Health Science Reviews

by Vieshal Gopal

Introduction:

Imagine a seemingly harmless pill, taken by over 100 million women worldwide, carrying hidden risks. We’re talking about oral contraceptives (OC), a popular method of birth control with a variety of applications. These tiny tablets hold the power to reshape lives but also harbour an unsettling secret. Studies have revealed that OC users face a 2-6-fold increased risk of venous thrombosis (VT), a potentially life-threatening condition. Interestingly, VT remains rare among OC users, occurring mostly when combined with other risk factors. This study aimed to uncover why some OC users are more susceptible to VT and what this means for women’s health.

The Research Question:

This study set out to answer a critical question: Why do some women using OC suffer from VT while the majority do not? The research aimed to determine if hypercoagulability, a state of increased blood clotting, could be detected long after OC-related VT using global clotting assays, such as thrombin generation and overall haemostasis potential (OHP) assays. Additionally, the study explored whether hypercoagulability could be attributed to thrombophilia, a condition that increases the risk of abnormal blood clot formation.

Methods:

Results and Implications:

Women who had experienced blood clots linked to birth control pills (OC-related VT) still had a higher tendency for blood clotting even after they had stopped taking the pills for several months. This increased blood clotting was detected through thrombin generation and OHP assays. Interestingly, it was not only attributed to thrombophilia, suggesting that other factors contribute to increased blood clotting.

Additionally, the study discovered that people with a shorter APTT (a thromboplastin blood test) were more likely to develop blood clots while using OCs. This emphasizes that APTT can be a useful indicator for predicting the risk of blood clots in OC users.

Conclusion:

This study sheds light on the long-lasting impact of OC use on women’s coagulation profiles. It highlights the need for further investigation into hypercoagulability and its underlying causes in OC users. While thrombophilia plays a role, it appears that additional factors contribute to the elevated risk of VT. This research emphasizes the importance of personalized healthcare for women using oral contraceptives to mitigate potential risks and ensure their well-being.

Reference:

Doma, S. A., Vučnik, M., Mijovski, M. B., Peternel, P., & Stegnar, M. (2013). Enhanced thrombin generation in women with a history of oral contraception-related venous thrombosis. Thrombosis Research, 132(5), 621-626.

by Siyabonga Msipa

Pancreatic ductal adenocarcinoma is the most common and aggressive form of pancreatic cancer. With only a 5-year survival rate of less than 10%, classical treatments like surgery, chemotherapy, and radiation have not shown significant improvements in clinical outcomes.

Surgery is currently the best curative treatment option for localized PDAC but due to late diagnosis about 80% of patients are ineligible for the surgery because at this stage the disease would have already progressed and spread to other parts of the body. As a result, nearly all patients are offered conventional chemotherapy. However, this only modestly increases the survival rate due to therapy resistance and associated toxicity. These are therefore some of the factors that contribute to PDAC having the worst survival rate in comparison to all other cancers. 

The major difficulty in effectively treating PDAC is its tumor microenvironment which significantly contributes to therapy resistance, tumor progression and metastasis of the cancer. The tumor microenvironment refers to the environment around a tumor, which is composed of the surrounding blood vessels, different cell types, immune cells, and the extracellular matrix. It is largely composed of cancer cells which interact with these components in complex ways.

This study seeks to understand the effects of chemotherapy on the Pancreatic ductal adenocarcinoma tumor microenvironment using a technology called Single cell RNA sequencing (scRNA-seq).

Methods

scRNA-seq is an incredible technique that helps researchers to see the differences between individual cells, within the same tissue or tumor and how they respond to treatments. To do this the researchers collected tumor samples from 27 PDAC patients. Single cells were isolated from the tumor, and their RNA was extracted, reverse transcribed  into cDNA, which was then amplified and sequenced. The data was then cleaned up and was ready for further analysis. By analyzing the data generated from this sequencing the researchers could then gain information about the tumor itself and how the cells in the tumor respond to the treatment.

Results

A computational technique called unsupervised clustering combined with a method called uniform manifold approximation and projection (UMAP) was used to group cells that shared similar characteristics together. This analysis revealed ten unique cells clusters.

