ABSTRACT
BACKGROUND: Deaths from unrecognised oesophageal intubation continue despite national campaigns emphasising the importance of capnography to confirm tracheal intubation. A two-person verbal intubation check is recommended in consensus guidelines intended to prevent such deaths. This check can be performed by the intubator with their assistant, either as a one-step process (identification of sustained exhaled carbon dioxide) or as a two-step process (adding identification of the tracheal tube passing through the vocal cords during videolaryngoscopy). METHODS: In two hospitals we introduced two-person checking of tracheal intubation. In one hospital this involved the one-step process and in the other the two-step process. We used anonymous online questionnaires before, during, and after these changes to collect opinions from anaesthetists and their assistants regarding the feasibility and acceptability of these changes. RESULTS: Most intubators (116/149, 78%) and intubators' assistants (70/72, 97%) reported that the two-person verbal intubation check would reduce the likelihood of unrecognised oesophageal intubation. Benefits and lack of negative aspects were reported for both one-step and two-step two-person intubation checks in both centres. Intubators judged that the checks improved communication and teamwork (118/149, 79%); intubators' assistants reported feeling more empowered to voice concerns if needed (69/72, 96%), a flattened team hierarchy (53/72, 74%), and feeling more valued as team members (64/72, 89%). Most intubators (122/149, 82%) and intubators' assistants (68/72, 94%) planned to continue using the two-person intubation check for all future intubations. CONCLUSIONS: Our results suggest that a two-person verbal intubation check is feasible and acceptable to all members of the intubating team.
ABSTRACT
BACKGROUND: Different sedation regimens have been used to facilitate awake tracheal intubation, but the evidence has not been synthesised robustly, particularly with respect to clinically important outcomes. We conducted a systematic review and network meta-analysis to determine the sedation techniques most likely to be associated with successful tracheal intubation, a shorter time to successful intubation and a lower risk of arterial oxygen desaturation. METHODS: We searched for randomised controlled trials of patients undergoing awake tracheal intubation for any indication and reporting: overall tracheal intubation success rate; tracheal intubation time; incidence of arterial oxygen desaturation; and other related outcomes. We performed a frequentist network meta-analysis for these outcomes if two or more sedation regimens were compared between included trials. We also performed a sensitivity analysis excluding trials with a high risk of bias. RESULTS: In total, 48 studies with 2837 patients comparing 33 different regimens were included. Comparing overall awake tracheal intubation success rates (38 studies, 2139 patients), there was no evidence suggesting that any individual sedation regimen was superior. Comparing times to successful tracheal intubation (1745 patients, 24 studies), any sedation strategy was superior to placebo. When we excluded trials with a high risk of bias, we found no evidence of a difference between any interventions for time to successful tracheal intubation. Thirty-one studies (1753 patients) suggested that dexmedetomidine and magnesium sulphate were associated with a reduced risk of arterial oxygen desaturation compared with other interventions, but excluding trials with a high risk of bias suggested no relevant differences between interventions. The quality of evidence for each of our outcomes was low. CONCLUSIONS: To maximise effective and safe awake tracheal intubation, optimising oxygenation, topical airway anaesthesia and procedural performance may have more impact than any given sedation regimen.
