Recovery of SARS-CoV-2 from large volumes of raw wastewater is enhanced with the inuvai R180 system.

Wastewater-based epidemiology (WBE) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a powerful tool to complement syndromic surveillance. Although detection of SARS-CoV-2 in raw wastewater may be prompted with good recoveries during periods of high community prevalence, in the early stages of population outbreaks concentration procedures are required to overcome low viral concentrations. Several methods have become available for the recovery of SARS-CoV-2 from raw wastewater, generally involving filtration. However, these methods are limited to small sample volumes, possibly missing the early stages of virus circulation, and restrained applicability across different water matrices. The aim of this study was thus to evaluate the performance of three methods enabling the concentration of SARS-CoV-2 from large volumes of wastewater: i) hollow fiber filtration using the inuvai R180, with an enhanced elution protocol and polyethylene glycol (PEG) precipitation; ii) PEG precipitation; and iii) skimmed milk flocculation. The performance of the three approaches was evaluated in wastewater from multiple wastewater treatment plants (WWTP) with distinct singularities, according to: i) effective volume; ii) percentage of recovery; iii) extraction efficiency; iv) inhibitory effect; and v) the limits of detection and quantification. The inuvai R180 system had the best performance, with detection of spiked control across all samples, with average recovery percentages of 68% for porcine epidemic diarrhea virus (PEDV), with low variability. Mean recoveries for PEG precipitation and skimmed milk flocculation were 9% and 14%, respectively. The inuvai R180 enables the scalability of volumes without negative impact on the costs, time for analysis, and recovery/inhibition. Moreover, hollow fiber ultrafilters favor the concentration of different microbial taxonomic groups. Such combined features make this technology attractive for usage in environmental waters monitoring.

Real-world data for pediatric medulloblastoma: can we improve outcomes?

Medulloblastoma (MB) is a malignant embryonal tumor that develops especially in childhood, with overall survival (OS) at 5 years of up to 70%. The objective of this study is to analyze treatment delivery variables in a retrospective cohort and evaluate the impact of these treatment quality parameters on survival. From 2000 to 2018, 40 pediatric patients with medulloblastoma, treated according to current international protocols, were retrospectively analyzed. Treatment delivery quality indicators were analyzed including the extent of surgery, radiotherapy (RT) parameters, and chemotherapy variables, related with time and dose-intensity deviations. With a median follow-up of 74 months (range, 6-195), OS at 5 years was 74 ± 7%, 81 ± 8% for standard-risk, and 55 ± 16% for high-risk patients (p = 0.090). Disease-free survival at 5 years was not significantly affected by extent of surgery (p = 0.428) and RT-related variables such as surgery-RT interval (p = 0.776) neither RT duration (p = 0.172) or maintenance chemotherapy compliance (p = 0.634). Multivariate analysis identified risk groups predictive of worse DFS (p = 0.032) and leptomeningeal dissemination associated with inferior OS (p = 0.029).Conclusion: Treatment delivery optimization has improved survival rates of patients with MB. Despite this, in our study, we have not established a clear influence of the considered radiotherapy and chemotherapy treatment quality parameters on outcomes. What is Known: • Improvement in treatment modalities during the last decades has reached a 5-year OS of up to 70% in these patients. • Extent of resection and radiotherapy parameters such as interval between surgery-radiotherapy and radiotherapy duration has been described as probable survival prognostic factors. What is New: • Differences in medulloblastoma survival rates between prospective studies and retrospective series. • The impact on survival of the three main treatment variables, surgery, radiotherapy and chemotherapy, susceptible to improvement.

A wastewater-based epidemiology tool for COVID-19 surveillance in Portugal.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater produced interest in its use for sentinel surveillance at a community level and as a complementary approach to syndromic surveillance. With this work, we set the foundations for wastewater-based epidemiology (WBE) in Portugal by monitoring the trends of SARS-CoV-2 RNA circulation in the community, on a nationwide perspective during different epidemiological phases of the pandemic. The Charité assays (E_Sarbecco, RdRP, and N_Sarbecco) were applied to monitor, over 32-weeks (April to December 2020), the dynamics of SARS-CoV-2 RNA at the inlet of five wastewater treatment plants (WWTP), which together serve more than two million people in Portugal. Raw wastewater from three Coronavirus disease 2019 (COVID-19) reference hospitals was also analyzed during this period. In total, more than 600 samples were tested. For the first weeks, detection of SARS-CoV-2 RNA was sporadic, with concentrations varying from 103 to 105 genome copies per liter (GC/L). Prevalence of SARS-CoV-2 RNA increased steeply by the end of May into late June, mainly in Lisboa e Vale do Tejo region (LVT), during the reopening phase. After the summer, with the reopening of schools in mid-September and return to partial face-to-face work, a pronounced increase of SARS-CoV-2 RNA in wastewater was detected. In the LVT area, SARS-CoV-2 RNA load agreed with reported trends in hotspots of infection. Synchrony between trends of SARS-CoV-2 RNA in raw wastewater and daily new COVID-19 cases highlights the value of WBE as a surveillance tool, particularly after the phasing out of the epidemiological curve and when hotspots of disease re-emerge in the population which might be difficult to spot based solely on syndromic surveillance and contact tracing. This is the first study crossing several epidemiological stages highlighting the long-term use of WBE for SARS-CoV-2.

