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1.
Hered Cancer Clin Pract ; 22(1): 10, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877502

ABSTRACT

BACKGROUND: Lynch syndrome is the most common cause of hereditary colorectal and endometrial cancer. Lifestyle modification may provide an opportunity for adjunctive cancer prevention. In this study, we aimed to characterise modifiable risk factors in people with Lynch syndrome and compare this with international guidelines for cancer prevention. METHODS: A cross-sectional study was carried out utilizing survey methodology. Following public and patient involvement, the survey was disseminated through patient advocacy groups and by social media. Self-reported demographic and health behaviours were collected in April 2023. Guidelines from the World Cancer Research Fund (WCRF) were used to compare percentage adherence to 9 lifestyle recommendations, including diet, physical activity, weight, and alcohol intake. Median adherence scores, as a surrogate for lifestyle risk, were calculated and compared between groups. RESULTS: 156 individuals with Lynch syndrome participated from 13 countries. The median age was 51, and 54% were cancer survivors. The mean BMI was 26.7 and the mean weekly duration of moderate to vigorous physical activity was 90 min. Median weekly consumption of ethanol was 60 g, and 3% reported current smoking. Adherence to WCRF recommendations for cancer prevention ranged from 9 to 73%, with all but one recommendation having < 50% adherence. The median adherence score was 2.5 out of 7. There was no significant association between median adherence scores and age (p = 0.27), sex (p = 0.31), or cancer history (p = 0.75). CONCLUSIONS: We have characterised the modifiable risk profile of people living with Lynch syndrome, outlining targets for intervention based on lifestyle guidelines for the general population. As evidence supporting the relevance of modifiable factors in Lynch syndrome emerges, behavioural modification may prove an impactful means of cancer prevention.

3.
BMJ Open ; 14(1): e076907, 2024 01 12.
Article in English | MEDLINE | ID: mdl-38216183

ABSTRACT

INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.


Subject(s)
COVID-19 , Adult , Humans , COVID-19/prevention & control , SARS-CoV-2 , Longitudinal Studies , Quarantine , Australia
4.
JCO Precis Oncol ; 8: e2300196, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38207227

ABSTRACT

PURPOSE: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied in Lynch syndrome. METHODS: Searches were conducted on MEDLINE, Embase, and Web of Science for cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Adjusted hazard ratios (HRs) and 95% CIs for colorectal and endometrial cancers were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462), and the meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. RESULTS: A total of 770 citations were reviewed. Eighteen studies were identified for qualitative synthesis, with seven colorectal cancer (CRC) studies eligible for meta-analysis. Obesity (HR, 2.38 [95% CI, 1.52 to 3.73]) was associated with increased CRC risk. There was no increased CRC risk associated with smoking (HR, 1.04 [95% CI, 0.82 to 1.32]) or alcohol intake (HR, 1.32 [95% CI, 0.97 to 1.81]). Type 2 diabetes mellitus (T2DM) and some dietary factors might increase risk of CRC although more studies are needed. In a qualitative synthesis of three endometrial cancer cohort studies, female hormonal risk factors and T2DM may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. CONCLUSION: Lifestyle recommendations related to weight and physical activity may also be relevant to cancer prevention for individuals with Lynch syndrome. Further high-quality prospective cohort studies, in particular, including endometrial cancer as an end point, are needed to inform evidence-based cancer prevention strategies in this high-risk population.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , Endometrial Neoplasms , Female , Humans , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Diabetes Mellitus, Type 2/epidemiology , Endometrial Neoplasms/epidemiology , Obesity/epidemiology , Prospective Studies , Risk Factors
5.
J Neurol Surg Rep ; 84(3): e92-e102, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37635841

ABSTRACT

Meningiomas that invade the confluens sinuum are rare and require extensive preoperative planning. Here, we describe the surgical and radio-oncological management of an aggressive large occipital meningioma invading the superior sagittal sinus, torcula, right and left transverse sinus down to the level of the jugular bulb in a 21-year-old female patient. Details of the surgical approach are presented to highlight the planned staged resection of this tumor at the level of the torcula to initially debulk the lesion while preserving venous outflow through the patent's sinus. Once the tumor fully occluded the confluens, a second-stage en bloc resection ensued. Postsurgical adjuvant radiation therapy was delivered via fractionated external beam therapy which has provided local control of the tumor since. This case is being discussed in the context of the pertinent literature to demonstrate the highly complex interdisciplinary and staged management of partially intravascular meningiomas involving the major venous sinuses.

