/50). Of those with EEG‐confirmed seizures, only 62% (16/26) received ASM. In the non‐seizure group, 38% (9/24) received ASM during monitoring. ASM was administered 42 times, of which 45% (19) were considered appropriate.SignificanceIn this Ugandan NE population, incidence of seizures was high and clinical manifestations frequent. Clonic, autonomic and automatisms were most common. Clinical management was challenging, with both under and overtreatment evident. Respiratory impairment due to autonomic seizures frequently went unrecognized and is a prominent concern, particularly in settings without neonatal intensive care.

Progressive Bulbar Palsy Care: Exploring the Potential of Functional MRI for Early Detection

Progressive bulbar palsy (PBP) is a neurodegenerative disorder impacting motor neurons involved in speech, swallowing, and breathing. Early diagnosis is challenging due to limited diagnostic tools. Functional MRI (fMRI) holds promise for detecting early biomarkers and tracking disease progression, potentially improving clinical management. This study aims to explore the utility of fMRI in developing imaging biomarkers for the early detection, prognostication, and monitoring of PBP. By addressing existing gaps in the literature, the research seeks to demonstrate how fMRI can enhance diagnostic accuracy, provide predictive insights into disease progression, and improve patient outcomes. A systematic literature review was conducted using databases such as Google Scholar. The search focused on articles published from 2018 onwards, using keywords related to PBP and fMRI. Inclusion criteria included peer-reviewed studies involving human subjects relevant to the use of fMRI in PBP. Exclusion criteria excluded non-peer-reviewed articles, non-English publications, and studies not specifically addressing fMRI in PBP. Data synthesis involved both qualitative and quantitative analyses of identified biomarkers, diagnostic accuracy, and prognostic value. The review identified several fMRI biomarkers that show potential for early detection and monitoring of PBP. These biomarkers, derived from functional and structural changes in corticobulbar pathways, offer enhanced sensitivity compared to traditional diagnostic methods. Predictive models based on fMRI metrics can forecast disease progression, aiding in personalized treatment planning. The study concludes that integrating fMRI into clinical practice could lead to earlier interventions, more accurate prognostic assessments, and improved management of PBP, ultimately enhancing patient quality of life and outcomes.

Clinical characteristics, progression patterns and treatment outcomes in microsporidial keratoconjunctivitis: a prospective study in Thailand.

To assess the clinical characteristics, progression patterns, and treatment outcomes of microbiologically confirmed microsporidial keratoconjunctivitis (MKC). This prospective cross-sectional study included patients with superficial punctate epithelial keratitis clinically suspected of MKC. Comprehensive slit-lamp examinations were conducted, and corneal scraping was performed for Gram-chromotrope staining and polymerase chain reaction (PCR) analysis. A standardized questionnaire gathered demographic data, clinical features, and risk behaviors. Treatment regimens and corneal findings, including medication and frequency, were documented at each visit. PCR confirmed the diagnosis of MKC in 96 out of 117 eyes (82.1%), identifying Vittaforma corneae in 93.7% of cases, Microsporidium sp. in 4.2%, and Encephalitozoon hellem in 2.1%. All cases exhibited similar characteristics and pattern of progression, including elevated epithelial lesions in diffused distribution (34.1%), typical target lesions (31.3%), and subepithelial infiltrations (41.7%). Treatment with topical moxifloxacin, with or without oral albendazole, followed by topical steroids for subepithelial infiltrates, led to clinical improvement within approximately two weeks, with 52% of patients achieving complete recovery. This study identifies key clinical features and progression patterns in MKC. Topical fluoroquinolone monotherapy, or its combination with topical steroids or oral albendazole, results in favorable visual outcomes without corneal scarring. These insights may inform and enhance clinical management of MKC.

Cell-free pregnancy-associated microRNAs in blood plasma as potential biomarker in early diagnosis of ectopic pregnancy.

