Effect of testosterone replacement therapy on lower urinary tract symptoms: A systematic review and network meta-analysis.

OBJECTIVE: In this study, we aimed to perform a network meta-analysis (NMA) to investigate the effects of different testosterone replacement therapy (TRT) administration routes on lower urinary tract symptoms (LUTS) in aging men with late-onset hypogonadism (LOH). METHODS: A systematic search of PubMed, Embase, The Cochrane Library, CNKI, WanFang Data, and VIP was conducted to identify randomized controlled trials (RCTs) reporting data on International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) level, or prostate volume. NMA was performed, and subgroup analysis was conducted to assess the impact of TRT duration on outcomes. RESULTS: A total of 21 RCTs involving 2453 participants were included. For pairwise meta-analysis, p values for TRT delivered by transdermal, intramuscular, and oral routes were as follows: IPSS: 0.93, 0.20, and 0.76; PSA level: 0.20, 0.27, and 0.98; prostate volume: 0.18, 0.04, and 0.16. There were no significant differences in IPSS, PSA level, or prostate volume between TRT routes. In subgroup analysis, long-term intramuscular TRT significantly decreased IPSS (p = 0.03), short-term transdermal TRT increased PSA levels (p < 0.001), and short-term intramuscular TRT increased the prostate volume (p = 0.04). Other forms of TRT showed no significant change in IPSS, PSA level, and prostate volume compared with the placebo. Indirect comparison of the three administration routes demonstrated no significant differences in IPSS, PSA level, and prostate volume. Nevertheless, surface under the cumulative ranking curve analysis indicated that intramuscular TRT had an 83% probability of being the best method for decreasing IPSS. CONCLUSIONS: The results demonstrate that TRT does not worsen LUTS regardless of the administration route. Intramuscular TRT may be the preferred treatment for aging men with LOH and LUTS. Intramuscular TRT may be the preferred treatment for men with LOH and LUTS. Further research is warranted to validate these findings and optimize TRT management strategies.

Alzheimer's Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments.

Background: Alzheimer's disease (AD) and epilepsy represent two complex neurological disorders with distinct clinical manifestations, yet recent research has highlighted their intricate interplay. This review examines the association between AD and epilepsy, with particular emphasis on late-onset epilepsy of unknown etiology, increasingly acknowledged as a prodrome of AD. It delves into epidemiology, pathogenic mechanisms, clinical features, diagnostic characteristics, treatment strategies, and emerging biomarkers to provide a comprehensive understanding of this relationship. Methods: A comprehensive literature search was conducted, identifying 128 relevant articles published between 2018 and 2024. Results: Findings underscore a bidirectional relationship between AD and epilepsy, indicating shared pathogenic pathways that extend beyond traditional amyloid-beta and Tau protein pathology. These pathways encompass neuroinflammation, synaptic dysfunction, structural and network alterations, as well as molecular mechanisms. Notably, epileptic activity in AD patients may exacerbate cognitive decline, necessitating prompt detection and treatment. Novel biomarkers, such as subclinical epileptiform activity detected via advanced electroencephalographic techniques, offer promise for early diagnosis and targeted interventions. Furthermore, emerging therapeutic approaches targeting shared pathogenic mechanisms hold potential for disease modification in both AD and epilepsy. Conclusions: This review highlights the importance of understanding the relationship between AD and epilepsy, providing insights into future research directions. Clinical data and diagnostic methods are also reviewed, enabling clinicians to implement more effective treatment strategies.

