Prevention Group

Breast cancer (BC) is one of the most common cancers worldwide; however, there is a lack of comprehensive data on survival outcomes and prognostic factors in Central Vietnam. This study aimed to estimate overall survival (OS) rates and identify key prognostic factors associated with mortality among BC patients in this region. This ambidirectional cohort study included 1,213 patients newly diagnosed with BC at Danang Oncology Hospital between January 2019 and December 2023. OS rates at 1, 3, and 5 years were estimated using the Kaplan-Meier method, and survival differences across molecular subtypes and TNM stages were evaluated using the log-rank test. Prognostic factors for mortality were assessed using a multivariable Cox proportional hazards model. The 1-, 3-, and 5-year OS rates were 97.4%, 91.0%, and 86.0%, respectively. The Luminal A subtype had the highest 5-year OS rate (91.5%), while the triple-negative subtype had the lowest (76.9%). Patients with stage IV disease had a 5-year OS rate of 29.5%. Significant predictors of higher mortality included unemployment [adjusted hazard ratio (aHR) 1.59], liver diseases (aHR 3.06), progesterone receptor-negative status (aHR 2.20), Ki-67 index ≥30% (aHR 2.13), and TNM stage III-IV (aHR 10.27). Surgical intervention was associated with a reduced risk of mortality (aHR 0.40). The study found relatively high OS rates in this cohort. However, advanced stage, unfavorable tumor characteristics, comorbidities, and socioeconomic disadvantage were associated with worse outcomes. Collaborative multicenter research using standardized data collection is necessary to validate and expand these findings across diverse settings, ultimately supporting efforts to improve survival outcomes in BC patients.

This PhD thesis explores the neuroimmune mechanisms in neck pain and investigates if musculoskeletal physiotherapy affects these mechanisms. The research aims to better understand the physiological processes of neck pain by examining both systemic inflammatory markers and spinal neuroinflammation, and by assessing how musculoskeletal interventions influence these neuroimmune responses. The thesis is divided into three parts. Part I: Systemic Inflammatory Markers in Neck Pain This section investigates whether people with neck pain exhibit elevated levels of systemic inflammatory markers compared to pain-free controls and how these markers relate to symptoms and pain persistence. It includes four chapters: Chapter 1 reviews neuroimmune interactions in musculoskeletal conditions, detailing the role of the immune and nervous systems and their interplay in spinal pain and nerve injury. It also discusses prospects for targeted therapies. Chapter 2 addresses the complexity of interpreting systemic inflammatory markers, cautioning against oversimplified conclusions due to potential confounding variables. Chapter 3 presents a cross-sectional study identifying associations between systemic neuroimmune markers and clinical, psychological, and lifestyle factors in people with non-specific neck pain and painful cervical radiculopathy. Chapter 4 describes a prospective cohort study that follows people with acute neck pain over six months, identifying distinct recovery trajectories based on inflammatory, clinical, and psychological profiles. Part II: Spinal Neuroinflammation in Cervical Radiculopathy This part focuses on developing and applying neuroimaging techniques to assess localised inflammation in the spinal cord and neuroforamina of patients with painful cervical radiculopathy. It includes two chapters: Chapter 5 introduces a pharmacokinetic model using the radiotracer [11C]DPA713 with dynamic PET/CT imaging to quantify neuroinflammation. The study establishes the model’s test-retest reliability. Chapter 6 applies this method to show that patients with painful cervical radiculopathy have increased tracer binding, indicating neuroinflammation, at affected sites compared to controls. It also explores correlations with clinical symptoms. Part III: Effects of Musculoskeletal Physiotherapy on Neuroimmune Mechanisms This section evaluates how musculoskeletal physiotherapy impacts systemic and localised neuroimmune responses. It includes five chapters: Chapter 7 is a systematic review and meta-analysis that suggests joint and nerve mobilisation can influence neuroimmune responses in animal models and some human studies, though research in humans remains limited. Chapter 8 introduces the CROM-VAS Test, a novel tool to assess short-term changes in pain intensity post-treatment. The test is shown to have good inter-rater reliability. Chapter 9 outlines the protocol for a randomised, placebo-controlled trial examining the effects of joint mobilisation and manipulation on systemic neuroimmune markers in people with persistent neck pain. Chapter 10 presents the results of this trial, which found no significant short-term changes in systemic markers following a single session of treatment. Chapter 11 shifts focus to localised inflammation, evaluating spinal neuroinflammation before and after a six-week neural tissue management intervention in two patients. The intervention showed potential in reducing neuroinflammation. The thesis concludes with a comprehensive discussion of the findings (Chapter 12), summaries in Dutch and English (Chapter 13), appendices (Chapter 14), and author information and publications (Chapter 15). Overall, this thesis highlights the complex neuroimmune landscape of neck pain and provides foundational evidence for the potential, yet still limited, impact of musculoskeletal physiotherapy on local neuroinflammation. It underscores the need for more mechanistic research for a better understanding of neck pain and the workingmechanisms of musculosksletal physiotherapy.

