External validation and comparison of magnetic resonance imaging-based risk prediction models for prostate biopsy stratification.

PURPOSE: Magnetic resonance imaging (MRI) is a promising tool for risk assessment, potentially reducing the burden of unnecessary prostate biopsies. Risk prediction models that incorporate MRI data have gained attention, but their external validation and comparison are essential for guiding clinical practice. The aim is to externally validate and compare risk prediction models for the diagnosis of clinically significant prostate cancer (csPCa). METHODS: A cohort of 4606 patients across fifteen European tertiary referral centers were identified from a prospective maintained database between January 2016 and April 2023. Transrectal or transperineal image-fusion MRI-targeted and systematic biopsies for PI-RADS score of ≥ 3 or ≥ 2 depending on patient characteristics and physician preferences. Probabilities for csPCa, defined as International Society of Urological Pathology (ISUP) grade ≥ 2, were calculated for each patients using eight models. Performance was characterized by area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Subgroup analyses were performed across various clinically relevant subgroups. RESULTS: Overall, csPCa was detected in 2154 (47%) patients. The models exhibited satisfactory performance, demonstrating good discrimination (AUC ranging from 0.75 to 0.78, p < 0.001), adequate calibration, and high net benefit. The model described by Alberts showed the highest clinical utility for threshold probabilities between 10 and 20%. Subgroup analyses highlighted variations in models' performance, particularly when stratified according to PSA level, biopsy technique and PI-RADS version. CONCLUSIONS: We report a comprehensive external validation of risk prediction models for csPCa diagnosis in patients who underwent MRI-targeted and systematic biopsies. The model by Alberts demonstrated superior clinical utility and should be favored when determining the need for a prostate biopsy.

The impact of prostate volume estimation on the risk-adapted biopsy decision based on prostate-specific antigen density and magnetic resonance imaging score.

PURPOSE: Utility of prostate-specific antigen density (PSAd) for risk-stratification to avoid unnecessary biopsy remains unclear due to the lack of standardization of prostate volume estimation. We evaluated the impact of ellipsoidal formula using multiparametric magnetic resonance (MRI) and semi-automated segmentation using tridimensional ultrasound (3D-US) on prostate volume and PSAd estimations as well as the distribution of patients in a risk-adapted table of clinically significant prostate cancer (csPCa). METHODS: In a prospectively maintained database of 4841 patients who underwent MRI-targeted and systematic biopsies, 971 met inclusions criteria. Correlation of volume estimation was assessed by Kendall's correlation coefficient and graphically represented by scatter and Bland-Altman plots. Distribution of csPCa was presented using the Schoots risk-adapted table based on PSAd and PI-RADS score. The model was evaluated using discrimination, calibration plots and decision curve analysis (DCA). RESULTS: Median prostate volume estimation using 3D-US was higher compared to MRI (49cc[IQR 37-68] vs 47cc[IQR 35-66], p < 0.001). Significant correlation between imaging modalities was observed (τ = 0.73[CI 0.7-0.75], p < 0.001). Bland-Altman plot emphasizes the differences in prostate volume estimation. Using the Schoots risk-adapted table, a high risk of csPCa was observed in PI-RADS 2 combined with high PSAd, and in all PI-RADS 4-5. The risk of csPCa was proportional to the PSAd for PI-RADS 3 patients. Good accuracy (AUC of 0.69 and 0.68 using 3D-US and MRI, respectively), adequate calibration and a higher net benefit when using 3D-US for probability thresholds above 25% on DCA. CONCLUSIONS: Prostate volume estimation with semi-automated segmentation using 3D-US should be preferred to the ellipsoidal formula (MRI) when evaluating PSAd and the risk of csPCa.

The cytokine receptor Fn14 is a molecular brake on neuronal activity that mediates circadian function in vivo.