ABSTRACT
Symbiotic interactions play a vital role in maintaining the phosphate (Pi) nutrient status of host plants and providing resilience during biotic and abiotic stresses. Serendipita indica, a mycorrhiza-like fungus, supports plant growth by transporting Pi to the plant. Despite the competitive behaviour of arsenate (AsV) with Pi, the association with S. indica promotes plant growth under arsenic (As) stress by reducing As bioavailability through adsorption, accumulation, and precipitation within the fungus. However, the capacity of S. indica to enhance Pi accumulation and utilization under As stress remains unexplored. Axenic studies revealed that As supply significantly reduces intracellular ACPase activity in S. indica, while extracellular ACPase remains unaffected. Further investigations using Native PAGE and gene expression studies confirmed that intracellular ACPase (isoform2) is sensitive to As, whereas extracellular ACPase (isoform1) is As-insensitive. Biochemical analysis showed that ACPase (isoform1) has a Km of 0.5977 µM and Vmax of 0.1945 Unit/min. In hydroponically cultured tomato seedlings, simultaneous inoculation of S. indica with As on the 14thday after seed germination led to hyper-colonization, increased root/shoot length, biomass, and induction of ACPase expression and secretion under As stress. Arsenic-treated S. indica colonized groups (13.33 µM As+Si and 26.67 µM As+Si) exhibited 8.28-19.14 and 1.71-3.45-fold activation of ACPase in both rhizospheric media and root samples, respectively, thereby enhancing Pi availability in the surrounding medium under As stress. Moreover, S. indica (13.33 µM As+Si and 26.67 µM As+Si) significantly improved Pi accumulation in roots by 7.26 and 9.46 times and in shoots by 4.36 and 8.85 times compared to the control. Additionally, S. indica induced the expression of SiPT under As stress, further improving Pi mobilization. Notably, fungal colonization also restricted As mobilization from the hydroponic medium to the shoot, with a higher amount of As (191.01 ppm As in the 26.67 µM As+Si group) accumulating in the plant's roots. The study demonstrates the performance of S. indica under As stress in enhancing Pi mobilization while limiting As uptake in the host plant. These findings provide the first evidence of the As-Pi interaction in the AM-like fungus S. indica, indicating reduced As uptake and regulation of PHO genes (ACPase and SiPT genes) to increase Pi acquisition. These data also lay the foundation for the rational use of S. indica in agricultural practices.
Subject(s)
Acid Phosphatase , Arsenic , Basidiomycota , Mycorrhizae , Arsenic/toxicity , Arsenic/metabolism , Basidiomycota/metabolism , Mycorrhizae/physiology , Phosphates/pharmacology , Phosphates/metabolism , Plant Roots/metabolism , Acid Phosphatase/metabolism , Acid Phosphatase/pharmacologyABSTRACT
Naturally, O-prenylation of 3-aryl-benzopyrans enhances the biological activities of these compounds. In this study, substituted O-prenylated 3-aryl-benzopyrans (21a-c, 22a-c, 23a-c, 24a-c 25a-c, 27 and 28) were synthesized and evaluated for osteogenic and cancer cell growth inhibitory potentials using cell-based in-vitro models. Amongst the target compounds, 21a, 22b, 23c, and 24c showed good osteogenic activity at 1 pM concentration, whereas 26 and 27 showed osteogenic activity at 100pM and 10nM, respectively. Compounds 21a, 22b, and 23c showed good cancer cell growth inhibitory activity against breast cancer cells (MCF-7 and MBA-231). Amongst active compounds, 27 presented the best anticancer activity against MDAMB-231 cells with selectivity towards non-cancerous cells [IC50 3.76 µM with SI 13.3]. The in-silico study of compounds showed their structural complementarities with the LBD of estrogen receptors and compliance with dragability parameters.
ABSTRACT
The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.
The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.
Subject(s)
Biodegradation, Environmental , Biological Availability , Charcoal , Metals, Heavy , Soil Pollutants , Charcoal/chemistry , Metals, Heavy/metabolism , Soil Pollutants/metabolism , Agriculture , Soil/chemistry , Industrial Waste , Triticum , OryzaABSTRACT
Awake tracheal intubation (ATI) remains the "gold standard" technique in securing a definitive airway in conscious, self-ventilating patients with predicted or known difficult airways and the procedure is associated with a low failure rate. Since its inception a variety of techniques to achieve ATI have emerged and there have been accompanying advancements in pharmaceuticals and technology to support the procedure. In recent years there has been a growing focus on the planning, training and human factors involved in performing the procedure. The practice of ATI, does however, remain low around 1% to 2% of all intubations despite an increase in those with head and neck pathology. ATI, therefore, presents a skill that is key for the safety of patients but may not be practised with regularity by many anesthetists. In this article we therefore aim to highlight relevant guidance, recent literature and provide an update on the practical methods fundamental for successful ATI. We also discuss the crucial aspects of a safe airway culture and how this can help to embed training and maintenance of skills.
