Zingiber zerumbet: A Scoping Review of its Medicinal Properties.

Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plant's efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials.

Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis.

BACKGROUND: The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis. METHODS: For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524. FINDINGS: The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2-13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59-0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69-0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75-1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%). INTERPRETATION: The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma. FUNDING: Institut National du Cancer and Ligue Nationale Contre le Cancer.

Motorized spiral enteroscopy versus double-balloon enteroscopy: a case-matched study.

BACKGROUND AND AIMS: Motorized spiral enteroscopy (MSE) has been postulated to ease the complexities of the standard-of-care double-balloon enteroscopy (DBE). However, there are no comparative studies between MSE and DBE. This study aimed to compare the therapeutic outcomes and safety between MSE and DBE. METHODS: In this case-matched study, patients were matched 1:2 (MSE/DBE) by age, sex, body mass index, and American Society of Anesthesiology scores. Thirty-one patients who underwent MSE were compared with 62 patients who underwent DBE from 2014 to 2022. Our primary outcomes were to compare the technical and diagnostic success rates between DBE and MSE. Our secondary outcomes were to compare the therapeutic success and adverse event rates. RESULTS: The main indications for enteroscopy were suspected GI bleeding and positive radiologic findings. Prior abdominal surgery was reported in 35.5% and 22.6% of DBE and MSE patients, respectively. Most were antegrade enteroscopy (71%). We found no significant difference in the technical success (DBE 98.4% vs MSE 96.8%, P = .62), diagnostic success (DBE 66.1% vs MSE 54.8%, P = .25), and therapeutic success rates (DBE 62.8% vs MSE 52.9%, P = .62) between the groups. Adverse events occurred in 1 DBE and 11 MSE patients. Most were minor (n = 10, 25.6%). Two patients (5.1%) in the MSE group sustained deep lacerations in the proximal esophagus requiring hospitalization. One developed ileal perforation after MSE needing surgical repair. CONCLUSIONS: In patients requiring enteroscopy, the diagnostic and therapeutic performance of MSE is similar to DBE. An increased frequency of adverse events was observed with MSE. There are some restrictions in the indication because of the design of MSE.

Neurological Applications of Celery (Apium graveolens): A Scoping Review.

Apium graveolens is an indigenous plant in the family Apiaceae, or Umbelliferae, that contains many active compounds. It has been used traditionally to treat arthritic conditions, gout, and urinary infections. The authors conducted a scoping review to assess the quality of available evidence on the overall effects of celery when treating neurological disorders. A systematic search was performed using predetermined keywords in selected electronic databases. The 26 articles included upon screening consisted of 19 in vivo studies, 1 published clinical trial, 4 in vitro studies and 2 studies comprising both in vivo and in vitro methods. A. graveolens and its bioactive phytoconstituent, 3-n-butylphthalide (NBP), have demonstrated their effect on neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke-related neurological complications, depression, diabetes-related neurological complications, and epilepsy. The safety findings were minimal, showing that NBP is safe for up to 18 weeks at 15 mg/kg in animal studies, while there were adverse effects (7%) reported when consuming NBP for 24 weeks at 600 mg daily in human trials. In conclusion, the safety of A. graveolens extract and NBP can be further investigated clinically on different neurological disorders based on their potential role in different targeted pathways.

Scoping Review: Evaluation of Moringa oleifera (Lam.) for Potential Wound Healing in In Vivo Studies.

Wound healing is a natural process to restore damaged tissues due to loss of tissue integrity. Moringa oleifera (locally known as merunggai in Malaysia) has been traditionally used in various ailments, including for wound management. To evaluate the wound healing properties in M. oleifera, publications were searched and selected following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement with predetermined inclusion criteria. The databases searched for primary studies include PubMed, Google Scholar, Science Direct, LILACS, ClinicalTrials.gov, and CENTRAL. In total, 18 in vivo studies were included, which involved the leaves, while the remaining 5 studies involved other plant parts tested on excision, incision, dead space, abrasion, and burn-induced wound models. All studies reported significant wound healing abilities. Most studies used different topical formulations of aqueous leaves extract. The accumulation of collagen content and underlying wound healing mechanism through antimicrobial, antioxidant, and anti-inflammatory activities may be contributed by its bioactive phytochemical content, which has the potential to accelerate the wound contraction, increase the rate of epithelialization, and protect tissues against oxidative damage. In conclusion, M. oleifera showed wound healing potential but further studies are warranted to determine the main bioactive phytocompounds and safety.

