Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series.

Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities between the stimulated area and other brain regions, or to depression-associated networks. In this longitudinal, retrospective study, four female patients with treatment-resistant depression were implanted for stimulation in the nucleus accumbens area at our center. We analyzed the structural and functional connectivity of the stimulation area: the structural connectivity was investigated with probabilistic tractography; the functional connectivity was estimated by combining patient-specific stimulation volumes and a normative functional connectome. These structural and functional connectivity profiles were then related to four clinical outcome scores. At 1-year follow-up, the remission rate was 66%. We observed a consistent structural connectivity to Brodmann area 25 in the patient with the longest remission phase. The functional connectivity analysis resulted in patient-specific R-maps describing brain areas significantly correlated with symptom improvement in this patient, notably the prefrontal cortex. But the connectivity analysis was mixed across patients, calling for confirmation in a larger cohort and over longer time periods.

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.

Programming of subthalamic nucleus deep brain stimulation with hyperdirect pathway and corticospinal tract-guided parameter suggestions.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. Stimulation of the hyperdirect pathway (HDP) may mediate the beneficial effects, whereas stimulation of the corticospinal tract (CST) mediates capsular side effects. The study's objective was to suggest stimulation parameters based on the activation of the HDP and CST. This retrospective study included 20 Parkinson's disease patients with bilateral STN DBS. Patient-specific whole-brain probabilistic tractography was performed to extract the HDP and CST. Stimulation parameters from monopolar reviews were used to estimate volumes of tissue activated and to determine the streamlines of the pathways inside these volumes. The activated streamlines were related to the clinical observations. Two models were computed, one for the HDP to estimate effect thresholds and one for the CST to estimate capsular side effect thresholds. In a leave-one-subject-out cross-validation, the models were used to suggest stimulation parameters. The models indicated an activation of 50% of the HDP at effect threshold, and 4% of the CST at capsular side effect threshold. The suggestions for best and worst levels were significantly better than random suggestions. Finally, we compared the suggested stimulation thresholds with those from the monopolar reviews. The median suggestion errors for the effect threshold and side effect threshold were 1 and 1.5 mA, respectively. Our stimulation models of the HDP and CST suggested STN DBS settings. Prospective clinical studies are warranted to optimize tract-guided DBS programming. Together with other modalities, these may allow for assisted STN DBS programming.

The effect of medication event reminder monitoring on treatment adherence of TB patients.

BACKGROUND: TB control remains a serious public health problem, compounded by poor treatment adherence, which increases the likelihood of onward transmission. We evaluated the effectiveness of medication event reminder monitoring (MERM) upon treatment adherence in a high TB burden setting.METHODS: We conducted an open-label parallel group randomised controlled trial among pulmonary TB adults. Participants were provided with a MERM device to store their medications. In the intervention arm, the devices were set to provide daily medication intake reminders. Primary outcome was the proportion of patient-months in which at least 6/30 doses were missed. Secondary outcomes included 1) the proportion of patient-months in which at least 14/30 doses were missed, and 2) the proportion of doses missed.RESULTS: Of 2,142 patients screened, 798 (37.3%) met the inclusion criteria and 250 participants were enrolled. The mean ratio (MR) for poor adherence between the intervention and control groups was 0.72 (95% CI 0.55-0.86). The intervention was also associated with a reduction in the proportion of patients missing at least 14/30 doses (MR 0.61, 95% CI 0.54-0.68) and the percentage of total doses missed (MR 0.75, 95% CI 0.68-0.80).CONCLUSION: MERM is effective in improving TB treatment adherence in a resource-limited environment.

Lead-DBS v3.0: Mapping deep brain stimulation effects to local anatomy and global networks.