Subject(s)
Intubation, Intratracheal , Wakefulness , Humans , Intubation, Intratracheal/methods , Airway Management/methods , Clinical CompetenceABSTRACT
Objective: To determine the relative frequency of orbital lesions based on the site of origin and histopathology at a Tertiary care hospital (Mayo Hospital, Lahore Pakistan) from 1996 till 2022 (27 years). Methods: This descriptive case series included 2651 patients of all age groups presenting with orbital lesions who initially got enrolled at Institute of Ophthalmology Mayo Hospital, Lahore from 1996 till 2022. Of these, 583 patients left against medical advice. So, clinical data of 2068 patients were completely analyzed. Lesions were managed medically and/ or surgically. Final clinical diagnosis, with the help of histopathology, was used to classify the lesions. Results: There were 1258 (60.9%) adults and 810 (39.1%) children, 1358 (65.66%) were neoplastic while 710 (34.33%) non-neoplastic lesions. Amongst the neoplastic lesions, 405 (29.8 %) were benign and 953 (70.2%) malignant. Primary orbital lesions were 1676 (81.04%), Secondary orbital lesions were 300 (14.51%), Endocrine/ hematopoietic reticulo-endothelial system lesions were 84 (4.06%) and Metastatic lesions from distant organs were 08 (0.39%). Conclusion: Retinoblastoma, rhabdomyosarcoma, optic nerve gliomata were common in children. Pleomorphic adenoma & adenocystic carcinoma of lacrimal gland, cavernous hemangioma, optic nerve meningioma, neurofibroma, schwannoma, squamous cell carcinoma of eyelid, carcinoma of maxillary antrum and lymphomas were more common in adults.
ABSTRACT
Background Giant cell tumors of the tendon sheath (GCTTS) of the hand are considered the second most common benign tumors of the hand after ganglion cysts. Excision biopsy is considered the standard treatment at present. They are notorious for having a very high rate of recurrence as given in many studies. Many factors are said to be associated with recurrence of the tumors. The goal of this study is to evaluate the long-term results of a series of 48 patients operated on at a single institute and to find out if there is any correlation between the proposed risk factors with recurrence. Methods A retrospective analysis was done in cases of GCTTS operated on between 2015 and 2021. The patients were invited for follow-up for a minimum of 2 years, and the patient files were reviewed. Further data were collected at follow-up including recurrence, range of movement, sensation, skin necrosis, scarring, and digital neuropathy. A data analysis was done. The correlation between the proposed risk factors and recurrence was calculated with the Pearson correlation coefficient. A p -value of less than 0.05 was considered statistically significant. Results During the 6 years, 48 patients were operated on. Recurrence was observed in eight patients (16%) at an average of 38.7 months from the time of surgery. Of the risk factors, tumors with satellite nodules and tumor adjacency to joint correlated significantly with recurrence. No complications were observed during follow-up. Conclusion GCTTS of the hand has a high propensity to recur. The presence of satellite nodules and proximity to interphalangeal joints are two important risk factors for recurrence. Magnification during surgery ensures complete excision of the tumor and reduces the chance of recurrence.
ABSTRACT
The frequency of recurrent rectal cancer has dropped significantly with improved surgical approaches and adjunctive therapies. These recurrences have proven challenging to obtain R0 resection with salvage operations. Meticulous planning, clear understanding of anatomy with imaging, and multispecialty support have become essential in local control and long-term survival with pelvic recurrence of rectal cancer. Technical considerations and prognosis indicators along with role of intraoperative radiation or boost radiation are discussed within.
