Neuromuscular mechanisms for the fast decline in rate of force development with muscle disuse - a narrative review.

The removal of skeletal muscle tension (unloading or disuse) is followed by many changes in the neuromuscular system, including muscle atrophy and loss of isometric maximal strength (measured by maximal force, Fmax). Explosive strength, i.e. the ability to develop the highest force in the shortest possible time, to maximise rate of force development (RFD), is a fundamental neuromuscular capability, often more functionally relevant than maximal muscle strength. In the present review, we discuss data from studies that looked at the effect of muscle unloading on isometric maximal versus explosive strength. We present evidence that muscle unloading yields a greater decline in explosive relative to maximal strength. The longer the unloading duration, the smaller the difference between the decline in the two measures. Potential mechanisms that may explain the greater decline in measures of RFD relative to Fmax after unloading are higher recruitment thresholds and lower firing rates of motor units, slower twitch kinetics, impaired excitation-contraction coupling, and decreased tendon stiffness. Using a Hill-type force model, we showed that this ensemble of adaptations minimises the loss of force production at submaximal contraction intensities, at the expense of a disproportionately lower RFD. With regard to the high functional relevance of RFD on one hand, and the boosted detrimental effects of inactivity on RFD on the other hand, it seems crucial to implement specific exercises targeting explosive strength in populations that experience muscle disuse over a longer time.

A Single Bout of On-Ice Training Leads to Increased Interlimb Asymmetry in Competitive Youth Hockey Athletes.

Interlimb asymmetry (ILA) refers to an anatomical or physiological imbalance between contralateral limbs, which can influence neuromuscular function. Investigating the influence of neuromuscular fatigue on ILA may be critical for optimizing training programs, injury rehabilitation, and sport-specific performance. The purpose of this study was to determine if a single bout of ice hockey-specific exercise creates or exacerbates lower-limb ILA. Before and after an on-ice training session, 33 youth ice-hockey athletes (14.9 [1.7] y; 11 females) performed 3 repetitions of a maximal vertical countermovement jump (CMJ), an eccentric hamstring contraction, and maximal isometric hip adduction and abduction contractions. Force- and power-related variables were analyzed to determine limb-specific neuromuscular function. The on-ice session reduced maximal isometric hip adduction (left: 7.3% [10.3%]; right: 9.5% [9.6%]) and abduction (left: 4.9% [6.9%]; right: 5.0% [8.1%]) force, but did not impair (P ≥ .10) CMJ performance (jump height, relative peak power, braking duration, and total duration). After the on-ice session, ILA was greater for CMJ propulsive impulse (6.3% [2.9%] vs 5.1% [2.6%]), CMJ braking rate of force development (19.3% [7.6%] vs 15.2% [6.4%]), and peak isometric hip adduction force (6.7% [5.5%] vs 6.1% [4.1%]). In conclusion, hockey-specific exercise leads to increased ILA for multiple force-related metrics, which may be a compensatory mechanism to maintain bilateral task performance when fatigued.

Immunity to measles in Italian children and adolescents: a persistent problem in view of measles elimination.

BACKGROUND: Despite efforts to increase coverage by two doses of measles vaccine in Italy, measles continues to circulate, with over 13 000 cases of disease since 2013. This study aimed to evaluate immunity to measles in Italian children and adolescents. METHODS: A total of 378 serum samples from subjects aged 9 months-18 years were collected in Northern, Central and Southern regions of Italy between 2012 and 2016. Specific IgG antibodies against measles were measured by a commercial ELISA kit. RESULTS: The frequency of IgG-positive samples ranged from 10.5% in infants under 1 year to 98.3% in children aged 6-7 years. The frequency of IgG was 72.2% in subjects aged 1-2 years, 85.6% in those aged 3-5 years and 88.3 and 86.8% in those aged 8-10 and 11-18 years, respectively. In Northern Italy, IgG prevalence was consistent with data on vaccination coverage, whereas some differences were observed in samples from subjects aged more than 8 years in Central and Southern Italy. CONCLUSIONS: Our findings confirm that a large proportion of children and adolescents in Italy are still susceptible to measles. While data on first- and second-dose measles vaccination are essential, they are not sufficient to identify susceptible population cohorts to be targeted by vaccination.