Three major groups of cells were identified as epithelial, T/ natural killer (NK), and myeloid cells. In addition to these major clusters, several other cell types were identified (Fig 3).

The researchers found that the epithelial compartment which refers to the cancer cells within the tumor microenvironment revealed a heterogeneous malignant subtype composition, with most tumors displaying a mixture of basal-like and classical-like cells. The classical subtype has a better prognosis, in contrast the basal subtype is associated with a more aggressive phenotype and patients respond poorly to treatment.

To understand how certain genes are active in these cancer cells in response to chemotherapy the researchers used a method called Gene Set Enrichment Analysis (GSEA). They found that the cancer cells from the chemotherapy treated group showed higher activity in genes related to processes called angiogenesis and EMT which are two critical factors that influence tumor growth and metastasis. Interestingly they observed that both the classical and basal-like cancer cells responded to the treatment in a similar way at the genetic level. In other words, the treatment didn’t cause classical cancer cells to shift to a more like basal-like expression.

Next the researchers wanted to understand how chemotherapy affected the communication between cells in the TME. PDCA is often characterised as having a highly immunosuppressive TME which means that the body’s immune system doesn’t recognize the cancer cells very well and the environment around the cancer cells suppresses the immune response.

The analysis revealed a potential effective treatment. The researchers found that a molecule called TIGIT found on the CD8 + T cells was overexpressed in the treatment naïve group. TIGIT is like a “brake” for these immune cells, stopping them from attacking normal cells. When someone has cancer, the cancer cell uses this molecule to stop immune cells from attacking them.

If TIGIT is blocked, as in release the brakes on the immune system, this can make the immune system more powerful in attacking the cancer. So, an effective therapy might involve blocking TGIT as the first-line treatment or together with chemotherapy.

Overall, scRNA-seq is a valuable technique that can be used to gain a deeper understanding of complex diseases and can help in the discovery on novel therapies that can benefit a lot of people.

Reference

Werba, G., Weissinger, D., Kawaler, E., Zhao, E., Despoina Kalfakakou, Surajit Dhara, Wang, L., Lim, H.B., Oh, G., Jing, X., Beri, N., Khanna, L., Gonda, T.A., Oberstein, P.E., Hajdu, C., Loomis, C.A., Heguy, A., Sherman, M.H., Lund, A.W. and Welling, T.H. (2023). Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment. Nature Communications, [online] 14(1). doi:https://doi.org/10.1038/s41467-023-36296-4.

by Cameron Timm

Imagine this: A busy city in Nigeria, where the streets are alive with the symphony of honking horns, revving engines, and the hurried footsteps of pedestrians. Among this lively chaos lies a silent danger that often goes unnoticed – road traffic injuries (RTI).

In Africa and various low- and middle-income countries, these injuries bear a heavy burden, with head injuries being a particularly concerning outcome. Researchers from the University of Ibadan and the University College Hospital embarked on a journey to unravel the incidence, causes, and severity of road traffic-related head injuries in a Nigerian academic neurosurgical practice.

Questioning the Unseen Danger

In this study, researchers from the University of Ibadan and the University College Hospital set out to answer a crucial question: What is the true extent of road traffic-related head injuries in Nigeria?

Peering behind the curtain: The How

To answer their question, the researchers took a retrospective cross-sectional approach, analyzing data from a prospective head injury registry at an academic neurosurgery practice in Nigeria. Their canvas spanned 7 years (August 2009 – June 2016), painting a picture of 1034 head injuries, out of which 80.6% were a result of all-terrain road traffic accidents. Within this mosaic of injuries, they noted a broad spectrum of ages, with an average of 33.06 years and the most common age group affected was 21-30 years, accounting for 27.7% of cases. The male-female ratio stood around 3:1, emphasizing the vulnerability of young males on the road.

Unveiling the Consequences: Results and Insights

Digging deeper into the canvas of injuries, the researchers found motorcycles and motor vehicles to be the exclusive culprits. More than half of the cases were due to motorcycle crashes, often involving vulnerable road users like pedestrians. A stunning revelation emerged – over 90% of these victims belonged to the low socioeconomic class, highlighting the inequality woven into the fabric of road safety.