The Asian Fabry Cardiomyopathy High-Risk Screening Study 2 (ASIAN-FAME-2): Prevalence of Fabry Disease in Patients with Left Ventricular Hypertrophy.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that commonly manifests cardiovascular complications. We aimed to assess the prevalence of FD in a Chinese population with left ventricular hypertrophy (LVH) whilst implementing a gender-specific screening approach. Methods: Patients with LVH, defined as a maximum thickness of the left ventricular septal/posterior wall ≥ 13 mm, were considered eligible. All patients with hypertrophic cardiomyopathy (HCM) were excluded. Plasma α-galactosidase (α-GLA) enzyme activity was assessed using a dried blood spot test. Males with low enzyme activity underwent genetic testing to confirm a diagnosis of FD whereas females were screened for both α-GLA and globotriaosylsphingosine concentration and underwent genetic analysis of the GLA gene only if testing positive for ≥1 parameter. Results: 426 unrelated patients (age = 64.6 ± 13.0 years; female: male = 113:313) were evaluated. FD was diagnosed in 3 unrelated patients (age = 69.0 ± 3.5 years, female: male = 1:2) and 1 related female subject (age = 43 years). Genetic analyses confirmed the late-onset cardiac variant GLA c.640-801G>A (n = 3) and the missense variant c.869T>C associated with classic FD (n = 1). Cardiac complications were the only significant findings associated with the late-onset c.640-801G>A mutation, manifesting as mild or severe concentric LVH. In contrast, the classic c.869T>C mutation FD exhibited multisystemic manifestations in addition to severe concentric LVH. Conclusions: The prevalence of FD is lower in Chinese patients with LVH when HCM is excluded. The pathological variant c.640-801G>A remains the most common cause of late-onset FD, while the detection of FD in females can be improved by utilizing a gender-specific screening method.

Neuropsychiatric symptom burden in early-onset and late-onset Alzheimer's disease as a function of age.

INTRODUCTION: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. METHODS: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. RESULTS: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). DISCUSSION: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. HIGHLIGHTS: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.

The role of the Alzheimer's Disease Neuroimaging Initiative in establishing the Dominantly Inherited Alzheimer Network.

The Dominantly Inherited Alzheimer Network (DIAN) initially was funded by the National Institute on Aging (NIA) in 2008 and thus was able to adopt and incorporate the protocols developed by the Alzheimer's Disease Neuroimaging Initiative (ADNI) that had been established by the NIA in 2004. The use of ADNI protocols for DIAN neuroimaging studies and assays of biological fluids for Alzheimer disease (AD) biomarkers permitted examination of the hypothesis that autosomal dominant AD (ADAD), studied by DIAN, and "sporadic" late-onset AD (LOAD), studied by ADNI, shared the same pathobiological construct. In a collaborative effort, the longitudinal DIAN and ADNI databases were compared and the findings supported the conclusion that ADAD and LOAD share a similar pathophysiology. The importance of the DIAN study thus is amplified by its relevance to LOAD, as characterized by the "parent" ADNI program.

Unilateral Pleural Effusion as an Initial Manifestation of Systemic Lupus Erythematosus in a Patient of Advanced Age.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that can manifest in older individuals, presenting unique diagnostic challenges because of its atypical presentations and comorbidities. Pleural effusion is a relatively uncommon manifestation of SLE, with studies suggesting a higher prevalence in older than younger patients. We herein report an atypical case of delayed-onset SLE in a 75-year-old man with left-sided pleural effusion as the initial presentation. This case underscores the difficulty of diagnosing SLE in patients of advanced age and the importance of considering a broad range of differential diagnoses, even in cases that may suggest a more common disease. This case also highlights the fact that unilateral pleural effusion can be an initial manifestation of SLE, and when the cause of the pleural effusion is unclear, SLE should be considered as a potential diagnosis.

Functional imaging in late-onset epilepsy: A focused review.

INTRODUCTION: About 25 % of new-onset epilepsies are diagnosed after age 65. Late-onset epilepsy (LOE) is predicted to become a major healthcare problem in the next 15 years as the global population increases and ages. Neurodegenerative disorders account for 10-20 % of LOE, while over 20 % of these patients have an unknown etiology. Established diagnostic tools such as FDG-PET and novel biomarkers of neurodegeneration including amyloid and tau PET hold a lot of promise in diagnosing and ruling out neurodegenerative disorders in these patients. METHODS: We conducted a literature search to identify articles involving LOE populations and using one or more functional neuroimaging techniques. RESULTS: A total of 5 studies were identified through Boolean searching and snowballing. These were highly heterogenous with respect to operational definitions of LOE, analyses and interpretation pipelines. CONCLUSION: While there is some evidence for feasibility and usefulness of FDG- and Amyloid PET in LOE, methodological heterogeneities in the available literature preclude any notable conclusions. Future research in this field will benefit from a consensus on epilepsy-specific analysis and interpretation guidelines for amyloid and tau PET.

Clinical and paraclinical features of first unprovoked seizures in the elderly.