Sputum neutrophil elastase associates with microbiota and Pseudomonas aeruginosa in bronchiectasis.

INTRODUCTION: Neutrophilic inflammation is a major driver of bronchiectasis pathophysiology, and neutrophil elastase activity is the most promising biomarker evaluated in sputum to date. How active neutrophil elastase correlates with the lung microbiome in bronchiectasis is still unexplored. We aimed to understand whether active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics. METHODS: An observational, cross-sectional study was conducted at the bronchiectasis programme of the Policlinico Hospital in Milan, Italy, where adults with bronchiectasis were enrolled between March 2017 and March 2019. Active neutrophil elastase was measured on sputum collected during stable state, microbiota analysed through 16S rRNA gene sequencing, molecular assessment of respiratory pathogens carried out through real-time PCR and clinical data collected. RESULTS: Among 185 patients enrolled, decreasing α-diversity, evaluated through the Shannon entropy (ρ -0.37, p<0.00001) and Pielou's evenness (ρ -0.36, p<0.00001) and richness (ρ -0.33, p<0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon entropy as detected between patients with neutrophil elastase ≥20 µg·mL-1 (median 3.82, interquartile range 2.20-4.96) versus neutrophil elastase <20 µg·mL-1 (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with Pseudomonas in the high-elastase group and with Streptococcus in the low-elastase group. Further confirmation of the association of Pseudomonas aeruginosa with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR. CONCLUSIONS: High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection.

UBC-Nepal expedition: acclimatization to high-altitude increases spinal motoneurone excitability during fatigue in humans.

KEY POINTS: Acute exposure and acclimatization to hypoxia are associated with an impairment and partial recovery, respectively, of the capability of the central nervous system to drive muscles during prolonged efforts. Motoneurones play a vital role in muscle contraction and in fatigue, although the effect of hypoxia on motoneurone excitability during exercise has not been assessed in humans. We studied the impact of fatigue on motoneurone excitability in normoxia, acute and chronic exposure (5050 m) to hypoxia. Performance was worse in acute hypoxia but recovered to the normoxic standard in chronic hypoxia, in parallel with an increased excitability of the motoneurones compared to acute exposure to hypoxia. These findings reveal that prolonged hypoxia causes a heightened motoneurone responsiveness during fatiguing exercise; such an adaptation might favour the restoration of performance where low pressures of oxygen are chronically present. ABSTRACT: The fatigue-induced failure of the motor cortex to drive muscles maximally increases in acute hypoxia (AH) compared to normoxia (N) but improves with acclimatization (chronic hypoxia; CH). Despite their importance to muscle output, it is unknown how locomotor motoneurones in humans are affected by hypoxia and acclimatization. Eleven participants performed 16 min of submaximal [25% maximal torque (maximal voluntary contraction, MVC)] intermittent isometric elbow flexions in N, AH (environmental chamber) and CH (7-14 days at 5050 m) (PI O2  = 140, 74 and 76 mmHg, respectively). For each minute of the fatigue protocol, motoneurone responsiveness was measured with cervicomedullary stimulation delivered 100 ms after transcranial magnetic stimulation (TMS) used to transiently silence voluntary drive. Every 2 min, cortical voluntary activation (cVA) was measured with TMS. After the task, MVC torque declined more in AH (∼20%) than N and CH (∼11% and 14%, respectively, P < 0.05), with no differences between N and CH. cVA was lower in AH than N and CH at baseline (∼92%, 95% and 95%, respectively) and at the end of the protocol (∼82%, 90% and 90%, P < 0.05). During the fatiguing task, motoneurone excitability in N and AH declined to ∼65% and 40% of the baseline value (P < 0.05). In CH, motoneurone excitability did not decline and, late in the protocol, was ∼40% higher compared to AH (P < 0.05). These novel data reveal that acclimatization to hypoxia leads to a heightened motoneurone responsiveness during fatiguing exercise. Positive spinal and supraspinal adaptations during extended periods at altitude might therefore play a vital role for the restoration of performance after acclimatization to hypoxia.

UBC-Nepal expedition: peripheral fatigue recovers faster in Sherpa than lowlanders at high altitude.