Ectopic pregnancy (EP) is one of the life-threatening disorders in early pregnancy and current strategies are inadequate in its clinical management. There is a need to identify more accurate biomarkers for early diagnosis of ectopic pregnancy. This case-control study was conducted in a group of 35 women diagnosed with ectopic pregnancy and 31 women with a normal singleton pregnancy. Patients' characteristics including the level of β-hCG, age, body mass index (BMI), and gestational age have been recorded. The plasma levels of cell-free hsa-miR-411, hsa-miR-433, and hsa-miR-524 were examined by qRT-PCR using specific primers. There was no statistically significant difference in maternal age, gestational age, and BMI between the two groups. β-hCG concentrations in EP were significantly lower than normal pregnancy group. Cell-free hsa-miR-411 and hsa-miR-433 had statistically significant differences in concentrations in women with EP and normal pregnancy. hsa-miR-411 and hsa-miR-433 had better diagnostic values for discriminating EP from normal pregnancy. Moreover, hsa-miR-411 and hsa-miR-433 showed a specificity of 61% and 53%, and a sensitivity of 72% and 79%, respectively. hsa-miR-411 and hsa-miR-433 microRNAs concentrations in plasma have potential as a predicting biomarker for early diagnosis of EP. However, further research is needed before using miRNAs in clinical practice for both diagnostic and therapeutic goals.

High-grade B-cell lymphoma not otherwise specified, with diffuse large B-cell lymphoma gene expression signatures: Genomic analysis and potential therapeutics.

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). This subgroup, representing ~60% of HGBCL, NOS, lack gene-expression signature of BL and double hit/dark zone lymphoma, but express DLBCL like signatures and are characterized by either GCB- or ABC-like mRNA signatures and exhibit higher genomic complexity, similar to de novo DLBCL, and show alteration in genes regulating B-cell activation (CD79B, MYD88, PRDM1, TBLIXR1, CARD11), epigenome (KMT2D, TET2) and cell cycle transition (TP53, ASPM). However, recurrent mutations in genes often mutated in BL (DDX3X, GNA13, CCND3), but rare in DLBCL, are also present in HGBCL-NOS, highlighting genetic heterogeneity. Consistent with mutation spectrum, frequent genomic CN alterations in genes regulating B-cell activation (del-PRDM1, gain-BCL6, -REL, -STAT3) and cell cycle regulators (del-TP53, del-CDKN2A, del-RB1, gain-CCND3) were observed. Pediatric cases showed GCB-DLBCL-like mRNA signatures, but also featured hallmark mutations of pediatric BL. Frequent oncogenic PIM1 mutations were present in adult HGBCL, NOS. In vitro analyses with pharmacologic or genetic inhibition of PIM1 expression triggered B-cell activation and NF-κB-induced apoptosis, suggesting that PIM1 is a rational therapeutic target.

Examining the relationships between patients' multimorbidity trajectories and prognostic outcomes after the initial hip fracture.

Hip fractures significantly affect patients' health and quality of life. Despite therapeutic treatments, many patients continue to experience poor prognoses that include recurrent fractures and mortality, especially the older ones. Therefore, understanding important factors associated with post-fracture prognoses is critical. This study focuses on patients' multimorbidity trajectories and examines how the trajectory's time span, number of coexisting chronic diseases, and sequential disease patterns relate to distinct prognostic outcomes. From the National Health Insurance Research Database in Taiwan, we obtain a sample of 128,822 patients who suffered an initial hip fracture between 1996 and 2011. We use this sample to analyze the relationships between multimorbidity trajectories and prognostic outcomes after an initial hip fracture. The results reveal that a patient's multimorbidity trajectory's time span and number of chronic diseases significantly associate with his or her post-fracture prognosis. In addition, essential sequential patterns of chronic diseases relate to post-fracture prognoses too. We then leverage the discovered relationships to develop a cross-attention neural network method for estimating patients' post-fracture prognoses and demonstrate its predictive utilities relative to several prevalent machine leaning methods. This study underscores the importance of leveraging the time span, number of chronic diseases, and sequential disease patterns in patients' multimorbidity trajectory profile to estimate their prognoses within three years of an initial hip fracture, which can support physicians' clinical decisions and patient management.

Proteomic and phosphoproteomic identified structural and functional changes in the aorta associate with age-dependent hypertension in male Sprague Dawley rats.

Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs) have been observed to have a potential association, with GBS potentially leading to cardiovascular complications. However, these observational studies may be influenced by confounding factors. This study aimed to assess the causal relationship between GBS and CVDs, including heart failure (HF), atrial fibrillation (AF), and coronary artery disease (CAD), using a two-sample bidirectional Mendelian randomization (MR) analysis. Datasets for GBS and CVDs were retrieved from the United Kingdom Biobank and analyzed using selected instrumental variables (IVs) related to genetic variations. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the reliability of the selected IVs. The analysis results were then visualized to illustrate the causal relationships. The study identified genetic variants as IVs for both GBS and CVDs. MR analysis revealed a significant causal effect of GBS on the increased risk of HF (Inverse variance weighted [IVW], p<0.05), but no significant causal relationship was found between GBS and AF or CAD. Similarly, no causal effect of CVDs on the occurrence of GBS was observed. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the results. This bidirectional MR analysis suggests a causal relationship between GBS and an increased risk of HF but not with AF or CAD, nor was a reverse causal effect of CVDs on GBS observed. These findings underscore the importance of considering cardiovascular complications, particularly HF, in the clinical management of patients with GBS in European populations.

