Research Articles (Surgery)

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Exosomal long non-coding RNAs in cancer : interplay, modulation, and therapeutic avenues
(KeAi Communications Co., 2024-09) Marima, Rahaba; Basera, Afra; Miya, Thabiso Victor; Damane, Botle Precious; Kandhavelu, Jeyalakshmi; Mirza, Sheefa; Penny, Clement; Dlamini, Zodwa; rahaba.marima@up.ac.za
In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients.
Noninvasive assessment of intracranial pressure : deformability index as an adjunct to optic nerve sheath diameter to increase diagnostic ability
(Springer, 2024-10) Netteland, Dag Ferner; Aarhus, Mads; Sandset, Else Charlotte; Padayachy, Llewellyn; Helseth, Eirik; Brekken, Reidar
BACKGROUND : Today, invasive intracranial pressure (ICP) measurement remains the standard, but its invasiveness limits availability. Here, we evaluate a novel ultrasound-based optic nerve sheath parameter called the deformability index (DI) and its ability to assess ICP noninvasively. Furthermore, we ask whether combining DI with optic nerve sheath diameter (ONSD), a more established parameter, results in increased diagnostic ability, as compared to using ONSD alone. METHODS : We prospectively included adult patients with traumatic brain injury with invasive ICP monitoring, which served as the reference measurement. Ultrasound images and videos of the optic nerve sheath were acquired. ONSD was measured at the bedside, whereas DI was calculated by semiautomated postprocessing of ultrasound videos. Correlations of ONSD and DI to ICP were explored, and a linear regression model combining ONSD and DI was compared to a linear regression model using ONSD alone. Ability of the noninvasive parameters to distinguish dichotomized ICP was evaluated using receiver operating characteristic curves, and a logistic regression model combining ONSD and DI was compared to a logistic regression model using ONSD alone. RESULTS : Forty-four ultrasound examinations were performed in 26 patients. Both DI (R = − 0.28; 95% confidence interval [CI] R < − 0.03; p = 0.03) and ONSD (R = 0.45; 95% CI R > 0.23; p < 0.01) correlated with ICP. When including both parameters in a combined model, the estimated correlation coefficient increased (R = 0.51; 95% CI R > 0.30; p < 0.01), compared to using ONSD alone, but the model improvement did not reach statistical significance (p = 0.09). Both DI (area under the curve [AUC] 0.69, 95% CI 0.53–0.83) and ONSD (AUC 0.72, 95% CI 0.56–0.86) displayed ability to distinguish ICP dichotomized at ICP ≥ 15 mm Hg. When using both parameters in a combined model, AUC increased (0.80, 95% CI 0.63–0.90), and the model improvement was statistically significant (p = 0.02). CONCLUSIONS : Combining ONSD with DI holds the potential of increasing the ability of optic nerve sheath parameters in the noninvasive assessment of ICP, compared to using ONSD alone, and further study of DI is warranted.
From incidence to intervention : a comprehensive look at breast cancer in South Africa
(Springer, 2024-03) Dlamini, Zodwa; Molefi, Thulo; Khanyile, Richard; Mkhabele, Mahlori; Damane, Botle Precious; Kokoua, Alexandre; Bida, Meshack; Saini, Kamal S.; Chauke-Malinga, Nkhensani; Luvhengo, Thifhelimbilu Emmanuel; Hull, Rodney; zodwa.dlamini@up.ac.za
The formidable impact of breast cancer extends globally, with South Africa facing pronounced challenges, including significant disparities in breast cancer screening, treatment and survival along ethnic and socioeconomic lines. Over the last two decades, breast cancer incidence has increased and now accounts for a substantial portion of cancers in women. Ethnic disparities in terms of screening, incidence and survival exacerbate the issue, leading to delayed diagnosis among Black patients and highlighting healthcare inequities. These concerning trends underscore the urgency of enhancing breast cancer screening while mitigating treatment delays, although obstacles within the healthcare system impede progress. The intersection of breast cancer and human immunodeficiency virus (HIV) further complicates matters and particularly affects the Black population. Tackling the aforementioned disparities in breast cancer in South Africa mandates a multifaceted strategy. Robust screening efforts, particularly those targeting marginalised communities, are crucial for early detection. Concurrently, expedited treatment initiation is imperative. Addressing HIV-related complexities requires tailored interventions to ensure effective care. These multifaceted disparities require pan African research and cooperation as well as tailored interventions to enhance breast cancer care within the African region.
