Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis.

PURPOSE: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. MATERIALS AND METHODS: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. RESULTS: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. CONCLUSIONS: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Ex vivo microscopic testicular sperm extraction at the time of radical orchiectomy in men with nonobstructive azoospermia (NOA): a scoping review.

Testicular tumor is the most common solid malignancy in males under 40 years of age. This malignancy is known to have a negative impact on male fertility. Therefore, several techniques for sperm retrieval have been proposed, including microdissection testicular sperm extraction (mTESE). The objective of this study was to review the literature on the outcomes of oncological (Onco)-mTESE at the time of radical orchiectomy. We conducted a comprehensive literature search through PubMed, Scopus, and Cochrane Central Controlled Register of Trials. Only studies reporting ex vivo mTESE in patients with testicular tumor were considered. Twelve papers met the inclusion criteria and were included in this review. Tumor size was identified as the sole preoperative factor influencing spermatogenesis. The considered studies demonstrated a satisfactory success rate for Onco-mTESE, associated with a similarly valid percentage of live healthy births through assisted reproductive technology. Currently, no comparison has been made between Onco-mTESE and conventional Onco-TESE, hence further assessment is required. In cases where the tumor completely replaces the cancer-bearing testicle, a contralateral micro-TESE may be a viable alternative. However, the surgeon should evaluate associated risks and benefits preoperatively. In conclusion, Onco-mTESE at the time of radical orchiectomy appears to be a promising therapeutic option for young patients with testicular tumors. Nevertheless, additional studies are necessary to achieve a definitive conclusion.

Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). MATERIALS AND METHODS: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). RESULTS: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). CONCLUSIONS: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Supervised Pelvic Floor Muscle Training Improves Sexual Function and Diminishes Sexual Distress in Women with Relapsing-Remitting Multiple Sclerosis: A Randomised Controlled Study.

This study investigates the impact of pelvic floor muscle training (PFMT) on sexual function and distress in women with multiple sclerosis (MS), a prevalent chronic nervous system disorder associated with sexual dysfunction. This study's primary aim was to assess the effectiveness of PFMT at improving sexual function and alleviating sexual distress in this population. In a randomised controlled trial, 82 women with MS were divided into two groups: Group A (41 women) underwent 12 weeks of PFMT, while Group B (41 women) served as a control group with no intervention. Both groups were assessed at the beginning and end of this study using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R). Statistical analysis, including Chi-square tests, was employed to compare the outcomes between the two groups, with a p-value of less than 0.05 considered significant. The results revealed no significant differences in baseline sexual function and distress between the groups. However, at the conclusion of the 12-week period, Group A exhibited statistically significant improvements in nearly all domains of FSFI and FSDS-R compared to Group B, except in the pain domain. This study concludes that PFMT can effectively enhance sexual function and reduce sexual distress in women suffering from MS. These findings underscore the potential of PFMT as a therapeutic intervention in managing sexual dysfunction associated with MS.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

The Renaissance of Male Infertility Management in the Golden Age of Andrology.

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.

Graphene-Ta2O5 heterostructure enabled high performance, deep-ultraviolet to mid-infrared photodetection.

Ultrafast, high sensitive, low cost photodetectors operating at room temperature sensitive from the deep-ultraviolet to mid-infrared region remain a significant challenge in optoelectronics. Achievements in traditional semiconductors using cryogenic operation and complicated growth processes prevent the cost-effective and practical application of broadband detectors. Alternative methods towards high-performance photodetectors, hybrid graphene-semiconductor colloidal quantum dots have been intensively explored. However, the operation of these photodetectors has been limited by the spectral bandwidth and response time. Here, we have demonstrated hybrid photodetectors operating from the deep-ultraviolet to the mid-infrared region with high sensitivity and ultrafast response by coupling graphene with a p-type semiconductor photosensitizer, nitrogen-doped Ta2O5 thin film. Photons with energy higher than the energy of the defect centers release holes from neutral acceptors. The holes are transferred into graphene, leaving behind ionized acceptors. Due to the advantage of two-dimensional heterostructure including homogeneous thickness, extending in a two-dimensional plane, large contact area between the N-Ta2O5 thin film and graphene, and the high mobility of carriers in graphene, holes are transferred rapidly to graphene and recirculated during the long lifetime of ionized acceptors. The photodetectors achieve a high photo-responsivity (up to 3.0 × 106 A W-1), ultrafast rise time (faster than 20 ns), and a specific detectivity (up to ∼2.2 × 1012 Jones). The work provides a method for achieving high-performance optoelectronics operating in the deep-ultraviolet to mid-infrared region.

