Abstract Objective: Finding a reliable preoperative predictor of complicated acute appendicitis (AA) has been a challenging diagnostic problem. The present study aimed to identify potential factors that may predict complicated AA in the pediatric emergency department (ED) based on routine, widely available laboratory tests on admission to the ED, including plasma sodium concentration. Methods: We retrospectively reviewed clinical and laboratory data of pediatric patients with AA who underwent emergency surgery at our department between January 2020 and December 2022. The patients were divided into two groups: histopathologically proven complicated AA (n = 80) and noncomplicated AA (n = 155). Results: Complicated AA was associated with reduced plasma sodium and chloride concentrations (p < 0.001, both), decreased values of lymphocytes (p = 0.002), elevated C-reactive protein (CRP) (p < 0.001), and elevated values of white blood cells (WBC) and neutrophils (p = 0.012 and 0.001, respectively). In binomial logistic regression, increased levels of CRP and WBC and decreased levels of sodium were predictors of complicated AA. The area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.764, 0.886). Conclusion: We identified mild hyponatremia and elevated CRP and WBC values as potential markers for distinguishing complicated from uncomplicated pediatric AA with implications for surgical approaches for treating complicated AA and conservative approaches for treating uncomplicated AA. Highlights of the Study Finding reliable preoperative predictors of complicated acute appendicitis (AA) has been a challenging diagnostic problem in emergency departments worldwide. We identified mild hyponatremia and elevated levels of C-reactive protein and white blood cells as potential markers for distinguishing between complicated and uncomplicated pediatric AA. Our study may have implications for surgical approaches in complicated disease and conservative approaches in uncomplicated disease. Routine blood tests can help emergency physicians discriminate between complicated and uncomplicated AA.

Abstract Histologic transformation to small cell lung cancer (tSCLC) is a rare but increasingly recognised mechanism of acquired resistance to tyrosine kinase inhibitors (TKI) in patients with epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC). Beyond its acknowledged role in TKI resistance, histologic transformation to SCLC might be an important, yet under-recognised, mechanism of resistance in NSCLC treated with immunotherapy. Our review identified 32 studies that investigated tSCLC development in patients with EGFR-mutated NSCLC treated with TKI therapy and 16 case reports of patients treated with immunotherapy. It revealed the rarity of tSCLC, with a predominance of EGFR exon 19 mutations and limited therapeutic options and outcomes. Across all analysed studies in EGFR-mutated NSCLC treated with TKI therapy, the median time to tSCLC development was ∼17 months, with a median overall survival of 10 months. Histologic transformation of EGFR-mutated NSCLC to SCLC is a rare, but challenging clinical problem with a poor prognosis. A small number of documented cases of tSCLC after immunotherapy highlight the need for rebiopsies at progression to diagnose this potential resistance mechanism. Further research is needed to better understand the mechanisms underlying this phenomenon and to develop more effective treatment strategies for patients with tSCLC.

Recent investigations have reported the benefits of using a tyrosine kinase inhibitor, dasatinib (DA), as well as programmed death-ligand 1 (PD-L1) inhibitors in the management of several solid tumors, including breast cancer. Nevertheless, the outcome of the combination of these inhibitors on HER2-positive breast cancer is not explored yet. Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data reveal that the combination significantly inhibits cell viability of both cancer cell lines as compared to monotreatment. Moreover, the combination inhibits epithelial-mesenchymal transition (EMT) progression and reduces cancer cell invasion by restoring E-cadherin and β-catenin expressions and loss of vimentin, major biomarkers of EMT. Additionally, the combination reduces the colony formation of both cell lines in comparison with their matched control. Also, the combination considerably inhibits the angiogenesis of the chorioallantoic membrane model compared with monotreatment. Molecular pathway analysis of treated cells shows that this combination blocks HER2, AKT, β-catenin, and JNK1/2/3 activities. Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer.

