Correlation dimension of high-dimensional and high-definition experimental time series.

The correlation dimension (CD) is a nonlinear measure of the complexity of invariant sets. First introduced for describing low-dimensional chaotic attractors, it has been later extended to the analysis of experimental electroencephalographic (EEG), magnetoencephalographic (MEG), and local field potential (LFP) recordings. However, its direct application to high-dimensional (dozens of signals) and high-definition (kHz sampling rate) 2HD data revealed a controversy in the results. We show that the need for an exponentially long data sample is the main difficulty in dealing with 2HD data. Then, we provide a novel method for estimating CD that enables orders of magnitude reduction of the required sample size. The approach decomposes raw data into statistically independent components and estimates the CD for each of them separately. In addition, the method allows ongoing insights into the interplay between the complexity of the contributing components, which can be related to different anatomical pathways and brain regions. The latter opens new approaches to a deeper interpretation of experimental data. Finally, we illustrate the method with synthetic data and LFPs recorded in the hippocampus of a rat.

Which protocol for prostate biopsies in patients with a positive MRI? Interest of systematic biopsies by sectors.

BACKGROUND: Current prostate biopsy (PBx) protocol for prostate cancer (PCa) diagnosis is to perform systematic biopsies (SBx) combined with targeted biopsies (TBx) in case of positive MRI (i.e. PI-RADS ≥ 3). To assess the utility of performing SBx in combination with TBx, we determined the added value of SBx brought to the diagnosis of PCa according to their sextant location and MRI target characteristics. METHODS: In our local prospectively collected database, we conducted a single-center retrospective study including all patients with a suspicion of PCa, who underwent transrectal ultrasound-guided (TRUS) prostate biopsies (PBx) with a prior MRI and a single lesion classified as PI-RADS ≥ 3. We have characterized the SBx according to their location on MRI: same sextant (S-SBx), adjacent sextant (A-SBx), ipsilateral side (I-SBx) and contralateral side (C-SBx). The added value of SBx and TBx was defined as any upgrading to significant PCa (csPCa) (ISUP ≥2). RESULTS: 371 patients were included in the study. The added value of SBx was 10% overall. Regarding the lesion location and the SBx sextant, the added value of SBx was: 5.1% for S-SBx, 5.4% for A-SBx, 4.9% for I-SBx and 1.9% for C-SBx. The overall added value of SBx was 6.8% for PI-RADS 3 lesions, 14% for PI-RADS 4 lesions and 6.7% for PI-RADS 5 lesions (p = 0.063). The added value of SBx for contralateral side was 1.9% (2/103), 3.1% (5/163) and 0% (0/105) for PI-RADS 3, PI-RADS 4 and PI-RADS 5 lesions, respectively (p = 0,4). The added value of SBx was lower when the number of TBx was higher (OR 0.57; CI 95% 0.37-0.85; p = 0.007). CONCLUSIONS: Our results suggest that the utility of performing SBx in the contralateral lobe toward the MRI lesion was very low, supporting that they might be avoided.

Solid herbal extract of Primula veris L. improves morphofunctional condition of rats' myocardium in chronic alcohol intoxication.

Background and aim: Chronic alcohol intoxication (CAI) induces heart damage. One of the promising ways of its treatment involves the administration of herbal medicinal products. The purpose of this study was to explore the effect of solid herbal extract of Primula veris L. (PVSHE) on the morphofunctional changes in rats' myocardium after CAI. Experimental procedure: CAI was simulated for 24 weeks. Loading testing was used to assess the functional condition of the heart, the functional assessment of mitochondria was based on the polarographic determination of oxygen consumption rate and determination of the indices of lipid peroxidation and antioxidant enzymes activity. We performed a microscopic examination of the left ventricle following the standard protocol of histological processing and h&e staining. Results and conclusion: PVSHE restricts the toxic effects of ethanol on the heart which was indicated by a higher rise in the rates of myocardial contraction (by an average of 3.9 times, P < 0.05) and relaxation (2.6 times under volume load, P < 0.05), LVP (by an average of 1.7 times, P < 0.05) and MISP (by an average of 1.5 times, P < 0.05). PVSHE caused an improvement in the functional state of rats' cardiac mitochondria exposed to CAI, which was demonstrated by on average 1.3-1.4 times (P < 0.05) as high RCR as compared to the control group. The histological examination of the myocardium of the animals treated with PVSHE showed the increase in the volume fraction of cardiac myocytes, and a 31.2% (P < 0.05) decline in the interstitial volume. Therefore, PVSHE has a protective effect on the heart after CAI.