Advances in nano-delivery of phytochemicals for glioblastoma treatment
(SpringerOpen, 2024-12) Ambele, Melvin Anyasi; Maebele, Lorraine Tshegofatso; Mulaudzi, Thanyani Victor; Kungoane, Tsholofelo; Damane, Botle Precious; melvin.ambele@up.ac.za
Glioblastoma (GBM) is an aggressive brain tumor characterized by cellular and molecular diversity. This diversity presents significant challenges for treatment and leads to poor prognosis. Surgery remains the primary treatment of choice for GBMs, but it often results in tumor recurrence due to complex interactions between GBM cells and the peritumoral brain zone. Phytochemicals have shown promising anticancer activity in in-vitro studies and are being investigated as potential treatments for various cancers, including GBM. However, some phytochemicals have failed to translate their efficacy to pre-clinical studies due to limited penetration into the tumor microenvironment, leading to high toxicity. Thus, combining phytochemicals with nanotechnology has emerged as a promising alternative for treating GBM. This review explores the potential of utilizing specific nanoparticles to deliver known anticancer phytochemicals directly to tumor cells. This method has demonstrated potential in overcoming the challenges of the complex GBM microenvironment, including the tight blood–brain barrier while minimizing damage to healthy brain tissue. Therefore, employing this interdisciplinary approach holds significant promise for developing effective phyto-nanomedicines for GBM and improving patient outcomes.
Gastric perforation biopsy : is it obsolete?
(Springer, 2024-04-27) Steyn, Petre Francois; Karusseit, V.O.L. (Otto); otto.karusseit@up.ac.za
PURPOSE The aim of the study was to test the established hypothesis that biopsies of spontaneous gastric perforations should be taken to rule out cancer. METHODS A prospective observational study was performed. Consecutive patients with spontaneous gastric perforation were included. Biopsies of the edges of the perforation were submitted for histological evaluation. The epithelial type as well as the nature of the pathology were evaluated. RESULTS Sixty-eight patients were included. Eight (12%) biopsies revealed duodenal origin. Sixty (88%) biopsies revealed gastric mucosa of which 33 (48%) could be specifically typed. All biopsies revealed benign ulceration. No malignancies were detected in these biopsies or on subsequent gastroscopic follow up. CONCLUSION This study suggests that routine intraoperative biopsy of gastric perforation may be questioned. Biopsy is probably better performed endoscopically after recovery.
The anatomical location of the great saphenous vein at the thigh and ankle : a neonatal cadaver study
(Spanish Association of Anatomy, 2024-03) Van Tonder, Daniel Johannes; Kathrada, Ahmad; Lokhandwala, Adnan; Van Niekerk, Martin Louis; Van Schoor, Albert-Neels
No abstract available.
Anatomical analysis of proximal tibia : selecting ideal sites for pediatric intraosseous infusion
(Spanish Association of Anatomy, 2024-07) Van Tonder, Daniel Johannes; Al Safadi, Layla; Samaha, Paula; Suleman, Farhana Ebrahim; Van Niekerk, Martin Louis; Van Schoor, Albert; Van Schoor, Albert-Neels
Intraosseous access is a safe and efficient method to administer medications to patients that require advanced life support when intravenous access is not easily available. This study aims to narrow down the ideal insertion site for intraosseous access within the proximal tibia in a pediatric population. The study utilized computed tomography scans that were retrospectively collected from scans of five infant patients between four weeks and two-years old, seven young children between two-years and six-years old, and ten children between six-years and twelve-years of age. Analysis of the computed tomography scans started at 10mm and extended to 50mm distally to the tibial tuberosity at 10mm increments. The smallest cortical thickness to medullary space ratio and most desirable cortical thickness to anteromedial border ratio across all three groups – infants, young children, and child – was identified as 10mm inferior to the tibial tuberosity. Meanwhile, the largest medullary space to anteromedial border ratio was at 10mm inferior to the tibial tuberosity for the infants and young child groups, and at 30mm for the child group. This study showed that, overall, the ideal needle insertion site to gain vascular access for an intraosseous infusion procedure in the proximal tibial in infants, young child, and children is 10mm distal to the tibial tuberosity.