6.
PLoS One ; 18(1): e0279990, 2023.
Article in English | MEDLINE | ID: mdl-36638130

ABSTRACT

INTRODUCTION: The provision of maternity services in Australia has been significantly disrupted in response to the COVID-19 pandemic. Many changes were initiated quickly, often with rapid dissemination of information to women. The aim of this study was to better understand what information and messages were circulating regarding COVID-19 and pregnancy in Australia and potential information gaps. METHODS: This study adopted a qualitative approach using social media and interviews. A data analytics tool (TIGER-C19) was used to extract data from social media platforms Reddit and Twitter from June to July 2021 (in the middle of the third COVID-19 wave in Australia). A total of 21 individual semi-structured interviews were conducted with those who were, or had been, pregnant in Australia since March 2020. Social media data were analysis via inductive content analysis and interview data were thematically analysed. RESULTS: Social media provided a critical platform for sharing and seeking information, as well as highlighting attitudes of the community towards COVID-19 vaccines in pregnancy. Women interviewed described wanting further information on the risks COVID-19 posed to themselves and their babies, and greater familiarity with the health service during pregnancy, in which they would labour and give birth. Health providers were a trusted source of information. Communication strategies that allowed participants to engage in real-time interactive discussions were preferred. A real or perceived lack of information led participants to turn to informal sources, increasing the potential for exposure to misinformation. CONCLUSION: It is vital that health services communicate effectively with pregnant women, early and often throughout public health crises, such as the COVID-19 pandemic. This was particularly important during periods of increased restrictions on accessing hospital services. Information and communication strategies need to be clear, consistent, timely and accessible to reduce reliance on informal and potentially inaccurate sources.


Subject(s)
COVID-19 , Pandemics , Female , Pregnancy , Humans , COVID-19 Vaccines , COVID-19/epidemiology , Qualitative Research , Pregnant Women , Postpartum Period , Parturition
7.
Crit Rev Oncol Hematol ; 175: 103729, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35662586

ABSTRACT

The perioperative period theoretically is a critical time of opportunity for the progression of pre-existing tumour micrometastasis. Therefore,the timing of introducing cancer therapies including chemotherapy, radiation therapy and immunotherapies in the postoperative period is important. A thorough exploration of the perioperative immune events at a cellular level in combination with an intricate review of available clinical rials was conducted to extrapolate the effects of oncological surgery on the perioperative immune milieu.This is timely in view of the recently published Checkmate-577 trial which demonstrated significant disease-free survival in carcinoma of the gastroesophageal junction with the use of adjuvant anti-programmed cell deathprotein 1(PD-1) immunotherapy.This review focusing in particular on perioperative immunosuppression, identifies potential modifiable factors, the effects of perioperative conditioning and optimisation, the most recent trials in the curative setting for Gastrointestinal malignancies and the new treatment avenues possible in the context of the combination of immunotherapy and major oncological gastrointestinal surgery.


Subject(s)
Gastrointestinal Neoplasms , Immunotherapy , Chemotherapy, Adjuvant , Esophagogastric Junction/pathology , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Humans , Immunity , Neoadjuvant Therapy , Progression-Free Survival
8.
J Med Imaging (Bellingham) ; 9(3): 031505, 2022 May.
Article in English | MEDLINE | ID: mdl-35310450

ABSTRACT

Purpose: Dental calculus forms on teeth during the life of an individual and its investigation can yield information about diet, health status, and environmental pollution. Currently, the analytical techniques used to visualize the internal structure of human dental calculus and entrapped inclusions are limited and require destructive sampling, which cannot always be justified. Approach: We used propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SR- µ CT ) to non-destructively examine the internal organization of dental calculus, including its microstructure and entrapped inclusions, on both modern and archeological samples. Results: The virtual histological exploration of the samples shows that PPC-SR- µ CT is a powerful approach to visualize the internal organization of dental calculus. We identified several important features, including previously undetected negative imprints of enamel and dentine growth markers (perikymata and periradicular bands, respectively), the non-contiguous structure of calculus layers with multiple voids, and entrapped plant remains. Conclusions: PPC-SR- µ CT is an effective technique to explore dental calculus structural organization, and is especially powerful for enabling the identification of inclusions. The non-destructive nature of synchrotron tomography helps protect samples for future research. However, the irregular layers and frequent voids reveal a high heterogeneity and variability within calculus, with implications for research focusing on inclusions.