Radical prostatectomy versus external-beam radiotherapy for localized prostate cancer: long-term effect on biochemical control-in search of the optimal treatment.

BACKGROUND: The optimal management of patients with clinically localized prostate carcinoma remains undefined due in part to the absence of well-designed, randomized trials. METHODS: This retrospective study comprised 505 patients diagnosed with low- or intermediate- risk prostate cancer in 1998-2005 and treated at Hospital Gregorio Marañón (Spain) with radical prostatectomy (RP) or external-beam radiotherapy (EBRT). No adjuvant therapy was administered. Biochemical relapse was defined as a prostate-specific antigen (PSA) level ≥0.4 ng/ml for RP cases and nadir + 2 for EBRT cases. RP was performed in 271 patients (53.6%) and EBRT in 234 patients (46.4%). The median follow-up was 60 months. The analysis end point was to compare the biochemical recurrence-free survival (bRFS) between the two groups. RESULTS: The 5-year bRFS rates for RP and EBRT were 79 ± 2% and 86 ± 2%, respectively (P = 0.48). Multivariate analysis indicated that initial PSA (P = 0.00), perineural invasion in the biopsy specimen (P = 0.00), Gleason score (P = 0.04), EBRT dose (P = 0.02), and positive margins (P = 0.00) were independent predictors of relapse. A decision tree model was constructed with these variables. In the EBRT cohort, a nadir PSA of <0.3 ng/ml was associated with the best 5-year bRFS (96.6 vs. 56.5% if nadir PSA > 1.3 ng/ml). Late biochemical failure (>5 years) was more frequent in the RT group and with low-dose EBRT (≤72 Gy). CONCLUSIONS: The biochemical failure rates were similar between PR and EBRT in low- and intermediate-risk subgroups. Outcome was determined by classic pre-treatment features, perineural invasion, low-dose EBRT (≤72 Gy), and nadir PSA value in the RT cohort.

Changes in systolic blood pressure in dogs with pituitary dependent hyperadrenocorticism during the first year of trilostane treatment.

BACKGROUND: Systemic hypertension (SH) is common in dogs and humans with hypercortisolism and can persist after treatment. OBJECTIVES: To evaluate changes in prevalence of SH and systolic blood pressure (SBP) in dogs with pituitary-dependent hyperadrenocorticism (PDH) during the first year of trilostane treatment, its relationship with disease control and selected laboratory variables, and their response to antihypertensive treatment. ANIMALS: Fifty-one dogs with PDH treated with trilostane Q12h. METHODS: Prospective case series study. Dogs were evaluated at diagnosis (T0) and 1, 3, 6, and 12 months (T12). Dogs were classified as nonhypertensive (SBP < 160 mm Hg) or hypertensive (SBP≥160 mm Hg) and subclassified according to target organ damage (TOD) risk. Hypertensive dogs were treated with benazepril and, if control of SH was not achieved, amlodipine was added. RESULTS: Prevalence of SH decreased from T0 (36/51) to T12 (17/37; P = .01). Changes in SBP during the study were influenced by the risk of TOD at T0. In severely hypertensive (SBP ≥ 180 mm Hg) dogs, the decrease in SBP was more pronounced whereas in normotensive (SBP < 140 mm Hg) dogs SBP increased slightly (P = .00). Blood pressure was not associated with disease control. Antihypertensive treatment was needed in 31/51 dogs, and in 13/31 dogs additional SH control with amlodipine was required. One third of nonhypertensive dogs at T0 required treatment with benazepril because SH developed during follow-up. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with PDH, SBP should be measured at every visit, regardless of disease control or SBP at diagnosis. More than 1 drug may be necessary to manage SH in affected dogs.

Prevalence and risk factors associated with systemic hypertension in dogs with spontaneous hyperadrenocorticism.