Following its introduction in 2014 and with support of a broad international community, the open-source toolbox Lead-DBS has evolved into a comprehensive neuroimaging platform dedicated to localizing, reconstructing, and visualizing electrodes implanted in the human brain, in the context of deep brain stimulation (DBS) and epilepsy monitoring. Expanding clinical indications for DBS, increasing availability of related research tools, and a growing community of clinician-scientist researchers, however, have led to an ongoing need to maintain, update, and standardize the codebase of Lead-DBS. Major development efforts of the platform in recent years have now yielded an end-to-end solution for DBS-based neuroimaging analysis allowing comprehensive image preprocessing, lead localization, stimulation volume modeling, and statistical analysis within a single tool. The aim of the present manuscript is to introduce fundamental additions to the Lead-DBS pipeline including a deformation warpfield editor and novel algorithms for electrode localization. Furthermore, we introduce a total of three comprehensive tools to map DBS effects to local, tract- and brain network-levels. These updates are demonstrated using a single patient example (for subject-level analysis), as well as a retrospective cohort of 51 Parkinson's disease patients who underwent DBS of the subthalamic nucleus (for group-level analysis). Their applicability is further demonstrated by comparing the various methodological choices and the amount of explained variance in clinical outcomes across analysis streams. Finally, based on an increasing need to standardize folder and file naming specifications across research groups in neuroscience, we introduce the brain imaging data structure (BIDS) derivative standard for Lead-DBS. Thus, this multi-institutional collaborative effort represents an important stage in the evolution of a comprehensive, open-source pipeline for DBS imaging and connectomics.

Programming of subthalamic nucleus deep brain stimulation for Parkinson's disease with sweet spot-guided parameter suggestions.

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson's disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort of 24 Parkinson's disease patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS' leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest (i) the best lead level, (ii) the best contact, and (iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56%. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41%. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact's effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects.

Adsorptive removal of phosphate from aqueous solutions using low-cost modified biochar-packed column: Effect of operational parameters and kinetic study.

Adsorption in the continuous mode plays a significant role in wastewater treatment. In this study, Mimosa pigra-derived biochar modified with 2 M AlCl3 salt was used to pack a lab-scale column to eliminate PO43- from aqueous solutions. The influence of the operational factors, such as inlet PO43- concentration (25-100 mg/L), flow rate (6-18 mL/min), and biochar bed height (1.5-4.5 cm), on the breakthrough curve was evaluated. The kinetic models of Adam-Bohart and Yoon-Nelson were utilized to analyze the experimental results. The best conditions were determined to be the influent PO43- strength of 50 mg/L, injection speed of 6 mL/min, and column height of 4.5 cm. These results can be applied in the design of large-scale columns for the sequestration of PO43- from wastewater.

[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.

Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor.

OBJECTIVE: The objective of this study was to obtain individual clinical and neuroimaging data of patients undergoing deep brain stimulation (DBS) for essential tremor (ET) from 5 different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS: We analyzed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (for 12 months) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data were used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS: Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement >50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural connectivity-based cerebellothalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a >50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION: Our multicenter ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of DBS in the future. ANN NEUROL 2022;91:602-612.

Patient-Specific Anisotropic Volume of Tissue Activated with the Lead-DBS Toolbox.

Deep brain stimulation is an effective neurosurgical intervention for movement disorders such as Parkinson's disease. Despite its success, the underlying mechanisms are still debated. One tool to better understand them is the Volume of Tissue Activated (VTA), that estimates the region activated by electrical stimulation. Different estimation approaches exist, these typically assume isotropic tissue properties and modelling of anisotropy is often lacking.The present work was aimed at developing and testing a method for patient-specific VTA estimation that incorporated an anisotropic conduction model. Our method was implemented within the open-source toolbox Lead-DBS and is accessible to the public.The present method was further tested with two patient cases and compared to a standard Lead-DBS pipeline for VTA estimation. This showed encouraging similarities in one test scenario and expected differences in another test scenario. Further validation with a wider cohort is warranted.

Characteristics of severe malaria in hospitalized children in Ho Chi Minh City from 2012 to 2019.

In Vietnam, severe malaria is currently rare but is a life-threatening disease. It may be misdiagnosed with other common diseases. This descriptive study aimed to characterize severe malaria and its clinical aspects, as well as outcomes of infected pediatric patients to improve case management. The case-series study was carried out based on medical records of children aged between one month and 15 years with malaria diagnosed by blood smear or rapid diagnostic test. Chi-squared test with the p values less than 0.05 were considered statistically significant. There were 47 cases enrolled in the study. The prevalence of severe malaria was 29.8% (57.1% in children under five). The morbidity was 71.4% in male and 28.6% in female. Common clinical signs of severe malaria were fever (100%), severe anemia (21.4%), hepatomegaly (85.7%), and splenomegaly (71.4%). Common biological abnormalities in severe malaria were anemia, thrombocytopenia, increased liver enzymes, and high CRP level. The severe malaria was mainly caused by P. falciparum (100%). The age range for those infected with P. falciparum was 6.5 ± 4.5 years (min 0.3; max 14.9). The successful rate of treatment was 92.9% with artesunate. Antimalarial treatment time was 9.0 (6 - 12) days for severe malaria, which was twice as many as that for non-severe malaria (p = 0.067). The current clinical and biological findings of severe malaria are different from those in previous times, which make it easy to be overlooked. Therefore, it's important to perform malaria diagnostic tests when there're clinical suggestions of severe malaria, including fever, hepatomegaly or splenomegaly.

