Severe Cases Research Articles

Visual grading of valvular regurgitation is inferior to measurement – results from the VIAVA-study (VIsual Assessment of VAlvular Regurgitation)

While the visual estimation of systolic left ventricular function by experienced examiners closely aligns with quantitative methodologies, the accuracy of visual estimation in determining the severity of valvular regurgitation using colour flow Doppler assessment of native heart valves remains largely unexplored. This study analysed the ability of 262 physicians to visually estimate the severity of 12 native valve regurgitations by grading colour Doppler transthoracic echocardiography loops in an online questionnaire. The assessments of the participants were compared to standardized quantitative evaluations conducted by certified echocardiography experts. Of the three valves to assess, evaluations by the participants showed the best correlation (Rs = 0.75, p < 0.0001) and agreement (percent agreement: 66.4%) with those of the experts in mitral valve regurgitation (MR). High agreement was observed for mild regurgitation across all valves (MR 94.5%, AR 80.3% and TR 88.7%), while consensus diminished in moderate (MR 55.9%, AR 49.5% and TR 55.0%) and severe regurgitation (MR 57.6%, AR 67.4%, TR 14.6%). The study underscores the potential utility of visual estimation of valvular regurgitation in clinical settings for identifying clinically relevant regurgitations. However, our findings also highlight the importance of integrating visual estimation with quantitative methods, particularly in moderate and severe cases of regurgitation.

Recalcitrant Torticollis: A Formidable Treatment Challenge.

There are few evidence-based practice guidelines for recalcitrant torticollis (RT), defined as torticollis that persists past 1 year of age despite conservative therapy. Available evidence recommends a combination of physical therapy (PT), occupational therapy (OT), botulinum toxin injection (BTI), and in the most severe cases, surgical release. This is a single-center, retrospective study conducted with Institutional Review Board approval. Inclusion criteria were diagnosis of congenital muscular torticollis before 1 year old and persistence of symptoms past 1 year despite conservative treatment between January 1, 2005, and January 30, 2023. Patients with incomplete data, acquired torticollis, confounding diagnoses, or who did not receive a diagnosis or conservative therapy before 1 year of age were excluded. Seventy-seven patients met the inclusion criteria. The average age at diagnosis was 4.5 ± 2.5 months. Initial treatment consisted of PT for 61 patients (79.2%), stretching exercises for 11 patients (14.3%), and OT for 4 patients (5.2%). Regardless of timing, 74 patients in total (96.1%) received PT for an average of 13.3 ± 8.6 months. Conservative treatment modalities led to the resolution of symptoms for 40 patients (51.2%) and improvement of symptoms for 35 patients (45.5%). Two patients received at least 1 BTI which led to further improvement of symptoms. One patient underwent operative intervention which consisted of sternocleidomastoid release. RT is a challenging clinical entity that requires diligent multidisciplinary care. Patients who present and begin conservative therapy before 1 year of age are likely to have improvement or resolution of symptoms without more advanced therapies.

Nutritional disorders and nutrition-related conditions: an underestimated clinical problem in systemic sclerosis

Nutritional disorders are significant but often underestimated complications in patients with systemic sclerosis (SSc). The most prevalent nutritional disorders in SSc are malnutrition, affecting up to 62.5% of patients, and sarcopenia, with a frequency of up to 42%. Thus, clinical vigilance is recommended for the detection of eating disorders in SSc patients, particularly those with gastrointestinal involvement, cardiopulmonary complications, an advanced disease stage, and high disease activity. Nutritional treatment should be carefully tailored to the patients’ clinical condition to ensure that it effectively addresses their specific needs. Studies focusing on enteral nutrition in SSc patients demonstrate its effectiveness in stabilizing or improving nutritional status in malnourished patients. In severe cases, parenteral nutrition offers viable options to support patient health. The findings highlight the importance of early nutritional assessment and intervention in improving patient outcomes and suggest that individualized nutritional therapy can be a critical component of comprehensive care for SSc patients.

