Clinical Management Research Articles

Patients carrying pathogenic SCN8A variants with loss‐ and gain‐of‐function effects can be classified into five subgroups exhibiting varying developmental and epileptic components of encephalopathy

AbstractObjectivePhenotypic heterogeneity presents challenges in providing clinical care to patients with pathogenic SCN8A variants, which underly a wide disease spectrum ranging from neurodevelopmental delays without seizures to a continuum of mild to severe developmental and epileptic encephalopathies (DEEs). An important unanswered question is whether there are clinically important subgroups within this wide spectrum. Using both supervised and unsupervised machine learning (ML) approaches, we previously found statistical support for two and three subgroups associated with loss‐ and gain‐ of‐ function vari‐ants, respectively. Here, we test the hypothesis that the unsupervised subgroups (U1–U3) are distinguished by differential contributions of developmental and epileptic components.MethodsWe predicted that patients in the U1 and U2 subgroups would differ in timing of developmental delay and seizure onset, with earlier and concurrent onset of both features for the U3 subgroup. Standard statistical procedures were used to test these predictions, as well as to investigate clinically relevant associations among all five subgroups.ResultsTwo‐population proportion and Kruskal–Wallis tests supported the hypothesis of a reversed order of developmental delay and seizure onset for patients in U1 and U2, and nearly synchronous developmental delay/seizure onset for the U3 (termed DEE) subgroup. Association testing identified subgroup variation in treatment response, frequency of initial seizure type, and comorbidities, as well as different median ages of developmental delay onset for all five subgroups.SignificanceUnsupervised ML approaches discern differential developmental and epileptic components among patients with SCN8A‐related epilepsy. Patients in U1 (termed developmental encephalopathy) typically gain seizure control yet rarely experience improvements in development, whereas those in U2 (termed epileptic encephalopathy) have fewer if any developmental impairments despite difficulty in achieving seizure control. This understanding improves prognosis and clinical management and provides a framework to discover mechanisms underlying variability in clinical outcome of patients with SCN8A‐related disorders.

The impact of genotype on age at loss of ambulation in individuals with Duchenne muscular dystrophy treated with corticosteroids: A single-center study of 555 patients.

Studies have demonstrated that certain genotypes in Duchenne muscular dystrophy (DMD) have milder or more severe phenotypes. These studies included individuals treated and not treated with corticosteroids and multiple sites with potentially varying standards of care. We aimed to assess genotype-phenotype correlations for age at loss of ambulation (LoA) in a large cohort of individuals with DMD treated with corticosteroids at one center. In this retrospective review of medical records, encounters were included for individuals diagnosed with DMD if prescribed corticosteroids, defined as daily deflazacort or prednisone or high-dose weekend prednisone, for 12 consecutive months. Encounters were excluded if the participants were taking disease-modifying therapy. Data were analyzed using survival analysis for LoA and Fisher's exact tests to assess the percentage of late ambulatory (>14 years old) individuals for selected genotypes. Overall, 3948 encounters from 555 individuals were included. Survival analysis showed later age at LoA for exon 44 skip amenable (p = .004), deletion exons 3-7 (p < .001) and duplication exon 2 (p = .043) cohorts and earlier age at LoA for the exon 51 skip amenable cohort (p < .001) when compared with the rest of the cohort. Individuals with deletions of exons 3-7 had significantly more late ambulatory individuals than other cohorts (75%), while those with exon 51 skip amenable deletions had significantly fewer (11.9%) compared with other cohorts. This confirms previous observations of genotype-phenotype correlations in DMD and enhances information for trial design and clinical management.

Endoscopic dacryocystorhinostomy in acute dacryocystitis: a multicenter study in China.