Depression, stigma and quality of life in people with drug-susceptible TB and drug-resistant TB in Vietnam.

BACKGROUND: Drug resistance poses a major barrier to global control of TB - a leading infectious cause of death. Depression and stigma occur commonly among people with TB. However, the relationship between drug-resistant forms of TB, depression and stigma are not well understood.OBJECTIVE: To compare depression, stigma and health-related quality of life (HRQoL), among people with drug-susceptible TB (DS-TB) and multidrug-resistant TB (MDR-TB).METHODS: A cross-sectional study of people treated for DS-TB and MDR-TB in four provinces of Vietnam. The survey included a stigma scale (Vietnamese Tuberculosis Stigma Scale), depression scale (9-item Patient Health Questionnaire) and HRQoL scale (Functional Assessment of Chronic Illness Therapy - Tuberculosis). Differences between the two populations were compared using linear regression.RESULTS: Eighty-one people with DS-TB and 315 people with MDR-TB participated in the study. People with MDR-TB had a higher prevalence of depression than those with DS-TB (difference 17.8%, χ² 8.64). The mean depression and stigma scores were higher for people with MDR-TB than those with DS-TB (adjusted difference [AD] 8.6 and 7.6 respectively). People with MDR-TB reported lower HRQoL than those with DS-TB (AD -23.8).CONCLUSION: Depression and stigma are common among people with TB in Vietnam. Strategies to prevent and treat depressive symptoms and stigma in people with TB are critical to a holistic, patient-centred approach to care.

Active case-finding in contacts of people with TB.

BACKGROUND: Exposure to people with TB substantially elevates a person's risk of tuberculous infection and TB disease. Systematic screening of TB contacts enables the early detection and treatment of co-prevalent disease, and the opportunity to prevent future TB disease. However, scale-up of contact investigation in high TB transmission settings remains limited.METHODS: We undertook a narrative review to evaluate the evidence for contact investigation and identify strategies that TB programmes may consider when introducing contact investigation and management.RESULTS: Selection of contacts for priority screening depends upon their proximity and duration of exposure, along with their susceptibility to develop TB. Screening algorithms can be tailored to the target population, the availability of diagnostic tests and preventive therapy, and healthcare worker expertise. Contact investigation may be performed in the household or at communal locations. Local contact investigation policies should support vulnerable patients, and ensure that drop-out during screening can be mitigated. Ethical issues should be anticipated and addressed in each setting.CONCLUSION: Contact investigation is an important strategy for TB elimination. While its epidemiological impact will be greatest in lower-transmission settings, the early detection and prevention of TB have important benefits for contacts and their communities.

Long-Term Outcome and Neuroimaging of Deep Brain Stimulation in Holmes Tremor: A Case Series.

BACKGROUND: Different deep brain stimulation (DBS) targets have been suggested as treatment for patients with pharmacologically refractory Holmes tremor (HT). We report the clinical and quality of life (QoL) long-term (up to nine years) outcome in four patients with HT treated with DBS (in thalamic ventral intermediate nucleus-VIM or in dentato-rubro-thalamic tract-DRTT). MATERIALS AND METHODS: The patients underwent routine clinical evaluations before and after DBS (typically annually). Tremor severity and activities of daily living (ADL) were quantified by the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTMTRS). QoL was assessed using the RAND SF-36-item Health Survey (RAND SF-36). In addition, we computed, in all four patients, the VTA based on the best stimulation settings using heuristic approaches included in the open source toolbox LEAD-DBS. RESULTS: In all patients, tremor and ADL improved significantly at one-year post-DBS follow-up (34-61% improvement in FTMTRS total score compared to baseline). In three out of four patients, the improvement of tremor was sustained no longer than two to three years and only in one patient was sustained up to nine years. In this patient, the largest intersection between VTA and DBS target has been observed. Scores for ADL deteriorated over the course of time, reaching worse levels compared to baseline already during the three-year post-DBS follow-up, in three out of four patients. Physical and mental health component scores of RAND SF-36 had very different outcome between patients and follow-ups and were not associated with tremor-related outcomes. CONCLUSIONS: The benefits of DBS in HT might not be always long lasting. Although QoL slightly improved, this change seemed to be independent of the motor outcome following DBS. The estimation of DBS target and VTA proximity could be a useful tool for DBS clinicians in order to facilitate the DBS programming process and optimize DBS treatment.