9.
J Gynecol Oncol ; 33(3): e24, 2022 05.
Article in English | MEDLINE | ID: mdl-35128855

ABSTRACT

OBJECTIVE: Vaccine efficacy among previously exposed, but currently uninfected women, i.e., those who have serological evidence of a prior human papillomavirus (HPV) infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to randomized controlled trials (RCTs) of HPV L1-based vaccines. METHODS: Searches were conducted on 08/16/20 on MEDLINE, Embase, Scopus and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Relative risks (RRs) of 6-month PI (6mPI), 12-month PI (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model. RESULTS: A total of 1,727 citations were reviewed. 8 studies, with a total of 9,569 SPDN participants, met all eligibility criteria. The RR of 6mPI (RR=0.22; 95% confidence interval [CI]=0.08-0.61; p=0.018), 12mPI (RR=0.20; 95% CI=0.05-0.80; p=0.035), CIN1+ (RR=0.13; 95% CI=0.05-0.30; p=0.003) and CIN2+ (RR=0.15; 95% CI=0.04-0.59; p=0.022) was significantly reduced in the vaccinated compared to the unvaccinated group. CONCLUSION: Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV16/18 infections, including 87% efficacy (95% CI=70%-95%; p=0.003) against HPV16/18 cervical dysplasia. HPV vaccination is highly effective among uninfected women, regardless of prior exposure history. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020206888.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , DNA, Viral , Female , Humans , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/prevention & control , Vaccination , Uterine Cervical Dysplasia/prevention & control
10.
Sci Rep ; 11(1): 24185, 2021 12 17.
Article in English | MEDLINE | ID: mdl-34921192

ABSTRACT

This paper presents the earliest evidence for the exploitation of lignite (brown coal) in Europe and sheds new light on the use of combustion fuel sources in the 2nd millennium BCE Eastern Mediterranean. We applied Thermal Desorption/Pyrolysis-Gas Chromatography-Mass Spectrometry and Polarizing Microscopy to the dental calculus of 67 individuals and we identified clear evidence for combustion markers embedded within this calculus. In contrast to the scant evidence for combustion markers within the calculus samples from Egypt, all other individuals show the inhalation of smoke from fires burning wood identified as Pinaceae, in addition to hardwood, such as oak and olive, and/or dung. Importantly, individuals from the Palatial Period at the Mycenaean citadel of Tiryns and the Cretan harbour site of Chania also show the inhalation of fire-smoke from lignite, consistent with the chemical signature of sources in the northwestern Peloponnese and Western Crete respectively. This first evidence for lignite exploitation was likely connected to and at the same time enabled Late Bronze Age Aegean metal and pottery production, significantly by both male and female individuals.

11.
Cancers (Basel) ; 13(16)2021 Aug 09.
Article in English | MEDLINE | ID: mdl-34439160

ABSTRACT

Response rates to the current gold standards of care for treating oesophageal adenocarcinoma (OAC) remain modest with 15-25% of patients achieving meaningful pathological responses, highlighting the need for novel therapeutic strategies. This study consists of immune, angiogenic, and inflammatory profiling of the tumour microenvironment (TME) and lymph node microenvironment (LNME) in OAC. The prognostic value of nodal involvement and clinicopathological features was compared using a retrospective cohort of OAC patients (n = 702). The expression of inhibitory immune checkpoints by T cells infiltrating tumour-draining lymph nodes (TDLNs) and tumour tissue post-chemo(radio)therapy at surgical resection was assessed by flow cytometry. Nodal metastases is of equal prognostic importance to clinical tumour stage and tumour regression grade (TRG) in OAC. The TME exhibited a greater immuno-suppressive phenotype than the LNME. Our data suggests that blockade of these checkpoints may have a therapeutic rationale for boosting response rates in OAC.