High Participant Satisfaction Achieved Using Cryolipolysis for Fat Reduction of the Abdomen and Flanks.

BACKGROUND: Patient-reported outcome (PRO) data evaluating the physical and psychosocial impact of cryolipolysis (CoolSculpting) treatment are limited. OBJECTIVES: The aim of this study was to assess, by means of PRO instruments, multidimensional aspects of satisfaction following cryolipolysis treatment of the flanks and abdomen. METHODS: This was a multinational, prospective, single-cohort, interventional study. The primary endpoint was the proportion of participants stating they were "satisfied" or "very satisfied" with treatment at 12 weeks post final treatment. Secondary endpoints included satisfaction categorized by treatment area, total number of treatment cycles, baseline BMI, and fat volume reduction measured by 3-dimensional photography at 12 weeks post final treatment. Exploratory endpoints assessed the physical and psychosocial impacts of treatment. Safety was monitored throughout the study. RESULTS: Of 112 participants who were treated, 74.1% were female. The mean age and BMI were 42.5 years and 24.9 kg/mg2, respectively. Of the 106 evaluable participants, 89.6% were "satisfied" or "very satisfied" with treatment results. Satisfaction was high regardless of body area(s), total number of treatment cycles, or baseline BMI. Mean [standard deviation] fat volume reduction was 264.8 [411.4] mL. Overall, 90.6% reported "noticeable" or "very noticeable" fat reduction, 89.6% were "likely" or "very likely" to treat additional areas, and 93.4% would recommend cryolipolysis to a friend. Twenty-four (21.4%) participants reported treatment-emergent adverse events; 23 (20.5%) reported these as adverse device effects. No serious device-related or unanticipated adverse effects occurred. CONCLUSIONS: Cryolipolysis (CoolSculpting) for fat reduction of the flanks and/or abdomen was well-tolerated and associated with high levels of satisfaction across multidimensional PROs.

Evaluation of inter- and intra-observer variations in prostate gland delineation using CT-alone versus CT/TPUS.

Background: This study aims to explore the role of four-dimensional (4D) transperineal ultrasound (TPUS) in the contouring of prostate gland with planning computed tomography (CT) images, in the absence of magnetic resonance imaging (MRI). Materials and methods: Five radiation oncologists (ROs) performed two rounds of prostate gland contouring (single-blinded) on CT-alone and CT/TPUS datasets obtained from 10 patients who underwent TPUS-guided external beam radiotherapy. Parameters include prostate volume, DICE similarity coefficient (DSC) and centroid position. Wilcoxon signed-rank test assessed the significance of inter-modality differences, and the intraclass correlation coefficient (ICC ) reflected inter- and intra-observer reliability of parameters. Results: Inter-modality analysis revealed high agreement (based on DSC and centroid position) of prostate gland contours between CT-alone and CT/TPUS. Statistical significant difference was observed in the superior-inferior direction of the prostate centroid position (p = 0.011). All modalities yielded excellent inter-observer reliability of delineated prostate volume with ICC > 0.9, mean DSC > 0.8 and centroid position: CT-alone (ICC = 1.000) and CT/TPUS (ICC = 0.999) left-right (L/R); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 0.998) anterior-posterior (A/P); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 1.000) superior-inferior (S/I). Similarly, all modalities yielded excellent intra-observer reliability of delineated prostate volume, ICC > 0.9 and mean DSC > 0.8. Lastly, intra-observer reliability was excellent on both imaging modalities for the prostate centroid position, ICC > 0.9. Conclusion: TPUS does not add significantly to the amount of anatomical information provided by CT images. However, TPUS can supplement planning CT to achieve a higher positional accuracy in the S/I direction if access to CT/MRI fusion is limited.