Background and Objective: Cyclins are the key regulator of the cell cycle and their over-expression has been seen in many cancers including breast cancer. Cyclin D1 is an oncoprotein encoded by CCND1 gene located on chromosome 11 (11q) which regulates cell cycle in shifting from G1 to S phase. It’s the main target for steroids and mitogenic growth hormones in breast epithelial cells. This study aimed to evaluate the relationship between Cyclin D1 G870A polymorphism and breast cancer risk in a population in the north of Iran.
 Methods: Whole blood samples collected from 82 patients with breast cancer and 66 healthy women. DNA was extracted and genotyping was performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) technique.
 Results: Genotypic prevalence of AA, AG, GG genotypes among patients were 40.2%, 35.3% and 24.4% and in controls were 30%, 47%, 23%, respectively. There was no significant difference in CCND1 G870A genotype polymorphism between patients and control group (p=0.32). Also, allelic prevalence of A and G alleles in breast cancer patients were 58% and 42%, in controls were 54% and 46%, respectively. The present study showed that there is no significant association between CCND1 G870A polymorphism with the risk of breast cancer.
 Conclusion: The results of this study revealed that there is no significant association between CCND1 G870A genetic polymorphism and the risk of breast cancer in the population of the north of Iran. More studies with larger samples of cases and controls would be beneficial.

BackgroundWomen’s Rugby-7’s continues to experience growth in its player involvement and subsequent popularity in the United States. ObjectiveEvaluate the medical cost and severity profile associated with player injuries in U.S. Women’s Rugby-7’s.DesignProspective epidemiological study.SettingU.S. Women’s Rugby-7’s regional tournaments between 2010–2015.Participants248 injury encounters during 79 U.S. tournament match days between 2010–2015.InterventionsThe Rugby Injury Survey & Evaluation (RISE) Report methodology was applied, following the rugby consensus statement. After injury data collection, International Classifications of Diseases -10 – Clinical Modifications (ICD-10-CM) injury diagnosis codes and Current Procedural Terminology (CPT) programs were evaluated for cost analysis using institutional charges in US dollars (US$). Main Outcome MeasurementsThe costs (U.S. Dollars $) of injuries are sorted by year of play, positions, body regionality, and ICD-10-CM codes. Time lost due to injury, Current Procedural Terminology (CPT), and Healthcare Common Procedure Coding System (HCPCS) were also formulated for injuries.ResultsThe average annual costs of injuries among U.S. Women’s Rugby-7 players were $7,443 between 2010–2015. With over a 2.3-time increase in costs between 2011 and 2012. Back positions encountered the most cost when injured. Fractures of all types constituted the highest cost incurred among all ICD-10-code types. ConclusionsBy using a standardized medical coding system involving injury diagnosis, it would allow teams and stakeholders to be prepared for regional tournaments and the injuries encountered As a result, there is a more significant initiative to explore player injury epidemiology of this contact sport. However, there is a paucity of literature that addressed The purpose of this study was to evaluate the medical costs and severity associated with player injuries in U.S. Women’s Rugby-7’s.