Personality, Aging, and Alzheimer's Disease: Implications for Psychoneuroimmunology and Personalized Medicine.

Psychoneuroimmunology (PNI) advancements may revolutionize personalized medicine by identifying systemic biomarkers that enhance diagnosis and treatment. Inflammatory pathways connect personality traits with cognitive performance, aging-related disorders, and mortality risks. Studies have demonstrated the critical interactions between personality and various biological systems like the hypothalamic-pituitary-adrenal (HPA) axis. The gut-brain axis also affects behaviors and psychological states in older adults, with specific gut microbiota influencing cognition, mood, and personality. These findings underscore the practical implications of understanding personality-biology interactions. They can support preventive and personalized medicine for aging-associated disorders. Specifically, personality changes are prevalent in Alzheimer's disease (AD) patients, impacting clinical management and caregiver stress. Non-cognitive factors, such as personality traits and psychiatric symptoms, may serve as early markers of AD. Traits like high Neuroticism and low Openness can predict initial AD stages, often before a formal diagnosis. Personality alterations in AD are also linked to cerebrospinal fluid (CSF) and vascular imaging biomarkers, which can track AD pathology and serve as predictors. Dynamic personality assessment can aid in timely diagnosis, monitoring progression, and evaluating treatmentsof AD. Understanding personality traits is crucial for predicting burnout, lifespan, and intervention success. Integrating personality and PNI biomarkers into patient profiles will support the development of personalized and systems medicine.

Clinical and Analytical Presentation of Central Precocious Puberty: A 20-Year Cross-Sectional Study

Objectives − This study aims to compare the clinical and analytical presentation of Central precocious puberty (CPP), considering age.Methods − An observational, cross-sectional study was conducted on children diagnosed with CPP at a level III hospital, between January 2002 and April 2022. Clinical, auxological, sociodemographic, laboratory, and imaging parameters were analyzed.Results − Out of the 52 children studied, the majority were girls (N=44). The median age of puberty onset in girls was 6.79 years and the mean age at first consultation of 8.13 years, with a significantly lower age at hospital referral (7.65 years; P=0.045) compared to boys. Idiopathic etiology was predominant in both. In girls, breast development appeared at older mean ages (P=0.009), while pubic hair growth and accelerated growth were associated with younger ages at puberty onset (P=0.021; P=0.018, respectively). Basal and peak levels of gonadotropin hormones were higher in girls, although not statistically significant. In girls, age at puberty onset correlated negatively with standard deviation of body mass index (P=0.023), while age at first consultation correlated positively with bone age (P&lt;0.001), and was associated with younger ages at Gonadotropin-Releasing Hormone stimulation test (P=0.020).Conclusion − This study provides innovative and relevant findings that enhance understanding of CPP presentation according to age, thereby improving clinical management of this condition.

The diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis.

To investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM). A total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM. The AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P<0.001). The Kappa coefficients were 1 for CD8+, CD4+/CD8 + ratios and the combined EBV analysis, indicating a 100% consistency with the clinical diagnosis. Significant differences were also observed in the CD3+, CD4+, CD16 + CD56+, and CD19 + lymphocyte subsets between the IM group and the healthy group (P<0.05). The evaluation of CD8 + and CD4+/CD8 + ratios in peripheral blood lymphocytes represents a significant advancement in the diagnosis of IM. Peripheral blood lymphocyte testing offers a reliable, sensitive, and specific diagnostic tool to enhance the clinical management of children with IM.