A Severe Case of Plasmodium falciparum Malaria in a 44-Year-Old Caucasian Woman on Return to Western Romania from a Visit to Nigeria

Malaria is currently the most prevalent life-threatening infectious disease in the world. In this case report, we present a 44-year-old Caucasian woman with a low level of education and no significant past medical history who presented to the emergency room of the Emergency County Hospital of Arad, Romania, with a general affected state, a fever of 38.5 °C, chills, weakness, headache, muscle pain, nausea, icterus, and watery diarrheal stool. A viral infection was initially suspected, and the patient was transferred to the Infectious Diseases Department. The anamnesis revealed that the patient traveled to Nigeria (Ado Ekiti) and returned to Romania 14 days before presenting to the hospital without following antimalarial prophylaxis. A peripheral blood smear was conducted and revealed parasitemia with ring forms of Plasmodium falciparum (P. falciparum) of 10–15% within the red blood cells. Parasitemia increased within a day to 15–18%, and her health rapidly deteriorated. She was transferred to the Victor Babeș Infectious Disease Hospital in Bucharest for the urgent initiation of antimalarial treatment. The patient’s condition continued to worsen rapidly, and she succumbed to her illness due to multi-organ failure. This report details the first documented case of malaria imported from Nigeria to Romania. People traveling to malaria-endemic areas should be educated about preventing this parasitic infection, both by adopting measures to reduce the risk of mosquito bites and by using appropriate chemoprophylaxis. In the context of resuming travel after the COVID-19 pandemic, understanding and adhering to prophylactic measures is crucial to avoid tragic situations, as highlighted in this case report.

Association between RANTES/CCL5 levels with Plasmodium infections and malaria severity: a systematic review

BackgroundMalaria continues to be a significant global health concern, and developing effective therapeutic strategies requires an understanding of the immune response to the disease. This systematic review synthesized the current body of research on the role of regulated on activation, normal T cell expressed and secreted (RANTES)—in the pathogenesis and disease severity of malaria.MethodsA systematic review protocol was registered with PROSPERO under the registration number CRD42024535822. The systematic review was conducted following PRISMA guidelines to identify studies examining RANTES levels in individuals infected with Plasmodium species. Searches were performed across multiple databases, including ProQuest, Journals@Ovid, Embase, Scopus, PubMed, and MEDLINE. Further searches were performed in Google Scholar. Quality assessment was done using the Joanna Briggs Institute (JBI) critical appraisal tools. Alterations in RANTES levels in patients with malaria were synthesized narratively.ResultsA comprehensive search of major databases identified 22 studies meeting inclusion criteria, predominantly focusing on Plasmodium falciparum and Plasmodium vivax infections. RANTES levels were found to vary significantly across different severities of malaria, with several studies reporting lower levels in severe cases compared to non-malarial controls. However, inconsistencies were observed in the alterations of RANTES levels between severe and non-severe malaria cases.ConclusionTaken together, the finding of this systematic review underscore the complex regulation of RANTES in malaria pathophysiology. Future research should focus on longitudinal assessments to elucidate the dynamic role of RANTES throughout the course of malaria and recovery, to potentially inform the design of novel therapeutic strategies.

Correction of Severe Pterygium Colli with a Staged, Double, Posterior and Lateral Approach: A Case Report

AbstractPterygium colli is a rare congenital disorder characterized by excessive skin in the lateral and posterior neck, often associated with genetic syndromes such as Turner's syndrome or Klippel–Feil syndrome. Severe presentations present special challenges for surgeons since its diagnosis is not always evident and its treatment often results in important scaring. Surgical correction of the typical cases mostly involves a lateral approach, but in this “special” case, we used a double, posterior and lateral approach. A 15-month-old girl with prenatal diagnosis of a cystic lesion in the posterior neck presented with massive neck webbing at birth. Genetic studies ruled out chromosomal disorders and RASA 1 mutations. Surgical correction involved a modified posterior approach combined with a lateral approach 1 year later. The cervical tissue redundancy was successfully reduced achieving a good aesthetic outcome with very acceptable scars. At 1 year of follow-up, the patient continues with good neck appearance and mobility. The goal of surgical treatment of pterygium colli is achieving a harmonious neck contour with good function and minimal scarring while minimizing complications and sequelae. No consensus exists on the optimal approach for its correction, emphasizing the need for individualized treatment considering patient-specific characteristics, particularly in the severe cases.

