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Tolvaptan slowed the rates of total kidney volume (TKV) growth and renal function decline over a 3-year period in patients with autosomal dominant polycystic kidney disease (ADPKD) enrolled in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 34 trial (NCT00428948). In this post hoc analysis of Japanese patients from TEMPO 34, we evaluated whether the effects of tolvaptan on TKV and on renal function are interrelated.

One hundred and forty-seven Japanese patients from TEMPO 34 were included in this analysis (placebo, n = 55; tolvaptan, n = 92). Tolvaptan-treated patients were stratified into the responder group (n = 37), defined as tolvaptan-treated patients with a net decrease in TKV from baseline to year 3, and the non-responder group (n = 55), defined as tolvaptan-treated patients with a net increase in TKV.

Mean changes during follow-up in the placebo, responder, and non-responder groups were 16.99%, - 8.33%, and 13.95%, respectively, for TKV and - 12.61, - 8.47, and - 8.58mL/min/1.73m

, respectively, for estimated glomerular filtration rate (eGFR). Compared with the placebo group, eGFR decline was significantly slowed in both the responder and non-responder groups (P < 0.05).

Tolvaptan was effective in slowing eGFR decline, regardless of TKV response, over 3years in patients with ADPKD in Japan. Treatment with tolvaptan may have beneficial effects on slowing of renal function decline even in patients who have not experienced a reduction in the rate of TKV growth by treatment with tolvaptan.

Tolvaptan was effective in slowing eGFR decline, regardless of TKV response, over 3 years in patients with ADPKD in Japan. Treatment with tolvaptan may have beneficial effects on slowing of renal function decline even in patients who have not experienced a reduction in the rate of TKV growth by treatment with tolvaptan.

Immune checkpoint inhibitors (ICPis) are associated with multi-organ immune-related adverse effects. Here, we examined the incidence rate, recovery rate, and risk factors of acute kidney injury complicated with ICPis (ICPi-AKI) and evaluted the association between ICPi-AKI and mortality in Japanese patients.

We analyzed 152 consecutive patients receiving ICPis between 2015 and 2019. A logistic regression analysis was performed to identify risk factors for ICPi-AKI incidence and Cox regression analysis was performed to evaluate the association between ICPi-AKI and mortality.

The mean patient age was 67 ± 10years, with the median baseline serum creatinine level of 0.78mg/dL. Twenty-seven patients (18%) developed ICPi-AKI, and 19 (73%) of them recovered. Pembrolizumab use and liver diseases were significant risk factors for the ICPi-AKI incidence. During the follow-up, 85 patients (59%) died, 17 patients (63%) with ICPi-AKI and 68 (54%) patients without ICPi-AKI, respectively. The ICPi-AKI incidence was not independently associated with mortality (adjusted hazard ratio, 0.85; 95% confidence intervals, 0.46-1.61).

Our finding suggest that pembrolizumab use and liver diseases are associated with a higher risk of ICPi-AKI development, but ICPi-AKI did not affect mortality. Future multi-center studies are needed to develop optimal management and prevention strategies for this complication in patients receiving ICPis.

Our finding suggest that pembrolizumab use and liver diseases are associated with a higher risk of ICPi-AKI development, but ICPi-AKI did not affect mortality. Future multi-center studies are needed to develop optimal management and prevention strategies for this complication in patients receiving ICPis.

Powder technology was developed to bring together the mechanical features and high porosity of titanium. However, the high porosity may theoretically compromise mechanical resistance. Literature is deficient about the use and safety profile of cementless femoral implants built using additive manufacturing (in particular electron beam melting technology, EBM). The purpose of this study was to evaluate the survival rates and the reason for revisions (especially implant breakage) of the first two EBM-built stems at a mid-term follow-up, using a joint arthroplasty registry.

The registry of Prosthetic Orthopedic Implant (RIPO) was investigated about cementless stems implanted from 2010 to 2017. Stems built with EBM technology (Parva and Pulchra stems; Adler Ortho, Milan, Italy) were compared to all the other cementless stems implanted during the same period, acting as control group. The survival rates and reasons for revision were assessed.

No stem breakage occurred. At 5-year follow-up, the survival rates of the two cohorts were not statistically different (96.8% EBM stems, 98.0% standard cementless stems; p > 0.05). In the EBM stems, aseptic loosening occurred in 1.7% of the cases at the latest follow-up.

This large cohort showed that mechanical resistance is not a concern in EBM stems at mid-term follow-up. However, larger populations and longer follow-ups are needed to further validate these results.

This large cohort showed that mechanical resistance is not a concern in EBM stems at mid-term follow-up. However, larger populations and longer follow-ups are needed to further validate these results.

To investigate whether radiomics features extracted from magnetic resonance imaging (MRI) of patients with biopsy-proven atypical ductal hyperplasia (ADH) coupled with machine learning can differentiate high-risk lesions that will upgrade to malignancy at surgery from those that will not, and to determine if qualitatively and semi-quantitatively assessed imaging features, clinical factors, and image-guided biopsy technical factors are associated with upgrade rate.