REVISÃO DE LITERATURA: MANEJO DO PACIENTE COM COLANGITE ESCLEROSANTE PRIMÁRIA

The primary sclerosing cholangitis (PSC) is a progressive, idiopathic, immune mediated disease, characterized by intra or extrahepatic cholestasis, Inflammation and fibrosis of the bile ducts, which may progress to liver cirrhosis or cholangiocarcinoma (CCA) in the vast majority of patients. Objective: Analyze what the current literature discusses about the management of PSC. Method: A systematic review was carried out using the PubMed and SciELO database, applying the descriptors "Primary Sclerosing Cholangitis" AND "Cholangite" AND "Clinical management" AND Cholangiocarcmoma. Discussion: It is more common in men, with an average diagnosis at 35 years old. The PSC has a wide range of symptoms and stages of the disease. In the beginning, symptoms are rare and patients may be asymptomatic. The most commonly found symptoms are pruritus, fatigue, right upper quadrant abdominal pain, jaundice, fever, and weight loss. In about 75% of patients with PSC, liver function tests are chronically abnormal and fluctuating with a most commonly found pattern of cholestatic condition with elevation of alkaline phosphatase (AF) and yglutamyl transferase (GGT). Although endoscopic retrograde cholangiopancreatography (ERCP) is conventionally considered the gold standard test for the diagnosis of PSC, the main modality of choice currently for Imaging diagnosis in patients with suspected PSC is magnetic resonance cholangiopancreatography (CPRM). Due to the absence of effective medical therapy for PSC, liver transplantation (LT) remains the only curative option. There is little evidence for the use of medications as a way to inhibit the progression of the disease. Still several new drugs are under investigation, representing the potential to improve survival and clinical outcomes in PSC. Final considerations: We conclude that it is extremely important to approach the management of PSC. The diagnosis is a great challenge since its clinical, laboratory and imaging aspects overlap, as it was portrayed during this exposure. Nevertheless, due to the various differential diagnoses ofjaundice with cholestatic pattern, the etiological search is crucial and the absence of effective medical therapy, with several new drugs under analysis, should guide further studies to improve the survival and clinical outcomes of these patients. Another point to be considered is that there is a scarcity of data in the literature that address the PSC in the Brazilian population.

Penetrating intraorbital wooden foreign bodies involving the right frontal lobe of the brain: A rare case report

Background: Penetrating orbital trauma from a wooden foreign object is rare and challenging to identify, as it cannot be detected with a computed tomography (CT) scan. This report highlights the clinical presentation, diagnosis, and management of such a case. Case Description: A 19-year-old female experienced penetrating orbital trauma from a wooden object following a traffic accident. She intermittently visited the hospital with eye swelling and headache, without visible penetrating wounds on the palpebra. The swelling persisted for weeks, accompanied by increasing signs of ocular and cerebral infection. The suspicion of a non-metallic foreign body penetrating the brain was confirmed 3 months after the initial visit, delayed by the hidden entry wound between the eyelid and eyeball and orbital edema mimicking non-penetrating trauma. A multidisciplinary team managed the case. Procedures included debridement, retro-orbital exploration, retro-orbital abscess evacuation, and frontal basal trephination exploration, successfully removing the wooden object that had penetrated the medial orbit, frontal bone, and brain, along with cerebral abscess evacuation. Postoperative CT scans showed complete removal of the foreign object and successful abscess evacuation. The patient showed improvement in ocular symptoms, resolution of headaches, and no wound leakage. She was discharged on the 14th day after completing antibiotic treatment and having the dressing removed. Conclusion: This case is notable for its rarity, high risk of misdiagnosis, and potentially fatal consequences if not promptly managed. We emphasize the importance of patient involvement in routine consultations, careful anamnesis, clinical examination, and a multidisciplinary approach for optimal outcomes.

A rare case of mucocele of the Blandin and Nuhn glands with review of literature

Oral mucocele is the most common benign minor salivary gland lesion of the oral cavity. Usually it occurs on lower lip, buccal mucosa and ventral surface of the tongue and rarely seen on ventral surface of the tongue, floor of mouth and palate. It is classified in two types of lesions, one is extravasation type which is more common and other is retention type. We present case report of a 37-year-old healthy male with complaint of swelling on ventral surface of the tongue, which was sessile, soft and fluctuant with smooth overlying mucosa with diagnosis of mucocele associated with Blandin and Nuhn gland. Management included marsupialization and drainage of thick mucus secretions. This article discusses on clinical features, diagnosis and management of mucoceles associated with Blandin and Nuhn gland.

