Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India.

BACKGROUND: Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. MATERIALS AND METHODS: We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan-Meier methods. RESULTS: A total of 30 patients were identified. The median age was 25.5 (range, 18-45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8-85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4-87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3-98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3-83.3%]). CONCLUSIONS: Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Fear about adverse effect on fertility is a major cause of COVID-19 vaccine hesitancy in the United States.

Although COVID-19 vaccine access has increased nationwide, vaccination rates have been slow-moving, with many studies showing significant vaccine hesitancy in the U.S. We conducted an online survey using Amazon Mechanical Turk (MTurk) to identify reasons for vaccine hesitancy among unvaccinated adults between June 30 and July 1, 2021. We found that 58% of unvaccinated respondents were worried about unknown long-term adverse effects. Of these, 41% believed that the COVID-19 vaccines can negatively impact reproductive health and or fertility, and 38% were unsure of the effects on fertility. Our study demonstrates that fear regarding COVID-19 vaccine adverse effects and belief that they can negatively impact fertility is a major cause of vaccine hesitancy in the United States. We identified that urban residents, married individuals, those born outside the U.S., those with health insurance, and people with higher education and income greater than $100,000 felt that the vaccine would affect fertility more than their counterparts did. Finally, we found that 48% of unvaccinated respondents cited 'more information and research conducted on the COVID-19 vaccines' as the action that would most encourage vaccine uptake.

COVID-19 vaccination not associated with increased risk of erectile dysfunction.

Although mRNA COVID-19 vaccines have proven to be safe and effective against SARS-CoV-2, vaccination rates have slowed, with some individuals citing impotence as a concern. Therefore, we conducted a survey of the US males to evaluate the impact of COVID-19 vaccination on erectile function. We hypothesized that vaccinated men would not have a higher risk of ED compared to unvaccinated men. Amazon Mechanical Turk (MTurk) was utilized to survey the US adult male population between August 26 and September 2, 2021. Survey participation was open to 1000 males over the age of 18 and currently living in the United States regardless of vaccination status or the past medical history of COVID-19. Selection criteria included respondents ≥45 years old, no history of physician-diagnosed ED, biologically born, and identify as male. Participants completed an anonymous 16-question survey that included a multidimensional scale used to evaluate ED, the International Index of Erectile Function (IIEF-5). Among vaccinated men, the median IIEF-5 score was 20 [16-24] compared to 22 [17.5-25] in the unvaccinated group (p = 0.195). The multivariable-adjusted analysis demonstrated that vaccination against COVID-19 was not associated with increased risk of ED. Overall, this cross-sectional survey showed that COVID-19 vaccination was not associated with an increased risk of erectile dysfunction in males 45 years and older.

ChIPprimersDB: a public repository of verified qPCR primers for chromatin immunoprecipitation (ChIP).

Chromatin immunoprecipitation (ChIP) has ushered in a new era of scientific discovery by allowing new insights into DNA-protein interactions. ChIP is used to quantify enriched genomic regions using qPCR, and more recently is combined with next generation sequencing (ChIP-seq) to obtain a genome wide profile of protein binding sites. Nevertheless, ChIP-qPCR remains an integral component of this technology for quality control purposes, before the library preparation and sequencing steps. In addition, ChIP-qPCR remains more time- and cost-effective for many focused projects in which the DNA regions of interest are already known. However, the DNA oligonucleotide primers needed for ChIP-qPCR are more challenging to design than for other qPCR projects. Here, we present the first public repository for ChIP oligonucleotides that have been verified to perform well in ChIP-qPCR experiments. ChIPprimersDB was developed by manual screening of publications to ensure primer quality and provide additional specific information on the ChIP experiments where the primers have been used. In addition to the primer sequences, the database includes information about the antibody, cells and tissues used in the experiment, information on the experimental design, and a direct link to the original publication. The database is linked at https://umiamihealth.org/bascom-palmer-eye-institute/research/clinical-and-laboratory-research/ocular-oncology-laboratory/chip-primers and hosted at https://www.chipprimers.com/.

