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Low volume sampling technologies have gained popularity as they are minimally invasive, reduce patient burden, enhance population diversity, and have the potential to facilitate decentralized clinical trials. Herein, we validated a Gyrolab assay to measure soluble Mucosal Addressin Cell Adhesion Molecule 1 (sMAdCAM-1) in dried blood samples collected using two low volume sampling devices, Mitra and Tasso-M20. This validated assay was implemented in a proof-of-concept study to compare three low volume sampling devices (Mitra, Tasso-M20 and TassoOne Plus) with serum collected via venipuncture from healthy volunteers receiving etrolizumab. We observed significantly higher concentration of sMAdCAM-1 in dried blood samples collected using Mitra and Tasso-M20 compared to serum in some paired samples, which was attributed to interference from the dried blood extraction buffer. To mitigate this interference, samples required substantial dilution into the appropriate buffer, which negatively impacted the detectability of sMAdCAM-1 with the Gyrolab assay. By employing the Quanterix single molecule array (Simoa), known for its superior assay sensitivity, the interference was minimized in the diluted samples. Both liquid blood collected in TassoOne Plus and dried blood collected using Mitra and Tasso-M20 demonstrated great concordance with serum for sMAdCAM-1 measurement. However, a bias was observed in Mitra dried blood samples, presumably due to the different sample collection sites in comparison with venipuncture and Tasso devices. Our study highlights the potential of low volume sampling technologies for biomarker analysis, and underscores the importance of understanding the challenges and limitations of these technologies before integrating them into clinical studies.

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[This corrects the article DOI: 10.3389/fendo.2024.1338420.].

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Locally advanced cervical cancer poses a significant challenge to fertility-sparing treatments. Pelvic radiotherapy impairs reproductive potential owing to ovarian, uterine, and endometrial side effects. This study presents a literature review of the main fertility-sparing therapeutic alternatives for locally advanced cervical cancer and a case report of the first childbirth following uterine transposition for gynecological malignancies.

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Combined endurance and resistance training, also known as "concurrent training", is a common practice in exercise routines. While concurrent training offers the benefit of targeting both cardiovascular and muscular fitness, it imposes greater physiological demands on the body compared to performing each modality in isolation. Increased protein consumption has been suggested to support adaptations to concurrent training. However, the impact of protein supplementation on responses to low-volume concurrent training is still unclear. Forty-four untrained, healthy individuals (27 ± 6 years) performed two sessions/week of low-volume high-intensity interval training on cycle ergometers followed by five machine-based resistance training exercises for 8 weeks. Volunteers randomly received (double-blinded) 40 g of whey-based protein (PRO group) or an isocaloric placebo (maltodextrin, PLA group) after each session. Maximal oxygen consumption (VO2max) and overall fitness scores (computed from volunteers' VO2max and one-repetition maximum scores, 1-RM) significantly increased in both groups. The PRO group showed significantly improved 1-RM in all major muscle groups, while the PLA group only improved 1-RM in chest and upper back muscles. Improvements in 1-RM in leg muscles were significantly greater in the PRO group versus the PLA group. In conclusion, our results indicate that adaptations to low-volume concurrent training, particularly leg muscle strength, can be improved with targeted post-exercise protein supplementation in untrained healthy individuals.