Characteristics of severe malaria in hospitalized children in Ho Chi Minh City from 2012 to 2019

@#In Vietnam, severe malaria is currently rare but is a life-threatening disease. It may be misdiagnosed with other common diseases. This descriptive study aimed to characterize severe malaria and its clinical aspects, as well as outcomes of infected pediatric patients to improve case management. The case-series study was carried out based on medical records of children aged between one month and 15 years with malaria diagnosed by blood smear or rapid diagnostic test. Chi-squared test with the p values less than 0.05 were considered statistically significant. There were 47 cases enrolled in the study. The prevalence of severe malaria was 29.8% (57.1% in children under five). The morbidity was 71.4% in male and 28.6% in female. Common clinical signs of severe malaria were fever (100%), severe anemia (21.4%), hepatomegaly (85.7%), and splenomegaly (71.4%). Common biological abnormalities in severe malaria were anemia, thrombocytopenia, increased liver enzymes, and high CRP level. The severe malaria was mainly caused by P. falciparum (100%). The age range for those infected with P. falciparum was 6.5 ± 4.5 years (min 0.3; max 14.9). The successful rate of treatment was 92.9% with artesunate. Antimalarial treatment time was 9.0 (6 – 12) days for severe malaria, which was twice as many as that for non-severe malaria (p = 0.067). The current clinical and biological findings of severe malaria are different from those in previous times, which make it easy to be overlooked. Therefore, it’s important to perform malaria diagnostic tests when there’re clinical suggestions of severe malaria, including fever, hepatomegaly or splenomegaly.

Directional Local Field Potentials in the Subthalamic Nucleus During Deep Brain Implantation of Parkinson's Disease Patients.

Segmented deep brain stimulation leads feature directional electrodes that allow for a finer spatial control of electrical stimulation compared to traditional ring-shaped electrodes. These segmented leads have demonstrated enlarged therapeutic windows and have thus the potential to improve the treatment of Parkinson's disease patients. Moreover, they provide a unique opportunity to record directional local field potentials. Here, we investigated whether directional local field potentials can help identify the best stimulation direction to assist device programming. Four Parkinson's disease patients underwent routine implantation of the subthalamic nucleus. Firstly, local field potentials were recorded in three directions for two conditions: In one condition, the patient was at rest; in the other condition, the patient's arm was moved. Secondly, current thresholds for therapeutic and side effects were identified intraoperatively for directional stimulation. Therapeutic windows were calculated from these two thresholds. Thirdly, the spectral power of the total beta band (13-35 Hz) and its sub-bands low, high, and peak beta were analyzed post hoc. Fourthly, the spectral power was used by different algorithms to predict the ranking of directions. The spectral power profiles were patient-specific, and spectral peaks were found both in the low beta band (13-20 Hz) and in the high beta band (20.5-35 Hz). The direction with the highest spectral power in the total beta band was most indicative of the 1st best direction when defined by therapeutic window. Based on the total beta band, the resting condition and the moving condition were similarly predictive about the direction ranking and classified 83.3% of directions correctly. However, different algorithms were needed to predict the ranking defined by therapeutic window or therapeutic current threshold. Directional local field potentials may help predict the best stimulation direction. Further studies with larger sample sizes are needed to better distinguish the informative value of different conditions and the beta sub-bands.

A comparison of digital chest radiography and Xpert® MTB/RIF in active case finding for tuberculosis.