ObjectiveTo identify the differences in risk-factors between sexes and age in US rugby-7s.DesignLogistic regression.SettingUSA Rugby tournaments (U-19 to Elite; 2010–2016).Participants1,307 (68%=men, 31%=women) injured U.S. Rugby-7s players.Assessment of Risk FactorsA cross-sectional analysis using the RISERugby Injury Registry. Anthropometric data, injury mechanism, and other factors were tabulated by HNF injuries. Logistic regression determined relationship between sex and HNF injuries. A multivariable model was used to calculate the probability of HNF injuries and differences between sex.ResultsFrom 2010–2016, 1,679 match injuries were seen (68%=men, 32%=women). A total of 474 (28%) HNF injuries were documented. The most commonly injured body part was the head (48%) with concussions (40%). Final model revealed sex, age, position during contact, contact surface, and play legality were significantly associated with HNF injuries. Controlling for play-legality and position during contact, U18-men injured during contact with an opposing player had the highest probability of HNF injuries (51%) and a higher probability than U18 women (P=0.004). Meanwhile, women 18–24 (P=0.019) and over 30 (P=0.042) had a higher probability of HNF injury when injured during contact with the ground.ConclusionsUnder-18 male players involved in contact with players were most at risk for HNF injuries. Adult women 18–24 and 30-years old had a higher probability of sustaining a HNF injury during contact with the ground. Tackle techniques/execution, break falls, including collisions, employed by new rugby-7s players, should be studied for injury reduction.

ObjectiveTo investigate the medical diagnosis and procedural coding cost of concussions in U.S. rugby-7s.DesignProspective descriptive epidemiological study.SettingUSA Rugby rugby-7s geographic union tournament series (79 tournament-days, 2010–2015).ParticipantsTournament players (n=164; female=27%; male=73%) sustaining acute head injuries during matches in the RISERugby Injury Registry.Assessment of Risk FactorsInjury diagnosis and medical billing coding for concussion diagnosis, and the financial cost of tournament-treatment interventions.Outcome MeasuresInternational Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) were computed after player concussion injury encounters. Financial cost (US$=dollars) was calculated after initial encounter, evaluation/recommendation for further treatment and follow-up were made for each player.Main ResultsTournament series encountered head injuries (15.1%; n=164) most often coded as a wound and/or laceration (74%), followed by fractures (9%). Costs were most often in the form of sideline evaluation, first aid/wound care, ice/compression, and post-match cephalic imaging (n=153). Meanwhile, 13.4% (n=22; male=15, female=7) of all head injuries which were coded by the ICD-10 system as an acute concussive injury without any additional co-diagnosis. Concussions at 18.2% (n=4) needed hospitalization and further imaging studies. The total estimated direct medical costs of concussive injuries was US$4,332 (US$197 per player concussion).ConclusionsHead injuries were common in our US Rugby-7s cohort, with men being treated for concussions more than women players. Concussed players needing higher institutional care supports tournaments series will need quality acute sideline treatment to address these injuries.