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OBJECTIVE: In recently published phase III trials, overall survival (OS) differences were demonstrated in patients with secondary vs. De Novo and low vs. high volume metastatic hormone-sensitive prostate cancer (mHSPC). We hypothesized that these factors may also be attributable in real-world setting of new intensified combination therapies and in metastatic castration resistant prostate cancer (mCRPC) patients. MATERIALS AND METHODS: We relied on an institutional tertiary-care database to identify mHSPC and subsequent mCRPC patients. The main outcome consisted of time to mCRPC and OS. Patients were stratified according to De Novo vs. secondary and low vs. high volume mHSPC and mCRPC, respectively. RESULTS: Of 504 mHSPC patients, 371 (73.6%) were De Novo vs. 133 (26.4%) secondary mHSPC. Patients with De Novo and high volume mHSPC harbored shorter time to mCRPC and OS than secondary and low volume mHSPC patients (both P < 0.01). After stratification regarding disease volume, median time to mCRPC differed significantly between De Novo high volume (DNHV) vs. De Novo low volume (DNLV) vs. secondary high volume (SecHV) vs. secondary low volume mHSPC patients (SecLV, P < 0.001). Similarly in OS analyses, median OS was 44 vs. 53 vs. 88 vs. 120 months for respectively DNHV vs. SecHV vs. SecLV vs. DNLV mHSPC (P < 0.001). After progression to mCRPC, the effect of onset of metastatic disease and metastatic volume was still observed (all P < 0.01). CONCLUSION: Patients with DNHV mHSPC harbor worse prognosis in a real world setting and in the light of combination therapies. This effect is also discernible in the context of mCRPC.

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BACKGROUND: Droplet microfluidics with push-pull and microdialysis sampling from brain slices, cultured cells and engineered tissues produce low volume mass limited samples containing analytes sampled from the extracellular space. This sampling approach coupled to mass spectrometry (MS) detection allows evaluation of time-dependent chemical changes. Our goal is an approach for continuous sampling and segregation of extracellular samples into picoliter droplets followed by the characterization of the droplets using nanoelectrospray ionization (nESI) MS. The main focus here is the optimization of the carrier oil for the microfluidic device that neither affects the stability of picoliter droplets nor compatibility with MS detection of a range of analytes. RESULTS: We developed and characterized a 1-octanol-assisted ultra-small volume droplet microfluidic nESI MS system for the analysis of neurotransmitters in distinct samples including cerebrospinal fluid (CSF). The use of a 1-octanol oil phase was effective for generation of aqueous droplets as small as 65 pL and enabled detection of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) in water and artificial CSF. Continuous MS analysis of droplets for extended periods up to 220 min validated the long-term stability of droplet generation and analyte detection by nESI-MS. As an example, ACh response demonstrated a linear working range (R2 = 0.99) between 0.4 µM and 25 µM with a limit of detection of 370 nM (24 amol), enabling its quantitation in rodent CSF. SIGNIFICANCE: The established droplet microfluidics - nESI MS approach allows the analysis of microenvironments at high spatiotemporal resolution. The approach may allow microsampling and monitoring of spatiotemporal dynamics of neurochemicals and drugs in the brain and spinal cord of live animals.

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As stewards of public and environmental health, mosquito control agencies are rightfully concerned about impacts on nontarget organisms. This study examined the impact of a modern, pyrethroid based ground adulticide program using ultra-low volume applications in a metropolitan county in central Florida. Nontarget insects and mosquitoes were collected in a before-after control-impact design at 21 sites over 1.5 years. While mosquitoes were reduced, we found no evidence for reduction of nontarget insects, regardless of taxon. Night-flying Lepidoptera may experience greater risk than other nontarget taxa, but overall effects of adulticide missions on this group were low and inconsistent. Instead, meteorology, habitat, and phenology dominate patterns of nontarget abundance. Mosquito reduction was more clearly observed and corrected post-mission reduction was consistent with results expected in complex urban and suburban treatment zones.