The clinicopathological landscape of thyroid cancer in South Africa—a multi-institutional review
(Wiley, 2024-12) Conradie, Wilhelmina; Luvhengo, Thifhelimbilu E.; Lubbe, Jeanne Adele; Afrogheh, Amir H.; Bestbier, Aneldi; Bhuiyan, Mirza; Bombil, Ifongo; Cacala, Sharon Raye; Cairncross, Lydia; Changfoot, Chanel; Edge, Jenny; Jackson, Brandon Spencer; Jehle, Hansjorg S.; Jonas, Lusanda; Lukusa, Mpoyi Ruphin; Makgoka, Malose; Martin, Lindi; Nel, Daniel; Patel, Mohamed Quraish; Sishuba, Nosisa Thabile; Razack, Rubina; Baatjes, Karin
BACKGROUND : In South Africa (SA), data on the incidence of thyroid cancer is limited. Papillary thyroid carcinoma is by far the most common malignancy in developed countries; however, a preponderance of follicular thyroid cancer in developing countries, despite iodized salt, has been observed. The aim of this study was to describe the national landscape of thyroid cancer in SA with reference to pathological subtypes, surgical outcomes, and treatments offered. METHODS : A multi-institutional retrospective review of thyroid cancer patients operated on between January 2015 and December 2019 was performed. Public hospitals with associated academic institutions were included. Data were collected from theater registers, pathology, and radiology records. Statistical analysis was done to determine intergroup significance. RESULTS : A total of 464 thyroid cancer cases from 13 centers across five SA provinces were identified. Most patients presented with a mass (67%). Ultrasound was performed in 82% of patients, and 16.3% underwent surgery without pre-operative cytology. Of the histologically confirmed thyroid cancers, 61.8% were papillary and 22.1% follicular thyroid cancer. There was a significant association between subtype and geographical area, and T-stage and operation performed. Surgical complication rates included hematoma in 1.8%, post-operative hypocalcemia in 28.7%, and recurrent laryngeal nerve injury in 3.5%. CONCLUSION : This first national review describes the landscape of thyroid cancer in SA, revealing considerable differences compared to international studies. It provides valuable insight into the unique South African experience with this disease. In addition, this study serves as an impetus towards a prospective national registry with real-world data informing contextualized guidelines.
Holomics and artificial intelligence-driven precision oncology for medullary thyroid carcinoma : addressing challenges of a rare and aggressive disease
(MDPI, 2024-10) Luvhengo, Thifhelimbilu Emmanuel; Moeng, Maeyane Stephens; Sishuba, Nosisa T.; Makgoka, Malose; Jonas, Lusanda; Mamathuntsha, Tshilidzi G.; Mbambo, Thandanani; Kagodora, Shingirai B.; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
BACKGROUND/OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer comprising a disproportionate share of thyroid cancer-related mortalities, despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, which are designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for patients with MTC. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, which is an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. METHODS: This article reviews how AI-driven precision oncology can enhance the diagnostic workup, staging, risk stratification, management, and follow-up care of patients with MTC by processing vast amounts of complex data quickly and accurately. Articles published in English language and indexed in Pubmed were searched. RESULTS: AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in the management of MTC enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. CONCLUSIONS: The integration of holomics and AI in the management of patients with MTC represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of treatment and care of patients with MTC. By leveraging AI and holomics, we can strive toward making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being at all ages.
