Pulmonary Histoplasmosis: Clinical and Imagistic Characteristics

Histoplasmosis is a condition caused by infection with a fungus, called Histoplasma capsulatum. The fungus can be found in the environment in an inactive form (spores), particularly in soil with great amount of bird or bat droppings. Infection occurs when a person inhales the spores and sometimes it can become aggressive especially when the immunity is low or the person has been in contact with a very high amount of fungi. The magnitude of symptoms correlates with the amount of fungi in contact with the patient. About 90% of patients are usually asymptomatic or presenting very few symptoms. However, in immunosuppressed patients, the infection can spread and affect several organs and systems like eyes, liver, spleen, central nervous system, hematological manifestations, joint manifestations. In patients with pre-existing lung disease chronic pulmonary histoplasmosis is not uncommon

Synthesis, characterization, and in vitro-in ovo toxicological screening of silibinin fatty acids conjugates as prodrugs with potential biomedical applications

Silibinin (SIL), the most active phytocompound from Silybum marianum (L.), exerts many biological effects but has low stability and bioavailability. To overcome these drawbacks, the current research proposed the synthesis of silibilin oleate (SIL-O) and silibilin linoleate (SIL-L) derivatives as prodrugs with potentially optimized properties for biomedical applications, and the establishment of their in vitro-in ovo safety profiles. The physicochemical characterization of the obtained compounds using density functional theory (DFT) calculations, and Raman and 1H liquid-state nuclear magnetic resonance (NMR) spectroscopy confirmed the formation of SIL-O and SIL-L complexes. Computational predictions revealed that these lipophilic derivatives present a lower drug-likeness score (-29.96 for SIL-O and -23.55 for SIL-L) compared to SIL, but an overall positive drug score (0.07) and no risk for severe adverse effects. SIL-O and SIL-L showed no cytotoxicity or impairment in cell migration at low concentrations, but at the highest concentration (100 µM), they displayed distinct toxicological profiles. SIL-L was more cytotoxic (on cardiomyoblasts - H9c2(2-1), hepatocytes - HepaRG, and keratinocytes - HaCaT) than SIL-O or SIL, significantly inhibiting cell viability (< 60%), altering cellular morphology, reducing cell confluence (< 70%), and inducing prominent apoptotic-like nuclear features. At the concentration of 100 µM, SIL-O presented an irritation score (IS) of 0.61, indicating a lack of irritant effect on the chorioallantoic membrane (CAM), while SIL-L was classified as a slight irritant with an IS of 1.99. These findings outline a more favorable in vitro and in ovo biocompatibility for SIL-O compared to SIL-L, whose applications are dosage-limited due to potential toxicity

Evaluating the Impact of Obsessive-Compulsive Symptoms and Personality Types on Perinatal Depressive Symptoms

Perinatal depression (PPD) presents a significant public health concern, often influenced by psychological and personality factors. This study investigated the impact of personality traits, particularly neuroticism, and obsessive-compulsive disorder (OCD) symptoms on the severity of PPD. The primary aim was to quantify the contributions of these factors to the risk and severity of PPD to enhance early intervention strategies. A total of 47 pregnant women with depressive symptoms per DSM-5 criteria at “Pius Brinzeu” County Emergency Hospital in Timisoara, Romania, were enrolled in this cross-sectional study, as well as 49 women without depressive symptoms as controls. Personality traits were assessed using the NEO Five-Factor Inventory (NEO-FFI), and OCD symptoms were measured using the Obsessive-Compulsive Inventory (OCI). Depression severity was evaluated using the Edinburgh Postnatal Depression Scale (EPDS). This set of questionnaires were administered antepartum and postpartum. The logistic regression analysis highlighted neuroticism as a significant predictor of PPD severity, with an increase in neuroticism associated with a higher risk of PPD (coefficient = 0.24, p p = 0.009). Higher OCD symptomatology, particularly ordering and hoarding, were linked with increased depression scores. Specifically, the total OCI score significantly predicted the EPDS score (coefficient = 0.03, p = 0.003). Furthermore, significant increases in EPDS anxiety and depression scores were observed in the perinatal period, indicating worsening of symptoms (anxiety coefficient = 0.51; p < 0.001). The findings suggest that personality traits like neuroticism and OCD symptoms significantly contribute to the severity of PPD. Interventions targeting these specific traits could potentially mitigate the risk and severity of perinatal depression, underscoring the need for personalized treatment plans that consider these psychological dimensions