To report the clinical profile, endoscopic dacryocystorhinostomy (En-DCR) management, and acute dacryocystitis (AD) outcomes in China. Clinical data of 554 adult AD patients (554 eyes) who presented in 7 tertiary eye care centers for 10y from Jan 2010 to Mar 2020 were retrospectively analyzed. Clinical profile, En-DCR management, and outcomes of all cases were recorded. The anatomical and functional success were evaluated for 12mo post-operation. The analysis included 149 males and 368 females with a median age of 55.2y (range: 18-84y). There were 459 eyes with a history of epiphora or purulent secretion. The time between a symptom of lacrimal duct obstruction and acute onset was 1 to 540 (66.1±58.2)mo. Fifty-nine eyes had a history of the previous acute attack. Seventy-four eyes developed a cutaneous fistula, while 11 eyes had post septal cellulitis pre-operation. En-DCR with an anatomical success of 91.7% and functional success of 90.1%. The success rate of the patients with a history of acute episodes and the preoperative fistula was lower than the overall success rates. En-DCR can be performed during an acute episode in AD with a success rate of over 90%.

The role of cardiac acoustic biomarkers in monitoring patients with heart failure: A systematic literature review.

Heart failure (HF) creates a considerable clinical, humanistic and economic burden on patients and caregivers as well as on healthcare systems. To attenuate the significant burden of HF, there is a need for enhanced management of patients with HF. The use of digital tools for remote non-invasive monitoring of heart parameters is gaining traction, and cardiac acoustic biomarkers (CABs) have been proposed as a complementary set of measures to assess heart function alongside traditional methods such as electrocardiogram and echocardiography. We conducted a systematic literature review to evaluate associations between CABs and HF outcomes. Embase and MEDLINE databases were searched for recent studies published between 2013 and 2023 that evaluated CABs in patients with HF. Additional grey literature (i.e., conference, congress and pre-print publications from January 2021 to May 2023) searches were included. Two reviewers independently examined all articles; a third resolved conflicts. Data were extracted from articles meeting inclusion criteria. Extracted studies underwent quality and bias assessments using the Joanna Briggs Institute (JBI) critical appraisal tools. In total, 3074 records were screened, 73 full-text articles were assessed for eligibility and 27 publications were included. Third heart sound (S3) and electromechanical activation time (EMAT) were the CABs most often reported in the literature for monitoring HF. Fifteen publications discussed changes in S3 characteristics and its role in HF detection or outcomes: six studies highlighted S3 assessment among various groups of patients with HF; four studies evaluated the strength or amplitude of S3 with clinical outcomes; five studies assessed the relationship between S3 presence and clinical outcomes; and one study assessed both S3 presence and amplitude in relation to HF clinical outcomes. Eleven publications reported on EMAT and its derivatives: five studies on the relationship between EMAT and HF and six studies on the association of EMAT and HF clinical outcomes. Studies reporting the first and fourth heart sound, left ventricular ejection time and systolic dysfunction index were limited. Published literature supported S3 and EMAT as robust CAB measures in HF that may have value in remote clinical monitoring and management of patients with HF. Additional studies designed to test the predictive power of these CABs, and others less well-characterized, are needed. This work was funded by Astellas Pharma Inc.

Contribution of [18F]FET PET in the Management of Gliomas, from Diagnosis to Follow-Up: A Review

Gliomas, the most common type of primary malignant brain tumors in adults, pose significant challenges in diagnosis and management due to their heterogeneity and potential aggressiveness. This review evaluates the utility of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) positron emission tomography (PET), a promising imaging modality, to enhance the clinical management of gliomas. We reviewed 82 studies involving 4657 patients, focusing on the application of [18F]FET in several key areas: diagnosis, grading, identification of IDH status and presence of oligodendroglial component, guided resection or biopsy, detection of residual tumor, guided radiotherapy, detection of malignant transformation in low-grade glioma, differentiation of recurrence versus treatment-related changes and prognostic factors, and treatment response evaluation. Our findings confirm that [18F]FET helps delineate tumor tissue, improves diagnostic accuracy, and aids in therapeutic decision-making by providing crucial insights into tumor metabolism. This review underscores the need for standardized parameters and further multicentric studies to solidify the role of [18F]FET PET in routine clinical practice. By offering a comprehensive overview of current research and practical implications, this paper highlights the added value of [18F]FET PET in improving management of glioma patients from diagnosis to follow-up.