PURPOSE: The prevalence of unprovoked seizures and epilepsy rises significantly in later life stages. This study examines various factors in elderly patients (over 65 years) with their first unprovoked seizures, comparing findings with younger patients. METHODS: We analyzed electronic medical records of individuals with first unprovoked seizures retrospectively. Diagnosis was based on patient history and witness accounts, and exclusion of other potential causes. Data included demographics, physical examination, seizure characteristics, neuroimaging, EEG findings, laboratory markers, potential causes, prescribed anti-seizure medications (ASMs) at diagnosis and follow-up, seizure-related injuries and hospital stay length. RESULTS: We enrolled 391 patients (mean age 73.02 ± 16.5, 219 females). Most had late-onset (≥65 years) seizures (n = 295, 75.5 %). Status epilepticus was diagnosed in 10.2 %, more in the late-onset group. Elderly patients most often had focal seizures with impaired consciousness, while younger patients had focal to bilateral tonic-clonic seizures. (55.9 % vs 36.5 %). Late-onset seizures were linked to cerebrovascular diseases, small vessel disease, and cerebral atrophy, while early-onset cases were associated with brain tumors or unknown causes. Brain imaging revealed potentially epileptogenic abnormalities in 59.1 %. Positive paraneoplastic or autoimmune antibodies were found in 0.8 %. Abnormal EEGs were present in 25.9 %, more in the late-onset group. Most patients were discharged with levetiracetam (LEV) or lamotrigine (LTG) monotherapy. Nine patients with late-onset seizures died during in-hospital follow-up. CONCLUSION: Our findings can contribute to the improved identification and characterization of patients with late-onset seizures, facilitating targeted diagnostics and appropriate treatment in this challenging patient population.

Continuous prediction and clinical alarm management of late-onset sepsis in preterm infants using vital signs from a patient monitor.

BACKGROUND AND OBJECTIVE: Continuous prediction of late-onset sepsis (LOS) could be helpful for improving clinical outcomes in neonatal intensive care units (NICU). This study aimed to develop an artificial intelligence (AI) model for assisting the bedside clinicians in successfully identifying infants at risk for LOS using non-invasive vital signs monitoring. METHODS: In a retrospective study from the NICU of the Máxima Medical Center in Veldhoven, the Netherlands, a total of 492 preterm infants less than 32 weeks gestation were included between July 2016 and December 2018. Data on heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 1 Hz were extracted from the patient monitor. We developed multiple AI models using 102 extracted features or raw time series to provide hourly LOS risk prediction. Shapley values were used to explain the model. For the best performing model, the effect of different vital signs and also the input type of signals on model performance was tested. To further assess the performance of applying the best performing model in a real-world clinical setting, we performed a simulation using four different alarm policies on continuous real-time predictions starting from three days after birth. RESULTS: A total of 51 LOS patients and 68 controls were finally included according to the patient inclusion and exclusion criteria. When tested by seven-fold cross-validations, the mean (standard deviation) area under the receiver operating characteristic curve (AUC) six hours before CRASH was 0.875 (0.072) for the best performing model, compared to the other six models with AUC ranging from 0.782 (0.089) to 0.846 (0.083). The best performing model performed only slightly worse than the model learning from raw physiological waveforms (0.886 [0.068]), successfully detecting 96.1 % of LOS patients before CRASH. When setting the expected alarm window to 24 h and using a multi-threshold alarm policy, the sensitivity metric was 71.6 %, while the positive predictive value was 9.9 %, resulting in an average of 1.15 alarms per day per patient. CONCLUSIONS: The proposed AI model, which learns from routinely collected vital signs, has the potential to assist clinicians in the early detection of LOS. Combined with interpretability and clinical alarm management, this model could be better translated into medical practice for future clinical implementation.

Have epilepsy outcomes changed for children with tuberous sclerosis complex in Queensland, Australia?