Discrete Pools of Oligomeric Amyloid-ß Track with Spatial Learning Deficits in a Mouse Model of Alzheimer Amyloidosis.

Despite increasing appreciation that oligomeric amyloid-ß (Aß) may contribute to cognitive decline of Alzheimer disease, defining the most critical forms has been thwarted by the changeable nature of these aggregates and the varying methods used for detection. Herein, using a broad approach, we quantified Aß oligomers during the evolution of cognitive deficits in an aggressive model of Aß amyloidosis. Amyloid precursor protein/tetracycline transactivator mice underwent behavioral testing at 3, 6, 9, and 12 months of age to evaluate spatial learning and memory, followed by histologic assessment of amyloid burden and biochemical characterization of oligomeric Aß species. Transgenic mice displayed progressive impairments in acquisition and immediate recall of the trained platform location. Biochemical analysis of cortical extracts from behaviorally tested mice revealed distinct age-dependent patterns of accumulation in multiple oligomeric species. Dot blot analysis demonstrated that nonfibrillar Aß oligomers were highly soluble and extracted into a fraction enriched for extracellular proteins, whereas prefibrillar species required high-detergent conditions to retrieve, consistent with membrane localization. Low-detergent extracts tested by 82E1 enzyme-linked immunosorbent assay confirmed the presence of bona fide Aß oligomers, whereas immunoprecipitation-Western blotting using high-detergent extracts revealed a variety of SDS-stable low-n species. These findings show that different Aß oligomers vary in solubility, consistent with distinct localization, and identify nonfibrillar Aß oligomer-positive aggregates as tracking most closely with cognitive decline in this model.

Neuronal overexpression of human VAPB slows motor impairment and neuromuscular denervation in a mouse model of ALS.

Four mutations in the VAMP/synaptobrevin-associated protein B (VAPB) gene have been linked to amyotrophic lateral sclerosis (ALS) type 8. The mechanism by which VAPB mutations cause motor neuron disease is unclear, but studies of the most common P56S variant suggest both loss of function and dominant-negative sequestration of wild-type protein. Diminished levels of VAPB and its proteolytic cleavage fragment have also been reported in sporadic ALS cases, suggesting that VAPB loss of function may be a common mechanism of disease. Here, we tested whether neuronal overexpression of wild-type human VAPB would attenuate disease in a mouse model of familial ALS1. We used neonatal intraventricular viral injections to express VAPB or YFP throughout the brain and spinal cord of superoxide dismutase (SOD1) G93A transgenic mice. Lifelong elevation of neuronal VAPB slowed the decline of neurological impairment, delayed denervation of hindlimb muscles, and prolonged survival of spinal motor neurons. Collectively, these changes produced a slight but significant extension in lifespan, even in this highly aggressive model of disease. Our findings lend support for a protective role of VAPB in neuromuscular health.

Plication for Severe Peyronie's Deformities Has Similar Long-Term Outcomes to Milder Cases.