Perforated peptic ulcer : a case series and an African perspective
(Medpharm Publications, 2024-02) Malefahlo, Thabiso M.; Montwedi, Daniel; Karusseit, V.O.L. (Otto); otto.karusseit@up.ac.za
BACKGROUND: Perforation of peptic ulcer (PPU) is the most morbid complication of peptic ulcer disease (PUD) with scant recent reports from sub-Saharan Africa. The aim of this study was to describe a PPU series from a single centre in South Africa and contrast the findings with other recent reports from sub-Saharan Africa. METHODS: A retrospective study of PPU at Kalafong Hospital in Pretoria was performed. The relationship of patient demographics, risk factors, ulcer pathology and severity scores to mortality were analysed. Recent similar reports from sub-Saharan Africa were reviewed and the findings compared to the current study and findings from high income countries (HIC). RESULTS: The study comprised 121 patients. The majority were black men with an average age of 46.6 years, with few comorbidities. A large proportion of patients admitted to risk factors and most presented to hospital 48 hours after the onset of symptoms. The majority (71%) of the perforations occurred in the stomach. The patient sex, age, risk factors and the mortality at 4% were similar to other African studies, although perforations were mainly duodenal in most of the African studies. The median age of patients in the East African studies was lower by 13 years. Patients in HIC series of PPU were older, more likely to be female, have duodenal perforations and a higher mortality than in the African series. CONCLUSION: Patients were mostly smokers, presented late to hospital and had gastric perforations. The findings of low mortality and male predominance concurred with those of other sub-Saharan African reports and were the opposite of trends in HIC.
Non-technical skills for neurosurgeons : an international survey
(Elsevier, 2024) Cavallo, S.M.; Pellencin, E.; Carone, G.; Castelli, N.; Ayadi, R.; Olldashi, F.; Al Anazi, A.; Kanaan, I.; Garcia Colmena, F.; Ajler, P.; Socolovsky, M.; Knosp, E.; Raftopoulos, C.; Rodrigues, J.C., Jr.; Enchev, Y.P.; Xu, B.; Chul-Kee, P.; Rotim, K.; Posti, J.; Meyer, B.; Shimamoto, H.; Makhambetov, Y.; Frosen, J.; Chandra, S.P.; Cappabianca, P.; Piatelli, G.; Genitori, L.; Germanò, A.; Sabatino, G.; Bernucci, C.; Giussani, C.; Olivi, A.; Locatelli, D.; Stefini, R.; Castrioto, C.; Mangiola, A.; Fontanella, M.M.; Tacconi, L.; Conti, C.; Skrap, M.; El Abbadi, N.; Sharma, M.R.; Shamim, M.S.; Sharif, S.; Farias, J.P.; Florian, I.S.; Gushcha, A.O.; Rasulic, L.; Vulekovic, P.; Ang, B.T.; Lagares, A.; Diez Valle, R.; Ensenat, J.; Ley Urzaiz, L.; Barcia Albacar, J.A.; Kupanur, S.S.; Regli, L.; Dunn, I.F.; Adelson, D.; Bederson, J.; Levi, A.D.; Alturky, A.Y.; Matula, C.; Cortes, B.; Xiang, W.; Li, T.; El-Ghandour, N.M.F.; Kanai, R.; Patir, R.; Misra, B.K.; Dwarakanath, S.; Servadei, F.; Tomasello, F.; Casali, C.; Unsgard, G.; Morcos, J.J.; Souhil, T.; Khoja, I.; Kehayov, I.; Vukic, M.; Ziebell, M.; Gulisano, H.A.; Tange, M.; Kurozumi, K.; Locatelli, M.; Garbossa, D.; Gomez Amador, J.L.; Rodriguez, A.O.; Ashkan, K.; Lim, M.; Maleki, M.; Agrawal, A.; Naik, A.; Sciubba, D.M.; Kim, L.J.; Spinner, R.J.; McDonald, P.; Pavesi, G.; Moiyadi, A.; Padayachy, Llewellyn; Meling, T.R.; Di Meco, F.; Perin, A.