12.
Ann Surg ; 274(5): 814-820, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34310355

ABSTRACT

BACKGROUND AND AIMS: The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes. STUDY DESIGN: An observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre and post FLOT assessment of sarcopenia and pulmonary physiology. RESULTS: 175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (P = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34% + 25%; P < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%. CONCLUSION: FLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Agents/therapeutic use , Esophageal Neoplasms/therapy , Esophagectomy/methods , Esophagogastric Junction , Neoplasm Staging , Thoracic Wall/surgery , Adenocarcinoma/diagnosis , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/diagnosis , Female , Humans , Male , Middle Aged , Treatment Outcome
13.
J Hum Evol ; 156: 102985, 2021 07.
Article in English | MEDLINE | ID: mdl-34051612

ABSTRACT

Neanderthals are known primarily from their habitation of Western Eurasia, but they also populated large expanses of Northern Asia for thousands of years. Owing to a sparse archaeological record, relatively little is known about these eastern Neanderthal populations. Unlike in their western range, there are limited zooarchaeological and paleobotanical studies that inform us about the nature of their subsistence. Here, we perform a combined analysis of carbon and nitrogen stable isotopes on bone collagen and microbotanical remains in dental calculus to reconstruct the diet of eastern Neanderthals at Chagyrskaya Cave in the Altai Mountains of Southern Siberia, Russia. Stable isotopes identify one individual as possessing a high trophic level due to the hunting of large- and medium-sized ungulates, while the analysis of dental calculus also indicates the presence of plants in the diet of this individual and others from the site. These findings indicate eastern Neanderthals may have had broadly similar subsistence patterns to those elsewhere in their range.


Subject(s)
Archaeology , Caves , Diet/history , Neanderthals , Plants , Animals , History, Ancient , Humans , Isotopes/analysis , Russia
14.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Article in English | MEDLINE | ID: mdl-33972424

ABSTRACT

The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.


Subject(s)
Biological Evolution , Ecology/methods , Hominidae/microbiology , Metagenome/genetics , Microbiota/genetics , Mouth/microbiology , Africa , Animals , Bacteria/classification , Bacteria/genetics , Biofilms , Dental Plaque/microbiology , Geography , Gorilla gorilla/microbiology , Hominidae/classification , Humans , Pan troglodytes/microbiology , Phylogeny
15.
Br J Cancer ; 125(4): 479-494, 2021 08.
Article in English | MEDLINE | ID: mdl-33903730

ABSTRACT

Oesophageal cancer (OC) is an inflammation-associated malignancy linked to gastro-oesophageal reflux disease, obesity and tobacco use. Knowledge of the microenvironment of oesophageal tumours is relevant to our understanding of the development of OC and its biology, and has major implications for understanding the response to standard therapies and immunotherapies, as well as for uncovering novel targets. In this context, we discuss what is known about the TME in OC from tumour initiation to development and progression, and how this is relevant to therapy sensitivity and resistance in the two major types of OC. We provide an immunological characterisation of the OC TME and discuss its prognostic implications with specific comparison with the Immunoscore and immune-hot, -cold, altered-immunosuppressed and -altered-excluded models. Targeted therapeutics for the TME under pre-clinical and clinical investigation in OCs are also summarised. A deeper understanding of the TME will enable the development of combination approaches to concurrently target the tumour cells and TME delivering precision medicine to OC patients.


Subject(s)
Drug Resistance, Neoplasm , Esophageal Neoplasms/immunology , Disease Progression , Humans , Precision Medicine , Tumor Microenvironment
16.
World Neurosurg ; 150: e144-e154, 2021 06.
Article in English | MEDLINE | ID: mdl-33684581