Intraoperative bulbocavernosus reflex neuromonitoring has been utilized to protect bowel, bladder, and sexual function, providing a continuous functional assessment of the somatic sacral nervous system during surgeries where it is at risk. Bulbocavernosus reflex data may also provide additional functional insight, including an evaluation for spinal shock, distinguishing upper versus lower motor neuron injury (conus vs. cauda syndromes) and prognosis for postoperative bowel and bladder function. Continuous intraoperative bulbocavernosus reflex monitoring has been utilized to provide the surgeon with an ongoing functional assessment of the anatomical elements involved in the S2-S4 mediated reflex arc including the conus, cauda equina and pudendal nerves. Intraoperative bulbocavernosus reflex monitoring typically includes the electrical activation of the dorsal nerves of the genitals to initiate the afferent component of the reflex, followed by recording the resulting muscle response using needle electromyography recordings from the external anal sphincter. Herein we describe a complementary and novel technique that includes recording electromyography responses from the external urethral sphincter to monitor the external urethral sphincter reflex. Specialized foley catheters embedded with recording electrodes have recently become commercially available that provide the ability to perform intraoperative external urethral sphincter muscle recordings. We describe technical details and the potential utility of incorporating external urethral sphincter reflex recordings into existing sacral neuromonitoring paradigms to provide redundant yet complementary data streams. We present two illustrative neurosurgical oncology cases to demonstrate the utility of the external urethral sphincter reflex technique in the setting of the necessary surgical sacrifice of sacral nerve roots.

<div>Abstract<p>Dietary intake of B vitamins and methionine might associate with carcinogenesis due to their role in DNA synthesis and methylation. Owing to the previous inconsistent findings on gastric cancer risk, we aimed to examine the associations between dietary intakes of B vitamins and methionine and the risk of gastric cancer, according to sodium intake.</p><p>We included 86,820 Japanese individuals who completed a validated food frequency questionnaire with 138 food items in the Japan Public Health Center–based Prospective Study. Cox proportional hazards regression was used to obtain HRs and 95% confidence intervals (CI) of gastric cancer according to separate intakes of folate, vitamin B6, vitamin B12, and methionine after adjusting for confounding factors, including <i>Helicobacter pylori</i> and atrophic gastritis in the subgroup analysis.</p><p>We identified 2,269 gastric cancer cases within a median of 15.4 years of follow-up. We found no association between any of the dietary intakes of folate, vitamin B6, vitamin B12, or methionine with the risk of gastric cancer. In the stratified analysis by sodium intake, we observed a positive association between folate intake and risk of gastric cancer among participants with a high sodium intake (≥4.5 g/day) [HR = 1.28 (95% CI, 1.06–1.56), <i>P</i><sub>trend</sub> = 0.001; <i>P</i><sub>interaction</sub> = 0.02]. Meanwhile, there was no association between folate intake and risk of gastric cancer among participants with low sodium intake (<4.5 g/day) [HR = 0.94 (95% CI, 0.73–1.21), <i>P</i><sub>trend</sub> = 0.49].</p><p>In conclusion, we found no association between any dietary intakes of folate, vitamin B6, vitamin B12, and methionine with the risk of gastric cancer.</p>Prevention Relevance:<p>The increased intake of B vitamins and methionine in populations with adequate dietary intake of these nutrients showed no association with the risk of gastric cancer.</p></div>

Several studies have investigated the association between alcohol consumption and pancreatic cancer risk. However, these studies reported inconsistent results. This study included 95,812 participants from the Japan Public Health Center-Based Prospective Study, whose alcohol drinking habit was collected through the questionnaire of the baseline survey in 1990 to 1994 for Cohort I and in 1993 to 1995 for Cohort II, and followed-up until December 2013. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted Cox proportional hazard regression models. During 1,969,101 person-years of follow-up, 598 patients (315 men and 283 women) were newly diagnosed with pancreatic cancer. No association was observed between alcohol consumption at baseline and pancreatic cancer risk in either men or women, even in the analyses conducted among men stratified by facial flushing responses or smoking status. When the population was limited to men whose alcohol drinking habit remained unchanged from the baseline survey to the 5-year follow-up survey, a significant association was observed in drinkers with alcohol consumption of 1 to 299 g/week compared with non/occasional drinkers (multivariable-adjusted HR, 1.73; 95% CI, 1.15-2.60). A significant association between alcohol consumption and pancreatic cancer risk was observed when the population was limited to men with a 5-year unchanged alcohol drinking habit and was particularly strong in never smokers. This study suggested an association between continuous alcohol consumption and pancreatic cancer risk in the Japanese population. However, further investigations using other cohort studies are required.