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Background: Maternal mortality in the United States is rising and many deaths are preventable. Emergencies, such as postpartum hemorrhage, occur less frequently in non-teaching, rural, and urban low-birth volume hospitals. There is an urgent need for accessible, evidence-based, and sustainable inter-professional education that creates the opportunity for clinical teams to practice their response to rare, but potentially devastating events. Objective: To assess the feasibility of virtual simulation training for the management of postpartum hemorrhage in low-to-moderate-volume delivery hospitals. Study design: The study occurred between December 2021 and March 2022 within 8 non-academic hospitals in the United States with low-to-moderate-delivery volumes, randomized to one of two models: direct simulation training and train-the-trainer. In the direct simulation training model, simulation faculty conducted a virtual simulation training program with participants. In the train-the-trainer model, simulation faculty conducted virtual lessons with new simulation instructors on how to prepare and conduct a simulation course. Following this training, the instructors led their own simulation training program at their respective hospitals. The direct simulation training participants and students trained by new instructors from the train-the-trainer program were evaluated with a multiple-choice questionnaire on postpartum hemorrhage knowledge and a confidence and attitude survey at 3 timepoints: prior to, immediately after, and at 3 months post-training. Paired t-tests were performed to assess for changes in knowledge and confidence within teaching models across time points. ANOVA was performed to test cross-sectionally for differences in knowledge and confidence between teaching models at each time point. Results: Direct simulation training participants (n=22) and students of the train-the-trainer instructors (n=18) included nurses, certified nurse midwives and attending physicians in obstetrics, family practice or anesthesiology. Mean pre-course knowledge and confidence scores were not statistically different between direct simulation participants and the students of the instructors from the train-the-trainer course (79%+/-13 versus 75%+/-14, respectively, P-value=.45). Within the direct simulation group, knowledge and confidence scores significantly improved from pre- to immediately post-training (knowledge score mean difference 9.81 [95% CI 3.23-16.40], P-value<.01; confidence score mean difference 13.64 [95% CI 6.79-20.48], P-value<.01), which were maintained 3-months post-training. Within the train-the-trainer group, knowledge and confidence scores immediate post-intervention were not significantly different compared with pre-course or 3-month post-course scores. Mean knowledge scores were significantly greater for the direct simulation group compared to the train-the-trainer group immediately post-training (89%+/-7 versus 74%+/-8, P-value<.01) and at 3-months (88%+/-7 versus 76%+/-12, P-value<.01). Comparisons between groups showed no difference in confidence and attitude scores at these timepoints. Both direct simulation participants and train-the-trainer instructors preferred virtual education, or a hybrid structure, over in-person education. Conclusion: Virtual education for obstetric simulation training is feasible, acceptable, and effective. Utilizing a direct simulation model for postpartum hemorrhage management resulted in enhanced knowledge acquisition and retention compared to a train-the-trainer model.

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BACKGROUND AND AIMS: The adenoma detection rate (ADR), recognized as a surrogate marker for colorectal cancer incidence and mortality reduction, is closely linked to the efficacy of bowel cleansing. However, there is a dearth of evidence examining the impact on ADR when employing two distinct very low-dose bowel cleansing products. This study sought to compare ADR in a fecal immunochemical occult blood testing (iFOBT) based organized screening program by utilizing 1L polyethylene glycol plus ascorbate (1L-PEGA) versus magnesium citrate plus picosulphate (SPMC), both administered in a split-dose regimen. METHODS: We conducted a comparative, parallel, randomized, noninferiority, and low-intervention clinical trial, the study targeted individuals from a population colorectal cancer screening program aged 50-69 with a positive iFOBT result scheduled for a work-up colonoscopy in the morning. Participants were randomized to either 1L-PEGA or SPMC for bowel cleansing. Main outcome was ADR. Secondary outcomes were bowel preparation quality, individuals' safety, tolerability and satisfaction. RESULTS: A total of 1,002 subjects were included, 501 in each group. There were no differences between groups with respect to pooled ADR (SPMC, 56.5% [52.1-60.8]; 1L-PEGA, 53.7% [49.3-58.0]; RR 0.95 [0.85-1.06]); therefore, SPMC demonstrated noninferiority in ADR compared to 1L-PEGA (difference, 2.8%; 2-sided 95% lower confidence limit (LCL), -3.4). In addition, there were no significant differences in mean lesions regardless of size and location between arms. Bowel preparation favored 1L-PEGA (96.2% vs. 89.2%; p<0.001) whereas SPMC exhibited significantly higher safety and tolerability, as evidenced by fewer non-serious treatment-emergent adverse events CONCLUSIONS: SPMC emerged as a noninferior laxative compared to 1L-PEGA concerning ADR. Despite the superior bowel preparation quality associated with 1L-PEGA, the safety, tolerability and overall satisfaction of participants were higher with SPMC. This trial was registered at ClinicalTrials.gov (EudraCT: 2019-003186-18) on March 18, 2019.