Enabling High-Performance Surfaces of Biodegradable Magnesium Alloys via Femtosecond Laser Shock Peening with Ultralow Pulse Energy.

The fast degradation rate and poor wear resistance of magnesium (Mg) alloys in physiological environments have limited their potential usage as next-generation biodegradable orthopedic implant materials. In this work, femtosecond laser shock peening (fs-LSP) was successfully applied to simultaneously improve the surface mechanical, corrosion, and tribocorrosion properties of WE43 Mg alloys in blood bank buffered saline solution at body temperature. Specifically, the treated surfaces of WE43 Mg alloys via fs-LSP with ultralow pulse energy were investigated under different power densities, confining mediums, and absorbent materials. It was found that the combination of a black tape and a quartz layer gave the optimum peening effect under a power density of 28 GW/cm2, which simultaneously strengthened the surface and reduced the corrosion kinetics. In addition, a rapid self-repassivation was observed in fs-LSP-treated WE43 surfaces during tribocorrosion, promising sustained corrosion resistance under mechanical loading, critical to the reliability of load-bearing implants. Finally, the subsurface microstructural evolution and residual stress development in WE43 after fs-LSP were discussed based on the results from transmission electron microscopy analysis and finite element simulations.

Quantitative CT Detects Undiagnosed Low Bone Mineral Density in Oncologic Patients Imaged With 18F-FDG PET/CT.

PURPOSE: We assessed the prevalence of low bone mineral density (BMD) in oncologic patients undergoing F-FDG PET/CT. PATIENTS AND METHODS: This is a retrospective analysis of 100 patients who underwent F-FDG PET/CT at a single center from October 2015 till May 2016. Quantitative CT (QCT) was used to assess BMD at the lumbar spine (BMDQCT) and femoral necks (BMDCTXA). SUVmax was used to evaluate metabolic activity of the bone marrow. Risk of osteoporosis-related fractures was calculated with femoral neck BMDCTXA and the FRAX algorithm, which was compared against measurements of CT attenuation of the trabecular bone at L1 (L1HU). RESULTS: Osteoporosis and osteopenia were respectively present in 16% and 46% of patients 50 years and older. Bone marrow SUVmax was correlated with BMD at the lumbar spine (ρ = 0.36, P < 0.001). Increased age and low marrow SUVmax were associated with low BMDQCT at the lumbar spine (both P < 0.001), whereas increased age, female sex, and low marrow SUVmax were associated with low BMDCTXA at the femoral necks (P < 0.001, P < 0.001, P = 0.01, respectively). L1HU had an area under the curve of 0.95 (95% confidence interval [CI], 0.90-0.99) for detecting increased risk for osteoporosis-related fracture, with best threshold of 125.8 HU (95% CI, 115.7-144.9) yielding sensitivity of 100% (95% CI, 0.92-1.00), specificity of 0.90 (95% CI, 0.76-0.97), and accuracy of 0.91 (95% CI, 0.79-0.97). CONCLUSIONS: Low BMD is frequent in oncologic patients undergoing F-FDG PET/CT. Decreased F-FDG avidity of the bone marrow correlates with decreased BMD, validating the link between osteoporosis and bone marrow fat. L1HU could be a simple and accurate approach for detecting patients at risk for osteoporosis-related fractures using PET/CTdata.

Sero-evaluation of Immune Responses to Vibrio cholerae in a Postelimination Setting.

Cholera remains a significant public health problem worldwide. In settings of declining incidence, serosurveillance may be used to augment clinical surveillance. We utilized dried blood spot sampling and cholera-specific antibody testing to examine the serologic profiles of vaccinated and unvaccinated children in southern Vietnam, where cholera was recently eliminated.

Online Learning Based on Online DCA and Application to Online Classification.

We investigate an approach based on DC (Difference of Convex functions) programming and DCA (DC Algorithm) for online learning techniques. The prediction problem of an online learner can be formulated as a DC program for which online DCA is applied. We propose the two so-called complete/approximate versions of online DCA scheme and prove their logarithmic/sublinear regrets. Six online DCA-based algorithms are developed for online binary linear classification. Numerical experiments on a variety of benchmark classification data sets show the efficiency of our proposed algorithms in comparison with the state-of-the-art online classification algorithms.

