Systematic Analysis of Transrectal Prostate Biopsies Using an Ink Method and Specific Histopathologic Protocol: A Prospective Study

Background. Transrectal prostate biopsy is the standard protocol for the screening for prostate cancer. It helps to locate prostatic adenocarcinoma and plan treatment. However, the increasing number of prostate biopsies leads to considerably greater costs for the pathology laboratories. In this study, we compare the traditional method with an ink method in combination with a systematic histopathologic protocol. Methods. Two hundred consecutive transrectal prostate biopsy specimens were received from the radiology department. They were separated into two groups: one hundred were processed as six different specimens in the usual manner. The other one hundred were submitted in six containers, the apex, base, and middle section of which were stained different colours. The samples subject to the ink method were embedded in paraffin and placed in two cassettes which were sectioned using a specific protocol. Results. The comparative study of the nonink and ink methods for histopathologic diagnosis showed no statistical differences as far as diagnostic categories were concerned (P  value < .005). The number of PIN diagnoses increased when the ink method was used, but no statistical differences were found. The ink method led to a cost reduction of 48.86%. Conclusions. Our ink method combined with a specific histopathologic protocol provided the same diagnostic quality, tumor location information as the traditional method, and lower pathology expenses

Neurologic Involvement in COVID-19: Cause or Coincidence? A Neuroimaging Perspective

Despite a large cohort of 103 patients with COVID-19, the authors found a large number of symptomatic patients with negative neuroimaging findings, and no conclusions can be drawn concerning concrete associations between neuroimaging and COVID-19. The rapid spread of the coronavirus disease 2019 (COVID-19) pandemic has shaken hospitals worldwide. Some authors suggest that neurologic involvement could further complicate the disease. This descriptive study is a cross-sectional review of 103 patients diagnosed with COVID-19 who underwent neuroimaging (of a total of 2249 patients with COVID-19 in our center). Analyzed variables were neurologic symptoms and acute imaging findings. The most frequent symptoms that motivated neuroimaging examinations were mild nonfocal neurologic symptoms, code stroke (refers to patients presenting with signs and symptoms of stroke whose hyperacute assessment and care is prioritized), focal neurologic symptoms, postsedation encephalopathy, and seizures. No cases of encephalitis or direct central nervous system involvement were detected. Thirteen patients presented with acute ischemic events, and 7, with hemorrhagic events; however, most reported multiple vascular risk factors. Despite the large cohort of patients with COVID-19, we found a large number of symptomatic patients with negative neuroimaging findings, and no conclusions can be drawn concerning concrete associations between neuroimaging and COVID-19

Precise enhancement quantification in post-operative MRI as an indicator of residual tumor impact is associated with survival in patients with glioblastoma

Glioblastoma is the most common primary brain tumor. Standard therapy consists of maximum safe resection combined with adjuvant radiochemotherapy followed by chemotherapy with temozolomide, however prognosis is extremely poor. Assessment of the residual tumor after surgery and patient stratification into prognostic groups (i.e., by tumor volume) is currently hindered by the subjective evaluation of residual enhancement in medical images (magnetic resonance imaging [MRI]). Furthermore, objective evidence defining the optimal time to acquire the images is lacking. We analyzed 144 patients with glioblastoma, objectively quantified the enhancing residual tumor through computational image analysis and assessed the correlation with survival. Pathological enhancement thickness on post-surgical MRI correlated with survival (hazard ratio: 1.98, p < 0.001). The prognostic value of several imaging and clinical variables was analyzed individually and combined (radiomics AUC 0.71, p = 0.07; combined AUC 0.72, p < 0.001). Residual enhancement thickness and radiomics complemented clinical data for prognosis stratification in patients with glioblastoma. Significant results were only obtained for scans performed between 24 and 72 h after surgery, raising the possibility of confounding non-tumor enhancement in very early post-surgery MRI. Regarding the extent of resection, and in agreement with recent studies, the association between the measured tumor remnant and survival supports maximal safe resection whenever possible

Minimizing acquisition-related radiomics variability by image resampling and batch effect correction to allow for large-scale data analysis