INTRODUCTION : Neurosurgery is considered a technically demanding specialty; nonetheless, it also requires non-technical skills (NTSs) to reach mastery. RESEARCH QUESTION : This study seeks to understand how important NTSs are perceived by neurosurgeons across diverse roles and socio-economic backgrounds. The objective is to identify key NTSs and explore their role in surgical precision, teamwork, and collaboration. MATERIAL AND METHOD : An international survey involving 372 neurosurgeons from various socio-economic and cultural contexts was conducted. The extensive sample and inclusive methodology provide a comprehensive perspective on the perceived importance of NTSs in neurosurgery. RESULTS : The survey results highlight the universal significance of NTSs among neurosurgeons. Attention to detail, humility, and self-awareness are considered essential for surgical precision, effective teamwork, and collaboration. The findings underscore the necessity for integrated training programs that combine NTSs with technical skills. DISCUSSION AND CONCLUSION : The study emphasizes the importance of effective training methods such as simulations, mentorship, and role-playing in equipping neurosurgeons to navigate the complexities of their profession. Future research should focus on optimizing teaching methods for NTSs, comparing traditional courses, online modules, and hybrid training programs. Addressing the global disparity in neurosurgical care, particularly in low- and middle-income countries, is crucial for improving patient outcomes worldwide.
Overcoming the challenges of phytochemicals in triple negative breast cancer therapy : the path forward
(MDPI, 2023-06-16) Alaouna, Mohammed; Penny, Clement; Hull, Rodney; Molefi, Thulo; Chauke-Malinga, Nkhensani; Khanyile, Richard; Makgoka, Malose; Bida, Meshack; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. TNBC is thought to be produced by Wnt, Notch, TGF-beta, and VEGF pathway activation, which leads to cell invasion and metastasis. To address this, the use of phytochemicals as a therapeutic option for TNBC has been researched. Plants contain natural compounds known as phytochemicals. Curcumin, resveratrol, and EGCG are phytochemicals that have been found to inhibit the pathways that cause TNBC, but their limited bioavailability and lack of clinical evidence for their use as single therapies pose challenges to the use of these phytochemical therapies. More research is required to better understand the role of phytochemicals in TNBC therapy, or to advance the development of more effective delivery mechanisms for these phytochemicals to the site where they are required. This review will discuss the promise shown by phytochemicals as a treatment option for TNBC.
Position statement on the definition, incidence, diagnosis and outcome of acute on chronic pancreatitis
(Elsevier, 2023-03) Bouca-Machado, Tiago; Bouwense, Stefan A.W.; Brand, Martin; Demir, Ihsan Ekin; Frokjær, Jens Brondum; Garg, Pramod; Hegyi, Peter; Lohr, J.-Matthias; De-Madaria, Enrique; Pandanaboyana, Sanjay; Pedersen, Jan Bech; Rebours, Vinciane; Sheel, Andrea; Singh, Vikesh; Smith, Martin; Windsor, John A.; Yadav, Dhiraj; Drewes, Asbjorn Mohr
BACKGROUND : Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis. METHODS : A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process. RESULTS : The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis. CONCLUSIONS : Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.
Immunomodulatory gene-splicing dysregulation in tumorigenesis : unmasking the complexity
(MDPI, 2023-08-10) Maebele, Lorraine Tshegofatso; Mulaudzi, Thanyani Victor; Yasasve, Madhavan; Dlamini, Zodwa; Damane, Botle Precious; zodwa.dlamini@up.ac.za
Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.