INTRODUCTION: Penile plication (PP) for Peyronie's disease (PD) is an established treatment option for mild to moderate curvature, but scant data exist regarding its utility in severe deformities. AIM: To evaluate long-term outcomes among men undergoing PP for PD, comparing severe to mild/moderate penile deformities. METHODS: We performed a retrospective review of patients who underwent PP for PD between 2009 and 2017. All patients underwent multiple parallel tunical plication without degloving. Severe PD was defined as either curvature ≥60 degrees or biplanar curvature ≥35 degrees. Patient demographics and surgical outcomes were analyzed. A modified PD Questionnaire and International Index of Erectile Function (IIEF)-5 were administered by telephone. MAIN OUTCOME MEASURE: Long-term patient-reported outcomes were evaluated from a modified survey incorporating the PD Questionnaire and IIEF-5. RESULTS: Of 327 PP patients, 102 (31%) responded to the telephone survey at a median 59.5 months (interquartile range 28.3-84) since surgery. Patients were equally distributed into severe (n = 51) and mild/moderate (n = 51) groups. Despite a greater mean degree of curvature in severe compared to mild/moderate patients (71.6 degrees vs 37.7 degrees, respectively, P < .001), correction of penile curvature was achieved in 91% of patients, with a mean change of 60.7 degrees in severe cases compared to 31.4 degrees in mild/moderate cases (P < .001). Equal numbers of patients in severe and mild/moderate groups reported improvement of penile curvature (74.5% vs 74.5%, P = 1.0) and sexual function (51.0% vs 49.0%, P = .84). PD Questionnaire metrics were likewise similar between severe and mild/moderate patients (P > .1), as were rates of subjective penile shortening (62.7% vs 62.7%, P = 1.0) and IIEF-5, both pre-operatively (19.5 vs 19.7, P = .9) and post-operatively (19.4 vs 17.6, respectively, P = .15). On multivariate logistic regression, worsening sexual function was significantly associated with increased age (odds ratio 1.07, P = .01) and pre-operative IIEF (odds ratio 1.14, P = .02). CLINICAL IMPLICATIONS: PP should be considered in PD patients with severe deformities, as outcomes are favorable and comparable to those with milder curvature. STRENGTH & LIMITATIONS: This is a novel study evaluating long-term patient-reported outcomes after PP, comparing patients with severe deformity to those with mild/moderate curvature. The study was limited by retrospective design, relatively low survey response rate (31%), and lack of validated post-operative PD questionnaire. CONCLUSION: Long-term patient-reported outcomes of PP for severe PD deformities are comparable to mild/moderate cases, supporting broader application of PP beyond milder deformities. Reddy RS, McKibben MJ, Fuchs JS, et al. Plication for Severe Peyronie's Deformities Has Similar Long-Term Outcomes to Milder Cases. J Sex Med 2018;15:1498-1505.

Reconstruction after retrosigmoid approaches using autologous fat graft-assisted Medpor Titan cranioplasty: assessment of postoperative cerebrospinal fluid leaks and headaches in 60 cases.

BACKGROUND: Postoperative cerebrospinal fluid (CSF) leaks and headaches remain potential complications after retrosigmoid approaches for lesions in the posterior fossa and cerebellopontine angle. The authors describe a simple repair technique with an autologous fat graft-assisted Medpor Titan cranioplasty and investigate the incidence of postoperative CSF leaks and headaches using this technique. METHODS: A retrospective chart review was conducted on all cases (n = 60) of retrosigmoid craniectomy from September 2009 to May 2014 in patients who underwent fat graft-assisted cranioplasty. After obtaining a watertight dural closure and sealing off any visible mastoid air cells with bone wax, an autologous fat graft was placed over the dural suture line and up against the waxed-off air cells. The fat graft filled the retrosigmoid cranial defect and was then bolstered with a Medpor Titan (titanium mesh embedded in porous polyethylene) cranioplasty. A postoperative mastoid pressure dressing was applied for 48 h, and prophylactic lumbar drainage was not used. Factors examined in this study included postoperative CSF leak (incisional, rhinorrhea, otorrhea), pseudomeningocele formation, incidence and severity of postoperative headache, length of hospital stay, and length of follow-up. RESULTS: No patients developed postoperative CSF leaks (0 %), pseudomeningoceles (0 %), or new-onset postoperative headaches (0 %) with the described repair technique. There were no cases of graft site morbidity such as hematoma or wound infection. Mean duration of postoperative hospital stay was 3.8 days (range 2-10 days). Mean postoperative follow-up was 12.4 months (range 2.0-41.1 months). CONCLUSIONS: Our multilayer repair technique with a fat graft-assisted Medpor Titan cranioplasty appears effective in preventing postoperative CSF leaks and new-onset postoperative headaches after retrosigmoid approaches. Postoperative lumbar drainage may not be necessary.

Temporal Trends of Semen Quality and Fertility Rates Over the Course of a Decade: Data From King County, Washington.