Objective: To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CTimage correction method to reduce variability and improve radiomics classification in both phantom and clinical applications. Methods: CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases. Ninety-three radiomics features of first order and texture were extracted. Intraclass correlation coefficients (ICCs) between CT-acquisition protocols were evaluated to define sources of variability. Voxel size, ComBat, and singular value decomposition (SVD) compensation methods were explored for reducing the radiomics variability. The number of robust features was compared before and after correction using two-proportion z test. The radiomics classification accuracy (K-means purity) was assessed before and after ComBat- and SVD-based correction. Results: Fifty-three acquisition protocols in 13 tissue densities were analyzed. Ninety-seven liver metastases from 43 patients with CT from two vendors were included. Pixel size, reconstruction slice spacing, convolution kernel, and acquisition slice thickness are relevant sources of radiomics variability with a percentage of robust features lower than 80%. Resampling to isometric voxels increased the number of robust features when images were acquiredwith different pixel sizes (p < 0.05). SVD-based for thickness correction and ComBat correction for thickness and combined thickness–kernel increased the number of reproducible features (p < 0.05). ComBat showed the highest improvement of radiomics-based classification in both the phantom and clinical applications (K-means purity 65.98 vs 73.20). Conclusion: CT-image post-acquisition processing and radiomics normalization by means of batch effect correction allow for standardization of large-scale data analysis and improve the classification accuracy

Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19

Efficacy and safety clinical trial with efavirenz in patients diagnosed with adult Niemann-pick type C with cognitive impairment

Background:Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca (R)) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. Methods:This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. Discussion:NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression

Ecological momentary interventions for depression and anxiety

Ecological momentary interventions (EMIs) are becoming more popular and more powerful resources for the treatment and prevention of depression and anxiety due to advances in technological capacity and analytic sophistication. Previous work has demonstrated that EMIs can be effective at reducing symptoms of depression and anxiety as well as related outcomes of stress and at increasing positive psychological functioning. In this review, we highlight the differences between EMIs and other forms of treatment due to the nature of EMIs to be deeply integrated into the fabric of people's day-to-day lives. EMIs require unique considerations in their design, deployment, and evaluation. Furthermore, given that EMIs have been advanced by changes in technologies and that the use of behavioral intervention technologies for mental health has been increasing, we discuss how technologies and analytics might usher in a new era of EMIs. Future EMIs might reduce user burden and increase intervention personalization and sophistication by leveraging digital sensors and advances in natural language processing and machine learning. Thus, although current EMIs are effective, the EMIs of the future might be more engaging, responsive, and adaptable to different people and different contexts

Can the Macrogeometry of Dental Implants Influence Guided Bone Regeneration in Buccal Bone Defects? Histomorphometric and Biomechanical Analysis in Beagle Dogs

The aim of this experimental animal study was to assess guided bone regeneration (GBR) and implant stability (ISQ) around two dental implants with different macrogeometries. Forty eight dental implants were placed within six Beagle dogs. The implants were divided into two groups (n = 24 per group): G1 group implants presented semi-conical macrogeometry, a low apical self-tapping portion, and an external hexagonal connection (whereby the cervical portion was bigger than the implant body). G2 group implants presented parallel walls macrogeometry, a strong apical self-tapping portion, and an external hexagonal connection (with the cervical portion parallel to the implant body). Buccal (mouth-related) defects of 2 mm (c2 condition) and 5 mm (c3 condition) were created. For the control condition with no defect (c1), implants were installed at crestal bone level. Eight implants in each group were installed under each condition. The implant stability quotient (ISQ) was measured immediately after implant placement, and on the day of sacrifice (3 months after the implant placement). Histological and histomorphometric procedures and analysis were performed to assess all samples, measuring crestal bone loss (CBL) and bone-to-implant contact (BIC). The data obtained were compared with statistical significance set at p &lt; 0.05. The ISQ results showed a similar evolution between the groups at the two evaluation times, although higher values were found in the G1 group under all conditions. Within the limitations of this animal study, it may be concluded that implant macrogeometry is an important factor influencing guided bone regeneration in buccal defects. Group G1 showed better buccal bone regeneration (CBL) and BIC % at 3 months follow up, also parallel collar design can stimulate bone regeneration more than divergent collar design implants. The apical portion of the implant, with a stronger self-tapping feature, may provide better initial stability, even in the presence of a bone defect in the buccal area