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Advanced and metastatic prostate cancer is often incurable, but its dependency on certain molecular alterations may provide the basis for targeted therapies. A growing body of research has demonstrated that peroxisome proliferator-activated receptor gamma (PPARγ) is amplified as prostate cancer progresses. PPARγ has been shown to support prostate cancer growth through its roles in fatty acid synthesis, mitochondrial biogenesis, and co-operating with androgen receptor signalling. Interestingly, splice variants of PPARγ may have differing and contrasting roles. PPARγ itself is a highly druggable target, with agonists having been used for the past two decades in treating diabetes. However, side effects associated with these compounds have currently limited clinical use of these drugs in prostate cancer. Further understanding of PPARγ and novel techniques to target it, may provide therapies for advanced prostate cancer.
Subject(s)
Diabetes Mellitus , Prostatic Neoplasms , Male , Humans , PPAR gamma/agonists , Prostatic Neoplasms/pathology , Signal TransductionABSTRACT
BACKGROUND: Prostate cancer is the most common cancer in men in the developed world, with most deaths caused by advanced and metastatic disease which has no curative options. Here, we identified Mbtps2 alteration to be associated with metastatic disease in an unbiased in vivo screen and demonstrated its regulation of fatty acid and cholesterol metabolism. METHODS: The Sleeping Beauty transposon system was used to randomly alter gene expression in the PtenNull murine prostate. MBTPS2 was knocked down by siRNA in LNCaP, DU145 and PC3 cell lines, which were then phenotypically investigated. RNA-Seq was performed on LNCaP cells lacking MBTPS2, and pathways validated by qPCR. Cholesterol metabolism was investigated by Filipin III staining. RESULTS: Mbtps2 was identified in our transposon-mediated in vivo screen to be associated with metastatic prostate cancer. Silencing of MBTPS2 expression in LNCaP, DU145 and PC3 human prostate cancer cells reduced proliferation and colony forming growth in vitro. Knockdown of MBTPS2 expression in LNCaP cells impaired cholesterol synthesis and uptake along with reduced expression of key regulators of fatty acid synthesis, namely FASN and ACACA. CONCLUSION: MBTPS2 is implicated in progressive prostate cancer and may mechanistically involve its effects on fatty acid and cholesterol metabolism.
Subject(s)
Lipogenesis , Prostatic Neoplasms , Male , Humans , Animals , Mice , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Cell Line, Tumor , Prostatic Neoplasms/pathology , Cholesterol , Fatty Acids , Cell Proliferation , Gene Expression Regulation, Neoplastic , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolismABSTRACT
BACKGROUND: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. METHODS: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells. RESULTS: In silico observation revealed that moricin is a potential anticancer peptide, and protein-protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ÆB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells. CONCLUSIONS: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug.
ABSTRACT
Majority of different kinds of metabolites having therapeutic characteristics are thought to be stored in medicinal plants. So, the present study was aimed to explore the crude extract of leaves and stem of R. afghanicum for phytochemical screening and various pharmacological activities. Toxicological studies at 100â mg/kg showed 60 % mortality where its safe dose level was 90â mg/kg. Phytochemical screening revealed the presence of alkaloids, glycosides, flavonoids and tannins in both extracts. Bacterial strains were susceptible to (RLEt) and (RLM) crude extracts except Staphylococcus aureus. RSM showed maximum anti-inflammatory activity (20.16 %) followed by RSEt (20.14 %) where lowest activity was displayed by RLEt (18.46 %). Phytotoxic activity showed a substantial dose-dependent phyto-inhibition of Lemna minor. An outstanding cytotoxic potential was displayed with LD50 values of 9.46 and 13.03â µg/ml in both stem extracts. RLEt demonstrated a dose-dependent pain relief at 30, 60 and 90â mg/kg which was 31 %, 40 % and 52 % respectively. A considerable spasmolytic action was observed by the shrinkage of jejunum muscle in albino mice. RLEt at 1000â ppm showed (17â mm) and RLM at 1000â ppm showed (16â mm) zone of inhibition against Aspergillus niger. These findings support and corroborate the traditional applications of R. afghanicum for treating digestive, analgesic and inflammatory ailments.