Understanding oral malignancies: 2 case reports

The clinical presentation, diagnosis, and management of several squamous cell carcinoma cases are covered thoroughly. Roughly 94% of all mouth malignancies are squamous cell carcinomas. Race, gender, and age group differences exist in annual incidence and mortality rates. This percentage is 7.7 per 100,000 in the US. Like other carcinomas, intraoral carcinoma is more common in older adults, especially in men. Individuals with oral SCC have often known about an abnormality in that area for four to eight months prior to seeking professional medical attention. Early growth is characterized by little discomfort, which may account for the delay in seeking professional assistance. The clinical manifestations of oral SCC include exophytic, endophytic, leukoplakic, and erythroplakic, all of which exhibit apparent surface alterations.Tobacco usage, excessive alcohol consumption, HPV infection, eating little fruits and vegetables, prolonged sun exposure, and having a compromised immune system are risk factors. Improving outcomes requires early discovery and treatment, which may include chemotherapy, radiation therapy, surgery, or a combination of these. In order to improve the prognosis for oral cancer, early identification and intervention are crucial. Survival risk from squamous cell carcinoma is often low. This article emphasis on the clinical presentation of oral malignancies.

A deep dive into penetrating ocular trauma: Insights from a South Indian tertiary eye care center

Penetrating ocular trauma is a significant cause of visual impairment and blindness worldwide. In India, with its vast and diverse population, understanding the epidemiology and patterns of Penetrating ocular trauma is crucial for effective prevention and management. This study aims to investigate the prevalence, characteristics, and outcomes of penetrating ocular trauma in the South Indian population. By analyzing data from a tertiary eye care center in South India, this research seeks to contribute to the existing knowledge base and inform evidence-based interventions to reduce the burden of penetrating ocular trauma in this region.To analyze the clinical profile, management, and outcomes of penetrating ocular trauma cases at a tertiary eye care center in South India.A retrospective review of medical records from January 2024 to June 2024 was conducted. Data collected included demographic details, mode of injury, clinical presentations, management approaches, and visual outcomes.Out of 150 cases, 120 were male (80%) and 30 female (20%). The majority of cases occurred in the 20-40 age group (60%). Common causes included workplace accidents (45%), domestic injuries (30%), and road traffic accidents (15%). Initial visual acuity varied from no light perception to &amp;#62;6/18. Surgical intervention was required in 90% of cases. Post-operative follow-up indicated that 60% achieved a visual acuity of 6/60 or better, while 20% had no light perception.Penetrating ocular trauma predominantly affects young males in South India, with workplace injuries being a major cause. Early surgical intervention improves visual outcomes. Public awareness and safety measures could reduce the incidence of such injuries.

Arthroscopic assisted versus open core decompression for osteonecrosis of the femoral head: A systematic review and meta-analysis.

Minimally invasive treatment options for osteonecrosis of the femoral head (ONFH) have been a prominent area of research in recent years. Arthroscopic-assisted treatments have been applied in the clinical management of ONFH; however, high-quality evidence verifying their effectiveness and safety is still lacking. To systematically assess the clinical efficacy and safety of arthroscopic-assisted core decompression (AACD) in treating ONFH. A comprehensive literature search was conducted in PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, and the Chinese BioMedical Literature Database, from inception to June 25, 2024. We identified randomized controlled trials and non-randomized controlled studies on AACD for the treatment of ONFH based on predefined inclusion and exclusion criteria. A meta-analysis was performed using Review Manager 5.4.1 and Stata 17.0 software. The analyzed outcomes included operative time, intraoperative blood loss, length of hospital stay, postoperative femoral head collapse rate, Harris hip score, and postoperative complication rate. The Grades of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to assess the quality of evidence for the outcome indicators. A total of fourteen studies were included in this meta-analysis, comprising 1,063 patients-541 in the core decompression (CD) group and 522 in the AACD group. The meta-analysis revealed no significant differences between the two groups in terms of intraoperative blood loss, length of hospital stay, 12-month postoperative Harris hip score, or overall postoperative complication rate (P > 0.05). However, the AACD group had a longer operative time (MD = 31.19, 95% Cl: 5.32 to 57.07, P = 0.02) and a lower overall postoperative femoral head collapse rate (RR = 0.49, 95% Cl: 0.27 to 0.89, P = 0.02) compared with the CD group. Additionally, the AACD group showed significant improvements in Harris hip scores at 3 months (MD = 6.39, 95% Cl: 5.44 to 7.33, P < 0.00001), 6 months (MD = 7.56, 95% Cl: 6.63 to 8.49, P < 0.00001), ≥ 24 months (MD = 7.00, 95% Cl: 4.80 to 9.21, P < 0.00001), and at the last follow-up (MD = 6.89, 95% Cl: 5.30 to 8.48, P < 0.00001) compared to the CD group. The GRADE evidence assessment indicated that the overall postoperative complication rate was supported by moderate-quality evidence, while the evidence for operative time, intraoperative blood loss, postoperative femoral head collapse rate, and Harris hip score was of low quality. The evidence for length of hospital stay was deemed very low quality. This meta-analysis suggests that AACD is an effective and safe treatment for patients with ONFH. However, due to the limited quantity and quality of the included studies, these results should be interpreted with caution. Further high-quality studies are recommended to confirm these findings.