Cost- effectiveness of a simplified acute malnutrition program: a secondary analysis of the OptiMA randomized clinical trial in the Democratic Republic of the Congo.

Acute malnutrition (AM) causes large loss of life and disability in children in Africa. Researchers are testing innovative approaches to increase efficiency of treatment programs. This paper presents results of a cost-effectiveness analysis of one such program in the Democratic Republic of the Congo (DRC) based on a secondary analysis of a randomized controlled trial Optimizing Treatment for Acute Malnutrition (OptiMA), conducted in DRC in 2018-20. 896 children aged 6-59 months with a mid-upper arm circumference (MUAC) <125 mm or with oedema were treated and followed for six months. Cost-effectiveness of OptiMA using ready-to-use therapeutic food (RUTF) at a tapered dose was compared with the standard national program in which severe cases (SAM) received RUTF proportional to weight, and moderate cases (MAM) were referred to another clinic for a fixed dose regimen of ready-to-use supplementary food. Cost analysis from provider perspective used data collected during the trial and from administrative records. Statistical differences were derived using t-tests. The mean cost per enrolled child under OptiMA was $123 [95%CI: 114-132], not statistically different from the standard group ($127 [95%CI: 118-136], p=0.549), while treatment success (i.e. recovery to MUAC > 125mm and no relapse for 6 months) under OptiMA was 9 percentage points higher (72% vs 63%, p=0.004). Among children with SAM at enrollment, there was no significant difference in treatment success between OptiMA and standard (70% vs 62%, p=0.12) but OptiMA's mean cost per enrolled child was 23% lower ($128 vs $166, p<0.0001). OptiMA was more effective at preventing progression to SAM among those enrolled with MAM (5% vs 16%, p<0.0001) with an incremental cost-effectiveness ratio (ICER) of $234 per progression to SAM prevented. Overall, OptiMA had significantly better outcomes and was no more expensive than standard care. Its adoption could enable more children to be successfully treated in contexts where therapeutic food products are scarce.

Evaluation of Severe ultrasound and gene diagnosis in cardiac index and shock patient index of shock patients.

The kidney is the most vulnerable organ in severe patients. In severe cases, the fatality rate of acute kidney damage is as high as 30% ∼ 60%. Severe ultrasound is a non-invasive method to evaluate renal blood flow. It can give a semi-quantitative score of renal blood flow and measure the Resistance Index (RI), which can reflect renal artery blood flow to a certain extent. There is little literature on hemodynamic regulation in septic shock patients, but almost no research report on the relationship between hemodynamics and RI exists. Therefore, this paper proposed the analysis of severe ultrasound and gene diagnosis in cardiac index and peripheral vascular RI of shock patients. This paper mainly expounded on detecting renal function parameters and RI in patients with viral shock to understand further the correlation between them and renal flow and RI. It could be seen from the experimental results that the P values before and after resuscitation in the two groups with and without elevated Cardiac Output (CO) were 0.41 and 0.12, respectively, which were more significant than 0.05. RI had no apparent relationship with CO, and RI could not be used as an evaluation index for patients with early septic shock.

Demographic and clinical profile of patients with acute biliary pancreatitis: an experience in Patan academy of health sciences