KEY POINTS: The reduced oxygen tension of high altitude compromises performance in lowlanders. In this environment, Sherpa display superior performance, but little is known on this issue. Sherpa present unique genotypic and phenotypic characteristics at the muscular level, which may enhance resistance to peripheral fatigue at high altitude compared to lowlanders. We studied the impact of gradual ascent and exposure to high altitude (5050 m) on peripheral fatigue in age-matched lowlanders and Sherpa, using intermittent electrically-evoked contractions of the knee extensors. Peripheral fatigue (force loss) was lower in Sherpa during the first part of the protocol. Post-protocol, the rate of force development and contractile impulse recovered faster in Sherpa than in lowlanders. At any time, indices of muscle oxygenation were not different between groups. Muscle contractile properties in Sherpa, independent of muscle oxygenation, were less perturbed by non-volitional fatigue. Hence, elements within the contractile machinery contribute to the superior physical performance of Sherpa at high altitude. ABSTRACT: Altitude-related acclimatisation is characterised by marked muscular adaptations. Lowlanders and Sherpa differ in their muscular genotypic and phenotypic characteristics, which may influence peripheral fatigability at altitude. After gradual ascent to 5050 m, 12 lowlanders and 10 age-matched Sherpa (32 ± 10 vs. 31 ± 11 years, respectively) underwent three bouts (separated by 15 s rest) of 75 intermittent electrically-evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets) of the dominant leg quadriceps, at the intensity which initially evoked 30% of maximal voluntary force. Trains were also delivered at minutes 1, 2 and 3 after the protocol to measure recovery. Tissue oxygenation index (TOI) and total haemoglobin (tHb) were quantified by a near-infrared spectroscopy probe secured over rectus femoris. Superficial femoral artery blood flow was recorded using ultrasonography, and delivery of oxygen was estimated (eDO2 ). At the end of bout 1, peak force was greater in Sherpa than in lowlanders (91.5% vs. 84.5% baseline, respectively; P < 0.05). Peak rate of force development (pRFD), the first 200 ms of the contractile impulse (CI200 ), and half-relaxation time (HRT) recovered faster in Sherpa than in lowlanders (percentage of baseline at 1 min: pRFD: 89% vs. 74%; CI200 : 91% vs. 80%; HRT: 113% vs. 123%, respectively; P < 0.05). Vascular measures were pooled for lowlanders and Sherpa as they did not differ during fatigue or recovery (P < 0.05). Mid bout 3, TOI was decreased (90% baseline) whereas tHb was increased (109% baseline). After bout 3, eDO2 was markedly increased (1266% baseline). The skeletal muscle of Sherpa seemingly favours repeated force production at altitude for similar oxygen delivery compared to lowlanders.

How to Process Sputum Samples and Extract Bacterial DNA for Microbiota Analysis.

Different steps and conditions for DNA extraction for microbiota analysis in sputum have been reported in the literature. We aimed at testing both dithiothreitol (DTT) and enzymatic treatments of sputum samples and identifying the most suitable DNA extraction technique for the microbiota analysis of sputum. Sputum treatments with and without DTT were compared in terms of their median levels and the coefficient of variation between replicates of both DNA extraction yield and real-time PCR for the 16S rRNA gene. Treatments with and without lysozyme and lysostaphin were compared in terms of their median levels of real-time PCR for S. aureus. Two enzyme-based and three beads-based techniques for DNA extraction were compared in terms of their DNA extraction yield, real-time PCR for the 16S rRNA gene and microbiota analysis. DTT treatment decreased the coefficient of variation between replicates of both DNA extraction yield and real-time PCR. Lysostaphin (either 0.18 or 0.36 mg/mL) and lysozyme treatments increased S. aureus detection. One enzyme-based kit offered the highest DNA yield and 16S rRNA gene real-time PCR with no significant differences in terms of alpha-diversity indexes. A condition using both DTT and lysostaphin/lysozyme treatments along with an enzymatic kit seems to be preferred for the microbiota analysis of sputum samples.

Pneumococcal colonization in older adults.