OBJECTIVE This study aimed to identify the frequency, severity, and risk factors associated with Hickman catheter-related complications in children with hemato-oncological malignancies at the largest pediatric tertiary care unit in Bosnia and Herzegovina. MATERIALS AND METHODS A cross-sectional study was conducted on a cohort of pediatric cancer patients who underwent Hickman central venous catheters (CVCs) between January 2019 and December 2022. Mechanical, infectious, and thrombotic Hickman catheter-related complications were evaluated and analyzed. We also investigated possible risk factors associated with these complications. RESULTS Seventy-one Hickman CVCs were inserted in 68 children (44 boys and 24 girls) at a mean age of 6.9 ± 4.6. Forty (58.8%) children had hematological malignancies and 28 (41.2%) solid cancers. The median follow-up after Hickman CVC insertion was 190 days (95% CI [160-212]) for 12 644 catheter days. During follow-up, 10 (14.1%) mechanical, 7 (9.9%) infectious, and 1 (1.4%) thrombotic complications were recorded (0.8, 0.48, and 0.08 for mechanical, infectious, and thrombotic complications per 1000 catheter days, respectively). A slightly higher incidence of complications was recorded in children with hematological malignancies (1.59 per 1000 catheter days) compared with children with solid cancers (1.22 complications per 1000 catheter days). CONCLUSION Using Hickman CVCs for long-term venous access in infusional chemotherapy for pediatric cancer patients is safe but is associated with significant morbidity.

Purpose There have been several studies into medical student career decision making in occidental countries (eg US, UK), but medical career selection in a Middle Eastern context has not been as well studied. This study aims to explore determinants underpinning medical students’ residency choice in Qatar. Patients and methods During the Fall semester of the 2022–2023 academic year, all (n=358) medical students from the College of Medicine at Qatar University were invited to participate in an online explorative questionnaire about students’ career choices and the factors determining their selection. Results Of the 358 students, 184 responded (51%). Respondents had a mean age of 20 years; the majority were female (73.9%), Qatari (54.3%), unmarried (97.3%), and enrolled in a pre-clerkship year (55.0%). The most important career determinant was specialty-specific factors. The relative importance of other determinants differed by gender and stage of training. Among our respondents, male students were more likely to rate role models and influencers as being important to their choice, while female students and Qatari students overall were more likely to cite societal obligation. Medical students in Qatar seemed to have career preferences in mind upon entry into medical education. Later-year students were more likely to identify the importance of work-life balance and place of practice, but were less likely to rank prestige and income as an important determinant. Conclusion The results of this baseline study suggest that socioeconomic and cultural context influence medical student career decisions.

Uterine leiomyosarcoma (uLMS) is a rare but aggressive cancer with a high metastatic potential and an unfavorable prognosis. A 54-year-old woman with a history of uterine fibroids clinically presented with a painless, palpable left breast mass measuring 20 mm. A core biopsy of the breast mass demonstrated a cellular spindle cell neoplasm (a potentially malignant smooth muscle neoplasm; B4). A wide local breast-mass excision was performed, revealing grade-2 leiomyosarcoma. A re-review of the uterine fibroids revealed that the largest one (200 × 130 mm), initially diagnosed as symplastic leiomyoma, was morphologically identical to the breast lesion. Additional diagnostic work-up revealed multiple liver and pulmonary metastases with a suspected metastatic sclerotic lesion in the L3 projection. The patient was subsequently treated with chemotherapy protocol for metastatic uLMS. The latest follow-up in September 2023 confirmed stable disease. This case highlights the importance of considering unusual metastatic patterns when evaluating breast masses, particularly in patients with a history of non-specific uterine conditions. Comprehensive diagnostic work-up, including imaging and histopathologic examinations, is crucial for an accurate diagnosis of uLMS and appropriate treatment selection. Further studies are needed to better understand the underlying mechanisms and optimal management strategies for metastatic uLMS.

