ABSTRACT High-risk Human Papillomaviruses (HPVs) and Epstein – Barr virus (EBV) are present and involved in several types of human carcinomas, including cervical and, head and neck cancers. Nevertheless, their presence and association in the pathogenesis of colorectal cancer is still nascent. The current study explored the association between the high-risk HPVs and EBV and tumor phenotype in colorectal cancers (CRCs) in the Qatari population. We found that high-risk HPVs and EBV are present in 69/100 and 21/100 cases, respectively. Additionally, 17% of the cases showed a copresence of high-risk HPVs and EBV, with a significant correlation only between the HPV45 subtype and EBV (p = .004). While the copresence did not significantly associate with clinicopathological characteristics, we identified that coinfection with more than two subtypes of HPV is a strong predictor of advanced stage CRC, and the confounding effect of the copresence of EBV in such cases strengthens this association. Our results indicate that high-risk HPVs and EBV can co-present in human CRCs in the Qatari population where they could plausibly play a specific role in human colorectal carcinogenesis. However, future studies are essential to confirm their copresence and synergistic role in developing CRCs.

High-risk human papillomaviruses (HPVs) are considered risk factors in the origin of several human malignancies, such as breast, cervical, head and neck, as well as colorectal cancers. However, there are no data reported on the HPV status in colorectal cancer in the State of Qatar. Therefore, we herein examined the presence of high-risk HPVs (16, 18, 31, 33, 35, 45, 51, 52, and 59), using polymerase chain reaction (PCR) in a cohort of 100 Qatari colorectal cancer patients, and their association with tumor phenotype. We found that high-risk HPV types 16, 18, 31, 35, 45, 51, 52, and 59 were present in 4, 36, 14, 5, 14, 6, 41, and 17% of our samples, respectively. Overall, 69 (69%) of the 100 samples were HPV positive; among these, 34/100 (34%) were positive for single HPV subtypes, while 35/100 (35%) of the samples were positive for two or more HPV subtypes. No significant association was noted between the presence of HPV and tumor grade, stage, or location. However, the presence of coinfection of HPV subtypes strongly correlated with advanced stage (stage 3 and 4) colorectal cancer, indicating that the copresence of more than one HPV subtype can significantly worsen the prognosis of colorectal cancer. The results from this study imply that coinfection with high-risk HPV subtypes is associated with the development of colorectal cancer in the Qatari population.

Objective: Sacrococcygeal teratoma is an extragonadal germ cell tumor that develops during fetal and neonatal periods and is associated with significant perinatal morbidity and even mortality. This study aimed to determine the clinicopathologic characteristics, the clinical outcomes, and postoperative complications of sacrococcygeal teratoma cases in the low-volume pediatric surgery service in a developing country. Materials and Methods: The study included data from all sacrococcygeal teratoma cases diagnosed from 2011 to 2020. All the relevant clinicopathologic data were recorded and analyzed. Results: A total of 7 pediatric (5 females and 2 males) patients with sacrococcygeal teratoma were identified, ranging in age from 3 to 222 days. A prenatal diagnosis was made in 57.1% of cases. The mean gestational age for all cases was 37.1 weeks (34-38 weeks), and the mean birth weight was 3285 g (range, 2300-4700 g). Preoperative alpha-fetoprotein levels had a mean value of 24.327 ng/mL (range, 649.7-110.600 ng/mL). The surgery involved resection of the primary tumor and coccygectomy in all cases. Three (42.9%) tumors were classified as Altman type II lesions, 2 (28.6%) tumors were type IV, and 2 remaining cases were types I and III, respectively. Histology was benign in 4 (57.1%) and immature in 3 patients (42.9%). The mean follow-up time was 101.4 months (30-146 months), with 2 recurrences of high-grade immature teratomas at 11 and 30 months following the surgery. Three patients had postoperative bladder and rectal dysfunctions. Conclusion: Sacrococcygeal teratomas are rare tumors associated with frequent postoperative dysfunctions. Recurrences may also be seen, particularly in immature, high-grade forms of sacrococcygeal teratomas.

Antibody-drug conjugates (ADCs) are novel, highly potent drugs composed of a small molecule of an anticancer drug (payload)attached to humanized antibody recognizing an epitope on the surface of cancer cells. ADCs are rapidly expanding in the oncology field. By 2022, >180 ADC-based clinical trials have been conducted [1]. Most of these clinical trials are in phases I or II [1]. Several ADCs have been approved and used for the treatment of various malignancies (e.g., brentuximab vedotin (BV) for the treatment of CD30+ lymphomas, trastuzumab emtansine (T-DM1) for advanced/metastatic/or early-stage high-risk HER2-positive breast cancer with residual disease after neoadjuvant treatment) [2]. Read more in the PDF.