Background: Acute pancreatitis is one of the most common causes of acute abdomen encountered in emergency department with wide range of severity from mild self-limiting disease to severe and rapidly progressive illness leading to multi organ failure and even death. Gall stones are leading cause of acute pancreatitis. This study has been carried out to find out demographic pattern and clinical profile of patients with acute biliary pancreatitis. Methods: This is a prospective cross-sectional study carried out in the department of surgery in Patan academy of health sciences (PAHS) in the time period between May 1, 2021 and April 30, 2022. The process of data collection was started after obtaining ethical approval from institutional review committee (IRC) of PAHS, and written informed consent was obtained from patients. Total sampling was done and 66 patients were enrolled into the study, who were diagnosed as acute biliary pancreatitis. Data was analyzed with SPSS ver 25 and Microsoft excel 2016. Results: Out of total 66 patients in the study 25 (37.9%) were male and 41 (62.1%) were female with male: female ratio of 1:1.64. Mean age was 48.42±16.62 years. ranging from 16-88 years. Epigastric abdominal pain was predominant presenting symptoms accounting for 57 (86.4%) cases. Pleural effusion was most common complication seen in 17 (25.8%) cases. Mortality occurs in 2 (3%) cases, both of cases had severe pancreatitis. Only 21 (31.8%) patients underwent cholecystectomy among which 13 (19.7%) interval and 8 (12.1%) index cholecystectomy. Conclusions: Female gender with age group of 40-60 years. predominates acute biliary pancreatitis. Though most of the cases are mild and have benign course, severe cases and patients with advanced age are associated with high mortality. Acceptance of index cholecystectomy is very low.

Anxiety, depression and access to mental health services among internally displaced persons in Mogadishu, Somalia: a cross-sectional survey

ObjectiveThe study aims to evaluate anxiety and depression levels and access to mental health services among internally displaced persons (IDPs) in Mogadishu, Somalia.DesignA community-based, cross-sectional survey was carried out in...

Stage-Specific Milk Yield Losses and Associated Sweating, Respiration, and Rectal Temperature Responses Under Varying THI Thresholds in Lactating and Dry Cows

Heat stress (HS) may result in changes in the behavior, endocrine system, and physiological characteristics of dairy cows, and it may even lead to death in severe cases. As the effects of global warming have become more notable, the prevalence of HS has increased among dairy cows. Therefore, comprehensive strategies, including not only cooling measures but also dietary adjustments and genetic improvements for heat tolerance, are required to help these animals regulate their body temperature and avoid HS. In addition, detecting HS signs is essential for both lactating and dry cows to ensure appropriate interventions. The temperature-humidity index (THI) is a widely used tool for evaluating the effects of HS on livestock. Since the physiological state of cattle significantly influences their responses to HS, it is imperative to establish specific THI thresholds for both lactating and dry cows to implement appropriate cooling regimens and optimize animal welfare. In this study, we used the THI to investigate the relationship between rectal temperature (RT), respiration rate (RR), and sweating rate (SR) in lactating and dry cows. We also explored the relationships between milk yield at different lactation stages and THI thresholds. The results indicated that lactating and dry cows had different THI thresholds based on their immediate physiological responses. Compared with lactating cows, dry cows had higher THI thresholds for RT, RR, and SR. In addition, cows in early-, intermediate-, and late-lactation stages under thermoneutral conditions produced significantly more milk than did those under mild, moderate, and severe HS conditions, indicating that milk yield losses occur under HS conditions. Taken together, these findings provide valuable insights into how HS can be mitigated in subtropical dairy farms. For lactating cows, implementing cooling measures is recommended when the THI reaches 66 to 67, whereas for dry cows, waiting until the THI reaches 73 is recommended. Milk yield losses may occur when lactating cows are under HS conditions. Therefore, appropriate cooling measures should be implemented at accurate THI thresholds to ensure optimal animal welfare for both lactating and dry cows.

Evaluating the Impact of Moderate and Severe Varicella Infections on Danish Children Under 18 Years Old: A Comprehensive Analysis From 2015 to 2023

Background: Varicella (chickenpox) caused by varicella-zoster virus (VZV) is a highly contagious pediatric disease. While it typically manifests as a mild disease, complications leading to hospitalization are not uncommon. Knowing the current disease burden, seasonality and risk groups is pivotal for evidence-based decisions on the introduction of a varicella vaccine. Methods: Using the Danish National Patient Register and medical helpline records from the Capital Region, we estimated the burden of VZV infections among children younger than 18 years in Denmark from 2015 to June 2023. Results: We identified 14,443 cases with annual incidence rates of 325/100,000 children for mild-to-moderate varicella cases (helpline calls), 35/100,000 for moderate-to-severe cases (outpatients) and 10/100,000 for severe cases (hospitalized). Mild cases were most prevalent in children aged 1–4 years, while moderate-to-severe cases were most prevalent among infants &lt;1 year old. Among hospitalized cases, 23.2% had underlying diseases and 47.3% experienced complications. In April 2022, rapid surge in all types of VZV cases occurred, where admissions surpassed the prepandemic level. Conclusion: This study documents that varicella is highly prevalent among Danish young children. Mild-to-moderately severe cases strain healthcare, causing increased helpline calls and posing a persistent hospitalization risk, especially for infants and children with underlying conditions.