Expanding the Spectrum of Autosomal Dominant ATP6V1A-Related Disease: Case Report and Literature Review

Background: Developmental and epileptic encephalopathies (DEE) are a group of disorders often linked to de novo mutations, including those in the ATP6V1A gene. These mutations, particularly dominant gain-of-function (GOF) variants, have been associated with a spectrum of phenotypes, ranging from severe DEE and infantile spasms to milder conditions like autism spectrum disorder and language delays. Methods: We aim to expand ATP6V1A-related disease spectrum by describing a six-year-old boy who presented with a febrile seizure, mild intellectual disability (ID), language delay, acquired microcephaly, and dysmorphic features. Results: Genetic analysis revealed a novel de novo heterozygous pathogenic variant (c.82G&gt;A, p.Val28Met) in the ATP6V1A gene. He did not develop epilepsy, and neuroimaging remained normal over five years of follow-up. Although ATP6V1A mutations have traditionally been linked to severe neurodevelopmental disorders, often with early-onset epilepsy, they may exhibit milder, non-progressive phenotypes, challenging previous assumptions about the severity of ATP6V1A-related conditions. Conclusions: This case expands the known clinical spectrum, illustrating that not all patients with ATP6V1A mutations exhibit severe neurological impairment or epilepsy and underscoring the importance of including this gene in differential diagnoses for developmental delays, especially when febrile seizures or dysmorphic features are present. Broader genotype–phenotype correlations are essential for improving predictive accuracy and guiding clinical management, especially as more cases with mild presentations are identified.

Molecular mechanisms of thalidomide effectiveness on COVID-19 patients explained: ACE2 is a new ΔNp63α target gene.

COVID-19 pandemic is caused by the SARS-CoV-2 virus, whose internalization and infection are mediated by the angiotensin-converting enzyme 2 (ACE2). The identification of novel approaches to tackle this step is instrumental for the development of therapies for the management of COVID-19 and other diseases with a similar mechanism of infection. Thalidomide, a drug sadly known for its teratogenic effects, has potent immunomodulatory and anti-inflammatory properties. Treatment with this drug has been shown to improve the immune functions of COVID-19 patients and proposed for the management of COVID-19 in clinical practice through drug repositioning. Here, we investigated the molecular details linking thalidomide to ACE2 and COVID-19, showing that in conditions mimicking SARS-CoV-2-associated cytokine storm, the transcription factor ΔNp63α and ACE2 are stabilized, and IL-8 production is increased. In such conditions, we found p63 to bind to and regulate the expression of the ACE2 gene. We previously showed that ΔNp63α is degraded upon thalidomide treatment and now found that treatment with this drug-or with its analogue lenalidomide-downregulates ACE2 in a p63-dependent manner. Finally, we found that thalidomide treatment reduces in vitro infection by pseudo-SARS-CoV-2, a baculovirus pseudotyped with the SARS-CoV-2 spike protein. Overall, we propose the dual effect of thalidomide in reducing SARS-CoV-2 viral re-entry and inflammation through p63 degradation to weaken SARS-CoV-2 entry into host cells and mitigate lung inflammation, making it a valuable option in clinical management of COVID-19. KEY MESSAGES: Thalidomide treatment results in p63-dependent ACE2 downregulation. ACE2 is a p63 transcriptional target. Thalidomide reduces the "cytokine storm" associated to COVID-19. Thalidomide prevents viral re-entry of SARS-CoV-2 by p63-dependent ACE2 downregulation. Thalidomide is a modulator of SARS-CoV-2 or other ACE2-dependent infections. ACE2 is modulated by a pharmacological substance.