Whole-exome sequencing reveals novel genomic signatures and potential therapeutic targets during the progression of rectal neuroendocrine neoplasm.

Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

The role of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in determining the severity of pre-eclampsia in antenatal women: A case control study

Pre-eclampsia (PE) remains a significant global health concern, affecting 2-8% of pregnancies and contributing to maternal and perinatal morbidity and mortality. Characterized by hypertension and proteinuria after 20 weeks of gestation, PE often involves systemic inflammation and endothelial dysfunction. Its exact etiology is multifactorial, involving immune dysregulation and vascular abnormalities. Early identification of high-risk pregnant women is crucial to mitigate adverse outcomes. In India, PE affects 8-10% of pregnancies.Inflammatory markers such as the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) have emerged as potential indicators of systemic inflammation. Elevated NLR and PLR levels in PE suggest a role in the disorder's pathophysiology, reflecting immune responses to placental ischemia and pro-inflammatory cytokine release.This study aims to compare NLR and PLR levels between PE patients and normotensive pregnant women, evaluate their association with PE severity, and discuss their potential as predictive biomarkers. A case-control study was conducted with 84 participants, following eligibility criteria via convenient sampling. Demographic characteristics, obstetric history, and CBC-derived biomarkers were assessed.Among 84 pregnant women, 42 had preeclampsia (PE) and 42 were normotensive. The PE group had significantly higher Neutrophil-to-Lymphocyte Ratios (5.11 ± 2.88 vs. 2.74 ± 0.78) and Platelet-to-Lymphocyte Ratios (108 ± 46.7 vs. 85.4 ± 29.4) compared to controls. PE incidence peaked between 34-38 weeks. Higher PLR and NLR values were linked to severe PE. ANC booking was lower in the PE group. Obesity trends were not statistically significant.Significant associations were found between elevated NLR and PLR and PE severity, highlighting their potential clinical utility.Our findings indicate NLR and PLR as valuable biomarkers for predicting and managing PE. Integration of these markers into routine prenatal care could enhance clinical management and improve maternal and fetal outcomes.

Enhancing variant of uncertain significance (VUS) interpretation in neurogenetics: collaborative experiences from a tertiary care centre

BackgroundThe findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes...

Sex disparities in myocardial infarction related cardiogenic shock.

Women are underrepresented In cardiovascular disease research, constituting only 30 % of the cardiogenic shock (CS) population. Consequently, guidelines are mainly based on male patients. This study aims to comprehensively examine the sex-specific aspects of acute myocardial infarction (AMI)-related CS, encompassing presentation, treatment and outcomes. Patients with CS undergoing percutaneous coronary intervention (PCI) between 2017 and 2021 were identified using the national Netherlands Heart Registration. Mortality was assessed using the Kaplan Meier method, and logistic regression was performed to investigate differences in clinical management between sexes. Furthermore, a sensitivity analysis excluding patients with out-of-hospital cardiac arrest (OHCA) was conducted. Among 2274 patients, 614 (27 %) were female. Women were older (70 vs. 66 years, p < 0.001) and presented with longer symptom duration (> 3 h: 52 % vs. 37 %, p < 0.001). Men more often presented with multivessel disease (62 % vs. 56 %, p < 0.001), a prior myocardial infarction (23 % vs. 15 %, p < 0.001) and after an OHCA (46 % vs. 29 %, p < 0.001). A trend towards more usage of mechanical circulatory support in men was observed (adjusted OR 0.86, 95 % CI 0.67-1.09). Mortality, both adjusted and unadjusted, was not statistically different for men and women. Women with CS present with distinct clinical characteristics, including longer symptom duration, underscoring the importance of symptom recognition. Furthermore, men present at younger age and with more OHCA. Mortality in men and women was similar despite differences in presentation and clinical management.