Noninvasive intracranial pressure assessment by optic nerve sheath diameter : automated measurements as an alternative to clinician-performed measurements
(Frontiers Media, 2023-02-01) Netteland, Dag Ferner; Aarhus, Mads; Smistad, Erik; Sandset, Else Charlotte; Padayachy, Llewellyn; Helseth, Eirik; Brekken, Reidar
INTRODUCTION : Optic nerve sheath diameter (ONSD) has shown promise as a noninvasive parameter for estimating intracranial pressure (ICP). In this study, we evaluated a novel automated method of measuring the ONSD in transorbital ultrasound imaging. METHODS : From adult traumatic brain injury (TBI) patients with invasive ICP monitoring, bedside manual ONSD measurements and ultrasound videos of the optic nerve sheath complex were simultaneously acquired. Automatic ONSD measurements were obtained by the processing of the ultrasound videos by a novel software based on a machine learning approach for segmentation of the optic nerve sheath. Agreement between manual and automated measurements, as well as their correlation to invasive ICP, was evaluated. Furthermore, the ability to distinguish dichotomized ICP formanual and automaticmeasurements of ONSD was compared, both for ICP dichotomized at 20 mmHg and at the 50th percentile ( 14 mmHg). Finally, we performed an exploratory subgroup analysis based on the software’s judgment of optic nerve axis alignment to elucidate the reasons for variation in the agreement between automatic and manual measurements. RESULTS : A total of 43 ultrasound examinations were performed on 25 adult patients with TBI, resulting in 86 image sequences covering the right and left eyes. The median pairwise difference between automatically and manually measured ONSD was 0.06mm (IQR −0.44 to 0.38mm; p = 0.80). The manually measured ONSD showed a positive correlation with ICP, while automatically measured ONSD showed a trend toward, but not a statistically significant correlation with ICP. When examining the ability to distinguish dichotomized ICP, manual and automatic measurements performed with similar accuracy both for an ICP cuto at 20 mmHg (manual: AUC 0.74, 95% CI 0.58–0.88; automatic: AUC 0.83, 95% CI 0.66–0.93) and for an ICP cuto at 14 mmHg (manual: AUC 0.70, 95% CI 0.52–0.85; automatic: AUC 0.68, 95% CI 0.48–0.83). In the exploratory subgroup analysis, we found that the agreement between measurements was higher in the subgroup where the automatic software evaluated the optic nerve axis alignment as good as compared to intermediate/poor. CONCLUSION: The novel automatedmethod ofmeasuring theONSD on the ultrasound videos using segmentation of the optic nerve sheath showed a reasonable agreement with manual measurements and performed equally well in distinguishing high and low ICP.
Targeting stem cells in the colorectal cancer microenvironment to avert drug resistance in pursuit of novel oncotherapies
(Biolife Sas, 2023-09) Damane, Botle Precious; Marima, Rahaba; Mulaudzi, Thanyani; Dlamini, Zodwa; Zodwa.Dlamini@up.ac.za
Several studies have demonstrated the heightened prevalence of colorectal cancer (CRC) among young black men. Most of these men present with already metastasized CRC. Cancer stem cells (CSCs) play a pivotal role in CRC metastasis and drug resistance. The plasticity of CSCs promotes therapeutic resistance by continuously dividing into different phenotypes thwarting therapeutic targets. Phenotypic changes affect the expression of highly heterogeneous surface biomarkers. Identifying molecular and cell surface biomarkers is important for diagnosis, decision-making, and determining clinical outcomes. Furthermore, CSCs promote cancer initiation, development, advancement, relapse, and therapeutic resistance by altering the tumor microenvironment (TME). Cancer-favoring molecular signaling pathways may contribute to differentiating CSCs into TME components that create favorable conditions conducive to cancer progression. In turn, different TME components may differentially stimulate CSCs, prompting proliferation into diverse cancer cell phenotypes. This review describes the mechanisms of CSCs in promoting CRC and elucidates how the TME and CSCs work synergistically to sustain cancer development, evoke relapse, and promote therapeutic resistance. These cancer-promoting mechanisms can be antagonized by identifying different CSC phenotypes and targeting them for cancer therapy.
Spontaneous resolution of a patient with a symptomatic pheochromocytoma
(Elsevier, 2024-07) Jackson, Brandon Spencer; Ndhlebe, Gugulethu; Suleman, Farhana Ebrahim; brandon.jackson@up.ac.za
A 56-year-old woman presented with a 2-year history of chronic persistent right upper quadrant abdominal pain that was associated with intermittent nausea, vomiting, and unintentional weight loss. She had been on antihypertensive treatment—hydrochlorothiazide and amlodipine—for 2 years. Her blood pressure, 125/73 mm Hg, was well con- trolled and did not appear to be labile. She had tenderness in the right upper quadrant of the abdomen with no palpable masses. Oral analgesia was prescribed for the pain.