To survive, organisms must adapt to a staggering diversity of environmental signals, ranging from sensory information to pathogenic infection, across the lifespan. At the same time, organisms intrinsically generate biological oscillations, such as circadian rhythms, without input from the environment. While the nervous system is well-suited to integrate extrinsic and intrinsic cues, how the brain balances these influences to shape biological function system-wide is not well understood at the molecular level. Here, we demonstrate that the cytokine receptor Fn14, previously identified as a mediator of sensory experience-dependent synaptic refinement during brain development, regulates neuronal activity and function in adult mice in a time-of-day-dependent manner. We show that a subset of excitatory pyramidal (PYR) neurons in the CA1 subregion of the hippocampus increase Fn14 expression when neuronal activity is heightened. Once expressed, Fn14 constrains the activity of these same PYR neurons, suggesting that Fn14 operates as a molecular brake on neuronal activity. Strikingly, differences in PYR neuron activity between mice lacking or expressing Fn14 were most robust at daily transitions between light and dark, and genetic ablation of Fn14 caused aberrations in circadian rhythms, sleep-wake states, and sensory-cued and spatial memory. At the cellular level, microglia contacted fewer, but larger, excitatory synapses in CA1 in the absence of Fn14, suggesting that these brain-resident immune cells may dampen neuronal activity by modifying synaptic inputs onto PYR neurons. Finally, mice lacking Fn14 exhibited heightened susceptibility to chemically induced seizures, implicating Fn14 in disorders characterized by hyperexcitation, such as epilepsy. Altogether, these findings reveal that cytokine receptors that mediates inflammation in the periphery, such as Fn14, can also play major roles in healthy neurological function in the adult brain downstream of both extrinsic and intrinsic cues.

Presence of pharmaceutical contaminants of emerging concerns in two rivers of western Cuba and their relationship with the extracellular enzymatic activity of microbial communities.

In recent years, the concern derived from the presence of emerging contaminants in the environment and the possible effects on the One Health trilogy has increased. This study determined the concentration of pharmaceutical contaminants of emerging concern and their relationship with the extracellular enzymatic activity of microbial communities from two rivers in western Cuba. Two sampling stations were analyzed; one in the Almendares River (urban) and the other in the San Juan River (rural), taking into account the pollution sources that arrive at these stations and previous physicochemical characterizations. Extracellular protease, acid phosphatase, alkaline phosphatase, lipase, and catalase activities in water and sediments were determined and correlated with contaminants of emerging concern determined by liquid chromatography with mass spectrometry. This study evidenced the presence of different pharmaceutical contaminants found in the categories of antihypertensives, stimulants, anti-inflammatories, and antibiotics in both rivers. Concentrations of contaminants of emerging concern were greater in the Almendares River compared to the San Juan River. In addition, through the canonical redundancy analysis, the influence of these contaminants on the extracellular enzymatic activities of microbial communities was documented, where in most cases they inhibit protease, phosphatase, and lipase activities and enhance catalase activity in response to oxidative stress. The present investigation constitutes the first report in Cuba of the presence of pharmaceutical contaminants of emerging concern and one of the few works that exist in the Latin American region.

Radiographic Study of Transcrestal Sinus Floor Elevation Using Osseodensification Technique with Graft Material: A Pilot Study.

This pilot study aimed to evaluate the level of implant success after transcrestal sinus floor elevation (tSFE) using the osseodensification technique (OD) combined with beta-tricalcium phosphate (ß-TCP) by analyzing clinical and radiographic results. Moreover, the increase in bone height was analyzed immediately after surgery, 3 months after, and before loading by taking standardized radiographic measurements. Thirteen patients, four males and nine females, with a mean age of 54.69 ± 5.86 years, requiring the placement of one implant in the upper posterior maxilla, with a residual bone height of <8 mm and a minimum bone width of 5 mm, participated in the study. The bone gain data was obtained using cone-beam computed tomography (CBCT) immediately after surgery and twelve months after the placement. The correlation between initial and final bone height with implant stability was also assessed. The results were analyzed using SPSS 23 software (p < 0.05). The results of the study indicated a 100% implant success rate after a follow-up period of twelve months. Preoperative main bone height was 5.70 ± 0.95 mm. The osseodensification technique allowed a significant increase of 6.65 ± 1.06 mm immediately after surgery. After a twelve-month follow-up, a graft material contraction of 0.90 ± 0.49 mm was observed. No correlation was observed between the bone height at the different times of the study and the primary stability of the implant. Considering the limitations of the size sample of this study, the osseodensification technique used for transcrestal sinus lift with the additional bone graft material (ß-TCP) may provide a predictable elevation of the maxillary sinus floor, allowing simultaneous implant insertion with adequate stability irrespective of bone height limitations.