Duration-dependent margins for prostate radiotherapy-a practical motion mitigation strategy.

BACKGROUND AND OBJECTIVE: The magnitude of intra-fractional prostate displacement (change from initial position over time) is associated with the duration of the patient lying on the radiotherapy treatment couch. This study reports a minute-by-minute association and calculates the impact of this displacement on duration-dependent margins using real-time intra-fractional position data monitored by four-dimensional transperineal ultrasound (4D TPUS). MATERIALS AND METHODS: A total of 55 patients were recruited prospectively. Intra-fractional position of the prostate was monitored in real-time using a 4D TPUS Clarity® system. A total of 1745 monitoring sessions were analysed. Van Herk's margin recipe (2.5∑ + 1.64((σ2 + σp2)1/2 - σp)) was used to estimate the duration-dependant margins for every minute, up to the 15th minute. Linear regression analysis was then performed on the overall margins against time and direction. RESULTS: The mean intra-fractional position was 0.76 mm Inferior (Inf), 0 mm Lateral (Lat) and 0.94 mm Posterior (Post) at the 15th minute. A minimum margin expansion of 2.42 mm (Superior/Inf), 1.02 mm (Left/Right) and 2.65 mm (Anterior/Post) was required for an 8­minute treatment compared to 4.29 mm (Sup/Inf), 1.84 mm (Lt/Rt) and 4.63 mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (R2 = 0.99) in all directions (p < 0.01). However, while there was no statistically significant difference (p = 0.10) in the required margin expansion in the Sup/Inf and Ant/Post directions respective of the time duration, the margins were much bigger compared to those in the Lt/Rt direction (p < 0.01). CONCLUSION: We report our experience in deriving the minimum duration-dependant margin to generate the required planning target volume for prostate radiotherapy. The required margin increases linearly in all directions within the 15-min duration; thus, the margin will depend on the duration of the technique chosen (IMRT/VMAT/3DCRT/proton).

Intra-patient and inter-patient comparisons of DNA damage response biomarkers in Nasopharynx Cancer (NPC): analysis of NCC0901 randomised controlled trial of induction chemotherapy in locally advanced NPC.

BACKGROUND: Inter-patient heterogeneity in radiation-induced DNA damage responses is proposed to reflect intrinsic variations in tumour and normal tissue radiation sensitivity, but the prediction of phenotype by a molecular biomarker is influenced by clinical confounders and assay reproducibility. Here, we characterised the intrapatient and inter-patient heterogeneity in biomarkers of DNA damage and repair and radiation-induced apoptosis. METHODS: We enrolled 85 of 172 patients with locally advanced nasopharynx cancer from a randomised controlled phase II/III trial of induction chemotherapy added to chemo-radiotherapy. G0 blood lymphocytes were harvested from these patients, and irradiated with 1, 4, and 8 Gy ex vivo. DNA damage induction (1 Gy 0.5 h) and repair (4 Gy 24 h) were assessed by duplicate γH2AX foci assays in 50-100 cells. Duplicate FLICA assays performed at 48 h post-8 Gy were employed as surrogate of radiation-induced apoptosis; %FLICA-positive cells were quantified by flow cytometry. RESULTS: We observed limited intrapatient variation in γH2AX foci and %FLICA readouts; median difference of duplicate foci scores was - 0.37 (IQR = - 1.256-0.800) for 1 Gy 0.5 h and 0.09 (IQR = - 0.685-0.792) for 4 Gy 24 h; ICC of ≥0.80 was observed for duplicate %FLICA0Gy and %FLICA8Gy assays of CD4+ and CD8+ T lymphocytes. As expected, we observed wide inter-patient heterogeneity in both assays that was independent of intrapatient variation and clinical covariates, with the exception of age, which was inversely correlated with %FLICAbackground-corrected (Spearman R = - 0.406, P < 0.001 [CD4+]; R = - 0.220, P = 0.04 [CD8+]). Lastly, an exploratory case-control analysis indicates increased levels of γH2AX foci at 4 Gy 24 h in patients with severe late radiotherapy-induced xerostomia (P = 0.05). CONCLUSION: Here, we confirmed the technical reproducibility of DNA damage response assays for clinical implementation as biomarkers of clinical radiosensitivity in nasopharynx cancer patients.