Subject(s)
Alkaloids , Rhododendron , Animals , Mice , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Pakistan , Phytochemicals/pharmacologyABSTRACT
The study aimed to determine the prevalence of continuity of illicit drug use and its associated factors among Malay opioid users receiving methadone treatment in Kelantan, Malaysia. This cross-sectional study involved a total of 150 respondents. Sociodemographic characteristic of participants, level of religiosity, and quality of life were collected using the self-administered questionnaires. The prevalence of continuity illicit drug use was 38.7% (n = 58) by self-report and 40.7% (n = 61) by positive urine test result for drugs. Positive hepatitis C status and high quality of life in the psychological health domain were associated with low continuity of illicit drug use by self-reported data and urine drug test results. In conclusion, the continuity of illicit drug use among methadone program users is still high, especially among those on methadone therapy for less than 2 years.
Subject(s)
Illicit Drugs , Opioid-Related Disorders , Humans , Methadone , Malaysia , Opioid-Related Disorders/epidemiology , Cross-Sectional Studies , Quality of Life , Opiate Substitution TreatmentABSTRACT
This study elucidates the mechanism of CCL25 and CCR9 in rheumatoid arthritis (RA). RA synovial fluid (SF) expresses elevated levels of CCL25 compared to OA SF and plasma from RA and normal. CCL25 was released into RA SF by fibroblasts (FLS) and macrophages (MΦs) stimulated with IL-1ß and IL-6. CCR9 is also presented on IL-1ß and IL-6 activated RA FLS and differentiated MΦs. Conversely, in RA PBMCs neither CCL25 nor CCR9 are impacted by 3-month longitudinal TNF inhibitor therapy. CCL25 amplifies RA FLS and monocyte infiltration via p38 and ERK phosphorylation. CCL25-stimulated RA FLS secrete potentiated levels of IL-8 which is disrupted by p38 and ERK inhibitors. CCL25 polarizes RA monocytes into nontraditional M1 MΦs that produce IL-8 and CCL2. Activation of p38 and ERK cascades are also responsible for the CCL25-induced M1 MΦ development. Unexpectedly, CCL25 was unable to polarize RA PBMCs into effector Th1/Th17 cells. Consistently, lymphokine like RANKL was uninvolved in CCL25-induced osteoclastogenesis; however, this manifestation was regulated by osteoclastic factors such as RANK, cathepsin K (CTSK), and TNF-α. In short, we reveal that CCL25/CCR9 manipulates RA FLS and MΦ migration and inflammatory phenotype in addition to osteoclast formation via p38 and ERK activation.
Subject(s)
Arthritis, Rheumatoid/immunology , Cell Differentiation/immunology , Chemokines, CC/immunology , Macrophages/immunology , Osteoclasts/immunology , Receptors, CCR/immunology , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Cells, Cultured , Chemokine CCL2/immunology , Chemokine CCL2/metabolism , Chemokines, CC/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Fibroblasts/cytology , Fibroblasts/immunology , Fibroblasts/metabolism , Humans , Interleukin-8/immunology , Interleukin-8/metabolism , Macrophages/cytology , Macrophages/metabolism , Monocytes/cytology , Monocytes/immunology , Monocytes/metabolism , Osteoclasts/cytology , Osteoclasts/metabolism , Phosphorylation , Receptors, CCR/metabolism , Signal Transduction/immunology , Synovial Fluid/cytology , Synovial Fluid/immunology , Synovial Fluid/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Arsenic (As) is a toxic metalloid that is present in natural surroundings in many forms with severe consequences to sustainable agriculture and human health. Plant growth-promoting Rhizobia have been found involved in the induction of plant tolerance under various biotic and abiotic stresses. An endofungal Rhizobium species associated with arbuscular mycorrhizal fungi (AMF) Serendipita indica deploy beneficial role in the promotion of plant growth and tolerance against various biotic and abiotic stresses. In the current study, we have determined the role of endofungal Rhizobium species in protection of host plant growth under As stress. We observed that endofungal Rhizobium species strain Si001 tolerate AsV up to 25 mM and its inoculation enhances tomato seed germination and seedling growth. A hyper-colonization of Rhizobium species Si001 in tomato roots was observed under As stress and results in modulation of GSH and proline content with reduced ROS. Rhizobium species Si001 colonization in host plant recovered pigment contents (chlorophyll-a and chlorophyll-b up to 189.5% and 192%, respectively), photosynthesis (157%), and water use efficiency (166%) compared to As-treated plants. Interestingly, bacterial colonization results in 40% increased As accumulation in the root, while a reduction in As translocation from root to shoot up to 89% was observed as compared to As treated plants. In conclusion, endofungal Rhizobium species Si001 association with the host plant may improve plant health and tolerance against As stress with reduced As accumulation in the crop produce.
