Nevin Manimala

Blood. 2024 Apr 11:blood.2023022269. doi: 10.1182/blood.2023022269. Online ahead of print.

ABSTRACT

Use of surrogates as primary endpoints is commonplace in hematology/oncology clinical trials. As opposed to prognostic markers, surrogates are endpoints that can be measured early and yet can still capture the full effect of treatment, as it would be captured by the true outcome (e.g., overall survival). We discuss the level of evidence of the most commonly used endpoints in hematology and share recommendations on how to apply and evaluate surrogate endpoints in research and clinical practice. Based on the statistical literature, this clinician-friendly review intends to build a bridge between clinicians and surrogacy specialists.

PMID:38603637 | DOI:10.1182/blood.2023022269

Zhonghua Nan Ke Xue. 2023 May;29(5):436-440.

ABSTRACT

OBJECTIVE: To analyze the blood flow parameters of the cavernous arteries of ED patients after injection of vasoactive drugs, and to explore the differences in blood flow of the cavernous arteries in different erectile states.

METHODS: Retrospectively analyzed the penile cavernous arterial blood flow parameters of 2568 adult male ED patients after injection of the vasoactive drug (alprostadil). The patients were divided into three groups: maintaining erection group with EHS (erection hardness score) ≥ 3 and sustained erection time ≥ 20 minutes (967 cases), nonpersistent erection group with EHS≥3 and sustained erection time<5 minutes (788 cases), and incomplete erection group with EHS<3 (813 cases). Compared the parameters of age, EHS, duration of erection, cavernous artery peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) among the three groups respectively. The maintaining erection group was divided into the youth group (757 cases) which aged less than 40 years old and the middle-aged and elderly group (210 cases) with 40 years old or over. The parameters of PSV, EDV and RI between the two groups were compared. The incomplete erection group were divided into the good blood supply group (407 cases) with the bilateral PSV ≥35cm/s and the insufficient blood supply group (252 cases) with the bilateral PSV<35cm/s. The parameters of age, EHS, EDV and RI between the two groups were compared.

RESULTS: The age, PSV, EDV and RI of the three groups were significantly different (P<0.01). In the maintaining erection group, the PSV of the young group was significantly higher than that of the middle-aged and elderly group (P<0.05), but there was no statistically significant difference in EDV and RI (P>0.05). In the incomplete erection group, the EHS, PSV, EDV, and RI of the good blood supply group were significantly higher than those of the insufficient blood supply group (P<0.05), while the age was significantly lower than that of the latter (P<0.01).

CONCLUSION: The injection of vasoactive drugs combined with color Doppler ultrasound can directly reflect the blood supply of the cavernous arteries of the penis. The better the erection state, the better the blood supply of cavernous arteries. The middle-aged and elderly people are more likely to have cavernous arteries problem of insufficient blood supply than the young people.

PMID:38602761

Zhonghua Nan Ke Xue. 2023 May;29(5):414-419.

ABSTRACT

OBJECTIVE: To explore the association between atypical small acinar proliferation (ASAP) and subsequent diagnosis of intermediate and high risk prostate cancer (PCa), and analyze whether delaying repeat biopsy timing is safe and effective.

METHODS: From June 2000 to June 2022, we retrospectively analyzed the clinical data of 276 patients accepting prostatic biopsy and diagnosed with ASAP in China-Japan Union Hospital of Jilin University. 54.7% (151/276) patients had a repeat biopsy. We used statistic methods to process the data.

RESULTS: 25.2%（38/151）patients were diagnosed with PCa on repeat biopsy. Among them, 78.9%（30/38）patients had Gleason score (GS) 3+3 and 21.1% (8/38) had GS 3+4 disease. There were 4 and 6 patients got RP respectively in the two cohorts. Only 5.3% (8/151) of ASAP patients were diagnosed as intermediate risk PCa in repeated biopsy and specially, no high risk PCa was identified in our study.

CONCLUSION: It was safe and valid to delay the repeat biopsy.

PMID:38602757

Zhonghua Nan Ke Xue. 2023 May;29(5):409-413.

ABSTRACT

OBJECTIVE: To investigate the impact of retaining part of the urethral mucosa on postoperative urinary control, erectile function, and ejaculatory function in patients undergoing holmium laser enucleation of the prostate (HoLEP) surgery.

METHODS: A retrospective analysis was conducted on 176 benign prostatic hyperplasia (BPH) patients who underwent surgical treatment at our hospital from January 2019 to January 2022, including 80 cases of modified HoLEP surgery and 96 cases of standard HoLEP surgery. Preoperative and postoperative clinical data were collected and analyzed.