Extracorporeal membrane oxygenation in acute respiratory distress syndrome caused by elderly tuberculous meningitis: a case report and review of the literature

Diagnosing and clinical management of tuberculous meningitis (TBM) are still challenging for clinicians. Analysis of cerebrospinal fluid (CSF) is an important diagnostic tool for patients with suspected central nervous system (CNS) diseases. Acute respiratory distress syndrome (ARDS), an inflammatory lung injury, can be treated by mechanical ventilation, fluid management, and even extracorporeal membrane oxygenation (ECMO). In addition, metagenomic next-generation sequencing (mNGS) can facilitate the detection of atypical, rare pathogens in clinical specimens. We report a case of a 65-year-old man with ARDS caused by TBM. He was admitted with a fever and shaking. Despite aggressive initial treatment, the patient progressed rapidly and developed ARDS. Without positive results of mNGS and culture, anti-tuberculosis (TB) treatment was started. In order to improve oxygenation levels, he was placed on veno-venous ECMO for 8 days. On day 47, the tracheotomy catheter was pulled out and sealed. The patient was conscious and could communicate with family members as normal.

Utility of interleukin-6 to identify serious bacterial infections in febrile infants aged ≤60 days.

The aim of this study is to investigate the utility of interleukin-6 (IL-6) in the early diagnosis of serious bacterial infections (SBI) in febrile infants and to compare it with C-reactive protein (CRP). Retrospective study conducted in the paediatric emergency department in Gothenburg, Sweden, on previously healthy, full-term infants aged ≤60 days with fever without a source (FWS) from 2014 to 2017. We included 536 infants with FWS, of whom IL-6 was analysed in 364 (68%) and CRP was analysed in 494 (92%). Approximately 70% of the infants presented with a fever duration of less than 12 h. The prevalence of SBIs was 14.8% (95% CI,11.3-18.9) in the IL-6 group and 17.8% (95% CI,14.5-21.5) in the CRP group. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of IL-6 ≥50 ng/L were 93%, 66%, 98% and 33%, respectively. For CRP ≥20 mg/L, the sensitivity, specificity, NPV, and PPV were 76%, 89%, 95%, and 55%, respectively. Logistic regression analysis showed that CRP was significantly associated with SBI (p < 0.0001) in the entire population, whereas IL-6 was not. Interleukin-6 showed high sensitivity and NPV, which might assist in identifying SBIs early in febrile infants. However, IL-6 was not shown to be superior to CRP and further studies are needed to investigate whether IL-6 should be incorporated in clinical management.

The Clinical Utility of Finding Unexpected Subclinical Spikes Detected by High-Density EEG During Neurodiagnostic Investigations.

This study aimed to analyze the frequency of unexpected subclinical spikes (USCS) in pediatric patients who underwent high-density electroencephalogram (HD-EEG). Of the 4481 successful HD-EEG studies, 18.5% (829) were abnormal, and 49.7% of these abnormal studies showed SCS, of which 64.1% were USCS. USCS were found to be correlated with attention/concentration deficits and executive dysfunction, often accompanied by the dual psychiatric diagnosis of ADHD. MRI revealed abnormal findings in 32.6% of the subjects with USCS, such as abnormal signal or signal hyperintensity in brain parenchyma, temporal or arachnoid cysts, and vascular malformations. Moreover, the USCS group who received neuropsychiatric testing scored lower than the population mean on Full-Scale Intelligence Quotient, Working Memory Index, and Processing Speed Index. This study highlights the potential of USCS as biomarkers that can lead to changes in clinical management and outcomes, provide valuable information about pathophysiological mechanisms, and suggest potential treatment pathways.