BACKGROUND: Little is known about pneumococcal carrier states in older adults. The main aim of this study was to evaluate pneumococcal colonization patterns among older adults in two centres in Milan, Italy, before the widespread use of the 13-valent pneumococcal vaccine (PCV13) in this age group, to investigate demographic and clinical features that are associated with pneumococcal colonization and to estimate the potential coverage offered by PCV13. RESULTS: Among 417 adults ≥65 years old (171, 41.1 %, ≥75 years), 41 (9.8 %) were pneumococcal carriers. Univariate and multivariate analyses revealed that pneumococcal colonization was significantly less common among individuals with underlying co-morbidities than among those without (odds ratio [OR] 0.453, 95 % confidence interval [CI] 0.235-0.875, p = 0.018; adjusted OR 0.503, 95 % CI 0.255-0.992, p = 0.047). Moreover, among these patients, those with cardiac disease had a significantly lower risk of colonization (OR 0.308, 95 % CI 0.119-0.795, p = 0.015; adjusted OR 0.341, 95 % CI 0.13-0.894, p = 0.029). Only one vaccinated subject who received 23-valent polysaccharide pneumococcal vaccine (PPV23) was colonized. Twenty-five (89.3 %) of the subjects who were <75 years old and 9 (75.0 %) of those who were ≥75 years old were colonized by at least one of the serotypes that is included in PCV13, with serotype 19 F being the most common. Respiratory allergies as well as overall co-morbidities were more common in subjects who were positive for only non-PCV13 serotypes compared with negative subjects and those who were carriers of only PCV13 serotypes. CONCLUSIONS: Although this study included a relatively small number of subjects and has been performed in a limited geographic setting, results showed that pneumococcal colonization in older people is common, and the monitoring of carriers can offer useful information about the circulation of this pathogen among older people and the potential protective effect of pneumococcal vaccines. Because the colonization in most cases involves the strains that are included in PCV13, this vaccine could be useful in the prevention of pneumococcal infections in the overall population of older people. In subjects with respiratory allergies and in those with co-morbidities, the addition of the PPV23 to PCV13 should be recommended. Due to the low vaccination coverage, urgent educational programmes are required to inform older adults and their medical doctors of the risks of pneumococcal infection and the efficacy and safety of the available pneumococcal vaccines.

Measurement of lipocalin-2 and syndecan-4 levels to differentiate bacterial from viral infection in children with community-acquired pneumonia.

BACKGROUND: In this study, we evaluated the lipocalin-2 (LIP2) and syndecan-4 (SYN4) levels in children who were hospitalized for radiologically confirmed CAP in order to differentiate bacterial from viral infection. The results regarding the LIP2 and SYN4 diagnostic outcomes were compared with the white blood cell (WBC) count and C reactive protein (CRP) levels. METHODS: A total of 110 children <14 years old who were hospitalized for radiologically confirmed CAP were enrolled. Serum samples were obtained upon admission and on day 5 to measure the levels of LIP2, SYN4, and CRP as well as the WBC. Polymerase chain reaction of the respiratory secretions and tests on blood samples were performed to detect respiratory viruses, Streptococcus pneumoniae, and Mycoplasma pneumoniae. RESULTS: CAP was considered to be due to a probable bacterial infection in 74 children (67.3 %) and due to a probable viral infection in 16 children (14.5 %). Overall, 84 children (76.4 %) were diagnosed with severe CAP. The mean values of the WBC count and the LIP2 and SYN4 levels did not differ among the probable bacterial, probable viral, and undetermined cases. However, the CRP serum concentrations were significantly higher in children with probable bacterial CAP than in those with probable viral disease (32.2 ± 55.5 mg/L vs 9.4 ± 17.0 mg/L, p < 0.05). The WBC count was the best predictor of severe CAP, but the differences among the studied variables were marginal. The WBC count was significantly lower on day 5 in children with probable bacterial CAP (p < 0.01) and in those with an undetermined etiology (p < 0.01). The CRP and LIP2 levels were significantly lower 5 days after enrollment in all of the studied groups, independent of the supposed etiology of CAP (p < 0.01 for all comparisons). No statistically significant variation was observed for SYN4. CONCLUSIONS: Measuring the LIP2 and SYN4 levels does not appear to solve the problem of the poor reliability of routine laboratory tests in defining the etiology and severity of pediatric CAP. Currently, the CRP levels and WBC, when combined with evaluation of clinical data, can be used to limit the overuse of antibiotics as much as possible and to provide the best treatment to the patient.