Resistance of Black-lip learl oyster, Pinctada margaritifera, to infection by Ostreid herpes virus 1µvar under experimental challenge may be mediated by humoral antiviral activity.

Ostreid herpesvirus 1 (OsHV-1) has induced mass mortalities of the larvae and spat of Pacific oysters, Crassostrea gigas, in Europe and, more recently, in Oceania. The production of pearls from the Black-lip pearl oyster, Pinctada margaritifera, represents the second largest source of income to the economies of French Polynesia and many Pacific Island nations that could be severely compromised in the event of a disease outbreak. Coincidentally with the occurrence of OsHV-1 in the southern hemisphere, C. gigas imported from New Zealand and France into French Polynesia tested positive for OsHV-1. Although interspecies viral transmission has been demonstrated, the transmissibility of OsHV-1 to P. margaritifera is unknown. We investigated the susceptibility of juvenile P. margaritifera to OsHV-1 µvar that were injected with tissue homogenates sourced from either naturally infected or healthy C. gigas. The infection challenge lasted 14 days post-injection (dpi) with sampling at 0, 1, 2, 3, 5, 7 and 14 days. Mortality rate, viral prevalence, and cellular immune responses in experimental animals were determined. Tissues were screened by light microscopy and TEM. Pacific oysters were also challenged and used as a positive control to validate the efficiency of OsHV-1 µvar infection. Viral particles and features such as marginated chromatin and highly electron dense nuclei were observed in C. gigas but not in P. margaritifera. Mortality rates and hemocyte immune parameters, including phagocytosis and respiratory burst, were similar between challenged and control P. margaritifera. Herpesvirus-inhibiting activity was demonstrated in the acellular fraction of the hemolymph from P. margaritifera, suggesting that the humoral immunity is critical in the defence against herpesvirus in pearl oysters. Overall, these results suggest that under the conditions of the experimental challenge, P. margaritifera was not sensitive to OsHV-1 µvar and was not an effective host/carrier. The nature and spectrum of activity of the humoral antiviral activity is worthy of further investigation.

Medicinal plants for allergic rhinitis: A systematic review and meta-analysis.

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies.

Longitudinal post-radiotherapy plasma Epstein-Barr virus DNA trends inform on optimal risk stratification in endemic nasopharyngeal carcinoma.

OBJECTIVES: To characterize longitudinal changes in Epstein-Barr virus (EBV) DNA post-radiotherapy in nasopharyngeal carcinoma (NPC) patients, and investigate whether an early (0-2 weeks) or delayed (8-12 weeks) EBV DNA result better predicts for disease-free survival (DFS). MATERIALS AND METHODS: Histologically-confirmed NPC patients with ≥1 EBV DNA test quantified using the harmonized BamHI-W polymerase chain reaction-based assay at 0-2 and 8-12 weeks post-radiotherapy were included. RESULTS: We identified 302 patients with EBV DNA measured at 0-2 weeks post-radiotherapy; of which, 110 (36.4 %) underwent a repeat test at 8-12 weeks post-treatment. Patients harboring a detectable EBV DNA at 0-2 weeks experienced an inferior DFS (adjusted HR1-264 copies 1.72 [95 %CI: 1.05-2.83], P = 0.031; AHR≥265 copies 4.39 [95 %CI: 1.68-11.44], P = 0.002 relative to 0 copies/mL). At 8-12 weeks, we observed substantial shifts in EBV DNA readings from 0 to 2 weeks; 76/110 (69.1 %) and 34/110 (30.9 %) patients at 0-2 weeks versus 90/110 (81.8 %) and 20/110 (18.2 %) at 8-12 weeks recorded undetectable and detectable EBV DNA, respectively. Positive EBV DNA at 8-12 weeks was strongly associated with relapse (73.3 % [11/15] for 1-264; 80.0 % [4/5] for ≥265 subgroups had relapses versus 15.6 % [14/90] for 0 copies/mL). Area under receiver operating curve values for 2-year relapse rates were 0.817 (95 %CI: 0.725-0.909) for stage + EBV DNA8-12w versus 0.654 (95 %CI: 0.542-0.765) for stage + EBV DNA0-2w. CONCLUSION: EBV DNA is dynamic post-radiotherapy, and delayed EBV DNA testing better enriched for higher-risk NPC patients. This implicates trials investigating adjuvant chemotherapy intensification based on early EBV DNA testing.