BACKGROUND: Systemic hypertension (SH) is common in dogs with hyperadrenocorticism (HAC) however there are not many studies assessing its prevalence and risk factors. OBJECTIVES: To determine the prevalence and severity of SH in dogs with HAC and its association with clinical and laboratory findings to identify potential risk factors. ANIMALS: Sixty-six client owned dogs with spontaneous HAC. METHODS: Retrospective cross-sectional study. Medical records of dogs with HAC were reviewed. Systolic blood pressure (SBP) was measured using Doppler ultrasonography. Clinical signs, physical examination findings and clinicopathologic data (CBC, serum biochemistry and electrolytes, urinalysis and urinary culture, and adrenal function tests) were reviewed for analysis. RESULTS: Prevalence of SH (≥150 mm Hg) was 82% (54/66) and prevalence of severe SH (≥180 mm Hg) was 46% (30/66). All dogs with thrombocytosis had SH (P = .002), and a platelet count ≥438 × 103 /µL was 100% specific and 61.1% sensitive to predict SH (AUC = .802, P = .001). Median potassium levels were lower in hypertensive dogs (4.1 mEq/L, range 3.1-5.4 mEq/L) than in normotensive ones (4.5 mEq/L, range 4.0-5.0 mEq/L) (P = .007). Dogs with UPC ≥ 0.5 had higher median SBP than those without proteinuria (P = .03). Dogs with concurrent diabetes mellitus seemed to have a reduced risk of SH (OR = .118, 95%CI = .022-.626, P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic hypertension is common in dogs with HAC and is frequently severe. Blood pressure should be routinely assessed in these dogs, especially if thrombocytosis, proteinuria or low potassium concentrations are present.

Dietary supplementation with fermented defatted "alperujo" induces modifications of the intestinal mucosa and cecal microbiota of broiler chickens.

Nutraceuticals are not only nutritionally beneficial for animals but also their use as feed supplements may reduce environmental contamination. The effect of fermented defatted "alperujo," an olive oil by-product, supplementation on the intestinal health of broiler chickens was assessed by analyzing the intestinal mucosal morphology of the duodenum and the cecum. The microbiota of the cecum was also characterized by analyzing the V3-V4 region of the 16S rRNA gene on days 7, 14, 21, 28, 35, and 42. Supplemented broilers from 14 to 35 D of age showed an increase in villus height in the duodenum. This increase likely improved digestibility and absorption capacity during growth, leading to the observed increase in BW at day 35 of life. A progressive increase in crypt depth in both the duodenum and the cecum was also observed. This modification likely enhanced epithelial renewal, thus safeguarding the turnover capacity of the intestinal mucosa. Our molecular analysis of cecal microbiota suggests that this dietary supplement may favor the growth of certain bacteria and may control the spread of pathogenic bacteria by means of competitive exclusion.

Salvage brachytherapy for locally-recurrent prostate cancer after radiation therapy: A comparison of efficacy and toxicity outcomes with high-dose rate and low-dose rate brachytherapy.

BACKGROUND: Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques. METHODS AND MATERIALS: Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale. RESULTS: Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%-75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy <30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients. CONCLUSIONS: These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

Dry Needling on the Infraspinatus Latent and Active Myofascial Trigger Points in Older Adults With Nonspecific Shoulder Pain: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Shoulder pain is a prevalent condition in older adults. Some authors associate nonspecific shoulder pain with myofascial trigger points (MTrPs) in the infraspinatus muscle. Dry needling is recommended to relieve the MTrP pain of shoulders in the short term (<9 days). Active MTrPs dry needling improves shoulder pain and the irritability of the satellite MTrPs in the referred pain area. Nociceptive activity at a latent MTrP may influence motor activity and the sensitivity of MTrPs in distant muscles at a similar segmental level. Therefore, this study aimed to evaluate dry needling on 1 latent MTrP, in conjunction with 1 active MTrP, in the infraspinatus muscle of older adults with nonspecific shoulder pain. METHODS: A single-center, randomized, single-blinded, controlled study (NCT02032602) was carried out. Sixty-six patients aged 65 years and older with trigger points in the ipsilateral infraspinatus of the painful shoulder were randomly assigned to (1) of (2) treatment groups. A session of dry needling on the infraspinatus was performed in (1) the most hyperalgesic active and latent MTrP or (2) only the most hyperalgesic active MTrP. The Numeric Rating Scale, the pressure pain threshold (primary outcome) on the anterior deltoid and extensor carpi radialis brevis latent MTrPs, and grip strength were assessed before, after, and 1 week after the intervention. RESULTS: Statistically significant differences in the reduction of pain intensity (P ≤ .001; η = 0.159-0.269; d = 1.017-1.219) and the increase of pressure pain threshold (P < .001; η = 0.206-0.481; d = 0.870-1.924) were found for the (1) treatment group immediately and 1 week postintervention. Nevertheless, no statistical significant differences were found in grip strength (P >. 05; η = 0.006-0.033; d = 0.158-0.368). CONCLUSIONS: One dry needling intervention of the latent MTrP associated with the key active MTrP of the infraspinatus reduces pain intensity and the irritability of the satellite MTrPs located in the referred pain area in the short term in older adults with nonspecific shoulder pain.