Validity and Reliability of Two Field-Based Leg Stiffness Devices: Implications for Practical Use.

Leg stiffness is an important performance determinant in several sporting activities. This study evaluated the criterion-related validity and reliability of 2 field-based leg stiffness devices, Optojump NextR (Optojump) and Myotest ProR (Myotest) in different testing approaches. Thirty-four males performed, on 2 separate sessions, 3 trials of 7 maximal hops, synchronously recorded from a force platform (FP), Optojump and Myotest. Validity (Pearson's correlation coefficient, r; relative mean bias; 95% limits of agreement, 95%LoA) and reliability (coefficient of variation, CV; intraclass correlation coefficient, ICC; standard error of measurement, SEM) were calculated for first attempt, maximal attempt, and average across 3 trials. For all 3 methods, Optojump correlated highly to the FP (range r = .98-.99) with small bias (range 0.91-0.92, 95%LoA 0.86-0.98). Myotest demonstrated high correlation to FP (range r = .81-.86) with larger bias (range 1.92-1.93, 95%LoA 1.63-2.23). Optojump yielded a low CV (range 5.9% to 6.8%), high ICC (range 0.82-0.86), and SEM ranging 1.8-2.1 kN/m. Myotest had a larger CV (range 8.9% to 13.0%), moderate ICC (range 0.64-0.79), and SEM ranging from 6.3 to 8.9 kN/m. The findings present important information for these devices and support the use of a time-efficient single trial to assess leg stiffness in the field.

Paradoxic effects of metformin on endothelial cells and angiogenesis.

The biguanide metformin is used in type 2 diabetes management and has gained significant attention as a potential cancer preventive agent. Angioprevention represents a mechanism of chemoprevention, yet conflicting data concerning the antiangiogenic action of metformin have emerged. Here, we clarify some of the contradictory effects of metformin on endothelial cells and angiogenesis, using in vitro and in vivo assays combined with transcriptomic and protein array approaches. Metformin inhibits formation of capillary-like networks by endothelial cells; this effect is partially dependent on the energy sensor adenosine-monophosphate-activated protein kinase (AMPK) as shown by small interfering RNA knockdown. Gene expression profiling of human umbilical vein endothelial cells revealed a paradoxical modulation of several angiogenesis-associated genes and proteins by metformin, with short-term induction of vascular endothelial growth factor (VEGF), cyclooxygenase 2 and CXC chemokine receptor 4 at the messenger RNA level and downregulation of ADAMTS1. Antibody array analysis shows an essentially opposite regulation of numerous angiogenesis-associated proteins in endothelial and breast cancer cells including interleukin-8, angiogenin and TIMP-1, as well as selective regulation of angiopioetin-1, -2, endoglin and others. Endothelial cell production of the cytochrome P450 member CYP1B1 is upregulated by tumor cell supernatants in an AMPK-dependent manner, metformin blocks this effect. Metformin inhibits VEGF-dependent activation of extracellular signal-regulated kinase 1/2, and the inhibition of AMPK activity abrogates this event. Metformin hinders angiogenesis in matrigel pellets in vivo, prevents the microvessel density increase observed in obese mice on a high-fat diet, downregulating the number of white adipose tissue endothelial precursor cells. Our data show that metformin has an antiangiogenic activity in vitro and in vivo associated with a contradictory short-term enhancement of pro-angiogenic mediators, as well as with a differential regulation in endothelial and breast cancer cells.

The work to swing limbs in humans versus chimpanzees and its relation to the metabolic cost of walking.

Compared to their closest ape relatives, humans walk bipedally with lower metabolic cost (C) and less mechanical work to move their body center of mass (external mechanical work, WEXT). However, differences in WEXT are not large enough to explain the observed lower C: humans may also do less work to move limbs relative to their body center of mass (internal kinetic mechanical work, WINT,k). From published data, we estimated differences in WINT,k, total mechanical work (WTOT), and efficiency between humans and chimpanzees walking bipedally. Estimated WINT,k is ~ 60% lower in humans due to changes in limb mass distribution, lower stride frequency and duty factor. When summing WINT,k to WEXT, between-species differences in efficiency are smaller than those in C; variations in WTOT correlate with between-species, but not within-species, differences in C. These results partially support the hypothesis that the low cost of human walking is due to the concerted low WINT,k and WEXT.

