Top Ten Lessons Learned from Trials in Oligometastatic Cancers / Journal of the Korean Cancer Association, 대한암학회지

Recent evidence supports the role of aggressive local treatment in the oligometastatic setting. In this review, we discuss the top 10 lessons we have learned from trials in oligometastatic cancers. Major lessons learned pertain to definitions of oligometastatic disease, outcomes, toxicity, costs, and the combination of ablative therapies with systemic therapy, including immunotherapy. Barriers to accrual for trials and upcoming phase III trials are also reviewed. These lessons may help to inform clinical practice and may be the basis for future research in the oligometastatic space.

Students and faculty experiences, perceptions and knowledge on distress during the COVID-19 pandemic: A descriptive cross-sectional study

Background and Objective@#The University of the Philippines Manila (UPM) subcommittee on students in distress was convened during the COVID-19 pandemic to develop “plans, programs and mechanisms” to deal with students experiencing distress and mental health concerns. This study was conducted as one of the activities of the Subcommittee to inform policy to address the following research objective: to describe the experiences, perceptions, and knowledge of both students and faculty members of UP Manila regarding distress.@*Methods@#An online survey tool was created using the results from seven online focus group discussions among 20 faculty of UP Manila. The survey was conducted for one month among faculty and students sampled from the seven colleges of UP Manila and the three extension campuses of the Schools of Health Sciences. The different categories which were consistently perceived as important by both faculty and students as well as those with disparity in the perceptions between faculty and students were described and discussed.@*Results@#A total of 136 faculty (F) and 290 students (S) participated in the study, representing 39% vs 98% (F vs S) of the target sample, respectively. Results showed that among the effects of stressors for students, avoidance of schoolwork (F79 vs S70.3%) and sleep disturbance (F79.4 vs S72.4%), were perceived by both faculty and students as the most frequently perceived response of students to stress.Among the causes of stress, unclear boundaries between school and home (F73.5 vs S63.1%), family duties (F76.5 vs S50.7%), lack of socialization (F89 vs S57.6%), limited recreational activity (F76.5 vs S64.8%), adapting to new ways of socialization (F67.6 vs S53.8%), and internet signal (F99.3 vs S88.3%) were perceived by both faculty and students as the most frequently perceived causes of stress. Among the coping mechanisms, connecting with friends online (F86.8 vs S69.7%), listening to music (F72.8 vs S78.3%), browsing social media (F82.4 vs S81%), viewing movies (F84.6 vs S74.5%), and sleeping or resting (F67.6 vs S84.1%) were perceived by both faculty and students as the most employed by students to cope with stress.Results also show that there were marked disparities in the perceptions of faculty and students. Among the effects of stressors, the largest disparities were in non-performance in academics (F86 vs S51.7%) and academic failure (F76.5 vs S53.8%). Of the causative factors, the largest disparities were in the areas of death (F94.1 vs S14.5%) or sickness in the family (F66.9 vs S0%), family issues (F82.4 vs S24.5%), financial concerns (F89 vs S36.9%), absence of physical connectedness and interaction, (F94.9 vs S23.8%) lack of socialization (F89 vs S57.6%), owning a gadget (F73.5 vs S22.1%), and lack of funds for the internet (F79.4 vs S22.4%).Among the support systems available in the university (psychosocial, academic and wellness activities of the colleges), 70% of the faculty perceived that the students were aware of the support process offered by the university. In contrast, 28% of students were aware of the support services offered to them. @*Conclusion@#This study shows that UP Manila faculty and students perceived stress due to the effects of COVID-19 on teaching, learning, and everyday living. Distress among student respondents was commonly perceived to be caused by family concerns, environmental restrictions, connectivity issues, and experiencing a sense of lack. While support services and mental health programs have been in place within the university, only 28% of students perceive that students in distress were aware of the process in receiving support.