Teaching engineering ethics using BLOCKS game.

The aim of this study was to investigate the use of a newly developed design game called BLOCKS to stimulate awareness of ethical responsibilities amongst engineering students. The design game was played by seventeen teams of chemical engineering students, with each team having to arrange pieces of colored paper to produce two letters each. Before the end of the game, additional constraints were introduced to the teams such that they faced similar ambiguity in the technical facts that the engineers involved in the Challenger disaster had faced prior to the space shuttle launch. At this stage, the teams had to decide whether to continue with their original design or to develop alternative solutions. After the teams had made their decisions, a video of the Challenger explosion was shown followed by a post-game discussion. The students' opinion on five Statements on ethics was tracked via a Five-Item Likert survey which was administered three times, before and after the ethical scenario was introduced, and after the video and post-game discussion. The results from this study indicated that the combination of the game and the real-life incident from the video had generally strengthened the students' opinions of the Statements.

Gender survival differences in hepatocellular carcinoma: Is it all due to adherence to surveillance? A study of 1716 patients over three decades.

Background and Aims: Hepatocellular carcinoma (HCC) is one of the commonest causes of cancer-related death worldwide. Whether gender is an independent factor for HCC survival is debatable. We studied the influence of gender on the clinical characteristics of HCC and on survival. Methods: The study cohort comprised patients with HCC seen in our department from 1988 to 2021. Clinical data were prospectively collected. We studied and compared demography, HCC characteristics, and survival between females and males. Survival analysis was censored on October 31, 2015. Results: There were 1716 HCC patients. 343 (20.0%) were females. Females were significantly older at diagnosis (median 69 vs 62 years, P < 0.001). More females were diagnosed via regular HCC surveillance (37.9% vs 29.6%, P = 0.003). Hence, as expected, females had less-advanced HCC at diagnosis with smaller median tumor diameter (30 vs 39.5 mm, P = 0.038), lower frequency of portal vein tumor thrombus (19.4% vs 33.4%, P < 0.001), less distant metastases (7.7% vs 11%, P = 0.043), and earlier Barcelona Clinic Liver Cancer (BCLC) stages (0/A, 39.7% vs 28.4%, P < 0.001). On multivariable analysis, HCC diagnosis via surveillance but not female gender was an independent predictor of improved HCC survival. Conclusions: In this large cohort of multi-ethnic Asian patients, females with HCC were significantly more adherent to surveillance and hence presented with less advanced HCC with correspondingly better overall survival than males. The gender difference in survival is likely due to females having better adherence to HCC surveillance. Surveillance to diagnose early-stage HCC remains crucial in improving outcomes.