OBJECTIVE: Historically, epilepsy has been the most frequently presenting feature of tuberous sclerosis complex (TSC). Advances in TSC health care have occurred over the past decade; thus, we studied whether TSC epilepsy outcomes have changed. METHOD: A retrospective chart review was undertaken for all children with TSC in Queensland, Australia. Epilepsy outcome and TSC diagnosis data were extracted, and data were compared between children born before 2012 with those born in or after 2012. RESULTS: In this retrospective cohort, TSC diagnosis in children born in or after 2012 is now predominantly antenatal (51%, p < .05). Most patients with epilepsy are now known to have TSC before they develop epilepsy. Despite earlier TSC diagnosis, the frequency of epilepsy (85%) has not changed (p = .92), but diagnosis trends toward an earlier age (median = 3 months for patients born in or after 2012 vs. 5.5 months for those born before 2012, p = .23). Most (95%) patients had focal seizures as their initial clinical seizure type; it was rare (5%) for epileptic spasms (ES) to be the initial seizure type. The frequency of ES was lower in patients born in or after 2012 (36% vs. 50%, p = .27). Infantile (<24 months) onset ES was not associated with worse epilepsy outcome. Late onset ES was seen in 14%, and these patients had a lower rate of epilepsy remission. Lennox-Gastaut syndrome was seen in 7%. Febrile/illness-related status epilepticus occurred in 12% of patients, between 1 and 4 years of age. Despite many (78%) patients having multiple daily seizures at maximal seizure frequency, and 74% meeting criteria for treatment-refractory epilepsy, most patients achieved epilepsy remission (66%), either with epilepsy surgery (47%) or with age (53%). At the time of inclusion in this study, only 21% of patients had uncontrolled frequent (daily to 3 monthly) seizures and 14% had uncontrolled infrequent (3 monthly to <2 yearly) seizures. SIGNIFICANCE: This study provides updated information that informs the counseling of parents of newly diagnosed pediatric TSC patients.

Gut microbiota in preterm infants with late-onset sepsis and pneumonia: a pilot case-control study.

BACKGROUND: Late-onset sepsis (LOS) and pneumonia are common infectious diseases, with high morbidity and mortality in neonates. This study aimed to investigate the differences in the gut microbiota among preterm infants with LOS, or pneumonia, and full-term infants. Furthermore, this study aimed to determine whether there is a correlation between intestinal pathogenic colonization and LOS. METHODS: In a single-center case‒control study, 16 S rRNA gene sequencing technology was used to compare gut microbiota characteristics and differences among the LOS group, pneumonia group, and control group. RESULTS: Our study revealed that the gut microbiota in the control group was more diverse than that in the LOS group and pneumonia group (P < 0.05). No significant differences in diversity were detected between the LOS and pneumonia groups (P > 0.05). Compared with the control group, the abundances of Akkermansia, Escherichia/Shigella, and Enterococcus increased, while the abundances of Bacteroides and Stenotrophomonas decreased in the LOS and pneumonia groups. The pathogenic bacteria in infants with LOS were consistent with the distribution of the main bacteria in the intestinal microbiota. An increase in Escherichia/Shigella abundance may predict a high risk of LOS occurrence, with an area under the curve (AUC) of 0.773. CONCLUSION: Changes in the gut microbiota composition were associated with an increased risk of LOS and pneumonia. The dominant bacteria in the gut microbiota of the LOS group were found to be associated with the causative pathogen of LOS. Moreover, preterm infants exhibiting an elevated abundance of Escherichia/Shigella may be considered potential candidates for predicting the onset of LOS.

Reproductive life factors and estro-progestin exposure in women with early-onset Parkinson's disease compared to late-onset disease and controls: A retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is more common in men than women. Although hormonal factors may partially explain this difference, there are no studies evaluating reproductive life factors and exogenous estroprogestin exposure in women with Early Onset Parkinson Disease (EOPD). OBJECTIVE: To compare reproductive life factors and exogenous estroprogestin exposure among female patients with EOPD, late-onset Parkinson's disease (LOPD), and EOPD-matched unaffected controls. METHODS: We identified female patients with EOPD from 1989 to 2021, defining EOPD as PD with motor-symptoms onset before age 50 and LOPD as PD with motor onset after 50. We paired EOPD patients to age-matched, unaffected controls. We reviewed medical records to determine demographic characteristics, clinical history, and reported reproductive menopausal history (reviewing medical records). RESULTS: We included 87 EOPD patients, 84 LOPD patients, and 91 unaffected controls with information about reproductive life factors and exogenous estroprogestin exposure in their medical records. There were no significant differences in race, ethnicity, or BMI between the three groups. EOPD patients were more likely to have used hormonal contraception than LOPD patients (23/49 (47 %) vs 0/84 (0 %), p < 0.001). LOPD patients had higher numbers of pelvic surgeries (48/84 [57 %] in LOPD, 23/87 [26 %] in EOPD, p < 0.001) and higher usage of perimenopausal hormonal therapy (52/84 [62 %] in LOPD, 10/87 [11 %] in EOPD, p < 0.001) in LOPD than EOPD. CONCLUSIONS: Our study reports no significant difference in reproductive life factors and exogenous estroprogestin exposure between controls and EOPD patients, except for higher exposure to hormonal contraception in EOPD. There was no apparent difference in reproductive life factors and exogenous estroprogestin exposure between EOPD and LOPD patients. Our findings therefore do not observe that hormonal exposure is different between earlier onset of female EOPD compared to female LOPD patients, or between female EOPD patients and unaffected female controls.