Clinical and patient reported outcomes of Vitamin E diffused highly cross-linked polyethylene liner versus moderately cross linked polyethylene liner in total hip arthroplasty: A meta-analysis

Introduction@#In the modern era of Medicine, total hip arthroplasty (THA) is found to last longer than ever before due to the fact that there has been improved bearing surfaces and materials available. Despite these modern approaches, failure caused by polyethylene wear, aseptic loosening, instability and mispositioning and even infection could affect THA survival. In the course of addressing anti-wear characteristics of the conventional polyethylene surface various approaches have been made. To date, there are very limited studies done in which polyethylene liner is better.@*General Objective@#To compare the effects of vitamin E diffused highly cross-linked polyethylene liner versus moderately cross-linked polyethylene liner in THA. @*Methodology@#Meta-analysis research design was used in this study. The primary investigators conducted a comprehensive literature search from Medline, Cochrane Library, PubMed, Elsevier, Google Scholar, Embase and ClinicalTrial.gov as electronic database. All randomized controlled trials comparing the effects of vitamin E diffused highly cross-linked polyethylene liner versus moderately cross-linked polyethylene liner in THA were included in the review. @*Conclusions@#The investigation disclosed no statistical significance between moderately cross-linked polyethylene liner and vitamin E diffused highly cross-linked polyethylene liner in terms of migration, head penetration and wear on mediolateral, longitudinal and anteroposterior axes after 2 and 5 years of undergoing THA. Moreover, the data pertaining to patient reported outcomes and clinical outcomes measure also indicated no statistical significance between moderately cross-linked polyethylene liner and vitamin E diffused highly cross-linked polyethylene liner. This indicates that vitamin E diffused highly cross-linked polyethylene liner is comparable with the conventional moderately cross-linked polyethylene liner. Vitamin E-infused highly cross-linked polyethylene ( VEPE) showed an almost similar stability with regard to the wear rates and the component showed similar stability with that of moderately cross-linked polyethylene liner.

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore

INTRODUCTION@#Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore.@*METHODS@#Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission.@*RESULTS@#Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5).@*CONCLUSION@#The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.

The anti-venom potential of Andrographis paniculata (Burm.f.) Nees roots and its constituent skullcapflavone I

The anti-venom activity of Andrographis paniculata (Burm.f.) Nees roots (APR) dichloromethane crude extractsand a promising APR constituent, skullcapflavone I (SKI) was investigated by monitoring the inhibition of secretoryphospholipase A2 (sPLA2) of Naja philippinensis Taylor venom (NPV) crystallized samples. Gas chromatographymass spectrometry was used for the characterization of extracts, while molecular docking was utilized to understandanti-venom properties. Chromatographic analyses primarily revealed the presence of methoxylated flavones. NPV wasfound to have sPLA2 activity (0.0796 ± 0.0018 μmol/minutes/ml) that has been attributed to the poisonous effects.SKI (IC50: 51.1 ± 3.5 μg/ml), isolated from APR showed strong inhibitory effect on phospholipase activity comparedwith dichloromethane extracts of APR (IC50: 192.7 ± 10.9 μg/ml) indicating that SKI was the cause of the bioactivityin APR. Molecular docking simulations showed corresponding results with highly negative binding energies (−6.59 to−8.72 kcal/mol) predicted for the binding of SKI to PLA2 proteins. An important trend found was the presence of freebound Ca2+ lowered binding energies signifying that Ca2+ a has role in the binding of the SKI to PLA2 proteins. Theanti-venom property of APR and the pure compound SKI, upon further studies, could be the first line of defense in themedical protocol of snake venom neutralization.

The anti-venom potential of Andrographis paniculata (Burm.f.) Nees roots and its constituent skullcapflavone I

The anti-venom activity of Andrographis paniculata (Burm.f.) Nees roots (APR) dichloromethane crude extractsand a promising APR constituent, skullcapflavone I (SKI) was investigated by monitoring the inhibition of secretoryphospholipase A2 (sPLA2) of Naja philippinensis Taylor venom (NPV) crystallized samples. Gas chromatographymass spectrometry was used for the characterization of extracts, while molecular docking was utilized to understandanti-venom properties. Chromatographic analyses primarily revealed the presence of methoxylated flavones. NPV wasfound to have sPLA2 activity (0.0796 ± 0.0018 μmol/minutes/ml) that has been attributed to the poisonous effects.SKI (IC50: 51.1 ± 3.5 μg/ml), isolated from APR showed strong inhibitory effect on phospholipase activity comparedwith dichloromethane extracts of APR (IC50: 192.7 ± 10.9 μg/ml) indicating that SKI was the cause of the bioactivityin APR. Molecular docking simulations showed corresponding results with highly negative binding energies (−6.59 to−8.72 kcal/mol) predicted for the binding of SKI to PLA2 proteins. An important trend found was the presence of freebound Ca2+ lowered binding energies signifying that Ca2+ a has role in the binding of the SKI to PLA2 proteins. Theanti-venom property of APR and the pure compound SKI, upon further studies, could be the first line of defense in themedical protocol of snake venom neutralization.