Direct comparison between Grade Group assessed on systematic and MRI/ultrasound fusion targeted biopsies correlated to the radical prostatectomy specimens in patients with prostate cancer.

OBJECTIVES: To compare the correlation of Gleason score (GS) and ISUP grade determined by prostate biopsies (PBx) and radical prostatectomy (RP) specimens according to the biopsy technique: ultrasound randomised (RBx) vs. MRI/ultrasound fusion targeted (TBx). MATERIALS AND METHODS: Between March 2013 and June 2018, we retrospectively included patients who underwent RP for prostate cancer (PCa) histopathologically proven by RBx and/or TBx. All patients had a prebiopsy MRI by a single radiologist (using PI-RADS score), then transrectal RBx (12cores, blinded to MRI lesions) and TBx (2-4 cores/target) with elastic MRI/ultrasound fusion (UroStation™, Koelis, Grenoble, France). Histological findings were compared: PBx vs. RP. RESULTS: One hundred and four patients underwent RP after RBx and/or TBx. ISUP concordance rate was better with the association RBx+TBx 49% (51/104) vs. 43.3% with TBx (P=0.07) and 43.3% with RBx (P=0.13). With RBx, 50% of the patients were downgraded (52/104) against 42.3% (44/104) with TBx (P=0.088). The association RBx+TBx significantly decreased the rate of downgrading of the ISUP score compared to the ISUP score of RP 35.6% (37/104) vs. RBx (50%, P=0.0001) and vs. TBx (42.3%, P=0.016). CONCLUSION: In half of cases, the ISUP score was underestimated in RBx compared to RP specimens. Adding TBx to RBx significantly reduced downgrading. The combination of both biopsy techniques appeared to be the best protocol to get closer to ISUP score and GS of the RP specimens. LEVEL OF EVIDENCE: C.

Site-dependent shaping of field potential waveforms.

The activity of neuron populations gives rise to field potentials (FPs) that extend beyond the sources. Their mixing in the volume dilutes the original temporal motifs in a site-dependent manner, a fact that has received little attention. And yet, it potentially rids of physiological significance the time-frequency parameters of individual waves (amplitude, phase, duration). This is most likely to happen when a single source or a local origin is erroneously assumed. Recent studies using spatial treatment of these signals and anatomically realistic modeling of neuron aggregates provide convincing evidence for the multisource origin and site-dependent blend of FPs. Thus, FPs generated in primary structures like the neocortex and hippocampus reach far and cross-contaminate each other but also, they add and even impose their temporal traits on distant regions. Furthermore, both structures house neurons that act as spatially distinct (but overlapped) FP sources whose activation is state, region, and time dependent, making the composition of so-called local FPs highly volatile and strongly site dependent. Since the spatial reach cannot be predicted without source geometry, it is important to assess whether waveforms and temporal motifs arise from a single source; otherwise, those from each of the co-active sources should be sought.

In Vitro Wear of Glass-Ionomer Containing Restorative Materials.

STATEMENT OF PROBLEM: Advertisements of glass-ionomer-containing restorative materials recommend suitability as load-bearing permanent or semi-permanent restorations. Historically, unacceptably high wear rates limit clinical indications of glass-ionomer-containing restorations in this regard. OBJECTIVE: To compare the in vitro wear of contemporary glass-ionomer-containing dental materials commercially advertised for use in permanent dentition as load-bearing restorations in a chewing simulator. Resin composite was tested as a control. METHODS AND MATERIALS: A resin-modified glass ionomer (Ionolux, VOCO gmbH), a high viscosity glass-ionomer hybrid system (Equia Forte HT with Equia Coat, GC America), and a bioactive ionic resin with reactive glass filler (Activa Bioactive Restorative, Pulpdent) were evaluated. Filtek Supreme Ultra (3M ESPE) is a visible light-activated resin composite that served as a control. Standardized flat disk-shaped specimens (n=12/group) were submitted to 500,000 cycles with continuous thermal cycling against steatite antagonists. Volumetric wear was measured at 1000, 10,000, 200,000, and 500,000 cycles. RESULTS: There was a statistically significant difference in mean volumetric wear for Activa Bioactive Restorative (p=0.0081, 95% CI: 0.3973, 0.4982) and Equia Forte HT (p<0.001, 95% CI: 1.2495, 1.8493), but no statistically significant difference in mean volumetric wear for Ionolux (p=0.6653) compared to control. Activa Bioactive Restorative wore approximately 60% less than, and Equia Forte HT twice more than Filtek Supreme Ultra on average, respectively. CONCLUSIONS: Compared to a resin composite, contemporary glass-ionomer-containing restorative materials advertised for use as load-bearing restorations display measurably variable in vitro wear rates.