Neural Functioning in Late-Life Depression: An Activation Likelihood Estimation Meta-Analysis.

Late-life depression (LLD) is a relatively common and debilitating mental disorder, also associated with cognitive dysfunctions and an increased risk of mortality. Considering the growing elderly population worldwide, LLD is increasingly emerging as a significant public health issue, also due to the rise in direct and indirect costs borne by healthcare systems. Understanding the neuroanatomical and neurofunctional correlates of LLD is crucial for developing more targeted and effective interventions, both from a preventive and therapeutic standpoint. This ALE meta-analysis aims to evaluate the involvement of specific neurofunctional changes in the neurophysiopathology of LLD by analysing functional neuroimaging studies conducted on patients with LLD compared to healthy subjects (HCs). We included 19 studies conducted on 844 subjects, divided into 439 patients with LLD and 405 HCs. Patients with LLD, compared to HCs, showed significant hypoactivation of the right superior and medial frontal gyri (Brodmann areas (Bas) 8, 9), left cingulate cortex (BA 24), left putamen, and left caudate body. The same patients exhibited significant hyperactivation of the left superior temporal gyrus (BA 42), left inferior frontal gyrus (BA 45), right anterior cingulate cortex (BA 24), right cerebellar culmen, and left cerebellar declive. In summary, we found significant changes in activation patterns and brain functioning in areas encompassed in the cortico-limbic-striatal network in LLD. Furthermore, our results suggest a potential role for areas within the cortico-striatal-cerebellar network in the neurophysiopathology of LLD.

Intracranial vasculopathy: an important organ damage in young adult patients with late-onset Pompe disease.

BACKGROUND: Late-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients. RESULTS: Neuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging. CONCLUSIONS: Intracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.

Diverging Relationships among Amyloid, Tau, and Brain Atrophy in Early-Onset and Late-Onset Alzheimer's Disease.

PURPOSE: Alzheimer's disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research. MATERIALS AND METHODS: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests. RESULTS: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD. CONCLUSION: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism.

Identifying the earliest-occurring clinically targetable precursors of late-onset Alzheimer's disease.

Most cases of Alzheimer's disease (AD) are late-onset dementias (LOAD). However, research on AD is predominantly of early-onset disease (EOAD). The determinants of EOAD, gene variants of APP and presenilin proteins, are not the basic precursors of LOAD. Rather, multiple other genes and associated cellular processes underlie risk for LOAD. These determinants could be modified in individuals at risk for LOAD well before signs and symptoms appear. Studying brain cells produced from patient-derived induced-pluripotent-stem-cells (iPSC), in culture, will be instrumental in developing such interventions. This paper summarises evidence accrued from iPSC culture models identifying the earliest occurring clinically targetable determinants of LOAD. Results obtained and replicated, thus far, suggest that abnormalities of bioenergetics, lipid metabolism, digestive organelle function and inflammatory activity are primary processes underlying LOAD. The application of cell culture platforms will become increasingly important in research and also on LOAD detection, assessment, and treatment in the years ahead.

Testosterone therapy for functional hypogonadism in middle-aged and elderly males: current evidence and future perspectives.