review on combined biological effects of microwave and other physical or chemical agents

With the development of science and technology, microwave has been used in many fields such as industry, military, medicine and communication. People are living in a lapped and dynamic electromagnetic environment. Concerns about potential hazards of microwave are getting increasing attentions. The single biological effects of microwave were widely discussed which was considered harmful. Relevant safety standards had been formulated and applied. However, the real environment was more complex. Microwave was not the only factor that organisms might be affected. Other physical or chemical factors, such as ionizing radiation [IR], ultraviolet [UV], magnetic field and chemical drugs, often existed with the microwave radiation. Even the microwave itself could create combined exposure situation, because the environment consisted different frequency microwaves. Nuclear weapons and high-power radar could produce microwave and ionizing radiation. The ultraviolet ray and magnetic field generated by the instrument's operation could act on the human bodies along with the microwaves. The combination of radiofrequency therapy and chemotherapeutic agents was also commonly used in cancer therapy. Therefore, the combined biological effects of microwaves and other physical or chemical factors were very important. This review had covered the original articles in this aspect. In order to better, understand the combined biological effects; the comparative studies of different frequency microwaves were also included. Differences in biological effects were found among different frequency microwaves, and the combined biological effects contained both hazards and benefits. Findings in combined biological effects were very practical for rational uses of microwave technologies

Systemic lupus erythematosus with coexistent psoriasis vulgaris: A case report

@#<p style="text-align: justify;">We report a 42-year-old female with a 20-year history of systemic lupus erythematosus who subsequently developed psoriasis vulgaris. She has been on chronic, erratic prednisone and hydroxychloroquine intake prior to appearance of psoriatic lesions. Hydroxychloroquine and glucocorticoids are possible triggers of this phenomenon. Both diseases have a shared susceptibility loci and a shared Th17 pathophysiologic pathway.Treatment with methotrexate and selected biologics can target both disease mechanisms.</p>

Genetic polymorphisms in NAT1, NAT2, GSTM1, GSTP1 and GSTT1 and susceptibility to colorectal cancer among Filipinos

@#Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.

Progressive Supranuclear Gaze Palsy with Predominant Cerebellar Ataxia: A Case Series with Videos

Progressive supranuclear palsy (PSP) with predominant cerebellar ataxia (PSP-C) is a rare phenotype of PSP. The clinical and radiological features of this disorder remain poorly characterized. Through a retrospective case series, we aim to characterize the clinical and radiological features of PSP-C. Four patients with PSP-C were identified: patients who presented with prominent cerebellar dysfunction that disappeared with the progression of the disease. Supranuclear gaze palsy occurred at a mean of 2.0 ± 2.3 years after the onset of ataxia. Mild cerebellar volume loss and midbrain atrophy were detected on brain imaging, which are supportive of a diagnosis of PSP. Videos are presented illustrating the co-existence of cerebellar signs and supranuclear gaze palsy and the disappearance of cerebellar signs with disease progression. Better recognition and the development of validated diagnostic criteria would aid in the antemortem recognition of this rare condition.

Melatonin Protects Human Adipose-Derived Stem Cells from Oxidative Stress and Cell Death

BACKGROUND: Adipose-derived stem cells (ASCs) have applications in regenerative medicine based on their therapeutic potential to repair and regenerate diseased and damaged tissue. They are commonly subject to oxidative stress during harvest and transplantation, which has detrimental effects on their subsequent viability. By functioning as an antioxidant against free radicals, melatonin may exert cytoprotective effects on ASCs. METHODS: We cultured human ASCs in the presence of varying dosages of hydrogen peroxide and/or melatonin for a period of 3 hours. Cell viability and apoptosis were determined with propidium iodide and Hoechst 33342 staining under fluorescence microscopy. RESULTS: Hydrogen peroxide (1-2.5 mM) treatment resulted in an incremental increase in cell death. 2 mM hydrogen peroxide was thereafter selected as the dose for co-treatment with melatonin. Melatonin alone had no adverse effects on ASCs. Co-treatment of ASCs with melatonin in the presence of hydrogen peroxide protected ASCs from cell death in a dose-dependent manner, and afforded maximal protection at 100 µM (n=4, one-way analysis of variance P<0.001). Melatonin co-treated ASCs displayed significantly fewer apoptotic cells, as demonstrated by condensed and fragmented nuclei under fluorescence microscopy. CONCLUSIONS: Melatonin possesses cytoprotective properties against oxidative stress in human ASCs and might be a useful adjunct in fat grafting and cell-assisted lipotransfer.