[Morbidity of extended pelvic lymphadenectomy during robot-assisted laparoscopic prostatectomy for localized cancer prostate]. / Morbidité du curage ganglionnaire pelvien étendu au cours de la prostatectomie totale laparoscopique robot assistée.

OBJECTIVES: To assess the morbidity specific of extended pelvic lymphadenectomy during robot-assisted laparoscopic radical prostatectomy in a 8 year retrospective study. MATERIAL: We carried out a single-center, single-surgeon retrospective study on 342 consecutive patients who underwent a robot-assisted laparoscopic radical prostatectomy and extended pelvic lymphadenectomy, from July 2010 to March 2018. Postoperative complications were recorded up to 3 months after the operation. RESULTS: Thirty (8.8%) patients had at least one complication related to lymphadenectomy including 1 vascular injury (0.3%), 7 injuries of the obturator nerve (2%), 5 venous thromboembolic complications (1.5%) including 4 pulmonary embolisms, 10 symptomatic lymphoceles (2.9%) and 8 lymphoedemas (2.3%). Of these complications, 13 were classified Clavien 1 (43.3%), 8 Clavien 2 (26.7%), 7 Clavien 3a (23.3%) and 2 Clavien 3b (6.7%). In univariate analysis a high age (P=0.04), high BMI (P<0.01) and pT stage (P=0.02) were significantly associated with complication whereas in multivariate analysis, only age (P=0.02) and BMI (P<0.01) lived were. In univariate analysis high BMI (P=0.04) and lymph node involvement (P=0.04) were associated with lymphatic complication. We did not find any other specific risk factor for the other complications. CONCLUSION: With 8.8% of overall complications related to lymphadenectomy and 5% of complication classified Clavien grade 2 or higher, extended pelvic lymphadenectomy was not very morbid. Age and BMI were risk factors for a overall complication. BMI and lymph node involvement were risk factors for lymphatic complications. LEVEL OF PROOF: 4.

Toward Reflective Spiking Neural Networks Exploiting Memristive Devices.

The design of modern convolutional artificial neural networks (ANNs) composed of formal neurons copies the architecture of the visual cortex. Signals proceed through a hierarchy, where receptive fields become increasingly more complex and coding sparse. Nowadays, ANNs outperform humans in controlled pattern recognition tasks yet remain far behind in cognition. In part, it happens due to limited knowledge about the higher echelons of the brain hierarchy, where neurons actively generate predictions about what will happen next, i.e., the information processing jumps from reflex to reflection. In this study, we forecast that spiking neural networks (SNNs) can achieve the next qualitative leap. Reflective SNNs may take advantage of their intrinsic dynamics and mimic complex, not reflex-based, brain actions. They also enable a significant reduction in energy consumption. However, the training of SNNs is a challenging problem, strongly limiting their deployment. We then briefly overview new insights provided by the concept of a high-dimensional brain, which has been put forward to explain the potential power of single neurons in higher brain stations and deep SNN layers. Finally, we discuss the prospect of implementing neural networks in memristive systems. Such systems can densely pack on a chip 2D or 3D arrays of plastic synaptic contacts directly processing analog information. Thus, memristive devices are a good candidate for implementing in-memory and in-sensor computing. Then, memristive SNNs can diverge from the development of ANNs and build their niche, cognitive, or reflective computations.

Spatial Memory in a Spiking Neural Network with Robot Embodiment.

Cognitive maps and spatial memory are fundamental paradigms of brain functioning. Here, we present a spiking neural network (SNN) capable of generating an internal representation of the external environment and implementing spatial memory. The SNN initially has a non-specific architecture, which is then shaped by Hebbian-type synaptic plasticity. The network receives stimuli at specific loci, while the memory retrieval operates as a functional SNN response in the form of population bursts. The SNN function is explored through its embodiment in a robot moving in an arena with safe and dangerous zones. We propose a measure of the global network memory using the synaptic vector field approach to validate results and calculate information characteristics, including learning curves. We show that after training, the SNN can effectively control the robot's cognitive behavior, allowing it to avoid dangerous regions in the arena. However, the learning is not perfect. The robot eventually visits dangerous areas. Such behavior, also observed in animals, enables relearning in time-evolving environments. If a dangerous zone moves into another place, the SNN remaps positive and negative areas, allowing escaping the catastrophic interference phenomenon known for some AI architectures. Thus, the robot adapts to changing world.