Abstract Global brachial plexus injury (GBPI) mainly affects adults and causes severe life-changing consequences that lead to the deterioration of patients’ quality of life. Several surgical approaches have been described and reported in the literature to improve patients’ functional ability. A literature review is done on PubMed/MEDLINE and Embase using specific keywords to retrieve relevant articles assessing different surgical approaches for GBPI management. Inclusion and exclusion criteria were applied, and eligible articles were included in the review. The literature survey revealed that various surgical options had been used to manage GBPI patients. In this concise review, we discuss and compare the different surgical approaches related to GBPI and its outcome in terms of restoring elbow flexion and extension, shoulder abduction, and wrist and hand function. The primary surgical intervention relies mainly on transferring single or multiple nerves with/without nerve grafts to restore the function of the targeted muscle. Different techniques using a variety of nerve donors and recipients are compared to assess the functional outcomes of each option. Moreover, further options are addressed for delayed GBPI injuries or failed nerve transfer procedures, as in free functional muscle transfer techniques. In addition, information about brachial plexus injury cases faced in our center is presented along with our center’s approach to diagnosing and managing partial and GBPI cases.

The acute scrotum (AS) in the pediatric population is a medical emergency. AS is usually caused by testicular torsion (TT) and torsion of the appendix testis (TAT). The current study explored which demographic and clinical characteristics can help distinguish between TT and TAT. We analyzed all children ≤16 years who underwent surgical exploration for AS. The patients were divided into Group 1/TT and Group 2/TAT. Ninety patients were included in the study (24 with TT and 66 with TAT). The peak incidence of TT was significantly higher than in the TAT group (p<0.001). Scrotal pain was more prevalent in the TAT group (p=0.02), whereas systemic signs (nausea/vomiting and abdominal pain) affected more frequently the TT patients (p=0.003 and p<0.001, respectively). The duration of symptoms was significantly longer in the TAT group (p<0.001). The duration of symptoms in the TT cohort significantly impacted the testicular salvage (p=0.008). Color Doppler ultrasound (CDUS) findings of absent/decreased testicular blood flow in the affected testis strongly favored the diagnosis of TT (p<0.001). The older age, shorter duration of symptoms, systemic signs, and CDUS findings can help distinguish between the two most common acute scrotum causes.

From February 2023 (Volume 23, Issue 1), the title of the Bosnian Journal of Basic Medical Sciences will be changed to Biomolecules and Biomedicine. The new title reflects the increasing number of published research done on subcellular/molecular level as well as translational and clinical research contained in the term Biomedicine. Biomolecules and Biomedicine will continue to be published by the Association of Basic Medical Sciences of the Federation of Bosnia and Herzegovina. Read more in the PDF.

Placental insufficiency is a common cause of intrauterine growth restriction (IUGR). It affects ~10% of pregnancies and increases fetal and neonatal morbidity and mortality. Although Wnt and Hh pathways are crucial for embryonic development and placentation, their role in the pathology of IUGR is still not sufficiently explored. The present study analyzed the expression of positive regulators of the Wnt pathway, WNT5A and β-catenin, and the expression of the Hh pathway negative regulator suppressor of fused (SUFU). Immunohistochemical and reverse transcription-quantitative PCR (RT-qPCR) assays were performed on 34 IUGR and 18 placental tissue samples from physiologic singleton-term pregnancies. Epigenetic mechanisms of SUFU gene regulation were also investigated by methylation-specific PCR analysis of its promoter and RT-qPCR analysis of miR-214-3p and miR-378a-5p expression. WNT5A protein expression was higher in endothelial cells of placental villi from IUGR compared with control tissues. That was also the case for β-catenin protein expression in trophoblasts and endothelial cells and SUFU protein expression in trophoblasts from IUGR placentas. The SUFU gene promoter remained unmethylated in all tissue samples, while miR-214-3p and miR-378a-5p were downregulated in IUGR. The present results suggested altered Wnt and Hh signaling in IUGR. DNA methylation did not appear to be a mechanism of SUFU regulation in the pathogenesis of IUGR, but its expression could be regulated by miRNA targeting.

Introduction Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. Methods In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Results and discussion Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

Congenital anomalies (CA) are any abnormality present at birth, either structural or functional, that may potentially affect an infant’s health, development, and/or survival. There is a paucity of studies on clinical characteristics and outcomes of CA in Bosnia and Herzegovina, mainly due to the lack of a nationwide congenital malformations monitoring system. A 5-year hospital-based study was conducted to determine the prevalence at birth and clinical characteristics of selected major CA in Sarajevo Canton, Bosnia and Herzegovina. Ninety-one CA were observed from 2012 to 2016 (the overall prevalence was 39.6 cases/10,000 live births). The mean age of neonates at diagnosis was 3 days. The gastrointestinal tract was the most commonly affected system (76.9%), with esophageal atresia (EA) being the most frequent (17.6% of all CA). Major CA were more prevalent among preterm infants than term infants (P = .001), particularly in males (61.5% vs. 38.5%; P = .028; M:F ratio was 1.59). Multiple CA were seen in 37.4% of neonates. The overall mortality rate of neonates was 11%, and the median length of hospital stay was 19.8 days. Our study revealed the distribution and clinical patterns of common major CA in the largest tertiary care facility in Bosnia and Herzegovina. It also confirmed a relatively high mortality rate, which requires further efforts to improve the quality of neonatal care in the country.