The increasing prevalence of colon and lung cancer presents a considerable challenge to healthcare systems worldwide, emphasizing the critical necessity for early and accurate diagnosis to enhance patient outcomes. The precision of diagnosis heavily relies on the expertise of histopathologists, constituting a demanding task. The health and well‐being of patients are jeopardized in the absence of adequately trained histopathologists, potentially leading to misdiagnoses, unnecessary treatments, and tests, resulting in the inefficient utilization of healthcare resources. However, with substantial technological advancements, deep learning (DL) has emerged as a potent tool in clinical settings, particularly in the realm of medical imaging. This study leveraged the LC25000 dataset, encompassing 25,000 images of lung and colon tissue, introducing an innovative approach by employing a self‐organized operational neural network (Self‐ONN) to accurately detect lung and colon cancer in histopathology images. Subsequently, our novel model underwent comparison with five pretrained convolutional neural network (CNN) models: MobileNetV2‐SelfMLP, Resnet18‐SelfMLP, DenseNet201‐SelfMLP, InceptionV3‐SelfMLP, and MobileViTv2_200‐SelfMLP, where each multilayer perceptron (MLP) was replaced with Self‐MLP. The models’ performance was meticulously assessed using key metrics such as precision, recall, F1 score, accuracy, and area under the receiver operating characteristic (ROC) curve. The proposed model demonstrated exceptional overall accuracy, precision, sensitivity, F1 score, and specificity, achieving 99.74%, 99.74%, 99.74%, 99.74%, and 99.94%, respectively. This underscores the potential of artificial intelligence (AI) to significantly enhance diagnostic precision within clinical settings, portraying a promising avenue for improving patient care and outcomes. The synopsis of the literature provides a thorough examination of several DL and digital image processing methods used in the identification of cancer, with a primary emphasis on lung and colon cancer. The experiments use the LC25000 dataset, which consists of 25,000 photos, for the purposes of training and testing. Various techniques, such as CNNs, transfer learning, ensemble models, and lightweight DL architectures, have been used to accomplish accurate categorization of cancer tissue. Various investigations regularly show exceptional performance, with accuracy rates ranging from 96.19% to 99.97%. DL models such as EfficientNetV2, DHS‐CapsNet, and CNN‐based architectures such as VGG16 and GoogleNet variations have shown remarkable performance in obtaining high levels of accuracy. In addition, methods such as SSL and lightweight DL models provide encouraging outcomes in effectively managing large datasets. In general, the research emphasizes the efficacy of DL methods in successfully diagnosing cancer from histopathological pictures. It therefore indicates that DL has the potential to greatly improve medical diagnostic techniques.

Abstract Lipofibromatosis (LF) is a rare benign fibrofatty tumor of infancy and childhood with a predilection for distal extremities, poor margination, and a high local recurrence rate. We report a toddler who presented with an LF involving her right labiocrural fold. Imaging showed a soft tissue mass extending through the right labiocrural fold with possible infiltration into the underlying muscles. The mass was excised entirely, preserving adjacent structures. The histopathologic report revealed the mass to be LF. A 3-year follow-up revealed no disease recurrence. No other cases of LF in this localization have been presented in the literature. Despite its rarity, LF should be considered in diagnosing soft tissue neoplasms in children. Accurate diagnosis and proper surgical management with complete resection are essential to reduce the postoperative recurrence risk.

Angiogenesis is the process of forming new blood capillaries from pre-existing vessels. Even though it is essential during normal development, it plays a major role in cancer progression. Neratinib is a pan-human epidermal growth factor receptor (HER) inhibitor that has recently been approved for the treatment of HER2-positive breast cancer. However, its effects on angiogenesis and embryogenesis remain unknown. This study examined the antiangiogenic effects of neratinib using the chorioallantoic membrane (CAM) of chicken embryos. We also evaluated neratinib’s toxicity during the early stages of normal development using the chicken embryos, primary embryonic fibroblasts (EFBs), and human umbilical vein endothelial cells (HUVEC). Our findings revealed that neratinib significantly inhibited the CAM angiogenesis compared to controls by reducing vessel percentage area and the average vessel length. Furthermore, neratinib downregulated vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. At lower concentrations, neratinib was well-tolerated during early stages of normal development. Additionally, EFBs treated with neratinib showed no morphological or viability changes when compared to controls. However, at the highest concentration tested, neratinib treatment reduced HUVEC cell viability. This effect may be associated with the dysregulation of key apoptotic genes, including caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 (Bcl2) gene. Our findings indicate a novel potential application of neratinib as an antiangiogenic agent, exhibiting tolerable toxicity in the early stages of embryogenesis.

The social significance and quality of every human activity are proportional to its usefulness to the social community. Science belongs to the very top of the processes and events in the history of humankind that strongly influenced the development of society, which over time transformed it and contributed to the common good. Science produced new knowledge that made it possible for billions of people to rise out of poverty, develop industrialization and mass communication, eradicate many dangerous diseases for humankind, and enable humans to leave their footprints on the moon. Science is a human activity that produces new knowledge presented through innovations, patents, and publications, aimed at solving the problems facing humanity. Read more in the PDF.