Static internal representation of dynamic situations reveals time compaction in human cognition.

INTRODUCTION: The human brain has evolved under the constraint of survival in complex dynamic situations. It makes fast and reliable decisions based on internal representations of the environment. Whereas neural mechanisms involved in the internal representation of space are becoming known, entire spatiotemporal cognition remains a challenge. Growing experimental evidence suggests that brain mechanisms devoted to spatial cognition may also participate in spatiotemporal information processing. OBJECTIVES: The time compaction hypothesis postulates that the brain represents both static and dynamic situations as purely static maps. Such an internal reduction of the external complexity allows humans to process time-changing situations in real-time efficiently. According to time compaction, there may be a deep inner similarity between the representation of conventional static and dynamic visual stimuli. Here, we test the hypothesis and report the first experimental evidence of time compaction in humans. METHODS: We engaged human subjects in a discrimination-learning task consisting in the classification of static and dynamic visual stimuli. When there was a hidden correspondence between static and dynamic stimuli due to time compaction, the learning performance was expected to be modulated. We studied such a modulation experimentally and by a computational model. RESULTS: The collected data validated the predicted learning modulation and confirmed that time compaction is a salient cognitive strategy adopted by the human brain to process time-changing situations. Mathematical modelling supported the finding. We also revealed that men are more prone to exploit time compaction in accordance with the context of the hypothesis as a cognitive basis for survival. CONCLUSIONS: The static internal representation of dynamic situations is a human cognitive mechanism involved in decision-making and strategy planning to cope with time-changing environments. The finding opens a new venue to understand how humans efficiently interact with our dynamic world and thrive in nature.

Laparoscopic Appendectomy Performed by junior SUrgeonS: impact of 3D visualization on surgical outcome. Randomized multicentre clinical trial. (LAPSUS TRIAL).

BACKGROUND: The purpose of this study was to evaluate the effect of 3D visualization applied to laparoscopic appendectomy (LA) performed by young surgeons (YS). We considered both operative features and clinical outcomes, aiming to highlight the benefits that this technology could bring to novice surgeons and their laparoscopic training. METHODS: All the surgical procedures were performed by residents who had performed less than 20 appendectomies prior to the beginning of the study under the supervision of an expert surgeon. At the time of enrolment patients were randomized into two arms: Experimental arm (EA): laparoscopic appendectomy performed with laparoscopic 3D vision technology. Control arm (CA): laparoscopic appendectomy performed with the "standard" 2D technology. The primary endpoint was to find any statistically significant difference in operative time between the two arms. Differences in conversion rate, intra-operative complications, post-operative complications and surgeons' operative comfort were considered as secondary endpoints. RESULTS: We randomized 135 patients into the two study arms. The two groups were homogeneous for demographic characteristics, BMI and ASA scores. The characteristics of clinical presentation and anatomical position showed no significant difference. The operative time was longer in the CA (57.5 vs. 49.6 min, p = 0.048, 95% CI). In the subgroup of complicated appendicitis, this trend toward inferior operative time was confirmed without reaching statistical significance (2D = 60 min, 3D = 49.5 min, p = 0.082 95% CI). No intra-operative complications were observed in either group. The conversion rate was 5.6% (4 patients) in the 2D group and 4.6% (3 patients) in 3D group. CONCLUSION: The utilization of 3D laparoscopy was associated with reduction in operative time without influencing other parameters, in particular without altering the safety profile of the procedure.

The role of tibial nerve stimulation for enhanced postoperative recovery after colorectal surgery: a double-blind, parallel-group, randomized controlled trial.