Analysis of Vaginal Microbiota Variations in the Third Trimester of Pregnancy and Their Correlation with Preterm Birth: A Case-Control Study

This study conducted a detailed analysis of the vaginal microbiota in pregnant women to explore its correlation with preterm birth (PTB) outcomes. The primary objective was to identify microbial variations associated with increased PTB risk. Secondary objectives included investigating how changes in microbial composition relate to the local immune environment and PTB. Utilizing a retrospective case–control design, the study involved pregnant women with liveborn infants between 2019 and 2023. In total, 89 women who delivered preterm and 106 term deliveries were included. Data collection focused on third-trimester vaginal cultures. Statistically significant differences were observed between the preterm and full-term groups in several areas. The median white blood cell count (10.2 × 103/mm3 vs. 7.6 × 103/mm3, p = 0.009) and neutrophil count (7.2 × 103/mm3 vs. 5.1 × 103/mm3, p p p = 0.001) as indicated by the Nugent Score. The study noted a significant association of PTB with the presence of Candida spp. (OR = 1.84, p = 0.018), Gardnerella vaginalis (OR = 2.29, p = 0.003), Mycoplasma hominis (OR = 1.97, p = 0.007), and Ureaplasma urealyticum (OR = 2.43, p = 0.001). Conversely, a reduction in Lactobacillus spp. correlated with a decreased PTB risk (OR = 0.46, p = 0.001). The study provides compelling evidence that specific vaginal microbiota components, particularly certain pathogenic bacteria and an altered Lactobacillus profile, are significantly associated with PTB risk. These findings highlight the potential of targeting microbial factors in strategies aimed at reducing PTB rates. Further research is necessary to fully understand the complex interplay between microbial dynamics, host immunity, and PTB outcomes

Diagnosis and Management of Febrile Neutropenia in Pediatric Oncology Patients—A Systematic Review

Infectious diseases are associated with a high morbidity and mortality rate among pediatric cancer patients undergoing treatment or receiving a transplant. Neutropenia represents a potentially fatal complication of cancer treatment and is associated with a high risk of developing bacterial infections. Although febrile neutropenia (FN) can affect both adults and children, the latter has a higher chance of infections with an unknown origin. Prompt empiric broad-spectrum antibiotic administration is collectively considered the best therapeutic approach. This review aims to analyze the latest works from the literature regarding the therapeutic strategies, schemes, and approaches and the efficacy of these in pediatric febrile neutropenia. Following PRISMA guidelines, an advanced search on PubMed, Scopus, and Cochrane Library, using the keywords “febrile neutropenia”, “pediatric”, “cancer”, and “oncology”, was performed. A total of 197 articles were found to be eligible. After screening the abstracts and excluding unfit studies, 16 articles were analyzed. There were eight retrospective studies, five prospective studies, and two clinical trials. Altogether, these studies have described around 5000 episodes of FN. The median age of the participants was 7.6 years, and the underlying condition for most of them was acute leukemia. The infectious agent could only be determined in around one-fifth of cases, from which 90% were of bacterial origin. As such, empirical broad-spectrum antibiotics are used, with the most used treatment scheme comprising third- and fourth-generation cephalosporins and antipseudomonal penicillins. In order to improve the treatment strategies of FN episodes and to successfully de-escalate treatments toward narrower-spectrum antibiotics, hospitals and clinics should increase their efforts in identifying the underlying cause of FN episodes through blood culture urine culture and viral tests, wherever infrastructure enables it