This retrospective study included 127 patients with 139 breast lesions yielding ADH at biopsy who were assessed with multiparametric MRI prior to biopsy. Two radiologists assessed all lesions independently and with a third reader in consensus according to the BI-RADS lexicon. find more Univariate analysis and multivariate modeling were performed to identify significant radiomic features to be included in a machine learning model to discriminate between lesions that upgraded to malignancy on surgery from those that did not.

Of 139 lesions, 28 were upgraded to malignancy at surgery, while 111 were not upgraded. Diagnostic accuracy was 53.6%, specificity 79.2%, and sensitivity 15.3% for the model developed from pre-contrast features, and 60.7%, 86%, and 22.8% for the model developed from delta radiomics datasets. No significant associations were found between any radiologist-assessed lesion parameters and upgrade status. There was a significant correlation between the number of specimens sampled during biopsy and upgrade status (p = 0.003).

Radiomics analysis coupled with machine learning did not predict upgrade status of ADH. The only significant result from this analysis is between the number of specimens sampled during biopsy procedure and upgrade status at surgery.

Radiomics analysis coupled with machine learning did not predict upgrade status of ADH. The only significant result from this analysis is between the number of specimens sampled during biopsy procedure and upgrade status at surgery.In clinical practice, many patients with heart failure with reduced ejection fraction (HFrEF) are either not prescribed guideline-directed medical therapies for which they are eligible or are prescribed therapies at sub-target doses. The objective of this study was to examine the factors associated with not receiving guideline-directed medical therapies or receiving sub-target doses. We conducted a systematic review of articles published between January 2014 and May 2019 that described dosing patterns and factors associated with non-use and sub-target dosing of HFrEF therapies in clinical practice. Thirty-seven studies were included. The percentages of patients reaching target doses for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists ranged from 4 to 55%, 11 to 87%, 4 to 60%, and 22 to 80%, respectively. Older age and worsening renal function were associated with non-use and sub-target dosing, lower body mass index was commonly associated with non-use, and hyperkalemia and hypotension were commonly associated with sub-target dosing. In conclusion, several common patient characteristics are associated with non-use and sub-target dosing of medical therapy for HFrEF. These high-risk groups are in particular need of further studies to improve implementation of available medications and to define the role of novel therapies.

Breast cancer (BC) is increasing in black South African women, but few studies have investigated its risk factors.

We conducted an analysis of reproductive factors and BC risk in the South African Breast Cancer (SABC) study-a population-based case-control study of black South African women from Soweto that included 399 cases and 399 matched controls. Information on lifestyle and reproductive history was obtained by interviews. Conditional logistic regression was used to determine the association of reproductive factors with BC, adjusting for potential confounding factors.

Seventy-five percent of all BC cases were ER+, 66% PR+, 30% HER2+, and 16% TN. None of the reproductive variables were associated with BC overall or by subtype in the overall population, nor in pre- (n = 135 cases) or in post-menopausal women separately. In HIV-negative pre-menopausal women (n = 97 cases), later age at first pregnancy and longer time between menarche and first full-time pregnancy were inversely related to BC risk (OR 0.89 (95% CI 0.82-0.97; and 0.93 95% CI 0.86-1.01, respectively).

In this population of black South African women, reproductive factors were not associated with BC risk.

In this population of black South African women, reproductive factors were not associated with BC risk.Population growth and an increase in communities' economies have led to a worldwide rise in water demand. The development of urban areas will cause excessive groundwater extraction, which will trigger environmental impacts, including a decline in groundwater levels. Changes in rainfall, land use, and the volume of urban wastewater recharge patterns will affect groundwater level fluctuations over a period of time. This study investigates the effects of rainfall, changes in irrigated agricultural land, and urban wastewater volume trends on groundwater level fluctuations in the Yogyakarta-Sleman groundwater basin, Indonesia, from 2011 to 2017. Analysis of the trend of each parameter was performed using the Mann-Kendall test. The results showed that the recharge area had a trend of deeper groundwater levels positively correlated with the decrease of irrigated agricultural land. In contrast, precipitation trends and urban wastewater volume were negatively associated with the groundwater level fluctuation trend. In the transit area, shallow groundwater levels were positively correlated with precipitation and urban wastewater volume. In contrast, there was an opposite trend in the area of irrigated agricultural land. In the discharge area, groundwater levels became deeper, which positively correlates with precipitation and irrigated agricultural land, while the urban wastewater trend was the opposite. Increasing of groundwater level in the transit area was 0.21-0.25 m/year, where recharge and discharge areas had a decreasing 0.10-0.26 m/year. Import water from municipal water networks and urban wastewater recharge significantly contributed to rising groundwater levels in the transit area. It occurs because urban wastewater in the transit is evenly distributed, but in recharge and discharge areas, groundwater recharge from urban wastewater is localized. The urbanization process did not always negatively impact groundwater resources and contribute to groundwater recharge, depending on managing the urban sewage.