Rheumatic heart disease manifesting as mitral stenosis and tricuspid regurgitation in a young Asian male: a case report

Abstract Background Rheumatic heart disease (RHD) is a major global health issue because of its potential to cause heart failure. While RHD has been reported more frequently in women, this case report highlights the clinical manifestations, diagnosis, and management of rheumatic multivalvular disease in a young Asian male. Case Summary A 46-year-old Asian man with a history of percutaneous mitral valvuloplasty (PMV) was admitted with dyspnoea and generalised oedema that severely hindered his quality of life. Transthoracic and transoesophageal echocardiography revealed severe mitral stenosis (MS), left atrial appendage (LAA) thrombus, and severe tricuspid regurgitation (TR) due to RHD. Following a comprehensive evaluation by a multidisciplinary team, we advised mitral valve replacement, LAA thrombectomy, and tricuspid valve annuloplasty based on the detailed imaging of the valve anatomy and the patient's low surgical risk. Surgical intervention led to considerable improvement in the patient's symptoms, enabling a return to routine activities. Discussion This case highlights the chronic nature of RHD and its potential to cause heart failure. This report emphasises the need for regular follow-up in patients with a history of RHD to detect potential complications and ensure timely management. The successful outcome in this case underscores the importance of a team-based approach for managing complex valvular heart disease.

Cardiac metastasis in uterine cervical cancer : Asystematic review and case study.

Cardiac metastasis from cervical cancer is rare and only scarcely documented. We aim to present anew case and systematically summarize the available literature. PubMed, Scopus, Web of Science, Central, and ClinicalTrials.gov were systematically searched following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. Results were screened via title, abstract, and full text. Additionally, the reference lists of all papers chosen for the review were screened. Eighty-one papers were identified, describing 86cases in total. Cardiac metastasis occurred at all stages of cervical cancer and in all age groups. Median time from initial diagnosis to diagnosis of cardiac metastasis was 12months. Patients mainly complained of dyspnea and chest pain, 60.8% had pathologic ECG (electrocardiographic) findings. The cardiac mass was most frequently detected by transthoracic echography. The most common tumor histology was squamous cell carcinoma. Chemotherapy and surgical interventions were the main treatment modalities. Median survival after diagnosis of cardiac metastasis was 3months. This largest review on cardiac metastases from cervical cancer confirmed the heart as avery infrequent site of metastasis. There are < 100 cases described in the literature, with very poor prognosis and undefined clinical management.

Acceptance of emerging renal oncocytic neoplasms: a survey of urologic pathologists.

Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities.

Identification of two molecularly and prognostically distinct subtypes in acral melanoma using network prediction method.

Acral melanoma, characterized by its aggressiveness and poor prognosis compared to other melanoma subtypes, poses significant challenges in clinical management. However, the molecular underpinnings driving the biological and clinical features of this disease remain poorly understood. In this study, our aim was to elucidate the molecular landscape and the correlation between subtypes and clinical features of acral melanoma. We conducted comprehensive analyses to dissect the molecular characteristics of acral melanoma, employing a combination of multi-omics data analysis and network-based disease gene prediction algorithms. Single-cell RNA-Seq data were utilized to investigate the contribution of immunocytes to the molecular classification of acral melanoma. Additionally, we used clinical samples to validate the correlation between new subtypes and the prognosis of acral melanoma and the expression of subtype markers and verified the interaction between macrophages and acral melanoma cells at cellular level. Our study reveals the existence of two distinct subtypes of acral melanoma exhibiting marked differences in clinical behaviour, cellular and molecular mechanisms. We identified a robust biomarker panel (EREG, VSIG4, FCGR3A and RAB20) that accurately distinguishes these two subtypes with an impressive AUC of 0.946, validated using clinical samples. Subtype I, characterized by thinner Breslow thickness, demonstrates a favourable prognosis, whereas Subtype II represents a high-risk subtype with a propensity for dermal invasion. Notably, the signature gene EREG of Subtype I is enriched in FCN1+ macrophages, known for promoting inflammatory and immune responses. Conversely, signature genes VSIG4 and FCGR3A of Subtype II are enriched in SPP1+ macrophages, which exhibit significant crosstalk with tumour cells. Our findings significantly enhance the understanding of the molecular landscape of acral melanoma and offer novel insights into its clinical management by identifying distinct subtypes and potential therapeutic targets. The findings have to be confirmed in different cohorts in the future for full validation.