Are lead, cadmium and mercury risk factors for resistant hypertension?

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) AIMS: To compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. METHODS: Cross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. RESULTS: 46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7-5.2) vs. rHT 3.6 (IQR 2.8-6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07-0.80) vs. rHT 0.30 (IQR 0.07-0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8-12.9) vs. rHT 7.3 (IQR 4.6-13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84-14.10, p=0.086) for Pb, OR = 1.80 (0.39-8.24, p=0.451), for Cd and OR = 2.31 (0.59-9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8-200.2), p=0.072). CONCLUSION: A higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg.

Effect of a nutraceutical combination on sleep quality among people with impaired sleep: a randomised, placebo-controlled trial.

In this randomised, placebo-controlled trial, adults with impaired sleep (Pittsburgh Sleep Quality Index ≥ 5) were randomly assigned using a minimization algorithm to receive a formulation containing L-theanine plus lemon balm, valerian, and saffron extracts, or placebo, during 6 weeks. Objective sleep quality parameters were measured using an actigraphy device. We enrolled and randomised 64 individuals, 31 from the active group and 27 from the placebo group completed the 6 week follow-up. Mean sleep efficiency remained unmodified in the active group, and increased by 3% in the placebo group, the between-group difference in the change was not statistically significant (p = 0.49). Total sleep time also improved more with placebo (13.0 vs. 1.33 min, p = 0.66). Time wake after sleep onset (WASO) decreased more in the active group (4.6% vs. 2.4%), but the difference was not significant (p = 0.33). Mean PSQI decreased by 3.11 points (32.3%) in the active group, and by 3.86 points (39.5%) in the placebo group (p = 0.41). SF-36 increased more with placebo (+ 18.3 in active, + 32.1 in placebo, p = 0.68). Salivary cortisol remained unchanged in both groups. No serious adverse events were reported. Among adults with impaired sleep, a nutraceutical combination did not improve objective or subjective sleep parameters more than a placebo infusion.

Treatment and Diagnostic Approach for Lhermitte-Duclos Disease and Suspected Cowden Syndrome.

Lhermitte-Duclos disease (LDD) is a rare entity, which may or may not be associated with Cowden syndrome (CS). The authors present a 26-year-old male with a history of emergency treatment due to acute obstructive hydrocephalus and apparent Chiari malformation. In posterior evaluation, mild cerebellar symptoms, mucocutaneous lesions, and a left hemispheric cerebellar lesion were evident. Initially, with the clinical evidence and the radiological study report of a cerebellar tiger-striped lesion, LDD with associated CS was suspected, and a genetic protocol was performed. The protocol included an endoscopy and thyroid ultrasound, and with symptom progression, a new neurosurgical procedure was performed. To complete the approach, we used the clinical criteria for PTEN hamartoma tumor syndrome established in 2013, and CS was diagnosed in the patient. In patients with radiological and clinical suspicion of LDD and CS, it should be mandatory to investigate the presence of other types of tumors due to their association with PTEN hamartomatous tumor syndrome, and in the absence of genetic study, the clinical criteria previously established in the literature should be sufficient to establish the diagnosis.

A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.

BACKGROUND: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. METHODS: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice. FINDINGS: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. INTERPRETATION: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC. FUNDING: The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the "European Union Next Generation EU/PRTR," the Regional Government of Castile and León (CSI144P20), European Union.

Transperineal or Transrectal Magnetic Resonance Imaging-targeted Biopsy for Prostate Cancer Detection.