The value of a PET scan in selecting the best lymph node to biopsy, and confirming the diagnosis of idiopathic multicentric Castleman disease with HLH and EBV viremia in a previously healthy adult

Introduction: Castleman disease (CD) is a rare lymphoproliferative disorder having a variegated clinical presentation. Diagnosis of the idiopathic HIV- and HHV8-negative multicentric CD (iMCD) subtype poses a challenge given its non-specific clinical manifestations. iMCD presents as diffuse lymphadenopathy with inflammatory manifestations, primarily driven by interleukin-6 (IL-6). Treatment includes suppressing the inflammation by targeting IL-6 with monoclonal antibodies such as siltuximab and, in severe cases, immuno-chemotherapy to control B- and plasma-cell activation. Case description: A previously healthy 43-year-old male presented to the emergency department with fever, night sweats, anasarca, anaemia, thrombocytopenia and acute renal insufficiency. Extensive blood and imaging workup was initiated. Several diagnoses were entertained including viral infections (comprising COVID-19), haemophagocytic lymphohistiocytosis, lymphoma and autoimmune conditions. Initial axillary lymph node biopsy was not diagnostics. A positron emission tomography (PET) scan showed diffuse and symmetrical cervical and hilar/mediastinal lymphadenopathies. A mediastinal lymph node biopsy was then performed and indicated iMCD. The patient was treated with high-dose steroids and siltuximab. An Epstein-Barr virus (EBV) PCR was positive, and rituximab was added to the treatment. The patient recovered and felt well after two months. Conclusions: Non-specific symptoms, non-diagnostic first biopsy and iMCD resemblance to haemophagocytic lymphohistiocytosis further complicated the diagnosis. A PET scan allowed the best selection of a lymph node to be biopsied. Anti-IL6 is the recommended treatment; however, we are lacking information on the duration of siltuximab, and the long-term toxicity and immunosuppressive effect of this treatment. The contribution of EBV reactivation in the development and treatment of iMCD needs further investigation.

Diabetic Ketoacidosis as a Debut and Immune-Mediated Complication Caused by Pembrolizumab: Case Report

Background/Objectives: Diabetic ketoacidosis (DKA) is an acute and potentially life-threatening complication characterized by the accumulation of ketone bodies in the blood, primarily occurring in patients with type 1 diabetes and occasionally in those with type 2 diabetes under certain conditions. DKA presents with symptoms such as polyuria, polydipsia, polyphagia, and, in severe cases, mental status changes. Identifying the triggering factor is crucial to prevent complications and effectively manage this medical emergency. Methods: This report describes the case of a 58-year-old male patient with stage IIIb nodular melanoma, diagnosed in November 2022. Results: After receiving five cycles of pembrolizumab, the patient developed de novo DKA, presenting with blurred vision, asthenia, adynamia, polyuria, and polydipsia. He was admitted to the emergency department with a blood glucose level of 764 mg/dL, confirming hyperglycemia and metabolic acidosis. He was transferred to the intensive care unit for fluid resuscitation and insulin infusion. After adequate clinical evolution and meeting the criteria for DKA resolution, possible autoimmune endocrinopathies secondary to immunotherapy were considered. Due to this complication, the oncological treatment was changed. Finally, the patient was discharged with the need to continue insulin therapy and oral hypoglycemic agents, along with thyroid hormone supplementation. Conclusions: The novelty of this case lies in the presentation of DKA as an immune-mediated complication induced by pembrolizumab, highlighting the importance of closely monitoring patients receiving immune checkpoint inhibitors to detect and manage emerging autoimmune endocrinopathies. It is essential to adjust oncological treatment according to the patient’s response and promptly manage autoimmune endocrinopathies to improve clinical outcomes and the patient’s quality of life.