RESULTS: At 3 months postoperatively, both groups showed significant improvement in maximum flow rate (Qmax), International Prostate Symptom Score (IPSS) , residual urine volume (RUV) , and quality of life (QOL) compared to pre-treatment values, with statistically significant differences (P<0.05) . There was a significant difference in QOL scores between the experimental and control groups (P<0.05) . At 3 months postoperatively, the incidence of urinary incontinence was significantly lower in the experimental group compared to the control group (P<0.05) . At 6 months postoperatively, both groups showed a significant increase in International Index of Erectile Function-5 (IIEF-5) scores compared to preoperative values (P<0.05) , with no significant difference between the two groups. The incidence of retrograde ejaculation in the experimental group was significantly lower than that in the control group (P<0.05) .

CONCLUSIONS: Retaining part of the urethral mucosa in HoLEP surgery can effectively treat BPH, providing significant advantages in terms of urinary control and playing a positive role in overall postoperative sexual function recovery.

PMID:38602756

Zhonghua Nan Ke Xue. 2023 May;29(5):402-408.

ABSTRACT

OBJECTIVE: To explore the mechanism of tetrahydroxynonene (4-HNE) in the androgen antagonistic effect of prostate cancer through the androgen receptor (AR) – mitogen activated protein kinase (MAPK) signaling pathway.

METHOD: Prostate cancer LNCaP cells were divided into wild-type group (NC, control group) and transfection group. The transfection group was further divided into empty vector transfection group (NC-L7 group) and GSTA4 gene transfection group (A0718, GSTA4-OE group). The GSTA4-OE group received LNCaP cell culture and GSTA4 plasmid transfection to construct LNCaP stable 4-HNE cell lines, while the control group received LNCaP cell culture without GSTA4 plasmid transfection. Stimulating prostate cancer cells with different concentrations of 4-HNE (0, 40, 80, 120μmol/L) to activate the AR signaling pathway, Western blot was used to detect the expression of AR, MAKp, AKT, and PKCα proteins. Sixty cases of prostate cancer tissues and sixty cases of benign prostatic hyperplasia tissues were selected. Immunohistochemical staining was used to determine the positive expression rate of 4-HNE in the aforementioned tissues. The correlation between the positive expression of 4-HNE and tumor Gleason grade, as well as the progression of prostate cancer to CRPC, was analyzed.

RESULT: The level of 4-HNE in the GSTA4-OE group cells was inhibited. Western blot analysis showed that compared with the control group, the GSTA4-OE group had PKC in cells α The protein expression level significantly decreased (P<0.05), while the expression levels of AR and AKT proteins significantly increased (P<0.05). After treating prostate cancer cells with 40, 80, and 120μmol/L 4-HNE, compared with the control group, the expression level of AKT in the treatment group was significantly reduced (P<0.01), while the expression levels of MAKP (P<0.01), PKC (P<0.01), and AR (P<0.01) were significantly increased. The immunohistochemical results showed that the positive rate of 4-HNE was 5.0% in 60 cases of benign prostatic hyperplasia tissue and 63.3% in 60 cases of prostate cancer tissue, with a statistically significant difference (P<0.01). The positive rates of 4-HNE in Gleason grades 1-5 were 41.2%, 50.0%, 63.6%, 81.8%, and 100.0%, respectively. The higher the Gleason grade, the higher the positive rate of 4-HNE, and the difference was statistically significant (P<0.05). During a follow-up period of 10-35 months, 33 patients advanced to CRCP, while 27 patients did not. The positive expression rate of 4-HNE in the two groups showed a statistically significant difference (P<0.01).

CONCLUSION: Under the action of 4-HNE, the expression of AR-MAPK pathway related proteins increase. 4-HNE may promote the progression of prostate cancer through the AR-MAPK pathway, and 4-HNE is expected to become a new therapeutic target for CRPC.

PMID:38602755

Zhonghua Nan Ke Xue. 2023 May;29(5):393-401.

ABSTRACT

OBJECTIVE: To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology, identify the possible factors influencing results of scoring, and construct a risk scoring model.

METHODS: We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis. Using paired sample t-test, we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology, analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores, and calculated and visualized the relative risk values of the factors through Poisson regression. From the continuous variables with statistical significance, we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis, established a risk scoring model, generated risk coefficients, and evaluated the predictive ability of the model using the ROC curve. Based on the results of imaging examination with statistically significant differences, we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves, decision curves and ROC curves.