BACKGROUND AND OBJECTIVE: A notable paradigm shift has emerged in the choice of prostate biopsy approach, with a transition from transrectal biopsy (TRBx) to transperineal biopsy (TPBx) driven by the lower risk of severe urinary tract infections. The impact of this change on detection of clinically significant prostate cancer (csPCa) remains a subject of debate. Our aim was to compare the csPCa detection rate of TRBx and TPBx. METHODS: Patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for clinically localized PCa at 15 European referral centers from 2016 to 2023 were included. A propensity score matching (PSM) analysis was performed to minimize selection biases. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). KEY FINDINGS AND LIMITATIONS: Of 3949 patients who met the study criteria, 2187 underwent TRBx and 1762 underwent TPBx. PSM resulted in 1301 matched pairs for analysis. Patient demographics and tumor characteristics were comparable in the matched cohorts. TPBx versus TRBx was associated with greater detection of csPCa, whether defined as International Society of Urological Pathology grade group ≥2 (51% vs 45%; OR 1.37, 95% CI 1.15-1.63; p = 0.001) or grade group ≥3 (29% vs 23%; OR 1.38, 95% CI 1.13-1.67; p = 0.001). Similar results were found when considering MRI-targeted biopsy alone and after stratifying patients according to tumor location, Prostate Imaging-Reporting and Data System score, and clinical features. Limitations include the retrospective nature of the study and the absence of centralized MRI review. CONCLUSIONS: Our findings bolster existing understanding of the additional advantages offered by TPBx. Further randomized trials to fully validate these findings are awaited. PATIENT SUMMARY: We compared the rate of detection of clinically significant prostate cancer with magnetic resonance imaging (MRI)-guided biopsies in which the sample needle is passed through the perineum or the rectum. Our results suggest that the perineal approach is associated with better detection of aggressive prostate cancer.

Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human.

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects. Here, we report that cabergoline, a dopaminergic agonist, reduces the risk of breast cancer post-pregnancy in a Brca1/P53-deficient mouse model, with implications for human breast cancer prevention. We show that a single dose of cabergoline administered post-pregnancy significantly delayed the onset and reduced the incidence of breast cancer in Brca1/P53-deficient mice. Histological analysis revealed a notable acceleration in post-lactational involution over the short term, characterized by increased apoptosis and altered gene expression related to ion transport. Over the long term, histological changes in the mammary gland included a reduction in the ductal component, decreased epithelial proliferation, and a lower presence of recombinant Brca1/P53 target cells, which are precursors of tumors. These changes serve as indicators of reduced breast cancer susceptibility. Additionally, RNA sequencing identified gene expression alterations associated with decreased proliferation and mammary gland branching. Our findings highlight a mechanism wherein cabergoline enhances the protective effect of pregnancy against breast cancer by potentiating postlactational involution. Notably, a retrospective cohort study in women demonstrated a markedly lower incidence of post-pregnancy breast cancer in those treated with cabergoline compared to a control group. Our work underscores the importance of enhancing postlactational involution as a strategy for breast cancer prevention, and identifies cabergoline as a promising, low-risk option in breast cancer chemoprevention. This strategy has the potential to revolutionize breast cancer prevention approaches, particularly for women at increased risk due to genetic factors or delayed childbirth, and has wider implications beyond hereditary breast cancer cases.

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H's (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

The Added Value of Side-specific Systematic Biopsy in Patients Diagnosed by Magnetic Resonance Imaging-targeted Prostate Biopsy.

BACKGROUND: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa). OBJECTIVE: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion. DESIGN, SETTING, AND PARTICIPANTS: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2. RESULTS AND LIMITATIONS: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set. CONCLUSIONS: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy. PATIENT SUMMARY: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.

Refining clinically relevant cut-offs of prostate specific antigen density for risk stratification in patients with PI-RADS 3 lesions.

BACKGROUND: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy. METHODS: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis. RESULTS: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%). CONCLUSIONS: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.

Split-night polysomnography at Fundación Santa Fe de Bogotá / Caracterización de estudios de noche partida en la Fundación Santa Fe de Bogotá

Abstract Introduction: The obstructive sleep apnea-hypopnea syndrome (OSAHS) is usually established using polysomnography (PSG). Most patients diagnosed with this condition receive treatment with continuous positive airway pressure (CPAP). The conventional approach requires performing a full-night PSG and CPAP titration over a two-night stay in a sleep laboratory, which is costly and may present scheduling difficulties. However, the combined use of polysomnography and CPAP titration in a single night, procedure known as split-night polysomnography (SNPSG), is less-expensive and is a time saving strategy for diagnosis and treatment. Objectives: To characterize the SNPSG studies conducted in the sleep laboratory of the Hospital Universitario Santa Fe de Bogotá (HUFSFB) and assess their performance in the diagnosis and treatment of OSAHS. Materials and methods: Retrospective, observational and longitudinal study performed on a sample of 221 patients. Results: 208 (94.1%) SNPSG studies were compatible with OSAHS. Most cases (54.7%) had a hypopnea apnea index (AHI) ≥30. Adequate CPAP titration was achieved in 78% of patients who had severe AHI (p=0.00). Conclusions: OSAHS was diagnosed and an adequate CPAP titration was achieved in most of the SNPSG studies of the analyzed sample.