Review of the Hazards and Contraindications of Etomidate.

Etomidate, an ultrashort-acting non-barbiturate sedative derived from imidazole, exerts potent inhibitory effects on the central nervous system. It is commonly employed for the induction of intravenous general anaesthesia or assisted anaesthesia. Recently, etomidate has emerged as an alternative to narcotics and novel psychoactive substances, leading to an increasing trend of abuse. Chronic overdose of etomidate can result in irreversible brain damage and various mental disorders. Severe cases may manifest as mental disturbances, behavioural disorders, self-mutilation and even death. The toxicological mechanisms of etomidate remain poorly understood. Additionally, there is limited information on the clinical symptoms and histopathological changes associated with etomidate poisoning and standardized detection methods for etomidate in blood, urine and hair are lacking. Consequently, further research on toxicological pathology and the development of reliable testing methods is crucial. This study reviews the metabolism, distribution, adverse reactions, poisoning manifestations, toxicology mechanisms and testing methods of etomidate.

The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient’s overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies.

Enhanced predictability and interpretability of COVID-19 severity based on SARS-CoV-2 genomic diversity: a comprehensive study encompassing four years of data.

Despite the end of the global Coronavirus Disease 2019 (COVID-19) pandemic, the risk factors for COVID-19 severity continue to be a pivotal area of research. Specifically, studying the impact of the genomic diversity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on COVID-19 severity is crucial for predicting severe outcomes. Therefore, this study aimed to investigate the impact of the SARS-CoV-2 genome sequence, genotype, patient age, gender, and vaccination status on the severity of COVID-19, and to develop accurate and robust prediction models. The training set (n = 12,038), primary testing set (n = 4,006), and secondary testing set (n = 2,845) consist of SARS-CoV-2 genome sequences with patient information, which were obtained from Global Initiative on Sharing all Individual Data (GISAID) spanning over four years. Four machine learning methods were employed to construct prediction models. By extracting SARS-CoV-2 genomic features, optimizing model parameters, and integrating models, this study improved the prediction accuracy. Furthermore, Shapley Additive exPlanes (SHAP) was applied to analyze the interpretability of the model and to identify risk factors, providing insights for the management of severe cases. The proposed ensemble model achieved an F-score of 88.842% and an Area Under the Curve (AUC) of 0.956 on the global testing dataset. In addition to factors such as patient age, gender, and vaccination status, over 40 amino acid site mutation characteristics were identified to have a significant impact on the severity of COVID-19. This work has the potential to facilitate the early identification of COVID-19 patients with high risks of severe illness, thus effectively reducing the rates of severe cases and mortality.

A Long-Term Follow-Up Study of Serum NFATc3 Levels in Pediatric Patients with Bronchial Asthma: A Prospective Observational Case-Control Investigation.

The early and precise diagnosis of asthma significantly impacts the long-term health outcomes of pediatric patients. The sensitivity and specificity of current biomarkers, however, are frequently limited. Our study aimed to evaluate the clinical significance of nuclear factor of activated T cells, cytoplasmic 3 (NFATc3), in pediatric bronchial asthma, focusing on its diagnostic and prognostic value for disease severity and recurrence. This observational, prospective case-control study involved 200 pediatric patients with bronchial asthma and 200 age- and sex-matched healthy controls, from January 2020 to January 2023. Follow-up varied from 1 to 3 years. We measured levels of NFATc3 and inflammatory cytokines interleukin-1β (IL-1β), IL-6, and TNF-α via enzyme-linked immunosorbent assay. NFATc3 and IL-1β levels at enrollment were markedly higher in patients with acute exacerbations and those classified as severe, compared with their less severe counterparts. Throughout the study, NFATc3, IL-1β, and IL-6 levels significantly increased in severe or acutely exacerbating cases. The diagnostic value of NFATc3 was assessed through receiver operating characteristic curve analysis, which showed its potential in diagnosing bronchial asthma and identifying severe cases. Spearman's analysis confirmed positive associations between peak NFATc3 and cytokine levels. Importantly, disease type, NFATc3 values at enrollment, as well as peak IL-6 levels were identified as independent risk factors for severe bronchial asthma. Elevated NFATc3 is linked with the severity of pediatric bronchial asthma and serves as a potential biomarker for diagnosis and severity prediction, emphasizing its role in guiding treatment strategies.