Risk Stratification of Elderly Patients Undergoing Spinal Surgery Using the Modified Frailty Index.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: To validate the 11-item modified Frailty Index (mFI) as a perioperative risk stratification tool in elderly patients undergoing spine surgery. METHODS: All consecutive cases of spine surgery in patients aged 65 years or older between July 2016 and June 2018 at a state-wide trauma center were retrospectively reviewed. The primary outcome was post-operative major complication rate (Clavien-Dindo Classification ≥ III). Secondary outcome measures included the rate of all complications, 6-month mortality and surgical site infection. RESULTS: A total of 348 cases were identified. The major complication rate was significantly lower in patients with an mFI of 0 compared to ≥ 0.45 (18.3% versus 42.5%, P = .049). As the mFI increased from 0 to ≥ 0.45 there was a stepwise increase in risk of major complications (P < .001). Additionally, 6-month mortality rate was considerably lower when the mFI was 0 rather than ≥ 0.27 (4.2% versus 20.4%, P = .007). Multivariate analysis demonstrated an mFI ≥ 0.27 was significantly associated with an increased incidence of major complication (OR 2.80, 95% CI 1.46-5.35, P = .002), all complication (OR 2.93, 95% CI 1.70-15.11, P < .001), 6-month mortality (OR 7.39, 95% CI 2.55-21.43, P < .001) and surgical site infection (OR 4.43, 95% CI 1.71-11.51, P = .002). The American Society of Anesthesiologists' (ASA) index did not share a stepwise relationship with any outcome. CONCLUSION: The mFI is significantly associated in a gradated fashion with increased morbidity and mortality. Patients with an mFI ≥ 0.27 are at greater risk of major complications, all-complications, 6-monthy mortality, and surgical site infection.

The impact of the COVID-19 pandemic on nasopharyngeal carcinoma patients - a national cancer centre experience.

Purpose or objective: The COVID-19 pandemic has resulted in significant healthcare implications, with care for cancer patients compromised due to resource diversion towards battling the pandemic. We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore, specifically via our nasopharyngeal carcinoma (NPC) treatment data. This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore. The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy, time to staging scans, time to treatment commencement, due to its clear protocol and algorithms for staging and treatment; thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery. Materials and methods: In this retrospective study, we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre. This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore, which may impact on healthcare seeking behaviour. Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays. Electronic medical records (EMR) were accessed. Only newly diagnosed NPC cases were included in our analysis. Patients with second synchronous primary malignancies or NPC disease recurrence were excluded. Data analysis was carried out using a combination of SPSS and Microsoft Excel. Results: Significantly, there was a reduction of 37-46.3% in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years. Despite the reduction in numbers of newly diagnosed NPC, there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years. All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines. Conclusion: We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time, encourage patient's confidence in their ability to seek care. With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore, this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization. It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery, as well as survival outcomes.

18F-FMISO PET-guided dose escalation with multifield optimization intensity-modulated proton therapy in nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to evaluate the radiotherapy planning feasibility of dose escalation with intensity-modulated proton therapy (IMPT) to hypoxic tumor regions identified on 18F-Fluoromisonidazole (FMISO) positron emission tomography and computed tomography (PET-CT) in NPC. MATERIALS AND METHODS: Nine patients with stages T3-4N0-3M0 NPC underwent 18F-FMISO PET-CT before and during week 3 of radiotherapy. The hypoxic volume (GTVhypo) is automatically generated by applying a subthresholding algorithm within the gross tumor volume (GTV) with a tumor to muscle standardized uptake value (SUV) ratio of 1.3 on the 18F-FMISO PET-CT scan. Two proton plans were generated for each patient, a standard plan to 70 Gy and dose escalation plan with upfront boost followed by standard 70GyE plan. The stereotactic boost was planned with single-field uniform dose optimization using two fields to deliver 10 GyE in two fractions to GTVhypo. The standard plan was generated with IMPT with robust optimization to deliver 70GyE, 60GyE in 33 fractions using simultaneous integrated boost technique. A plan sum was generated for assessment. RESULTS: Eight of nine patients showed tumor hypoxia on the baseline 18F-FMISO PET-CT scan. The mean hypoxic tumor volume was 3.9 cm3 (range .9-11.9cm3 ). The average SUVmax of the hypoxic volume was 2.2 (range 1.44-2.98). All the dose-volume parameters met the planning objectives for target coverage. Dose escalation was not feasible in three of eight patients as the D0.03cc of temporal lobe was greater than 75GyE. CONCLUSIONS: The utility of boost to the hypoxic volume before standard course of radiotherapy with IMPT is dosimetrically feasible in selected patients. Clinical trials are warranted to determine the clinical outcomes of this approach.

Gender differences in hemocyte immune parameters of bivalves: the Sydney rock oyster Saccostrea glomerata and the pearl oyster Pinctada fucata.