RESULTS: The results of paired sample t-test for 210 PCa patients showed statistically significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology (P < 0.001). There were significant differences in the body weight, BMI and PSA level as well as in all other factors but prostate calcification between the patients with consistent and those with inconsistent Gleason scores (all P < 0.05). An 8-factor prediction model was successfully constructed, which could predict the consistency of Gleason scores, with a better predicting performance than the single indicator within the model. The nomogram exhibited a C-index value of 0.85, with the calibration curve similar to the standard one, the threshold of the decision curve 0.10－0.92, and the area under the ROC curve higher than other predictive indicators.

CONCLUSION: Based on the demographic and clinical data on PCa patients, a risk prediction model and a column chart were successfully constructed, which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

PMID:38602754

IUCrJ. 2024 May 1. doi: 10.1107/S2052252524001830. Online ahead of print.

ABSTRACT

An X-ray absorption spectroscopy (XAS) electrochemical cell was used to collect high-quality XAS measurements of N-truncated Cu:amyloid-β (Cu:Aβ) samples under near-physiological conditions. N-truncated Cu:Aβ peptide complexes contribute to oxidative stress and neurotoxicity in Alzheimer’s patients’ brains. However, the redox properties of copper in different Aβ peptide sequences are inconsistent. Therefore, the geometry of binding sites for the copper binding in Aβ_4-8/12/16 was determined using novel advanced extended X-ray absorption fine structure (EXAFS) analysis. This enables these peptides to perform redox cycles in a manner that might produce toxicity in human brains. Fluorescence XAS measurements were corrected for systematic errors including defective-pixel data, monochromator glitches and dispersion of pixel spectra. Experimental uncertainties at each data point were measured explicitly from the point-wise variance of corrected pixel measurements. The copper-binding environments of Aβ_4-8/12/16 were precisely determined by fitting XAS measurements with propagated experimental uncertainties, advanced analysis and hypothesis testing, providing a mechanism to pursue many similarly complex questions in bioscience. The low-temperature XAS measurements here determine that Cu^II is bound to the first amino acids in the high-affinity amino-terminal copper and nickel (ATCUN) binding motif with an oxygen in a tetragonal pyramid geometry in the Aβ_4-8/12/16 peptides. Room-temperature XAS electrochemical-cell measurements observe metal reduction in the Aβ_4-16 peptide. Robust investigations of XAS provide structural details of Cu^II binding with a very different bis-His motif and a water oxygen in a quasi-tetrahedral geometry. Oxidized XAS measurements of Aβ_4-12/16 imply that both Cu^II and Cu^III are accommodated in an ATCUN-like binding site. Hypotheses for these Cu^I, Cu^II and Cu^III geometries were proven and disproven using the novel data and statistical analysis including F tests. Structural parameters were determined with an accuracy some tenfold better than literature claims of past work. A new protocol was also developed using EXAFS data analysis for monitoring radiation damage. This gives a template for advanced analysis of complex biosystems.

PMID:38602752 | DOI:10.1107/S2052252524001830

Zhonghua Nan Ke Xue. 2023 Jun;29(6):498-504.

ABSTRACT

OBJECTIVE: To explore the value of systematic male reproductive system ultrasonography in the diagnosis of azoospermia etiology.

METHODS: Retrospective analysis and classification statistics were conducted on the data of azoospermia cases who underwent systematic male reproductive system ultrasound examination at the First Affiliated Hospital of Ningbo University from January 2013 to January 2023.

RESULTS: A total of 375 cases were included in the group, of which 303 cases could be diagnosed by ultrasound, including 161 cases of obstructive causes, 110 cases of non obstructive causes, and 32 cases of mixed causes. Obstructive causes mainly include bilateral absence or underdevelopment of the seminal vesicles and vas deferens, non obstructive causes mainly include bilateral simple testicular dysplasia, and the most common combined causes are bilateral absence or underdevelopment of the seminal vesicles and vas deferens combined with bilateral testicular dysplasia. The main causes involved a single organ in 174 cases, with 82 cases, 43 cases, and 4 cases involving 2-4 organs, respectively. In addition, there are multiple accompanying ultrasound manifestations of non primary causes.

CONCLUSION: Systematic ultrasound examination can comprehensively evaluate the male reproductive system, effectively diagnose the causes of most azoospermia, and provide valuable imaging evidence for clinical treatment.

PMID:38602721

J Med Internet Res. 2024 Apr 11;26:e49163. doi: 10.2196/49163.