ABSTRACT

OBJECTIVE: Venous thromboembolism (VTE) is a significant contributor to postoperative morbidity and mortality. Prophylactic regimens for VTE involve mechanical prophylaxis and pharmacoprophylaxis. This systematic review and meta-analysis aimed to determine the efficacy and safety of pharmacoprophylaxis in comparison with any nonpharmacoprophylaxis regimen for the prevention of postoperative VTE in patients undergoing spinal surgery. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and ICRCTN were searched for comparative studies including both pharmacoprophylaxis and nonpharmacoprophylaxis post spinal surgery. The primary outcome was the incidence of VTE within the postoperative hospitalized period. Secondary outcomes included the incidence of spinal epidural hematoma, significant bleeding events, and other adverse events associated with VTE. The data was pooled using random-effects models of meta-analysis and relative risk (RR) was calculated. RESULTS: Four retrospective and 3 randomized controlled trials representing a total of 8373 patients were included. Overall, there was a significant decrease in postoperative deep venous thrombosis with pharmacoprophylaxis versus nonpharmacoprophylaxis (RR 0.42, 95% confidence interval 0.21-0.86, P = 0.02, I2 = 0%); however, there were no significant differences between the groups in the incidences of VTE (RR 0.31, 95% confidence interval 0.12-0.81, P = 0.02, I2 = 0%). The incidences of spinal epidural hematoma and significant bleeding events were rare and comparable in both groups. CONCLUSIONS: This systematic review and meta-analysis found a potential benefit with pharmacoprophylaxis post spinal surgery in the prevention of deep venous thrombosis. However, there is a need for future randomized controlled trials to investigate the efficacy and safety of pharmacoprophylaxis in spinal surgery across various spinal procedures.


Subject(s)
Neurosurgical Procedures/methods , Postoperative Complications/prevention & control , Spine/surgery , Venous Thromboembolism/prevention & control , Anticoagulants/therapeutic use , Humans , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Randomized Controlled Trials as Topic , Venous Thrombosis
17.
Dis Esophagus ; 34(11)2021 Nov 11.
Article in English | MEDLINE | ID: mdl-33723611

ABSTRACT

BACKGROUND: Chyle leakage is an uncommon but potentially life-threatening complication following esophageal resections. The optimal management strategy is not clear, with a limited evidence base. METHODS: Searches were conducted up to 31 December 2020 on MEDLINE, Embase, and Web of Science for randomized trials or retrospective studies that evaluated the management of chyle leakage following esophageal resection. Two authors independently screened studies, extracted data, and assessed for bias. The protocol was prospectively registered on PROSPERO (CRD: 42021224895) and reported in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: A total of 530 citations were reviewed. Twenty-five studies, totaling 1016 patients met the inclusion criteria, including two low-quality clinical trials and 23 retrospective case series. Heterogeneity of study design and outcomes prevented meta-analysis. The overall incidence of chyle leak/fistula was 3.2%. Eighteen studies describe management of chyle leaks conservatively, 17 by surgical ligation of the thoracic duct, 5 by pleurodesis, and 6 described percutaneous lymphangiography with thoracic duct embolization or disruption. CONCLUSIONS: The evidence base for optimal management of chyle leakage postesophagectomy is lacking, which may be related to its low incidence. There is a paucity of high-quality prospective studies directly comparing treatment modalities, but there is some low-certainty evidence that percutaneous approaches have reduced morbidity but lower efficacy compared with surgery. Further high-quality, prospective studies that compare interventions at different levels of severity are needed to determine the optimal approach to treatment.


Subject(s)
Chyle , Chylothorax , Humans , Prospective Studies , Retrospective Studies , Thoracic Duct
18.
Int J Mol Sci ; 22(3)2021 Jan 22.
Article in English | MEDLINE | ID: mdl-33499003

ABSTRACT

Radiotherapy remains one of the contemporary cornerstones of cancer treatment in the neoadjuvant, curative, adjuvant and palliative settings, either in isolation or as a multimodal approach. Moreover, recent advances in targeted immune checkpoint therapy have firmly established immunotherapy as the fourth pillar in cancer therapy alongside surgery, chemotherapy and notably radiotherapy. There is emerging evidence to suggest both radioresistance and reduced efficacy of immune checkpoint blockade (ICB) are potentiated by the tumour microenvironment (TME) and in fact modulating aspects of this immunosuppressive milieu is instrumental to unlocking anti-tumour immunity. The response rates of Upper Gastrointestinal (UGI) malignancies to ICB remains modest at 10-15%, compared to melanoma at 20-40%. Harnessing the effects of radiotherapy through remodelling of the TME using ICB as a radiosensitisor is an avenue showing promise. Here we explore the rationale behind combining radiotherapy with ICB, as a symbiotic relationship in shifting the balance in favour of anti-tumour immunity. We discuss the effects of radiotherapy on immunogenic cell death, the concept of the abscopal effect, the importance of the cGAS STING pathway, and their relevance in the context of the tumour microenvironment. Furthermore, dosing and timing of radiotherapy and ICB is now being evaluated for its synergistic effects on host tumour immunity, and we review the ongoing efforts and current available literature for single agent and dual agent ICB in combination multimodal therapy for both locally advanced operable and metastatic disease of the upper gastrointestinal tract.