Challenges in the Diagnosis and Management of Non-Severe Hemophilia

(1) Background: Mild and moderate hemophilia, synonymous with non-severe hemophilia (NSH), are of constant interest for the clinicians. Bleeding occurs usually after trauma, injury, surgery, or inhibitor development, sometimes leading to a shift of the clinical phenotype from mild to severe, even with life-threatening and unexpected outcomes. (2) Methods: We performed a retrospective observational study conducted on 112 persons with congenital coagulopathies, 26 of them with NSH, admitted to our clinic in the period 2000 to 2022. For the diagnosis, we used laboratory studies (complete blood cell count, coagulation assays, biochemistry, thromboelastography, genetic tests) and imaging investigations (X-ray, ultrasound, CT, MRI). We selected four cases confronted with pitfalls of diagnosis and evolution in order to illustrate the sometimes provocative field of NSH. (3) Results: Confronted with challenging cases with under-, missed or delayed diagnosis and severe consequences, we aimed at presenting four such selected cases with mild or moderate hemophilia, real pitfalls in our clinical activity. (4) Conclusions: In the field of NSH, if not timely recognized, tending sometimes to remain ignored by caregivers and patients themselves, we can be confronted with challenging diagnostic situations and life-threatening bleeds

Prothrombotic risk mutations and polymorphisms in patients with hemophilia A – a preliminary study / Polimorfismele și mutațiile cu risc protrombotic la pacienții cu hemofilie A - studiu preliminar

Introducere. Necesitatea explicării heterogenităţii clinice la pacienţii cu hemofilie (PcH), cu acelaşi grad de severitate sau cu aceeaşi mutaţie, a determinat preocupările de evaluare a coexistenţei polimorfismelor şi mutațiilor cu risc protrombotic, unice sau asociate. Obiectiv. Determinarea frecvenţei polimorfismelor şi mutațiilor cu risc prothrombotic la PcH în comparație cu populația generală. Metoda. Studiul a fost efectuat la 113 PcH consecutivi; s-a utilizat tehnologia PCR (reacţia de polimerizare în lanţ) cu scopul de a detecta: mutațiile factorului V Leiden - G 1691A (FVL) și al protrombinei (PT) - G 20210 A, polimorfismele metilentetrahidrofolat - reductazei (MTHFR) și ale inhibitorului activatorului de plasminogen tip1 (PAI-1). Rezultate. În lotul de studiu, 52,21% dintre pacienți au prezentat asocieri de polimorfisme sau mutaţii cu risc protrombotic, 40,70% un defect genic, iar la 7,08% nu s-a identificat modificări. Frecvența globală a fost caracterizată prin predominanţa polimorfismelor PAI-1, prezente la 82,29% și MTHFR la 52,21% din pacienți. Variante heterozigote ale PT G20210A, FV G1691A, MTHFR și PAI-1 au fost găsite în 7,96%, 9,73%, 39,82% și respectiv 53.98% din cazuri. În funcție de severitatea bolii, la 89 de pacienți cu hemofilie severă, frecvența polimorfismelor investigate a fost: 52,80%, pentru MTHFR, 5,61% pentru FVL G1691A, 8,99% pentru PT G20210A și 79,77% pentru PAI-1. Concluzii. Frecvența modificărilor genice FV, PT și PAI-1 în grupul nostru de studiu este mai mare decât la populația generală. Cu toate acestea, având în vedere distribuirea lor inegală în funcţie de diferite grupuri etnice și regiuni geografice, devin necesare studii mai ample şi mai cuprinzătoare la o populaţie de pacienţi reprezentativă pentru diferite grupe de vârstă și de sex

From European Association for Palliative Care Recommendations to a Blended, Standardized, Free-to-Access Undergraduate Curriculum in Palliative Medicine: The EDUPALL Project.

The World Health Organization recommends that "palliative care should be integrated as a routine element of all Undergraduate Medical Education." However, the provision of training for medical undergraduates is variable; only 18% of 51 European countries have mandatory training in palliative medicine. EDUPALL is an ERASMUS+ funded international collaborative project to develop and pilot an undergraduate program for training in palliative medicine. The objective of this study was to critically review and revise current European Association for Palliative Care (EAPC) Recommendations for the Development of Undergraduate Curricula in Palliative Medicine and translating these into an updated curriculum document. Clinicians, academics, and researchers from Romania, Ireland, Germany, Austria, Spain, and the United Kingdom reviewed the EAPC recommendations using a variant of consensus methodology, Nominal Group Technique. From the updated document, four working-groups translated each recommendation into a specific learning objective, and developed associated learning outcomes, stratified by domain: attitude, cognition, and skills. The outcomes and objectives were organized into discrete teaching units and transferred into a curriculum template, identifying notional hours, teaching, and assessment strategies. To ensure quality control, the draft template was circulated to experts from 17 European countries, together with a brief survey instrument, for peer review purposes. All 17 reviewers returned overwhelmingly positive comments. There was large agreement that: the teaching units were logically organized; learning outcomes covered core training needs; learning objectives provided guidance for teaching sessions; learning modalities were appropriately aligned; and assessment strategies were fit for purpose. An updated and standardized curriculum was developed, which provides a platform for the sequential development of the next phases of the EDUPALL project