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Background: In Iceland, a small number of kidney transplants from living donors (LDs) are performed at Landspitali University Hospital (LUH) in Reykjavik, while deceased donor transplants have until recently invariably been carried out abroad. In this study, we evaluated the outcome of kidney transplantation in Icelandic patients. Methods: This was a retrospective study that included all Icelandic residents who underwent kidney transplantation between 1 January 2000 and 31 December 2019. Data were obtained from the Icelandic End-Stage Kidney Disease Registry, medical records at LUH, and the Scandiatransplant database. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate from serum creatinine for recipients and donors aged >18 years, and the modified Schwartz equation for those aged ≤18 years. Survival was estimated using the Kaplan-Meier method, and the log-rank test was employed for group comparisons. Results: A total of 229 kidney transplants in 221 patients were performed during the 20-year period, of which 135 (58.9%) were from LDs. Transplants carried out at LUH were 118 (51.5%), of which 116 were from LDs. During a median follow-up of 7.4 years (range 0.1-20), 27 (12.2%) patients died, 20 (74%) of whom had a functioning graft. One-year patient survival was 99.1% [95% confidence interval (CI), 97.9-100], 5-year survival was 95.7% (95% CI, 92.7-98.7), and 10-year survival was 87.7% (95% CI, 82.4-93.4). Death-censored graft survival was 98.3% (95% CI, 96.6-100), 96.8% (95% CI, 94.4-99.2), and 89.2% (95% CI, 84.1-94.7) at 1, 5, and 10 years, respectively. Conclusions: Patient and graft survival are comparable with those of large transplant centers, demonstrating the feasibility of running a quality kidney transplant program in a small nation in collaboration with a larger center abroad.

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BACKGROUND AND AIM: Plasma exchange (PLEX) improves survival in patients with rodenticidal hepatotoxicity. However, predictors of treatment response are unknown. We aimed at assessing predictors of response to PLEX treatment in these patients. METHODS: Patients with rodenticidal hepatotoxicity from 2014 to 2023 managed in our department were included in this study. Kochi criteria (model for end-stage liver disease [MELD] score ≥ 36 or international normalized ratio [INR] ≥ 6 with hepatic encephalopathy [HE]) derived specifically for rodenticidal hepatotoxicity (PubMed IDentifier [PMID]: 26310868) were used to assess need for liver transplantation. We analyzed predictors of survival at one month. ∆Bilirubin, ∆MELD score and ∆INR were calculated as percentage change of the parameter after third PLEX session (or after last PLEX if < 3 PLEX sessions done) from baseline pre-PLEX value. RESULTS: Of 200 patients with rodenticidal hepatotoxicity, 114 patients were treated with low-volume PLEX (PLEX-LV). No patient had liver transplantation. Of 78 patients who fulfilled Kochi criteria, 32 patients were PLEX-LV eligible and underwent PLEX-LV (M: 10; age: 20.5, 7-70 years; median, range; acute liver failure: 24). Twenty-two (69%; acute liver failure: 14) of the 32 patients were alive at one month. Presence of HE (p = 0.03) and ∆MELD (p < 0.001) were significant predictors on univariate analysis, while ∆MELD (aOR = 0.88, 95% CI: 0.79-0.98, p = 0.01) was the only significant independent predictor of one-month transplant-free survival. Area under receiver operating characteristic (ROC) for ∆MELD was 0.93 (95% CI:0.85-1.00) and a decrease of ≥ 20% in MELD score while on PLEX-LV had 90% sensitivity and 90% specificity in predicting one-month survival. CONCLUSIONS: Decline in MELD while on PLEX-LV independently predicted one-month transplant-free survival in rodenticidal hepatotoxicity patients. This may help guide decision on stopping PLEX-LV in patients predicted to respond to treatment and to consider alternate treatment options in non-responders.