Rapid Disappearance of Poliovirus Type 2 (PV2) Immunity in Young Children Following Withdrawal of Oral PV2-Containing Vaccine in Vietnam.

BACKGROUND: Due to global shortage of inactivated poliovirus vaccine and withdrawal of oral vaccine containing poliovirus type 2 (PV2), a PV2-containing vaccine was not used in Vietnam May 2016 to October 2018. We assessed the population immunity gap to PV2. METHODS: A cross-sectional survey in children aged 1-18 months was carried out in January 2018. One blood sample per child was analyzed for presence of poliovirus neutralizing antibodies. In children with detectable anti-PV2 antibodies, a second sample was analyzed 4 months later to distinguish between passive (maternally derived) and active (induced by secondary transmission or vaccination) immunity. RESULTS: Sera were obtained from 1106/1110 children. Seroprevalence of PV2 antibodies was 87/368 (23.6%) at age 1-7 months, 27/471 (5.7%) at 8-15 months, and 19/267 (7.1%) at 16-18 months. Seroprevalence declined with age in the 1-7 months group; in the 8-18 months group there was no significant change with age. Four months later, 11/87 (14%), 9/27 (32%), and 12/19 (37%) remained seropositive in 1-7, 8-15, and 16-18 months age groups, respectively. CONCLUSIONS: We found declining immunity to PV2, suggesting Vietnam is at risk for an outbreak of type 2 vaccine-derived poliovirus following virus importation or new emergence.

Safety and immunogenicity of inactivated monovalent influenza A/H1N1 vaccine candidate manufactured in Vietnam.

We tested a new A/H1N1 inactivated influenza vaccine (IIV) manufactured by Institute of Vaccines and Medical Biologics (IVAC), Vietnam in 48 adults in a Phase 1, double-blinded, randomized, placebo-controlled trial. Two doses of unadjuvanted vaccine or placebo were administered three weeks apart. The vaccine was well tolerated with only transient mild local reactions and low-grade fever in a small proportion of the subjects. One serious adverse event considered unrelated to the study product was reported. The IVAC vaccine proved to be highly immunogenic with 91 percent (95% CI: 0.78, 1) of the subjects developing a ≥4 fold immune responses by hemagglutination inhibition (HAI) assay, and 96 percent (95% CI: 0.78, 1) by the microneutralization (MN) assay. Post-vaccination geometric mean titers (GMTs) were 283.7 (95% CI: 161.7, 497.5) in the HAI and 725.7 (95% CI: 411.3, 1280.3) in the MN assay. These promising results merit further development of the vaccine. ClinicalTrials.gov number: NCT01507779.

Epidemiology of acute diarrhea caused by rotavirus in sentinel surveillance sites of Vietnam, 2012-2015.

A prospective, multicentre study was conducted in four sentinel surveillance hospitals to assess the trend and epidemiology of acute diarrhea caused by Rotavirus in Vietnam. During the period 2012-2015, a total 8,889 children under 5 years of age were enrolled in the surveillance, and 8689 stool samples were collected. Of these cases, Rotavirus was most common pathogen 46.7% (4054 cases); in which 26.6% (1117) rotavirus-positive stool samples were evaluated to identify genotypes. The proportion of rotavirus positive specimens decreased annually from 54.7% in 2012 to 36.6% in 2015. Rotavirus was detected year-round, but most rotavirus gastroenteritis cases (77.1%) occurred between December and May, corresponding to the rotavirus seasonality. It is found that the peaks varied by regions. Rotavirus positivities varied between the youngest and oldest age, but children 6-11 months old (38.8%) and 12-23 months old (38.4%) counted for most cases. A significant higher number of diarrhea within 24 hours (8.3 times, 95%CI: 8.1-8.4 times) and higher proportion of severe dehydration (12.9%) in Rotavirus positive group than that in Rotavirus negative group (7.7 times, 95%CI: 7.6-7.9 times; and 9.7%, respectively). A downtrend of prevalence of G1P[8] was observed from 82% in 2013 to 15% in 2015. However, G2P[4] was found in 5% of samples in 2012, 9% in 2013, 36% in 2014, and 28% in 2015. Rotavirus infection is the most important cause of acute diarrhea among hospitalized children in Vietnam, and a rotavirus vaccination program for children may significantly reduce this disease.