Subject(s)
Arsenic , Mycorrhizae , Rhizobium , Solanum lycopersicum , Arsenic/toxicity , Chlorophyll , Humans , Plant Development , Plant Roots/microbiologyABSTRACT
OBJECTIVES: To test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard-of-care (SOC) systemic therapy in men with newly diagnosed oligo-metastatic prostate cancer. PATIENTS AND METHODS: A prospective, randomised, non-blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high-volume robotic surgery. We aimed to randomise 50 men with synchronous oligo-metastatic prostate cancer within an 18-month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaires to capture quality-of-life (QoL) data at baseline and 3 months post-randomisation; routine clinicopathological assessment to capture adverse events and prostate-specific antigen in both arms, plus standard perioperative parameters in the surgical arm. RESULTS: A total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60-83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow-up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo-metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication. CONCLUSION: It is feasible to randomise men with synchronous oligo-metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo-metastatic prostate cancer.
Subject(s)
Prostatic Neoplasms , Quality of Life , Feasibility Studies , Humans , Male , Prospective Studies , Prostatectomy/methods , Prostatic Neoplasms/pathology , Treatment OutcomeABSTRACT
Population inflation has led to the unprecedented increase in urbanization, thus causing negative impacts on environmental sustainability. Recently, there is an upsurge in the number of restaurants due to the changing lifestyles of the people round the globe. For instance, there were 167,490 food and beverage establishments in 2015, representing an annual growth rate of 5.1% since 2010 in Malaysia. The rapid growth of restaurants has implicated a negative impact due to the generation of highly polluted restaurant wastewater (RWW). RWW is mainly generated during the cooking, washing, and cleaning operations. RWW typically contain fat, oil, and grease (FOG) resulting from residues of meat, deep-fried food, baked items and butter, and has caused serious blockages of sewer due to clogging and eventually sewage backup. This has increased the required frequency of cleaning and sanitary sewer overflows (SSOs). Results from the previous studies have shown that FOG can be treated using physical, chemical, and biological processes. Different technologies have been applied for the treatment of FOG and other pollutants (COD, BOD, SS and NH4-N) present in RWW. Therefore, this review aims to provide an in-depth understanding of the characteristics of RWW, chemical and physical characteristics of FOG with the mechanism of its formation and utilization for biocomposites, biogas and biodiesel productions for circular bioeconomy. Besides, this review has discussed the potential treatment technologies comprehensively for RWW which is currently remain understudied. Integrated sustainable management of FOG with technoeconomic analysis of bioproducts, sustainable management with international initiatives and previous studies are also summarized. Hence, this review aims towards providing better alternatives in managing RWW at sources, including its treatment and potential of its biorefinery, therefore eventually contributing towards environmental sustainability.