Population aging is a global phenomenon driving research focus toward preventing and managing age-related disorders. Functional hypogonadism (FH) has been defined as the combination of low testosterone levels, typically serum total testosterone below 300-350 ng/dL, together with manifestations of hypogonadism, in the absence of an intrinsic pathology of the hypothalamic-pituitary-testicular (HPT) axis. It is usually seen in middle-aged or elderly males as a product of aging and multimorbidity. This age-related decline in testosterone levels has been associated with numerous adverse outcomes. Testosterone therapy (TTh) is the mainstay of treatment for organic hypogonadism with an identifiable intrinsic pathology of the HPT axis. Current guidelines generally make weak recommendations for TTh in patients with FH, mostly in the presence of sexual dysfunction. Concerns about long-term safety have historically limited TTh use in middle-aged and elderly males with FH. However, recent randomized controlled trials and meta-analyses have demonstrated safe long-term outcomes regarding prostatic and cardiovascular health, together with decreases in all-cause mortality and improvements in various domains, including sexual function, body composition, physical strength, bone density, and hematopoiesis. Furthermore, there are numerous insightful studies suggesting additional benefits of TTh, for instance in cardio-renal-metabolic conditions. Specifically, future trials should investigate the role of TTh in improving symptoms and prognosis in various clinical contexts, including sarcopenia, frailty, dyslipidemia, arterial hypertension, diabetes mellitus, fracture risk, heart failure, stable angina, chronic kidney disease, mood disorders, and cognitive dysfunction.

Linking preterm infant gut microbiota to nasograstric enteral feeding tubes: exploring potential interactions and microbial strain transmission.

Introduction: Preterm birth is a growing problem worldwide. Staying at a neonatal intensive care unit (NICU) after birth is critical for the survival of preterm infants whose feeding often requires the use of nasogastric enteral feeding tubes (NEFT). These can be colonized by hospital-associated pathobionts that can access the gut of the preterm infants through this route. Since the gut microbiota is the most impactful factor on maturation of the immune system, any disturbance in this may condition their health. Therefore, the aim of this study is to assess the impact of NEFT-associated microbial communities on the establishment of the gut microbiota in preterm infants. Material and methods: A metataxonomic analysis of fecal and NEFT-related samples obtained during the first 2 weeks of life of preterm infants was performed. The potential sharing of strains isolated from the same set of samples of bacterial species involved in NICU's outbreaks, was assessed by Random Amplification of Polymorphic DNA (RAPD) genotyping. Results: In the samples taken 48 h after birth (NEFT-1 and Me/F1), Staphylococcus spp. was the most abundant genera (62% and 14%, respectively) and it was latter displaced to 5.5% and 0.45%, respectively by Enterobacteriaceae. Significant differences in beta diversity were detected in NEFT and fecal samples taken at day 17 after birth (NEFT-3 and F3) (p = 0.003 and p = 0.024, respectively). Significant positive correlations were found between the most relevant genera detected in NEFT-3 and F3. 28% of the patients shared at least one RAPD-PCR profile in fecal and NEFT samples and 11% of the total profiles were found at least once simultaneously in NEFT and fecal samples from the same patient. Conclusion: The results indicate a parallel bacterial colonization of the gut of preterm neonates and the NEFTs used for feeding, potentially involving strain sharing between these niches. Moreover, the same bacterial RAPD profiles were found in neonates hospitalized in different boxes, suggesting a microbial transference within the NICU environment. This study may assist clinical staff in implementing best practices to mitigate the spread of pathogens that could threaten the health of preterm infants.

Cryptic late-onset myocarditis after coronavirus vaccination.

As we enter a new era of mRNA-based therapeutics, evidence on genetic or environmental factors that might predispose to unknown off-target side effects, gains in importance. Among these factors, exercise appears likely to have influenced otherwise cryptic cases of early-onset postvaccination myocarditis. And the existence of a distinct late-onset myocarditis is now being recognized. Here, three case-history reports suggest crypticity (the author's own case), unless provoked by a preexisting cardiac morbidity (one case), or by immune checkpoint blockade to enhance anticancer autoimmunity (several cases). These reports are supported by noninvasive fluorodeoxyglucose-based cardiac scan comparisons of multiple vaccinated and unvaccinated subjects. In pre-pandemic decades, applications for funds by the leading innovator in mRNA-based therapeutics seldom gained peer-review approval. Thus, at the start of the pandemic, the meager data on such side effects could justify only emergency approval. We must do better.