Subject(s)
Gastrointestinal Neoplasms/radiotherapy , Gastrointestinal Neoplasms/therapy , Immunotherapy/trends , Animals , Antigens/chemistry , Biomarkers , Cell Death , Chemoradiotherapy , Combined Modality Therapy , Disease Models, Animal , Dose Fractionation, Radiation , Gastrointestinal Neoplasms/immunology , Humans , Immunologic Factors/pharmacology , Inflammation , Melanoma/pathology , Membrane Proteins/metabolism , Mice , Neoplasm Metastasis , Nucleotidyltransferases/chemistry , Skin Neoplasms/pathology , Tumor Microenvironment/immunology , Upper Gastrointestinal Tract/pathology , Upper Gastrointestinal Tract/radiation effects
19.
Nat Commun ; 12(1): 632, 2021 01 27.
Article in English | MEDLINE | ID: mdl-33504791

ABSTRACT

Consuming the milk of other species is a unique adaptation of Homo sapiens, with implications for health, birth spacing and evolution. Key questions nonetheless remain regarding the origins of dairying and its relationship to the genetically-determined ability to drink milk into adulthood through lactase persistence (LP). As a major centre of LP diversity, Africa is of significant interest to the evolution of dairying. Here we report proteomic evidence for milk consumption in ancient Africa. Using liquid chromatography tandem mass spectrometry (LC-MS/MS) we identify dairy proteins in human dental calculus from northeastern Africa, directly demonstrating milk consumption at least six millennia ago. Our findings indicate that pastoralist groups were drinking milk as soon as herding spread into eastern Africa, at a time when the genetic adaptation for milk digestion was absent or rare. Our study links LP status in specific ancient individuals with direct evidence for their consumption of dairy products.


Subject(s)
Dairying , Feeding Behavior , Milk Proteins/metabolism , Africa, Eastern , Amino Acid Sequence , Animals , Archaeology , Bone and Bones/metabolism , Cattle , Collagen/metabolism , Dental Calculus/metabolism , Geography , Humans , Isotope Labeling , Lactase/metabolism , Lactoglobulins/chemistry , Milk Proteins/chemistry , Models, Molecular
20.
Proc Natl Acad Sci U S A ; 118(2)2021 01 12.
Article in English | MEDLINE | ID: mdl-33419922

ABSTRACT

Although the key role of long-distance trade in the transformation of cuisines worldwide has been well-documented since at least the Roman era, the prehistory of the Eurasian food trade is less visible. In order to shed light on the transformation of Eastern Mediterranean cuisines during the Bronze Age and Early Iron Age, we analyzed microremains and proteins preserved in the dental calculus of individuals who lived during the second millennium BCE in the Southern Levant. Our results provide clear evidence for the consumption of expected staple foods, such as cereals (Triticeae), sesame (Sesamum), and dates (Phoenix). We additionally report evidence for the consumption of soybean (Glycine), probable banana (Musa), and turmeric (Curcuma), which pushes back the earliest evidence of these foods in the Mediterranean by centuries (turmeric) or even millennia (soybean). We find that, from the early second millennium onwards, at least some people in the Eastern Mediterranean had access to food from distant locations, including South Asia, and such goods were likely consumed as oils, dried fruits, and spices. These insights force us to rethink the complexity and intensity of Indo-Mediterranean trade during the Bronze Age as well as the degree of globalization in early Eastern Mediterranean cuisine.


Subject(s)
Archaeology/methods , Dental Calculus/chemistry , Food/history , Asia , Asian People , Commerce/history , DNA, Mitochondrial , Food Analysis/methods , Fossils , Genome, Human , History, Ancient , Human Migration/history , Humans , Middle East
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