Assessing Muscle Mass in the Orthopedic Clinical Setting: Application of the Ultrasound Sarcopenia Index in Elderly Subjects with a Recent Femoral Fracture.

BACKGROUND: Sarcopenia poses a risk factor for falls, disability, mortality, and unfavorable postoperative outcomes. Recently, the Ultrasound Sarcopenia Index (USI) has been validated to assess muscle mass, and this study aimed to apply the USI in the clinical setting. METHODS: This prospective observational study included 108 patients aged >65 years, hospitalized for proximal femoral traumatic fracture. Patients were divided into two groups based on anamnestic data: patients with independent walking (IW) and patients requiring walking aid (WA) before admission. All the participants received an ultrasound examination. Other parameters evaluated were handgrip strength, limb circumferences, nutrition (MNA), and activity of daily living (ADL) scores. RESULTS: Fifty-six IW patients (83 ± 6 y; 38 females) and 52 WA patients (87 ± 7 y; 44 females) were recruited. The USI was significantly higher in the IW group compared to the WA group (p = 0.013, Cohen's d = 0.489). Significant correlations were found between the USI and other sarcopenia-associated parameters, such as handgrip strength, MNA, ADLs, other muscle ultrasound parameters, and limb circumferences. CONCLUSION: The application of the USI in the orthopedic surgery setting is feasible and might support the diagnosis of sarcopenia when combined with other measures of strength and function.

Non-transcriptional control of DNA replication by c-Myc.

The c-Myc proto-oncogene encodes a transcription factor that is essential for cell growth and proliferation and is broadly implicated in tumorigenesis. However, the biological functions required by c-Myc to induce oncogenesis remain elusive. Here we show that c-Myc has a direct role in the control of DNA replication. c-Myc interacts with the pre-replicative complex and localizes to early sites of DNA synthesis. Depletion of c-Myc from mammalian (human and mouse) cells as well as from Xenopus cell-free extracts, which are devoid of RNA transcription, demonstrates a non-transcriptional role for c-Myc in the initiation of DNA replication. Overexpression of c-Myc causes increased replication origin activity with subsequent DNA damage and checkpoint activation. These findings identify a critical function of c-Myc in DNA replication and suggest a novel mechanism for its normal and oncogenic functions.

UBC-Nepal Expedition: Motor Unit Characteristics in Lowlanders Acclimatized to High Altitude and Sherpa.

INTRODUCTION: With acclimatization to high altitude (HA), adaptations occur throughout the nervous system and at the level of the muscle, which may affect motor unit (MU) characteristics. However, despite the importance of MUs as the final common pathway for the control of voluntary movement, little is known about their adaptations with acclimatization. METHODS: Ten lowlanders and Sherpa participated in this study 7 to 14 d after arrival at HA (5050 m), with seven lowlanders repeating the experiment at sea level (SL), 6 months after the expedition. The maximal compound muscle action potential (M max ) was recorded from relaxed biceps brachii. During isometric elbow flexions at 10% of maximal torque, a needle electrode recorded the MU discharge rate (MUDR) and MU potential (MUP) characteristics of single biceps brachii MUs. RESULTS: Compared with SL, acclimatized lowlanders had ~10% greater MUDR, ~11% longer MUP duration, as well as ~18% lower amplitude and ~6% greater duration of the first phase of the M max (all P < 0.05). No differences were noted between SL and HA for variables related to MUP shape (e.g., jitter, jiggle; P > 0.08). Apart from lower near-fiber MUP area for Sherpa than acclimatized lowlanders ( P < 0.05), no M max or MU data were different between groups ( P > 0.10). CONCLUSIONS: Like other components of the body, MUs in lowlanders adapt with acclimatization to HA. The absence of differences between acclimatized lowlanders and Sherpa suggests that evolutionary adaptations to HA are smaller for MUs than components of the cardiovascular or respiratory systems.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.