The severity of the injuries painted a grim picture as more than half of the head injuries were moderate to severe, accompanied by a loss of consciousness in 93% of cases. The injuries extended beyond the head, affecting various organ systems in 50.5% of cases. Surgical interventions were needed, but many victims faced logistical challenges in receiving timely care.

A Glimmer of Hope: Implications and Beyond

As the sun sets on this study, its implications are clear. The researchers emphasized the urgent need for road safety interventions, especially targeting vulnerable road users and the economically disadvantaged. This study serves as a call to action for governments, policymakers, and communities to join hands in creating safer roads and protecting those who navigate them.

In a world where the streets are a canvas of life’s hustle and bustle, this study serves as a reminder that beneath the surface lies a perilous reality that demands attention, compassion, and change.

[Adeleye, A. O., Olowookere, K. G., & Olayemi, O. O. (2009). Clinicoepidemiological profiles and outcomes during first hospital admission of head injury patients in Ikeja, Nigeria: A prospective cohort study. Neuroepidemiology, 32(2), 136–141. https://doi.org/10.1159/000182821%5D

by Mqiniseli Dlamini

Diabetes is a global health concern, impacting more than 537 million adults globally, with adverse micro- and macrovascular complications as a vascular disease. In a recent meta-analysis led by Z. Wang and titled “Diabetic Retinopathy (DR) as a Potential Predictor of Stroke in Diabetes Mellitus Patients,” the primary objective was to elucidate a critical connection between diabetic retinopathy, a prevalent cause of blindness affecting approximately one-third of individuals with diabetes, and stroke, which ranks as the second leading cause of mortality among diabetic patients on a global scale. The frequency of stroke is known to be two to four times higher in people with diabetes than those without the condition, underscoring the importance of predicting and managing risk factors from a diabetic perspective.

This study sought to explore whether the presence of diabetic retinopathy could serve as an early indicator or predictor of the risk of stroke in individuals with diabetes mellitus, a condition with substantial healthcare implications. Understanding this link has the potential to improve both preventive and clinical management strategies for diabetic patients to mitigate the risk of stroke and its associated complications.

Researchers conducted a comprehensive search in electronic databases, seeking studies that explored the relationship between stroke and diabetic retinopathy. The research studies were divided into two groups, one focused on odds ratios and the other on hazard ratios, to thoroughly examine the relationship between DR and strokes. Additionally, a supplementary analysis was carried out on the ACCORD Eye study, which involved 3,472 patients who underwent baseline and year 4 eye examinations. This approach ensured a comprehensive and rigorous assessment of the link between DR and the risk of stroke. The primary outcome was stroke, including ischemic and haemorrhagic events. Covariates were selected through stepwise selection, and sensitivity analyses considered various DR severity levels.

Out of 20 papers reviewed, including 48 967 patients, they discovered a distinct connection between DR and strokes, indicating that the microvascular abnormalities associated with DR have substantial implications for cerebrovascular health. Notably, individuals with DR were found to have a 62% higher risk of experiencing a stroke compared to their diabetic counterparts without DR. To put it differently, having DR was linked to a 1.62 times higher likelihood of experiencing a stroke. This discovery highlights the significance of acknowledging the increased likelihood of stroke in individuals with diabetic retinopathy, especially among patients diagnosed with type 2 diabetes and those exhibiting more advanced stages of diabetic retinopathy. In cases of severe diabetic retinopathy, the risk of stroke is notably amplified. This emphasizes the need for vigilant monitoring and tailored interventions in these high-risk populations to prevent cerebrovascular complications.

References

Wang, Zicheng, Dan Cao, Xuenan Zhuang, Jie Yao, Ruoyu Chen, Yesheng Chen, Kangyan Zheng, and Liang Zhang. 2022. “Diabetic Retinopathy May Be a Predictor of Stroke in Patients With
Diabetes Mellitus.” Journal of the Endocrine Society 6 (8).