Spectrum and burden of movement disorder conditions in a tertiary movement disorders centre--a 10-year trend

<p><b>INTRODUCTION</b>The precise burden of movement disorder conditions in our movement disorders centre is unclear. This study investigated the clinical burden of the Movement Disorders Clinic (MDC) in National Neuroscience Institute (NNI) over 10 years, aiming to identify the burden and spectrum of movement disorders conditions, to facilitate future resource allocation.</p><p><b>MATERIALS AND METHODS</b>We identified all patient visits from January 2002 to December 2011 at MDC from the Movement Disorders (MD) database using a standardised data collection form.</p><p><b>RESULTS</b>There was a linear increase in the clinical burden of MDC during this period. Parkinsonism comprised 71.6% of this clinical burden of which 84.8% were Parkinson's disease (PD) patients. Dividing the incident cases of MD conditions into two 5 years' blocks, the proportion of PD cases had not changed. There was significant increase in time to diagnosis for PD, hemifacial spasm and dystonia.</p><p><b>CONCLUSION</b>There was nearly 4-fold increase in the burden of movement disorders conditions in our tertiary condition within a decade. However, we did not find increasing proportion of PD cases which would be in line with an ageing population. This could be due to the fact that we are still in the early stages of an ageing population and we postulate that this proportion will go up in the future. The increased time to diagnosis may indicate increasing waiting time to see a movement disorders specialist and that current outreach effort to promote awareness may not be reaching its target audience. The upward trend of clinical burden indicates a need for increased resource allocation to cope with demand for movement disorders services.</p>

Prevalence and control of hypercholesterolaemia as defined by NCEP-ATPIII guidelines and predictors of LDL-C goal attainment in a multi-ethnic Asian population

<p><b>INTRODUCTION</b>Few studies in Asia have assessed the burden of hypercholesterolaemia based on the global cardiovascular risk assessment. This study determines the burden of hypercholesterolaemia in an Asian population based on the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) guidelines, and examines predictors of low-density lipoprotein cholesterol (LDL-C) goal attainment.</p><p><b>MATERIALS AND METHODS</b>Five thousand and eighty-three Chinese, Malays and Asian-Indians living in Singapore were assigned to coronary heart disease (CHD)-risk category based on the NCEP-ATPIII guidelines. Awareness, treatment and control of hypercholesterolaemia based on risk- specific LDL-C goal were determined, including the use of lipid-lowering therapy (LLT). Cox-regression models were used to identify predictors of LDL-C above goal among those who were aware and unaware of hypercholesterolaemia.</p><p><b>RESULTS</b>One thousand five hundred and sixty-eight (30.8%) participants were aware of hypercholesterolaemia and 877 (17.3%) were newly diagnosed (unaware). For those who were aware, 39.3% participants received LLT. Among those with 2 risk factors, only 59.7% attained LDL-C goal. The majority of them were taking statin monotherapy, and the median dose of statins was similar across all CHD risk categories. Among participants with 2 risk factors and not receiving LLT, 34.1% would require LLT. Malays or Asian-Indians, higher CHD risk category, increasing body mass index (BMI), current smoking and lower education status were associated with higher risk of LDL-C above goal. Being on LLT reduced the risk of having LDL-C above goal.</p><p><b>CONCLUSION</b>The burden of hypercholesterolaemia is high in this multi-ethnic population especially those in the higher CHD risk categories, and might be partly contributed by inadequate titration of statins therapy. Raising awareness of hypercholesterolaemia, appropriate LLT initiation and titration, weight management and smoking cessation may improve LDL-C goal attainment in this population.</p>

Is EQ-5D a valid quality of life instrument in patients with Parkinson's disease? A study in Singapore