Resumen Introducción. El diagnóstico del síndrome de apnea/hipopnea obstructiva del sueño (SAHOS) se realiza mediante estudio de polisomnografía (PSG) y la mayoría de los pacientes con este diagnóstico recibe tratamiento con presión aérea positiva continua (CPAP). Este abordaje convencional requiere dos estudios de PSG: uno diagnóstico y otro de titulación. El uso combinado de PSG diagnóstica y de titulación en una sola noche, conocido como noche partida (PSGNP), es una alternativa diagnóstica y terapéutica válida que optimiza la utilización de tiempo y recursos. Objetivo. Caracterizar los estudios de PSGNP realizados en el laboratorio de sueño del Hospital Universitario de la Fundación Santa Fe de Bogotá (HUFSFB) y evaluar su desempeño. Materiales y métodos. Se realizó un estudio observacional analítico de tipo longitudinal retrospectivo de una muestra de 221 pacientes. Resultados. Se registraron 208 (94.1%) estudios de PSGNP compatibles con SAHOS, de los cuales la mayoría de los pacientes (54.7%) presentaron un índice de apnea hipopnea (IAH) >30. En 78% de los pacientes que presentaban IAH severo se logró una titulación adecuada del CPAP (p=0.00). Conclusiones. En la mayor parte de los estudios de PSGNP de la muestra analizada se diagnosticó SAHOS y se consiguió una titulación adecuada del CPAP.

Diferencias entre 2 electrocardiogramas sinusales como predictoras de fibrilación auricular: estudio de cohorte / Variations between 2 ECG as predictors of atrial fibrillation: Cohort study

Resumen Objetivo Evaluar la asociación entre las diferencias de mediciones de 2 ECG separados en el tiempo, con el desarrollo de fibrilación auricular (FA). Método Cohorte retrospectiva de 9,975 pacientes adultos, afiliados a la prepaga del Hospital Italiano de Buenos Aires, Argentina, con realización de al menos 2 ECG sinusales digitales entre 2006-2011. Se siguieron clínicamente para la detección de FA. Todas las mediciones electrocardiográficas y los deltas (diferencias entre los 2 ECG) fueron estandarizadas. Se estimaron los hazard ratio para desarrollo de FA, para cada delta de los distintos componentes electrocardiográficos utilizando un modelo de regresión de Cox. Resultados Durante una mediana de seguimiento de 3,5 años se detectaron 189 episodios de FA. El delta FC, delta intervalo ST y delta amplitud onda P se asociaron significativamente a FA. Ajustado por características clínicas y mediciones de ECG basal, el hazard ratio ajustado para FA fue 0.86 (IC95%: 0.75-0.98, p = 0.024) para delta FC; 1.12 (IC95%0.98-1.27, p = 0.082) para delta intervalo ST; y 1.21 (IC95%: 1.05-1.38, p = 0.006) para delta amplitud onda P. Conclusiones Las diferencias FC y amplitud onda P, entre mediciones de ECG, predicen FA en forma independiente de características clínicas y mediciones de ECG basal.

Abstract Objetive To evaluate the association between delta variations in the parameters of 2 sinusal ECG with atrial fibrillation (AF) onset. Method Retrospective cohort of 9,975 adult patients and members of the prepaid system at Hospital Italiano de Buenos Aires from Argentina, who had at least 2 sinusal ECG between 2006 and 2011. Population was followed up for detection of AF. All measurements and electrocardiographic deltas (differences between the 2 ECG) were standardized. Hazard ratio (HR) was estimated for the development of AF for each delta of the different ECG parameters using a Cox regression model. Results During a median follow up of 3.5 years, 189 patients (1.89%) developed AF. Heart rate delta, ST interval delta and P wave amplitude were predictors of AF. Hazard ratio Adjusted for clinical characteristics and ECGbasal values was 0,86 (CI95%: 0.75-0.98, p = 0.024) for heart rate delta, 1.12 (CI95%: 0.98-1.27, p = 0.082) for ST interval delta and 1.21 (CI95%: 1.05-1.38, p = 0.006) for P wave amplitude delta. Conclusion Differences of heart rate and P wave amplitude between ECG's measurements may predict AF, independently of clinical features and ECGbasal values.