Many authors have highlighted a high inter-individual variability in immune parameters of marine bivalves. A high number of studies have reported the impact of external factors on hemocytes immune parameters such as temperature, salinity, pollutants or pathogens. However, only a few of them considered the impact of intrinsic parameters such as sex. Therefore, the present study assessed the impact of gender on hemocytes functions on two marine bivalves. Our results led to the conclusion that the gender contributes to this inter-individual variability. When studying the impact of an environmental variable, a pathogen or a pollutant, the sex of each animal should be determined and taken into account in the analysis and interpretation of immune parameters.

Implant Removal Versus Implant Retention Following Posterior Surgical Stabilization of Thoracolumbar Burst Fractures: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: To compare biomechanical and functional outcomes between implant removal and implant retention following posterior surgical fixation of thoracolumbar burst fractures. METHODS: A search of the MEDLINE, EMBASE, Google Scholar and Cochrane Databases was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Of the 751 articles initially retrieved, 13 published articles pooling 673 patients were included. Meta-analysis revealed there was a statistically significant improvement in sagittal Cobb Angle by 16.48 degrees (9.13-23.83, p < 0.01) after surgical stabilization of thoracolumbar burst fractures. This correction decremented to 9.68 degrees (2.02-17.35, p < 0.01) but remained significant at the time of implant removal approximately 12 months later. At final follow-up, the implant removal group demonstrated a 10.13 degree loss (3.00-23.26, p = 0.13) of reduction, while the implant retention group experienced a 10.17 degree loss (1.79-22.12, p = 0.10). There was no statistically significant difference in correction loss between implant retention and removal cohorts (p = 0.97). Pooled VAS scores improved by a mean of 3.32 points (0.18 to 6.45, p = 0.04) in the combined removal group, but by only 2.50 points (-1.81 to 6.81, p = 0.26) in the retention group. Oswestry Disability Index scores also improved after implant removal by 7.80 points (2.95-12.64, p < 0.01) at 1 year and 11.10 points (5.24-16.96, p < 0.01) at final follow-up. CONCLUSIONS: In younger patients with thoracolumbar burst fractures who undergo posterior surgical stabilization, planned implant removal results in superior functional outcomes without significant difference in kyphotic angle correction loss compared to implant retention.

Posterior Instrumented Spinal Surgery Outcomes in the Elderly: A Comparison of the 5-Item and 11-Item Modified Frailty Indices.

STUDY DESIGN: Retrospective Cohort. OBJECTIVES: To validate the most concise risk stratification system to date, the 5-item modified frailty index (mFI-5), and compare its effectiveness with the established 11-item modified frailty index (mFI-11) in the elderly population undergoing posterior instrumented spine surgery. METHODS: A single centre retrospective review of posterior instrumented spine surgeries in patients aged 65 years and older was conducted. The primary outcome was rate of post-operative major complications (Clavien-Dindo Classification ≥ 4). Secondary outcome measures included rate of all complications, 6-month mortality and surgical site infection. Multi-variate analysis was performed and adjusted receiver operating characteristic curves were generated and compared by DeLong's test. The indices were correlated with Spearman's rho. RESULTS: 272 cases were identified. The risk of major complications was independently associated with both the mFI-5 (OR 1.89, 95% CI 1.01-3.55, P = .047) and mFI-11 (OR 3.73, 95% CI 1.90-7.30, P = .000). Both the mFI-5 and mFI-11 were statistically significant predictors of risk of all complications (P = .007 and P = .003), surgical site infection (P = .011 and P = .003) and 6-month mortality (P = .031 and P = .000). Adjusted ROC curves determined statistically similar c-statistics for major complications (.68 vs .68, P = .64), all complications (.66 vs .64, P = .10), surgical site infection (.75 vs .75, P = .76) and 6-month mortality (.83 vs .81, P = .21). The 2 indices correlated very well with a Spearman's rho of .944. CONCLUSIONS: The mFI-5 and mFI-11 are equally effective predictors of postoperative morbidity and mortality in this population. The brevity of the mFI-5 is advantageous in facilitating its daily clinical use.