In the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER−/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/−, AR+/−). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P ═ 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median: 5%, range 0%–50%). TIL levels were significantly higher in ALC than in PAC (P ═ 0.02). HER2 status had no impact on TIL distribution (P ═ 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody–drug conjugates (ADCs) for HER2-low breast cancers.

INTRODUCTION Early diagnosis and treatment of primary vesicoureteral reflux (VUR) are essential for preserving renal function. OBJECTIVES The study explored whether preoperative cystoscopic grading of refluxing ureteric orifices (UO) correlated with their shape in an institution with non-performance of hydrodistention of the UO in the diagnosis and grading of VUR. We also assessed the relationship between the UO shape and VUR grade with the effectiveness of endoscopic correction of primary VUR in children. METHODS This retrospective study included consecutive patients ≤15 years treated for primary VUR. The reflux grade was based on the results of preoperative voiding cystourethrography as mild, moderate, or severe. RESULTS Fifty-one patients with 77 renal refluxing units (RRU) underwent endoscopic treatment with Deflux®. VUR was bilateral in 51 % of patients. VUR was mild in 13 %, moderate in 53 %, and severe in 34 % of cases. The patients with mild and moderate VUR had stadium-shaped UOs in 60 % and 54 % RRUs, respectively. Horseshoe-shaped UOs constituted 42 % of UOs in patients with severe VUR, followed by 31 % of golf-hole UOs. The reflux resolution rate after the first endoscopic injection was 84 %. The preoperative VUR grade correlated with UOs shape (p < 0.001). No significant correlation between UOs configuration and the outcome of endoscopic treatment was seen (p = 0.452). The preoperative VUR grade negatively correlated with a favorable endoscopic treatment (p = 0.043). DISCUSSION AND CONCLUSION Our data indicate ureteral orifice shapes are closely related to preoperative VUR grade. There was no correlation between the UO configuration and the success rate of endoscopic treatment of VUR, in contrast to the significant negative correlation between the VUR grade and the success rate of endoscopic treatment.

OBJECTIVES Infection is still the leading cause of morbidity and mortality among burn patients worldwide. Isolation and identification of pediatric burn wound bacterial colonizers can prevent infection and improve burn trauma treatment. In this study, we explored early microbial colonizers within the burn wounds and the susceptibility of those isolates to antibiotics among hospitalized pediatric patients with minor and moderate burns, clinically significant infections and outcomes. METHODS A retrospective analysis of pediatric patients admitted to the inpatient pediatric surgical ward and treated for minor and moderate burns from 2009 to 2018 was performed. RESULTS One hundred six patients met the inclusion criteria. The mean age was 3.6 ± three years (0.2-14.1 years). The most common type of burn was scald burns (82.1%). The mean TBSA of the hospitalized pediatric burn cases was 8.5% (IQR, 6-12%). Seventy-nine (74.5%) patients had positive wound cultures at admission, regardless of the hospital admission day. Fifty-eight (73.4%) had one bacterial growth (mono isolate), while 21 (26.6%) had mixed growth or poly isolates. Among patients with mixed growth or poly isolate, 16 had two bacteria, three had three bacteria, and one had four bacteria isolated, totaling 105 isolated microorganisms (14 different species, 70.5% Gram-positive bacteria and 29.5% Gram-negative bacteria). Twelve patients (11%) developed clinically significant infections (eleven got burn wound infection, and one had septicemia). All patients received prophylactic systemic antibiotics. Only 35.2% of the isolated bacteria from the wounds were sensitive to the prophylactic antibiotics, and only ∼17% in case of clinically significant infections. We found a statistically significant difference in the length of hospital stay between patients with initially colonized samples of burn wounds compared with patients with initial negative samples (p = 0.008). All patients in the cohort survived hospital discharge. CONCLUSION Despite common bacterial colonization of acute burn wounds, only ∼10% of the patients developed clinically significant infections, a minority of which were sensitive to prophylactic antibiotics. Our findings indicate the need to refine the antibiotic approach in pediatric patients with minor/moderate burns in our local setting.