BACKGROUND: Postoperative ileus (POI) is the most common cause of prolonged hospital stay following abdominal surgery, despite an optimized enhanced recovery after surgery (ERAS) program. The aim of the study was to evaluate the role of postoperative transcutaneous electrical tibial nerve stimulation (TTNS) in the recovery of bowel function and in shortening hospital stay after colonic resection. METHODS: Patients having elective laparoscopic colonic surgery within an ERAS program at our institution between June 2016 and June 2019 were enrolled and randomly assigned to a treatment protocol with TTNS or sham electrical stimulation. The primary endpoint was the time of recovery of gastrointestinal motility, measured as the first passage of stool. Secondary endpoints included: first passage of flatus, length of hospital stay, and complication rate related to the use of TTNS. RESULTS: One hundred and seventy patients who had right hemicolectomy (median age 71 years (range 43-89 years); 47.5% women) and 170 patients who had left colectomy (median age 67 years range (37-92 years); 41.5% women) were enrolled. The only factor significantly affected by TTNS was time to first passage of flatus after right hemicolectomy (reduced from 46 to 33 h, p = 0.04). However, if only patients with low compliance to early oral nutrition (63 of 340; 18.5%) were considered, a statistically significant difference in time until first flatus (p < 0.01) and first bowel movement (p < 0.0001) and a shorter time until discharge (median 5 vs 7 days) were found in both left and right colectomies groups, respectively. CONCLUSIONS: TTNS may have a positive effect on gastrointestinal tract motility and recovery from POI after colorectal surgery in a selected group, who has low compliance with an ERAS program, without increasing the risk of complications.

Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis.

BACKGROUND: We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO). METHODS: Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1-17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14-42 days total). Primary endpoint: protocol-defined clinical improvement by Day 5 in the modified intention-to-treat (MITT) population (confirmed AHO, ≥1 dose of study treatment); differences between study arms were evaluated using a prespecified 15% noninferiority margin for daptomycin. RESULTS: Seventy-three patients per arm received treatment. Pathogens were isolated from 62% of patients (83% methicillin-susceptible Staphylococcus aureus, 9% methicillin-resistant S. aureus [MRSA]). Clinical improvement by Day 5 was observed in 55/71 (78%) daptomycin- and 58/70 (83%) comparator-treated MITT patients (95% confidence interval [CI]: -19.4, 7.4). This difference was not statistically significant; however, daptomycin did not meet the prespecified 15% noninferiority margin, since the lower bound of the 95% CI extended below 15%. Overall, 82% of daptomycin and 87% of comparator patients achieved clinical cure at the test-of-cure visit (secondary endpoint). More comparator patients had treatment-emergent (63% vs. 46%) and treatment-related (18% vs. 7%) adverse events. CONCLUSIONS: Differences between daptomycin and comparator for the primary endpoint were not statistically significant; however, prespecified noninferiority criteria for daptomycin were not met. With insufficient cases of confirmed MRSA, we could not evaluate daptomycin for MRSA AHO. Our nonvalidated protocol design yields valuable information for implementing future trials in AHO (ClinicalTrials.gov NCT01922011).

Universal principles justify the existence of concept cells.

The widespread consensus argues that the emergence of abstract concepts in the human brain, such as a "table", requires complex, perfectly orchestrated interaction of myriads of neurons. However, this is not what converging experimental evidence suggests. Single neurons, the so-called concept cells (CCs), may be responsible for complex tasks performed by humans. This finding, with deep implications for neuroscience and theory of neural networks, has no solid theoretical grounds so far. Our recent advances in stochastic separability of highdimensional data have provided the basis to validate the existence of CCs. Here, starting from a few first principles, we layout biophysical foundations showing that CCs are not only possible but highly likely in brain structures such as the hippocampus. Three fundamental conditions, fulfilled by the human brain, ensure high cognitive functionality of single cells: a hierarchical feedforward organization of large laminar neuronal strata, a suprathreshold number of synaptic entries to principal neurons in the strata, and a magnitude of synaptic plasticity adequate for each neuronal stratum. We illustrate the approach on a simple example of acquiring "musical memory" and show how the concept of musical notes can emerge.

Semantic Knowledge Representation for Strategic Interactions in Dynamic Situations.

Evolved living beings can anticipate the consequences of their actions in complex multilevel dynamic situations. This ability relies on abstracting the meaning of an action. The underlying brain mechanisms of such semantic processing of information are poorly understood. Here we show how our novel concept, known as time compaction, provides a natural way of representing semantic knowledge of actions in time-changing situations. As a testbed, we model a fencing scenario with a subject deciding between attack and defense strategies. The semantic content of each action in terms of lethality, versatility, and imminence is then structured as a spatial (static) map representing a particular fencing (dynamic) situation. The model allows deploying a variety of cognitive strategies in a fast and reliable way. We validate the approach in virtual reality and by using a real humanoid robot.

Spatial Properties of STDP in a Self-Learning Spiking Neural Network Enable Controlling a Mobile Robot.