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In this work, chain electrospray ionization (chain-ESI) was developed to efficiently ionize trace samples for mass spectrometry analysis. The primary ion source was found to have the ability to induce secondary electrospray ionization with an extraordinarily low sample consumption rate in the picoliters per minute (pLs/min). This allows low volume sample to generate substantial tandem mass spectrum (MS2) data for metabolite annotations. Notably, chain-ESI can effectively prevent the electro-redox reaction in the process of electrospray, so as to reflect the native state of the analytes. Furthermore, from a single Broussonetia papyrifera (B. papyrifera) trichome and a single A549 cancer cell, 1426 and 617 metabolites were detected respectively. All of those observations demonstrated that chain-ESI offers the advantages of direct, rapid analysis with extreme-low volumes and high coverage, enabling the measurement of bio-information in low volume samples.

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Advances in digital light projection(DLP) based (bio) printers have made printing of intricate structures at high resolution possible using a wide range of photosensitive bioinks. A typical setup of a DLP bioprinter includes a vat or reservoir filled with liquid bioink, which presents challenges in terms of cost associated with bioink synthesis, high waste, and gravity-induced cell settling, contaminations, or variation in bioink viscosity during the printing process. Here, we report a vat-free, low-volume, waste-free droplet bioprinting method capable of rapidly printing 3D soft structures at high resolution using model bioinks and model cells. A multiphase many-body dissipative particle dynamics model was developed to simulate the dynamic process of droplet-based DLP printing and elucidate the roles of surface wettability and bioink viscosity. Process variables such as light intensity, photo-initiator concentration, and bioink formulations were optimized to print 3D soft structures (∼0.4-3 kPa) with a typical layer thickness of 50µm, an XY resolution of 38 ± 1.5µm and Z resolution of 237 ± 5.4µm. To demonstrate its versatility, droplet bioprinting was used to print a range of acellular 3D structures such as a lattice cube, a Mayan pyramid, a heart-shaped structure, and a microfluidic chip with endothelialized channels. Droplet bioprinting, performed using model C3H/10T1/2 cells, exhibited high viability (90%) and cell spreading. Additionally, microfluidic devices with internal channel networks lined with endothelial cells showed robust monolayer formation while osteoblast-laden constructs showed mineral deposition upon osteogenic induction. Overall, droplet bioprinting could be a low-cost, no-waste, easy-to-use, method to make customized bioprinted constructs for a range of biomedical applications.

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PURPOSE: UK NICE guidelines recommend axillary node clearance (ANC) should be performed in all patients with biopsy-proven node-positive breast cancer having primary surgery. There is, however, increasing evidence such extensive surgery may not always be necessary. Targeted axillary dissection (TAD) may be an effective alternative in patients with low-volume nodal disease who are clinically node negative (cN0) but have abnormal nodes detected radiologically. This survey aimed to explore current management of this group to inform feasibility of a future trial. METHODS: An online survey was developed to explore current UK management of patients with low-volume axillary disease and attitudes to a future trial. The survey was distributed via breast surgery professional associations and social media from September to November 2022. One survey was completed per unit and simple descriptive statistics used to summarise the results. RESULTS: 51 UK breast units completed the survey of whom 78.5% (n = 40) reported performing ANC for all patients with biopsy-proven axillary nodal disease having primary surgery. Only 15.7% of units currently performed TAD either routinely (n = 6, 11.8%) or selectively (n = 2, 3.9%). There was significant uncertainty (83.7%, n = 36/43) about the optimal surgical management of these patients. Two-thirds (n = 27/42) of units felt an RCT comparing TAD and ANC would be feasible. CONCLUSIONS: ANC remains standard of care for patients with low-volume node-positive breast cancer having primary surgery in the UK, but considerable uncertainty exists regarding optimal management of this group. This survey suggests an RCT comparing the outcomes of TAD and ANC may be feasible.