Subject(s)
Restaurants , Wastewater , Environment , Fats/analysis , Fats/chemistry , Humans , Hydrocarbons/analysis , Sewage/chemistry , Wastewater/analysisABSTRACT
BACKGROUND: Elagolix is effective and safe for treating menorrhagia in women with uterine fibroid. However, it is reported to be associated with hypoestrogenism that can be alleviated by adding estradiol/norethindrone acetate. This systematic review and meta-analysis aimed to determine the effectiveness of elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid by comparing: elagolix versus placebo and elagolix versus estradiol/norethindrone acetate. METHODOLOGY: The Cochrane Central Register of Controlled Trials (CENTRAL 2021, Issue 3 of 12), MEDLINE databases (1980 to December week 1, 2020), and trial registries for relevant randomized clinical trials were used. All randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the dichotomous outcomes and mean differences with 95% confidence intervals. Data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence were assessed. RESULTS: Four randomized controlled trials with 1949 premenopausal women from 323 locations were included. Elagolix improved menstrual blood loss of less than 80 ml (RR 4.81, 95% CI 2.45 to 9.45; four trials, 869 participants; moderate quality evidence) or more than 50% reduction from baseline (RR 4.87, 95% CI 2.55 to 9.31; four trials, 869 participants; moderate quality evidence) compared to placebo. There was no difference in menstrual blood loss of less than 80 ml (RR 1.08, 95% CI 1.00 to 1.16; five trials, 1365 participants; moderate quality evidence) or more than 50% reduction from baseline between the elagolix (RR 1.08, 95% CI 1.01 to 1.15; five trials, 1365 participants; high quality evidence) and elagolix with estradiol/norethindrone acetate. In both comparisons, elagolix has reduced the mean percentage change in uterine and fibroid volume, improved symptoms, and health-related quality of life. More patients had hot flush, and bone mineral density loss in the elagolix treatment compared to both placebo and elagolix with estradiol/norethindrone acetate. CONCLUSIONS: Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women. Review registration PROSPERO CDR 42021233898.
Subject(s)
Leiomyoma , Menorrhagia , Uterine Neoplasms , Estradiol/therapeutic use , Female , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Hydrocarbons, Fluorinated , Leiomyoma/complications , Leiomyoma/drug therapy , Menorrhagia/drug therapy , Menorrhagia/etiology , Norethindrone Acetate , Pyrimidines , Quality of Life , Uterine Neoplasms/complications , Uterine Neoplasms/drug therapyABSTRACT
BACKGROUND: Febrile neutropenia (FN) is a life-threatening complication of Docetaxel-based chemotherapy regimens (DBRs). Prophylactic granulocyte-colony stimulating factor (G-CSF) can reduce the risk of FN. This study investigated the effect of G-CSF on FN in patients receiving DBRs for breast cancer. METHODS: Patients treated between 2015 and 2017 were identified from the hospital's pharmacy database and their medical records were examined retrospectively. Data from patients' first four cycles of DBR were collected. FN rate, FN associated length of hospital stay (FN-LOS), and chemotherapy dose modification/delay due to FN were compared between patients who did (G-CSF group) or did not (non-GCSF group) receive prophylactic G-CSF. RESULTS: Of the 276 included patients, 83.3% received a DBR as adjuvant or neoadjuvant therapy, and 50% received docetaxel as combination therapy. Prophylactic G-CSF was administered with the first cycle of a DBR in 69.9% of patients who were significantly less likely to experience FN compared to the non-G-CSF group (6.2% vs. 15.7%; odds ratio: 0.36 [95% CI: 0.16-0.82]; p = 0.020). Collectively and after the 4 DBR treatment cycles, FN rate (4.8 vs. 8.5; odds ratio: 0.54 [95% CI: 0.30-0.97]; p = 0.043) and the mean FN-LOS (3.55 vs. 5.28 days; t = -2.22; p = 0.037) were reduced in the G-CSF group. There was no difference in DBR dose delay/reduction between both groups in cycles 2-4. CONCLUSION: In patients receiving DBRs for breast cancer, prophylactic G-CSF significantly reduced both the rate of FN and duration of hospitalization for FN.