Wong, Ka-Ho, Katherine Hu, Cecilia Petersoon, Nazanin Sheibani, Georgios Tsivgoulis, Jennifer J Majersik, and Adam H de Havenon. 2020. “Diabetic Retinopathy and Risk of Stroke: A Secondary Analysis of the ACCORD Eye Study.” Stroke 51 (12): 3733-3736.

by Lutho Daza

OUTLINE

In this article, the researchers from the College of Health Sciences, Westville Campus in Kwazulu-Natal, conducted a study with the aim of answering the relationship between the morphology of the right coronary artery (RCA) and left coronary artery (LCA), which included the shape and the branching patterns of the RCA. In addition, the occurrence of a double RCA and the absence of the LCA using coronary angiograms.

The study was conducted to document the anatomical variations of the coronary artery. The RCA gives off the posterior intervertebral artery (PIB) with a dominance of 60%, and the codominance of 2.5% occurs when the circumflex branch (CX) and RCA provide the PIB. The presence of rare congenital anomalies of the coronary artery splitting. The geometric shape of the RCA is C-shaped and sigma-shaped, with the C-shape mostly associated with Atherosclerosis in their proximal middle region. The isolated absence of LCA occurs when the anterior intervertebral artery (AIB) and CX arise directly from the left aortic sinus rather than bifurcating from a common trunk. The occurrence of the AIB and CX outside the LCA is known as a secondary absence of LCA.

    METHODS

500 human coronary angiograms acquired from the cardiac catheterization of a private hospital in KwaZulu-Natal were reviewed. The branching pattern of RCA was classified into type A where a single RCA was present, type B where RCA dominance with left dominance, type C where RCA splits with co-dominance and type D where RCA splits with right dominance.

LCA was classified into type A where LCA is bifurcated into AIB and CX, type B, trifurcation into AIB, median, and CX arteries, type C is quadrifurcation into AIB, two median arteries, and CX artery, type D AIB and CX originate from aortic sinus and LCA is absent and type E the LCA is absent, AIB, median and CX arteries arose from left aortic sinus. The shape of RCA was classified as either C-shaped or S-shaped.

    RESULTS

RCA type A was the most prominent with 95.8% and a split of 4.2% of cases. RCA type B occurred in 3.6%, type C occurred in 0.4% and type D occurred in 0.2% of the study sample. LCA type A occurred in 65.8% and type B occurred in 20.4% of the study sample, type C had a prevalence of 1.6%. When LCA was absent, LCA type D occurred in 10.8% of cases and type E occurred in 1.4% of cases. RCA C-shaped was found in 68% of the heart and S-shaped was found in 32% of the study sample.

In the study, there was a significant correlation between split RCA and absent LCA with splitting of the RCA more prevalent in the absence than the presence of the LCA (Table 1).

Table 1. Data analysis showing results of Pearson chi-square (c2) tests.

LCA- Left coronary artery and RCA- Right coronary artery.

REFERENCE

Singh S, Ajayi N, Lazarus L, Satyapal KS. 2017. Anatomic study of the morphology of the right and left coronary arteries. Folia Morphologica 76(4):668-674.

by Mandisa Mabaso

Introduction

The Pulmonary veins transport oxygenated blood from the lungs to the left atrium of the heart. They are mainly located in the interlobular septa and drain each bronchopulmonary segment on the anterior surface of the bronchus. In addition, veins run between the segments, mediastinal, and fissural surfaces. Often, the veins of the middle lobe of the inferior lobe arise from those of the right medial. In addition, the right superior and middle pulmonary veins drain the right superior and middle lobes, while the right inferior and left inferior pulmonary veins drain the corresponding inferior lobes.

Aim

The aim of the study is to determine the incidence of different draining patterns of the right pulmonary vein at the hilum.

Methods

The study involved twenty-six formalin-fixed adult cadaveric lungs from Bangalore Medical College & Research Institute. The dissection initially involved identifying the structures at the hilum. Additionally, the pulmonary veins were picked up and their tributaries were traced peripherally by carefully dissecting the lung tissue using blunt forceps. Therefore, different patterns in the drainage of the pulmonary veins were noted.