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Globally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time-sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR - correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non-coagulopathic resuscitant has profound potential for application in trauma medicine.

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Two-stage revision with an antibiotic-loaded cement articulating spacer is a standard treatment for chronic prosthetic knee infection (PKI); however, mechanical complications can occur during the spacer period. There is limited evidence on the association between surgeon volume and mechanical complications after resection arthroplasty (RA) using an articulating spacer. This study aimed to compare the rates of mechanical complications and reoperation after RA with articulating spacers by surgeons with high volumes (HV) and low volumes (LV) of RA performed and analyzed the risk factors for mechanical failure. The retrospective study investigated 203 patients treated with PKIs who underwent RA with articulating spacers and were divided according to the number of RAs performed by the surgeons: HV (≥14 RAs/year) or LV (<14 RAs/year). Rates of mechanical complications and reoperations were compared. Risk factors for mechanical complications were analyzed. Of the 203 patients, 105 and 98 were treated by two HV and six LV surgeons, respectively. The mechanical complication rate was lower in HV surgeons (3.8%) than in LV surgeons (36.7%) (p < 0.001). The reoperation rate for mechanical complications was lower in HV surgeons (0.9%) than in LV surgeons (24.5%) (p < 0.001). Additionally, 47.2% of patients required hinge knees after mechanical spacer failure. Medial proximal tibial angle < 87°, recurvatum angle > 5°, and the use of a tibial spacer without a cement stem extension were risk factors for mechanical complications. Based on these findings, we made the following three conclusions: (1) HV surgeons had a lower rate of mechanical complications and reoperation than LV surgeons; (2) mechanical complications increased the level of constraint in final revision knee arthroplasty; and (3) all surgeons should avoid tibial spacer varus malalignment and recurvatum deformity and always use a cement stem extension with a tibial spacer.

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This study aims to determine the impact of 2 (low vs high volume) high-intensity interval training (HIIT) programs with Mediterranean diet (MedDiet) recommendations on health-related quality of life (HRQoL) and lifestyle modification, and to examine the relationships between the changes in anxiety and depression with HRQoL and lifestyle variables after myocardial infarction (MI). Participants (n = 80) were randomized to attention control or one of the two supervised HIIT groups (2 d/weeks). Surveys before and after intervention (16 weeks): HRQoL (SF-36), anxiety and depression (HADS), MedDiet adherence (MEDAS), and physical activity (PA) and sedentary behavior (SB) levels. After intervention, there were improvements (P < .05) in HRQoL, HADS scores, and MedDiet adherence, with higher PA level in both HIIT groups with no between-HIIT group differences. The HADS score decline correlated (P < .05) with both the increase in physical component of SF-36 (r = .42), the overall metabolic expenditure (r = .26), and adherence to the MedDiet (r = .24), and the reduction in the SB (r = .35). HIIT exercise intervention with MedDiet recommendations improved HRQoL, along with reduced anxiety and depression symptoms, and a healthier lifestyle after MI. Better mental health was related to higher values of PA and MedDiet adherence.

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BACKGROUND: Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen-induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV-TPE) efficacy in improving the transplant free survival in YP poisoning. METHODS: Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV-TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV-TPE details were captured. The study end point was clinical outcome of the patients. RESULTS: Among 36 patients, 19 underwent LV-TPE and 17 opted out of LV-TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV-TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV-TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. CONCLUSION: A well-timed LV-TPE improves the survival of patients with ALF due to YP poisoning.

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BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

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