Detection of neutralizing antibodies in COVID-19 patients from Steve Biko Academic Hospital Complex : a pilot study
(MDPI, 2023-07-03) Kgatle, Mankgopo; Chalwe, Joseph Musonda; Van der Westhuizen, Donald; Xu, Shuting; Damane, Botle Precious; Mathebela, Precious; Ueckermann, Veronica; Mayaphi, Simnikiwe; Rodrigues, Hosana Gomes; Moura-Alves, Pedro; Ndlovu, Honest; Mzizi, Yonwaba; Zongo, Lusanda; Hairwadzi, Henry; Vorster, Mariza; Zeevaart, Jan Rijn; Sathekge, Mike Machaba; mike.sathekge@up.ac.za
A correlation between neutralization activity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and protection against coronavirus disease 2019 (COVID-19) has been demonstrated by several studies. Here, we detect SARS-CoV-2 neutralizing antibody (NAB) production in COVID-19 patients from the Steve Biko Academic Hospital complex (SBAH), South Africa (SA). Samples from COVID-19 patients (mild to severe) were collected. SARS-CoV-2 rapid assays, genotyping (Delta and Omicron variants) and enzyme-linked immunosorbent assays (ELISA) were performed. IBM® Statistical Package for the Social Sciences (SPSS®) version 28 was used for inferential statistical analysis, and the data were presented using the Prism9 software (version 9.4.1). A total of 137 laboratory-confirmed COVID-19 patients, 12 vaccine recipients and 8 unvaccinated participants were evaluated. The production of SARS-CoV-2 NABs was observed in some of the COVID-19 cases, mainly in severe cases, although this should be noted with caution due to the small sample size of this pilot study. NABs were also observed in asymptomatic participants, with the most being found in recipients (n = 6) of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. We found a strong presence of NABs in COVID-19 patients, specifically in mild and severe cases. Severe infection was associated with higher NAB production (82%).
Transorbital neuroendoscopy-assisted resection of a giant optic pathway glioma in a neonate
(Springer, 2023-09) Maseko, Rodney; Mabogo, Maanda; Lockhat, Zarina I.; Makunyane, P.S. (Priscilla); Ahmad, Samia; Bida, Meshack; Padayachy, Llewellyn; lc.padayachy@up.ac.za
Congenitalgiant orbital tumors in infancy are relatively rare, especially when the tumors are associated with significant intracranial extension. We describe the use of a transorbital neuroendoscopy-assisted resection of such a lesion. While this approach is increasingly gaining popularity for certain anterior and middle skullbase lesions in adults, this report represents the youngest patient reported on where this minimally invasive approach has been successfully used to resect the intracranial tumor. This surgical approach obviated the need for a separate craniotomy, with the additional benefit of minimizing blood loss.
Unraveling the complex interconnection between specific Inflammatory signaling pathways and mechanisms involved in HIV-associated colorectal oncogenesis
(MDPI, 2023-02) Damane, Botle Precious; Mulaudzi, Thanyani Victor; Kader, Sayed Shakeel; Naidoo, Pragalathan; Savkovic, Suzana D.; Dlamini, Zodwa; Mkhize-Kwitshana, Zilungile Lynette; zodwa.dlamini@up.ac.za
The advancement of HIV treatment has led to increased life expectancy. However, people living with HIV (PLWH) are at a higher risk of developing colorectal cancers. Chronic inflammation has a key role in oncogenesis, affecting the initiation, promotion, transformation, and advancement of the disease. PLWH are prone to opportunistic infections that trigger inflammation. It has been documented that 15–20% of cancers are triggered by infections, and this percentage is expected to be increased in HIV co-infections. The incidence of parasitic infections such as helminths, with Ascariasis being the most common, is higher in HIV-infected individuals. Cancer cells and opportunistic infections drive a cascade of inflammatory responses which assist in evading immune surveillance, making them survive longer in the affected individuals. Their survival leads to a chronic inflammatory state which further increases the probability of oncogenesis. This review discusses the key inflammatory signaling pathways involved in disease pathogenesis in HIV-positive patients with colorectal cancers. The possibility of the involvement of co-infections in the advancement of the disease, along with highlights on signaling mechanisms that can potentially be utilized as therapeutic strategies to prevent oncogenesis or halt cancer progression, are addressed.

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