Response to short term ultraviolet stress in the reef-building coral Pocillopora capitata (Anthozoa: Scleractinia)

Coral reefs are impacted by a range of environmental variables that affect their growth and survival, the main factors being the high irradiance and temperature fluctuations. Specimens of Pocillopora capitata Verrill 1864 were exposed to photosynthetically active radiation (PAR) and ultraviolet radiation (UVR) for 32h under laboratory conditions. We examined lipid peroxidation (MDA), antioxidant enzyme activities (SOD, CAT, GPx and GST), chlorophyll a (Chl a), carotenoid pigments (CPs), mycosporine-like amino acids (MAAs), and expulsion of zooxanthellae. Our results revealed that corals exposed to UVR had relatively low levels of carotenoids and antioxidant enzyme activities compared to those exposed to PAR, as well as lower CPs/Chl a ratios. Although MAAs and CPs are rapidly produced as non-enzymatic antioxidants in response to UVR in corals, these were not sufficient, even in the dark phase of the experiment, to mitigate the damage caused by formation of reactive oxygen species (ROS), which caused breakdown of the symbiotic relationship between the zooxanthellae and the host animal to an extent 33 times greater than in the PAR treatment. In this study, it could be possible to distinguish that, parallel to the short-term adjustments, such as the amount of pigment in the algae or the sensitivity of the photosynthetic response reported in other species of coral, P. capitata exhibits at the enzymatic level a series of responses oriented to resist the effects derived from the propagation of ROS and, thus, to adapt to and maintain its reproductive capacity in shallow oceanic environments that commonly exhibit high UVR levels. Nevertheless, as a result of the inappropriate location of the artificial intercommunication structure of the Juluapan Lagoon with respect to the arrecifal area of study and therefore of the tides influence, other variables, such as the changes in short-term in turbidity, sediment inputs, nutrients, temperature and osmolarity, can act in combination and cause irreversible damage. The implementation of a management plan for the coralline reefs of the Mexican Pacific coast is required. Rev. Biol. Trop. 58 (1): 103-118. Epub 2010 March 01.

Los arrecifes de coral se ven afectados por una serie de variables ambientales que afectan su crecimiento y supervivencia, siendo los principales factores la alta irradiación y las fluctuaciones de temperatura. Los especímenes de Pocillopora capitata Verrill 1864 fueron expuestos a radiación activa fotosintéticamente (PAR) y radiación ultravioleta (RUV) por 32h en condiciones de laboratorio. Nosotros determinamos las concentraciones de peroxidación lipídica (MDA), actividades de enzimas antioxidantes (SOD, CAT, GPx y GST), clorofila a (Chl a), pigmentos carotenoides (CPS), aminoácidos tipo micosporina (MAAS), y la expulsión de las zooxantelas. Nuestros resultados muestran que los corales expuestos a los rayos UV presentaban niveles relativamente bajos de carotenoides y actividad de las enzimas antioxidantes en comparación con los expuestos al PAR, así como tasas de CPs/Chl a bajas. Aunque MAAs y CPs se producen rápidamente como antioxidantes no enzimáticos en respuesta a la radiación ultravioleta en los corales, éstos no fueron suficientes, incluso en la fase oscura del experimento, para mitigar los daños causados por la formación de especies reactivas de oxígeno (ROS), lo que provocó una ruptura en la relación simbiótica entre las zooxantelas y el coral con una relación 33 veces mayor que en el tratamiento de PAR. A nivel enzimático, P capitata presentó una serie de ajustes orientados a resistir los efectos derivados de la propagación de ROS y con ello favorecer su adaptación y capacidad reproductiva en ambientes oceánicos caracterizados por altos niveles de UVR.