Positive Unlabeled Learning Selected Not At Random (PULSNAR): class proportion estimation without the selected completely at random assumption

Positive and unlabeled (PU) learning is a type of semi-supervised binary classification where the machine learning algorithm differentiates between a set of positive instances (labeled) and a set of both positive and negative instances (unlabeled). PU learning has broad applications in settings where confirmed negatives are unavailable or difficult to obtain, and there is value in discovering positives among the unlabeled (e.g., viable drugs among untested compounds). Most PU learning algorithms make the selected completely at random (SCAR) assumption, namely that positives are selected independently of their features. However, in many real-world applications, such as healthcare, positives are not SCAR (e.g., severe cases are more likely to be diagnosed), leading to a poor estimate of the proportion, α, of positives among unlabeled examples and poor model calibration, resulting in an uncertain decision threshold for selecting positives. PU learning algorithms vary; some estimate only the proportion, α, of positives in the unlabeled set, while others calculate the probability that each specific unlabeled instance is positive, and some can do both. We propose two PU learning algorithms to estimate α, calculate calibrated probabilities for PU instances, and improve classification metrics: i) PULSCAR (positive unlabeled learning selected completely at random), and ii) PULSNAR (positive unlabeled learning selected not at random). PULSNAR employs a divide-and-conquer approach to cluster SNAR positives into subtypes and estimates α for each subtype by applying PULSCAR to positives from each cluster and all unlabeled. In our experiments, PULSNAR outperformed state-of-the-art approaches on both synthetic and real-world benchmark datasets.

Impact of COVID-19 Pandemic on Delay of Melanoma Diagnosis: A Systematic Review and Meta-Analysis

Introduction: Several studies have described how the restrictive measures due to COVID-19 have delayed melanoma diagnoses, resulting in an increased rate of more severe cases. Summarizing the sparse results in this context might help to understand the real impact of the COVID-19 pandemic on melanoma. We conducted a systematic review and meta-analysis to investigate how the clinical and prognostic factors of new melanoma diagnoses changed after COVID-19. Methods: A literature search in MEDLINE, EMBASE, and Scopus was conducted in September 2023. We included studies published in peer-reviewed journals reporting histopathological data on new diagnoses of cutaneous melanoma in adult patients during and/or after the lockdown compared to those diagnosed before the COVID-19 pandemic. A meta-analysis was conducted utilizing a random effects model. The between-study heterogeneity was assessed via Higgins’s I2 statistic. Publication bias was assessed using the Begg and Egger test. This study adhered to the updated PRISMA guidelines. The primary outcome was a comparison of melanoma thickness between the pre-COVID-19 and post-lockdown periods. The secondary outcomes were evaluations of the histopathological subtype, stage, and presence of ulceration and mitosis in melanomas diagnosed in these two pandemic phases. Results: The study included 45 articles. We found a significantly higher proportion of all factors indicating worse prognosis in the post-lockdown period compared to the pre-COVID-19 phase, including high thickness (SOR = 1.14, 95%CI 1.08–1.20 for 1–2 mm; SOR = 1.62, 95%CI 1.08–2.40, for &gt;2 mm), the presence of ulcerations (SOR = 1.35, 95%CI 1.18–1.54), nodular subtype (SOR = 1.19, 95%CI 1.07–1.32), the presence of mitosis (SOR = 1.57, 95% CI 1.17–2.11), and stage III (SOR = 1.39, 95%CI 1.19–1.52) and IV (SOR = 1.44, 95%CI 1.26–1.63). Limitations include the limited studies’ geographical distribution and moderate heterogeneity affecting meta-analysis estimates. Conclusions: Our meta-analysis provided evidence of more advanced melanomas diagnosed in the post-COVID-19 pandemic period, emphasizing the importance of creating and updating pandemic preparedness plans to limit the impact of any future events on oncological care.