Navigating complexity: healthcare providers’ experiences with integrating physical health promotion in psychosis outpatient services in Sweden

Background Individuals with psychotic disorders face an increased risk of physical health issues, leading to reduced life expectancy. Despite recommendations to integrate physical health promotion into mental healthcare, challenges persist, and mortality from somatic diseases continues to rise. Understanding healthcare providers’ perspectives is crucial to overcoming these barriers. This study aims to explore the experiences of healthcare providers working in direct patient care and as unit heads regarding factors influencing health promotion in Swedish psychosis outpatient units. Methods A qualitative descriptive study was conducted in two specialized psychosis outpatient units. Thirteen healthcare providers, including clinical case managers and three heads of units, were individually interviewed. Thematic analysis was used to analyze the data. Results Three main themes were generated: (1) Health care providers’ attitudes and competence. The health care provider’s values and beliefs influenced the engagement in health promotion. (2) Patient-related aspects. Understanding how different patient life components shaped the physical health and need for measurements (3) Organizational prerequisites. Prioritizing resources and leadership impact the experience of health promotion. Clinical case management appeared as a promising approach to coordinate/integrate physical and mental health care, evident in themes 1 and 3. Conclusions Beyond organizational factors, healthcare providers’ skills, patient understanding, and ethical reflection influence their motivation to engage in physical health promotion. The study included only 13 participants, representing various professions, including managers who provided specific leadership perspectives. Clinical case managers appear well-suited to address physical health promotion due to their proficiency in shared decision-making and coordination.

How text messaging can improve the management of nurse-led clinics: a trial of direct messaging in a hyperthyroid telephone clinic

How text messaging can improve the management of nurse-led clinics: a trial of direct messaging in a hyperthyroid telephone clinic

Trismus in cold-stunned Kemp's ridley (Lepidochelys kempii) and loggerhead (Caretta caretta) sea turtles.

To describe the presentation, clinical findings, diagnosis, treatment, and outcome of cases of trismus (lockjaw) in cold-stunned sea turtles. 4 Kemp's ridley (Lepidochelys kempii) and 1 loggerhead (Caretta caretta) sea turtle. Cold-stunned sea turtles that presented with difficulty or inability to open their jaw between 2009 and 2023 were included. Information retrieved from medical records included signalment, physical exam findings, diagnostic information, definitive diagnosis via either advanced imaging or histopathology, treatment, and clinical outcome. Turtles presented between 4 and 48 days into rehabilitation. Three were diagnosed by advanced imaging (CT or MRI), and 2 were diagnosed based on clinical signs and postmortem histopathology. Treatment was multimodal and consisted of antibiotics (5/5), nonsteroidal anti-inflammatories (5/5), vitamin E (3/5), intralesional steroid therapy (3/5), acupuncture (3/5), antifungals (2/5), anti-inflammatory parenteral steroids (2/5), physical therapy (2/5), therapeutic laser (2/5), and supportive feeding via either total parenteral nutrition (1/5), or tube feedings (2/5). Two animals were released, 2 died naturally, and 1 was euthanized. Trismus (lockjaw) is an uncommon finding in stranded cold-stunned sea turtles that can have a significant impact on animal welfare if not diagnosed and treated. This report describes the condition to aid clinical case management and resource allocation in rehabilitation facilities.

Cholangiocarcinoma – A Detailed Review on Indian Literature

Cholangiocarcinoma, the predominant malignancy of the biliary tract, is associated with a dismal prognosis, typically yielding a median survival of 7–10 months post-diagnosis. The disease predominantly manifests as obstructive jaundice, and most patients are treated with palliative care due to the advanced stage at presentation. Although a wealth of international literature exists on this topic, detailed review from Indian literature is sparse. This review aims to fill this gap by aggregating and analyzing available Indian data from the past few decade regarding cholangiocarcinoma. We comprehensively explore clinical presentations, pathological features, diagnostic approaches, and management protocols specific to the Indian context. Emphasis is placed on unique aspects of intervention for alleviating obstructive jaundice and intraluminal therapies as documented in Indian studies. To our knowledge, this is the only available review article in detail and comprehensively about cholangiocarcinoma solely based on Indian publications.