<p><b>INTRODUCTION</b>The purpose of the present study was to evaluate the validity of the EQ-5D in patients with Parkinson's disease (PD) in Singapore.</p><p><b>MATERIALS AND METHODS</b>In a cross-sectional survey, patients with PD completed English or Chinese version of the EQ-5D, the 8-item Parkinson's disease questionnaire (PDQ-8), and questions assessing socio-demographic and health characteristics. Clinical data were retrieved from patients' medical records. The validity of the EQ-5D was assessed by testing a-priori hypotheses relating the EQ-5D to the PDQ-8 and clinical data.</p><p><b>RESULTS</b>Two hundred and eight PD patients (English speaking: 135) participated in the study. Spearman correlation coefficients between the EQ-5D and PDQ-8 ranged from 0.25 to 0.75 for English-speaking patients and from 0.16 to 0.67 for Chinese-speaking patients. By and large, the EQ-5D scores were weakly or moderately correlated with Hoehn and Yahr stage (correlation coefficients: 0.05 to 0.43), Schwab and England Activities of Daily Living score (correlation coefficients: 0.10 to 0.60), and duration of PD (correlation coefficients: 0.16 to 0.43). The EQ-5D index scores for patients with dyskinesia or "wearing off" periods were significantly lower than those without these problems. The EQ-5D Visual Analog Scale (EQ-VAS) scores also differed for English-speaking patients with deferring dyskinesia, "wearing off" periods, or health transition status; however, such differences were not observed in patients who completed the survey in Chinese.</p><p><b>CONCLUSIONS</b>The EQ-5D questionnaire appears valid for measuring quality of life in patients with PD in Singapore. However, the validity of EQ-VAS in Chinese-speaking patients with PD should be further assessed.</p>

Wandering humeral head mimicking a breast mass

A 74-year-old woman was incidentally found to have a left breast mass. The mass could not be adequately compressed to be visualized on mammography. Ultrasonography showed a heavily-calcified rounded mass in the left axillary tail of the left breast. Chest radiograph confirmed that the mass was a migrated humeral head. Remotely-displaced fracture-dislocations of the humeral head are very rare and to our knowledge, displacement into the breast, clinically mimicking a breast mass, has not been previously described.

rare case of acute hydrocephalus following unilateral radical neck dissection

Radical neck dissection remains a well established surgical option in the management of head and neck malignancy. It is also the gold standard in managing occult neck disease, of which the primary is unknown. We report a case of 66-years old lady, a diagnosed case of nasopharyngeal carcinoma who completed radiotherapy 9 years ago, presenting with a left neck node. Fine needle aspiration cytology [FNAC] confirmed a metastatic undifferentiated carcinoma. Except for the obvious lymph node, subsequent panendoscopy and magnetic resonance imaging [MRI] were unremarkable. Left radical neck dissection was performed. Postoperatively, she developed drowsiness secondary to acute hydrocephalus. An emergent ventriculoperitoneal shunt was inserted and she showed marked improvement following that. Magnetic resonance venogram [MRV] demonstrated left dural venous drainage predominance. Clinical presentation and pathophysiology of hydrocephalus following radical neck dissection are discussed here

Early deep vein thrombosis: incidence in Asian stroke patients

<p><b>INTRODUCTION</b>Deep venous thrombosis (DVT) is thought to be less common in Asians than in the Caucasian population. The incidence of asymptomatic DVT in high-risk groups in the Asian population has not been well studied. While DVT incidence among Caucasian stroke patients has been extensively studied and the need for prophylaxis established, the lack of data in Asian patients leaves physicians with no firm basis for adopting prophylactic protocols in the local population. Our aim was to prospectively establish the incidence of early DVT in immobilised stroke patients in a heterogenous Asian population.</p><p><b>MATERIALS AND METHODS</b>We screened 44 patients with significant hemiplegia from acute stroke. Doppler ultrasound, the currently accepted method of investigation for DVT, was used to study patients on admission and at 1 week post-stroke. While there was no standard prophylactic regime in use, none of the patients received heparin and only 2 were given compression stockings.</p><p><b>RESULTS</b>The incidence of DVT at 1 week was 2.4%. Review at 1 month detected another patient with DVT, bringing the overall incidence at 1 month to 4.8%. This is lower than in Caucasian populations, but is similar to another local study on a different group of high-risk patients.</p><p><b>CONCLUSION</b>The low incidence of early DVT in hospitalised stroke patients of Asian ethnicity does not justify routine screening for this population. Further research to validate this should ideally include a comparison test for DVT as ultrasound may have inherently lower sensitivity in an asymptomatic population.</p>