ABSTRACT

BACKGROUND: Health apps are increasingly recognized as crucial tools for enhancing health care delivery. Many countries, particularly those in sub-Saharan Africa, can substantially benefit from using health apps to support self-management and thus help to achieve universal health coverage and the third sustainable development goal. However, most health apps published in app stores are of unknown or poor quality, which poses a risk to patient safety. Regulatory standards and guidance can help address this risk and promote patient safety.

OBJECTIVE: This review aims to assess the regulatory standards and guidance for health apps supporting evidence-based best practices in sub-Saharan Africa with a focus on self-management.

METHODS: A methodological framework for scoping reviews was applied. A search strategy was built and applied across the following databases, gray literature sources, and institutional websites: PubMed, Scopus, World Health Organization (WHO) African Index Medicus, OpenGrey, WHO Regional Office for Africa Library, ICTworks, WHO Directory of eHealth policies, HIS Strengthening Resource Center, International Telecommunication Union, Ministry of Health websites, and Google. The search covered the period between January 2005 and January 2024. The findings were analyzed using a deductive descriptive content analysis. The policy analysis framework was adapted and used to organize the findings. The Reporting Items for Stakeholder Analysis tool guided the identification and mapping of key stakeholders based on their roles in regulating health apps for self-management.

RESULTS: The study included 49 documents from 31 sub-Saharan African countries. While all the documents were relevant for stakeholder identification and mapping, only 3 regulatory standards and guidance contained relevant information on regulation of health apps. These standards and guidance primarily aimed to build mutual trust; promote integration, inclusion, and equitable access to services; and address implementation issues and poor coordination. They provided guidance on systems quality, software acquisition and maintenance, security measures, data exchange, interoperability and integration, involvement of relevant stakeholders, and equitable access to services. To enhance implementation, the standards highlight that legal authority, coordination of activities, building capacity, and monitoring and evaluation are required. A number of stakeholders, including governments, regulatory bodies, funders, intergovernmental and nongovernmental organizations, academia, and the health care community, were identified to play key roles in regulating health apps.

CONCLUSIONS: Health apps have huge potential to support self-management in sub-Saharan Africa, but the lack of regulatory standards and guidance constitutes a major barrier. Hence, for these apps to be safely and effectively integrated into health care, more attention should be given to regulation. Learning from countries with effective regulations can help sub-Saharan Africa build a more robust and responsive regulatory system, ensuring the safe and beneficial use of health apps across the region.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-025714.

PMID:38602718 | DOI:10.2196/49163

Am J Occup Ther. 2024 May 1;78(3):7803205070. doi: 10.5014/ajot.2024.050431.

ABSTRACT

IMPORTANCE: The importance of developing age-friendly environments is globally recognized. However, few clinical trials have comprehensively evaluated physical and social components of environments and examined the effects of offering support.

OBJECTIVE: To clarify the effectiveness of occupational therapy-based comprehensive environmental support for community-dwelling older adults.

DESIGN: A single-blind parallel-groups randomized controlled trial with blinded participants.

SETTING: Eight community-based settings under the long-term-care insurance system in regional towns and cities throughout Japan.

PARTICIPANTS: Sixty older adults age ≥65 yr who were new users of adult day care or adult day health care and allocated by stratified block randomization on the basis of age.

INTERVENTION: Comprehensive environmental support was provided to participants for 3 mo according to results on the Comprehensive Environmental Questionnaire for older adults (CEQ) to make improvements in environmental factors participants wanted to change to create a more satisfying life.

OUTCOMES AND MEASURES: The primary outcome measure was the Japanese Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) score at 3 mo postrandomization. Additionally, scores on the Short-Form Six-Dimension utility index were calculated.

RESULTS: The experimental group showed significant improvements in the SF-36’s Role/Social Component Summary (p = .005) and Role-Physical (p = .02), Role-Emotional (p = .01), and Mental Health (p = .05) domains, with moderate effect sizes. The number needed to treat was 3.46, showing statistical significance.

CONCLUSIONS AND RELEVANCE: Occupational therapy-based comprehensive environmental support based on CEQ scores was effective, resulting in moderate improvements in health-related quality of life among community-dwelling older adults. Plain-Language Summary: Older adults experience a decline in physical and mental functions along with changes in social relationships. These problems make it challenging for older adults to perform valuable occupations, thus reducing their quality of life. This study demonstrated that occupational therapy based on the Comprehensive Environmental Questionnaire for older adults can improve health-related quality of life among community-dwelling older adults. Our findings pave the way for the development of an effective compensatory intervention model in occupational therapy practice.

PMID:38602705 | DOI:10.5014/ajot.2024.050431