Influence of perinatal factors on full-term low-birth-weight infants and construction of a predictive model.

Being too light at birth can increase the risk of various diseases during infancy. To explore the effect of perinatal factors on term low-birth-weight (LBW) infants and build a predictive model. This model aims to guide the clinical management of pregnant women's healthcare during pregnancy and support the healthy growth of newborns. A retrospective analysis was conducted on data from 1794 single full-term pregnant women who gave birth. Newborns were grouped based on birth weight: Those with birth weight < 2.5 kg were classified as the low-weight group, and those with birth weight between 2.5 kg and 4 kg were included in the normal group. Multiple logistic regression analysis was used to identify the factors influencing the occurrence of full-term LBW. A risk prediction model was established based on the analysis results. The effectiveness of the model was analyzed using the Hosmer-Leme show test and receiver operating characteristic (ROC) curve to verify the accuracy of the predictions. Among the 1794 pregnant women, there were 62 cases of neonatal weight < 2.5 kg, resulting in an LBW incidence rate of 3.46%. The factors influencing full-term LBW included low maternal education level [odds ratio (OR) = 1.416], fewer prenatal examinations (OR = 2.907), insufficient weight gain during pregnancy (OR = 3.695), irregular calcium supplementation during pregnancy (OR = 1.756), and pregnancy hypertension syndrome (OR = 2.192). The prediction model equation was obtained as follows: Logit (P) = 0.348 × maternal education level + 1.067 × number of prenatal examinations + 1.307 × insufficient weight gain during pregnancy + 0.563 × irregular calcium supplementation during pregnancy + 0.785 × pregnancy hypertension syndrome - 29.164. The area under the ROC curve for this model was 0.853, with a sensitivity of 0.852 and a specificity of 0.821. The Hosmer-Leme show test yielded χ 2 = 2.185, P = 0.449, indicating a good fit. The overall accuracy of the clinical validation model was 81.67%. The occurrence of full-term LBW is related to maternal education, the number of prenatal examinations, weight gain during pregnancy, calcium supplementation during pregnancy, and pregnancy-induced hypertension. The constructed predictive model can effectively predict the risk of full-term LBW.

Genetic background of neonatal hypokalemia.

Neonatal hypokalemia (defined as a serum potassium level <3.5 mEq/L) is the most common electrolyte disorder encountered in clinical practice. In addition to common secondary causes, primary genetic etiologies are also closely associated with hypokalemia. Currently, a systematic characterization of these genetic disorders is lacking, making early recognition challenging and clinical management uncertain. This review will aid clinicians by summarizing the genetic background of neonatal hypokalemia from two aspects: (1) increased excretion of K+, whereby genetic factors primarily lead to increased renal Na+ influx, decreased H+ efflux, or reduced Cl- influx, ultimately resulting in increased K+ efflux; and (2) decreased extracellular distribution of K+, whereby genetic factors result in abnormalities in transmembrane ion channels, reducing outward potassium currents or generating inward cation leak currents. We describe over ten genetic diseases associated with neonatal hypokalemia, which involve pathogenic variants in dozens of genes and affect multiple target organs, including the kidneys, intestines, and skeletal muscle. For example, in the renal tubules, pathogenic variants in the SLC12A1 gene encoding the Na+-K+-2Cl- cotransporter lead to renal K+ loss, causing Bartter syndrome type I; in intestinal epithelial cells, pathogenic variants in the SLC26A3 gene result in a defective Cl⁻-HCO₃⁻ exchanger, causing congenital chloride diarrhea; and in skeletal muscle, pathogenic variants in the CACNA1S gene impact membrane calcium ion channels resulting in hypokalemic periodic paralysis. Given the wide variety of organs and genetic alterations that can contribute to neonatal hypokalemia, we believe this review will provide valuable insights for clinical diagnosis and treatment.