COVID-19 Clinical Features and Outcomes in Elderly Patients during Six Pandemic Waves

Many elderly patients with severe SARS-CoV-2 infections and COVID-19 infections are admitted to intensive care units. Age was previously identified as an independent risk factor for death and contributed to the greater severity of COVID-19. The elderly may have diminished lung functions, poor reactions to artificial ventilation, and compromised immune systems. However, it is yet uncertain how each pandemic wave and the predominant SARS-CoV-2 strains contribute to varying results and how patient groups such as the elderly are impacted. Comparing six COVID-19 pandemic waves, the objective of this study was to examine the variation in case severity, symptomatology, ICU hospitalizations, and mortality among SARS-CoV-2-infected elderly individuals. The study followed a retrospective design, including 60 eligible patients older than 70 years in each of the six pandemic wave groups, after matching them by the number of comorbidities and gender. SARS-CoV-2 infection during the first, third, and fourth pandemic waves had a significantly higher risk of mortality for hospitalized patients. Confusion and dyspnea at admission were significant risk factors for ICU admission in elderly patients (&beta; = 1.92, respectively &beta; = 3.65). The laboratory parameters identified decreased lymphocytes (&beta; = 2.11), elevated IL-6 (&beta; = 1.96), and procalcitonin (&beta; = 2.46) as the most significant risk factors. The third and fourth COVID-19 waves had considerably more severe infections (31.7% and 26.7%) than the sixth wave (13.3%). Median ICU stay and percentage of patients receiving oxygen support also differed across pandemic waves. However, mortality rates between the six pandemic waves were similar. The average length of hospitalization varied dramatically among the six pandemic waves. Although senior patients are more likely to have worse COVID-19 outcomes after hospitalization, this risk is mitigated by the greater prevalence of comorbidities and frailty among the elderly. The six pandemic waves that were specifically evaluated did not reveal considerably disproportionate variations in terms of patient mortality; however, during the fourth pandemic wave, there were likely more hospitalized patients with severe COVID-19 in Romania. It is probable that certain circulating SARS-CoV-2 strains were more infectious, resulting in an increase in infections and a strain on healthcare systems, which might explain the variations found in our research

Insights on Lipomatosis after Platinum-Based Chemotherapy Use in Pediatric Oncology: A Case Report

Agents of platinum-based chemotherapy, such as cisplatin or carboplatin, are used in the treatment of a wide range of malignancies that affect children, such as brain tumors, osteosarcoma, neuroblastoma, hepatoblastoma, and germ cell tumors (GCTs). The Cyclophosphamide Equivalent Dose (CED) calculator for reproductive risk does not take platinum-based chemotherapy into account, despite the fact that it accounts for the majority of chemotherapy medications that are typically administered for pediatric GCTs. As a result, exposure to platinum-based drugs throughout infancy can have predictable long-term effects such as infertility, as well as other rare encounters such as lipoma formation and lipomatosis. Lipomas are the most prevalent benign soft tissue tumor subtype. They may be either solitary entities or engaged in multiple lipomatosis, which may have a familial origin or be an acquired disorder. Chemotherapy is a possible cause of lipomatosis. Chemotherapy based on cisplatin has been linked to a variety of long-term consequences, including kidney damage, neurotoxicity, and pulmonary toxicity, and may even create secondary cancers. However, lipoma development is known to occur in fewer than 1 in 100 individuals, and only a few examples of multiple cutaneous lipomatosis triggered by this therapy have been documented. Here we present a very rare case of lipomatosis in a pediatric patient with GCT under cisplatin therapy, which might be the third report of this kind affecting children