Development of spiking neural networks (SNNs) controlling mobile robots is one of the modern challenges in computational neuroscience and artificial intelligence. Such networks, being replicas of biological ones, are expected to have a higher computational potential than traditional artificial neural networks (ANNs). The critical problem is in the design of robust learning algorithms aimed at building a "living computer" based on SNNs. Here, we propose a simple SNN equipped with a Hebbian rule in the form of spike-timing-dependent plasticity (STDP). The SNN implements associative learning by exploiting the spatial properties of STDP. We show that a LEGO robot controlled by the SNN can exhibit classical and operant conditioning. Competition of spike-conducting pathways in the SNN plays a fundamental role in establishing associations of neural connections. It replaces the irrelevant associations by new ones in response to a change in stimuli. Thus, the robot gets the ability to relearn when the environment changes. The proposed SNN and the stimulation protocol can be further enhanced and tested in developing neuronal cultures, and also admit the use of memristive devices for hardware implementation.

Diagnostic and therapeutic role of laparoscopy in perforated peptic ulcer in the elderly patients.

AIM: The purpose of this study is to analyze the outcome of elderly patients with perforated peptic ulcer comparing laparoscopic treatment versus open approach. METHODS: In our General and Emergency Surgery Unit in the last 3 years, 20 elderly patients with perforated peptic ulcer were performed. We considered elderly all patients over the age of 65 years (10 females and 10 males; the mean age was 75 years). 16 patients (80%) were submitted to laparoscopic repair with omentoplasty and 4 (20%) to open repair. The patients were classified using the Boye's score which influenced the choice of surgical treatment and the outcoEmergency Romame. The two groups were compared in terms of operative surgery times, complication rate, mortality and postoperative outcomes. DISCUSSION: Perforated peptic ulcer is a common abdominal disease that is treated by surgery. The potential advantages of laparoscopy, both in terms of diagnosis and therapy, are clear and the major advantages may be observed in cases with peritonitis secondary as a perforated peptic ulcer where laparoscopy allows the confirmation of the diagnosis, the identification of the position of the ulcer and the repair. With the age the risks of comorbidities increases multidisease syndrome. Elderly patients suffer from frailty syndrome. All these factors make the elderly patient a major challenge for a laparoscopy treatment. CONCLUSION: The laparoscopic approach is an effective method for treatment of perforated peptic ulcer in the elderly with a great diagnostic and therapeutic role. Nowadays more prospective randomized studies are needed to evaluate the effectiveness of laparoscopic versus open repair.

Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy.

BACKGROUND: Several studies had suggested the potential role of calcium signaling in prostate cancer (PCa) prognosis and agressiveness. We aimed to investigate selected proteins contributing to calcium (Ca2+ ) signaling, (Orai, stromal interaction molecule (STIM), and transient receptor potential (TRP) channels) and involved in cancer hallmarks, as independent predictors of systemic recurrence after radical prostatectomy (RP). METHODS: A case-control study including 112 patients with clinically localized PCa treated by RP between 2002 and 2009 and with at least 6-years' follow-up. Patients were divided into two groups according to the absence or presence of systemic recurrence. Expression levels of 10 proteins involved in Ca2+ signaling (TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, STIM1, STIM2, Orai1, Orai2, and Orai3), were assessed by immunohistochemistry using tissue microarrays (TMAs) constructed from paraffin-embedded PCa specimens. The level of expression of the various transcripts in PCa was assessed using quantitative polymerase chain reaction (qPCR) analysis. RNA samples for qPCR were obtained from fresh frozen tissue samples of PCa after laser capture microdissection on RP specimens. Relative gene expression was analyzed using the 2-▵▵Ct method. RESULTS: Multivariate analysis showed that increased expression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 was significantly associated with a lower risk of systemic recurrence after RP, independently of the prostate-specific antigen (PSA) level, percentage of positive biopsies, and surgical margin (SM) status (P = .007, P = .01, P < .001, P = .0065, P = .007, and P = .01, respectively). For TRPC4, TRPV5, and TRPV6, this association was also independent of Gleason score and pT stage. Moreover, overexpression of TRPV6 and Orai2 was significantly associated with longer time to recurrence after RP (P = .048 and .023, respectively). Overexpression of TRPC4, TRPV5, TRPV6, and Orai2 transcripts was observed in group R- (3.71-, 5.7-, 1.14-, and 2.65-fold increase, respectively). CONCLUSIONS: This is the first study to suggest the independent prognostic value of certain proteins involved in Ca2+ influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.