OBJECTIVE: To compare two community screening tests for TB: sputum examination using Xpert® MTB/RIF and chest radiography (CXR).METHOD: Men aged ≥15 years and women aged >45 years living in 96 sub-communes in Ca Mau, Viet Nam, were invited to provide a single sputum specimen that was tested using Xpert. Participants were also invited to attend a nearby location for digital radiography. Participants whose sputum was Xpert MTB-positive or whose CXR was reported as 'consistent with TB´ were requested to provide two further sputum specimens for culture. The sensitivities of the two tests for detecting TB (defined as sputum culture-positive for Mycobacterium tuberculosis) were compared.RESULTS: There were 72 985 eligible participants, of whom 57 597 (78.9%) participated in Xpert screening, 12 752 (17.5%) had CXR and 11 235 (15.4%) had both tests. We estimated that there were 59 cases of TB, of whom 20 were Xpert MTB-positive (programmatic sensitivity 34.0%) and 47 had CXR reported as 'consistent with TB´ (sensitivity 80.0%, P < 0.0001).CONCLUSION: In community-wide screening for TB, CXR is more sensitive than a single spontaneously expectorated sputum sample tested using Xpert, but it has a substantially lower participation rate.

What to expect from a non-suspicious prostate MRI? A review.

BACKGROUND: Many guidelines now recommend multiparametric MRI (mpMRI) prior to an initial or repeat prostate biopsy. However, clinical decision making for men with a non-suspicious mpMRI (Likert or PIRADS score 1-2) varies. OBJECTIVES: To review the most recent literature to answer three questions. (1) Should we consider systematic biopsy if mpMRI is not suspicious? (2) Are there additional predictive factors that can help decide which patient should have a biopsy? (3) Can the low visibility of some cancers be explained and what are the implications? SOURCES: A narrative review was performed in Medline databases using two searches with the terms "MRI" and "prostate cancer" and ("diagnosis" or "biopsy") and ("non-suspicious" or "negative" or "invisible"); "prostate cancer MRI visible". References of the selected articles were screened for additional articles. STUDY SELECTION: Studies published in the last 5 years in English language were assessed for eligibility and selected if data was available to answer one of the three study questions. RESULTS: Considering clinically significant cancer as ISUP grade≥2, the negative predictive value (NPV) of mpMRI in various settings and populations ranges from 76% to 99%, depending on cancer prevalence and the type of confirmatory reference test used. NPV is higher among patients with prior negative biopsy (88-96%), and lower for active surveillance patients (85-90%). The PSA density (PSAd) with a threshold of PSAd<0.15ng/ml/ml was the most studied and relevant predictive factor used in combination with mpMRI to rule out clinically significant cancer. Finally, mpMRI-invisible tumours appear to differ from a histopathological and genetic point of view, conferring clinical advantage to invisibility. LIMITATIONS: Most published data come from expert centres and results may not be reproducible in all settings. CONCLUSION: mpMRI has high diagnostic accuracy and in cases of negative mpMRI, PSA density can be used to determine which patient should have a biopsy. Growing knowledge of the mechanisms and genetics underlying MRI visibility will help develop more accurate risk calculators and biomarkers.

White hard clam (Meretrix lyrata) shells as novel filter media to augment the phosphorus removal from wastewater.

It is well recognized that filter media play a crucial role in constructed wetlands (CWs) for decontamination of phosphorus (P)-rich wastewater. This study investigates the suitability of raw white hard clam shells (WHC) and white hard clam shells thermally modified at 800 °C (WHC-M800) as potential media to enhance P treatment performance in CWs. The results indicated that both WHC and WHC-M800 displayed appropriate physicochemical properties, such as high porosity, excellent hydraulic conductivity, and rich Ca content. WHC-M800 exhibited a superior P adsorption capacity (38.7 mg/g) to WHC (12.8 mg/g). However, the practical utilization of WHC-M800 as filter media in CWs may be compromised, due to certain limitations, for example: extremely high pH values in the post-adsorption solutions; high weight losses during calcination and adsorption processes; low mechanical strength; and intensive energy consumption. In contrast, the WHC demonstrated significant advantages of reasonably high P adsorption capacity, locally abundant availability, low cost, and marginal side effects. The fractionation of inorganic P of WHC and WHC-M800 revealed that Ca-bounded P was the most dominant binding form, followed by loosely bound P, Fe-P, occluded P, and Al-P. The present study demonstrates that recycling of WHC shells as a potential substrate in CWs provides a feasible method for upgrading P removal in CWs. Additionally, it helps to reduce waste WHC shells in a simple, cheap, and eco-friendly way, thus can double environmental benefits.