Results

In 53.8% of dissected lungs, the right superior lobar vein and middle lobar vein unite to form the right superior pulmonary veins, Moreover, the right superior lobar vein drained the apical and anterior segments of the right upper lobe and also the medial and lateral segment of the right middle lobe from the anterior surface, whereas veins from the posterior segment of the upper lobe drained into the posterior aspect of the superior pulmonary vein. These lungs fall under Type A, whereby the right superior lobar vein (RSLV) and right middle lobar vein (RMLV) join to form the right superior pulmonary vein (RSPV) as seen in Figure 1.

In 26.6% of dissected lungs, the right superior lobar vein and the right middle lobar vein did not join, and all three lobar veins drained separately at the hilum. This belongs to Type B, whereby the right superior lobar vein (RSLV), right middle lobar vein (RMLV), and right inferior lobar vein (RILV) drain separately in Figure 3.

In 11.53% of dissected lungs, the right superior lobar vein received tributaries from the right upper lobe, whereas the right middle lobar vein joined with the inferior lobar vein to form the right inferior pulmonary vein (Figure 4). This belongs to Type C, where RSLV forms RSPV, and RMLV and RILV join to form the right inferior pulmonary vein (RIPV).

In 3.8% of dissected lungs, the right superior lobar vein, the right middle lobar vein, and the right inferior lobar vein drained into a common vein forming the right single unilateral central pulmonary vein (Figure 5). This belongs to Type D, where RSLV, RMLV, and RILV join to form the right unilateral single central pulmonary vein (RUSCPV).

Discussion

This study focuses on the drainage patterns of the right lung’s pulmonary veins, focusing on all three lobar veins which are RSLV, RMLV, and RILV. Variations in the vein numbers and course are common, and patients with separate ostium for the right middle lobar vein have higher atrial arrhythmia frequency as seen in Figure 3. Anomalysed veins can lead to the right ventricular diastolic overload, causing ectopic beats. Understanding the normal pulmonary venous anatomy is essential for pre-ablation planning and for the evaluation of post-ablation complications. Pulmonary veins trigger atrial fibrillation in patients with paroxysmal atrial fibrillation, and catheter ablation is a treatment strategy targeting these triggers. In addition, anatomic variation of the middle lobar vein draining into the inferior pulmonary vein is important for the right lobar lobectomy surgery.

Conclusion

The study found significant variations in pulmonary venous anatomy in 46.03% of dissected lungs, aiding in the classification of anatomical patterns based on drainage patterns of the right pulmonary vein at the hilum. The results confirm that there is considerable variation in the anatomy of pulmonary veins. Moreover, with the increasing use of cardiovascular imaging, variations in the pulmonary vein anatomy have become more appreciated, hence detailed knowledge of pulmonary venous anatomy and drainage patterns is important during mapping and ablation procedures.

References

Rajeshwari, M. S., & Ranganath, P. (2012). Variations in draining patterns of right pulmonary veins at the hilum and an anatomical classification. International Scholarly Research Notices, 2012.

By Jamie Langson

We’ve all experienced the sense of frustration that arises when we possess knowledge but lack the means to act upon it, haven’t we? For well over a century, scientists have been aware that roughly 90% of cancers have extra chromosomes, but couldn’t exactly determine what this aneuploidy did due to the lack of means for manipulation. This puzzling phenomenon was, in a sense, the unaddressed elephant in the oncology room. However, this changed recently when a team of researchers from Yale University School of Medicine discovered that the intuition of scientists from way back then, was indeed correct. The study, published in the journal Science, aimed to determine whether aneuploidy in cancer cells are drivers of the disease and whether it represents a form of “aneuploidy addiction.”

Various computational and functional techniques were employed to facilitate the analysis of aneuploidy in cancer. Among these techniques, the use of CRISPR stood out. The research team introduced a new approach to this gene-editing technique, enabling the removal of entire chromosomes from cancer genomes, a feat previously considered unattainable. They applied this method to melanoma, ovarian and gastric cancer cell lines. This groundbreaking technique is known as ReDACT, which stands for Restoring Disomy in Aneuploid cells using CRISPR Targeting. They utilized ReDACT-NS (negative selection), ReDACT-TR (telomere replacement) and ReDACT–CO (CRISPR only) to generate a panel of isogenic cells devoid of common aneuploidies, allowing for a detailed study of its effect.

Essentially, they successfully removed the third copy of the chromosome 1q, a genetic anomaly frequently observed in numerous cancers, known to be linked to disease progression, and repeatedly occurs early in cancer development. Upon removal, tumours from this subpopulation of cancer cells were unable to grow in both petri dishes and in live mice.

Another significant finding was that when MDM4 expression was increased by the additional third copy of chromosome 1q, p53 signalling was suppressed, consequently promoting tumour growth. Together, this was conclusive evidence that extra chromosomes within cancer cells are in fact, drivers of the disease. Furthermore, the study demonstrated that cancer becomes more sensitive to drugs due to aneuploidy in its genomes. The researchers therefore speculated that this “aneuploidy addiction,” similar to “oncogene addiction,” where the loss or inhibition of a single oncogene triggers cancer regression, may provide therapeutic vulnerabilities for cancer. For now, CRISPR is merely a tool, not a therapy, but the advances made by this team of researchers may point towards a new approach of targeting cancer in the future.

Reference
Girish, V., Lakhani, A.A., Thompson, S.L., Scaduto, C.M., Brown, L.M., Hagenson, R.A., Sausville, E.L., Mendelson, B.E., Kandikuppa, P.K., Lukow, D.A., Yuan, M.L., Stevens, E.C., Lee, S.N., Schukken, K.M., Akalu, S.M., Vasudevan, A., Zou, C., Salovska,B., Li, W., Smith, J.C., Taylor, A.M., Martienssen, R.A., Liu, Y., Sun, R., Sheltzer, J.M. (2023) Oncogene-like addiction to aneuploidy in human cancers. Science 381, 1-14. DOI: 10.1126/science.adg4521

by Ubuntu Hlatshwayo

by Ramses Peigou Wonkam

Introduction:
Have you ever wondered if we could spot a sneaky heart rhythm that often goes unnoticed but could lead to serious complications? Well, researchers have now unlocked a new method to catch this rhythm in its tracks, using the power of A.I.

The Problem:
Atrial fibrillation, a tricky little heart irregularity, often slips under the radar, increasing the risk of stroke and heart complications. Traditional methods like the ECG sometimes miss it, and without a confirmed diagnosis, treatments can be risky. This has been a long-standing challenge in heart care, with many strokes occurring without any clear reason, possibly due to this undetected irregularity.

The Brilliant Idea:
Researchers decided to tap into the advancements of machine learning. They believed that although atrial fibrillation might be playing hide and seek, it does leave behind some clues. By training an AI on ECGs, they hoped to spot these clues.

The Method:
The team gathered heart readings (ECGs) from a whopping 180,922 patients from the Mayo Clinic spanning decades! They then trained their AI model on a subset of this data and tested it on the rest. The primary goal was to see if the AI could identify atrial fibrillation even when the heart seemed to be beating just fine.

The Results:
The AI model did a stellar job! On its initial run, it detected atrial fibrillation with an accuracy of around 79.4%. But when the team decided to give the model more data from a patient’s first month, the accuracy shot up to an impressive 83.3%!

The Big Picture:
This is not just a win for technology but a giant leap for heart care. Early detection of atrial fibrillation means timely treatment, potentially saving countless lives. The marriage of AI and medical science seems to be a match made in heaven, and this study is a testament to that.

Reference:
AVa ZI, Noseworthy PA, Lopez-Jimenez F, Asirvatham SJ, Deshmukh AJ, Gersh BJ, Carter RE, Yao X, Rabinstein AA, Erickson BJ, Kapa S, Friedman PA. An artificial intelligence-enabled ECG algorithm for the identification of patients with atrial fibrillation during sinus rhythm: a retrospective analysis of outcome prediction. Lancet. 2019 Sep 7;394(10201):861-867. doi: 10.1016/S0140-6736(19)31721-0. Epub 2019 Aug 1. PMID: 31378392.