OBJECTIVE: There has been a widely reported decline in both semen quality and fertility rate, however to date these studies have not looked at a decline of both in the same time period within the same geographical area. The objective of this study was to determine if there existed a temporal trend in both semen parameters and fertility rates for the same geographic area (King County, WA) over time. MATERIALS AND METHODS: Semen parameters from sperm donors at Seattle sperm bank were obtained from 2008 to 2021. Sperm donations occurred in King County, WA. Donors were from within 50 miles of the donation site. Fertility rates were calculated for King County, WA using census data from SEER to find number of women aged 15-49 and the number of births were found using CDC Wonder data from 2006 to 2017. RESULTS: There were a total of 76,622 sperm donor semen analyses from King County, WA included in our study from 2008 to 2021. The fertility rate for King County, WA was calculated from 2006 to 2017. From 2008 to 2021, there was a statistically significant decline in semen quality over time for both sperm count (P < .01), total motile sperm count (P < .01), sperm concentration (P < .01), and progressive motility (P < .01). Additionally, from 2006 to 2017 there was a statistically significant decline in fertility rate (P < .01). CONCLUSION: We report a statistically significant decline in sperm parameters among donors and a corresponding decline in fertility rates from the same geographic area that warrants further investigation given the serious societal and economic impacts a shrinking population presents. While certainly not the sole contributing factor, declining sperm parameters likely need to be accounted for when accounting for declining fertility rates.

Contemporary Approach to Narrow Angles.

Glaucoma is the leading cause of irreversible blindness worldwide. Among all glaucoma types, primary angle closure glaucoma (PACG) affects approximately 23 million people worldwide, and is responsible for 50% of glaucoma-related blindness, highlighting the devastating consequences of this disease. The main mechanism of PACG is relative pupillary block. High-risk populations are female gender, Asian ethnicity, high hyperopia, short axial length, and a thick/anteriorly positioned lens. This review discusses the clinical diagnosis, classification, and management of patients with a narrow angle with and without intraocular pressure (IOP) elevation and glaucomatous optic nerve damage, including laser peripheral iridotomy (LPI), endocycloplasty (ECPL), lens extraction, and goniosynechialysis.

Ahmed ClearPath vs. Baerveldt Glaucoma Implant: A Retrospective Noninferiority Comparative Study.

PURPOSE: To compare the efficacy and safety of 2 nonvalved glaucoma drainage devices (GDDs): Ahmed ClearPath (ACP) vs. Baerveldt glaucoma implant (BGI). DESIGN: Single-center, retrospective, comparative study. PARTICIPANTS: Consecutive patients who underwent ACP or BGI surgery for glaucoma (250 mm2 or 350 mm2 models), had ≥ 6 months of follow-up, and no prior GDD implantation. METHODS: Chart review of ACP or BGI surgery in patients with glaucoma at Wills Eye Hospital (2020-2023). MAIN OUTCOME MEASURES: The primary outcome measure was surgical failure at the end of follow-up, defined as intraocular pressure (IOP) > 21 or < 6 mmHg at 2 consecutive visits, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Secondary outcome measures included the rate of postoperative complications and changes in best corrected visual acuity (BCVA), IOP, and glaucoma medications. RESULTS: A total of 128 eyes of 113 patients (63 ACP, 65 BGI) with similar baseline characteristics and a mean follow-up duration of 19.6 ± 10.8 (median 20.5) months were included. Surgical failure occurred in 12 eyes (9.4%) with no significant difference between ACP and BGI eyes (9.5% vs. 9.2%, respectively; P = 0.810). Reasons for failure included IOP > 21 mmHg (3/12, 25.0%), glaucoma reoperation (5/12, 41.7%), and tube removal (4/12, 33.3%). No eyes progressed to NLP vision. Kaplan-Meier survival analysis showed similar cumulative rate of surgical failure in both groups (P = 0.871). Both groups achieved significant IOP and medication reduction compared to their baseline. Final IOP, BCVA, and complication rates were similar in both groups, but medication number was significantly lower in the ACP group (P = 0.012). Both the 250 mm2 and 350 mm2 models had similar outcomes, but diplopia was significantly associated with the 350 mm2 model of either implant (P = 0.012). Univariate logistic regression analysis did not identify either tube type or plate size as predictors of surgical failure. CONCLUSIONS: This study compares the recently approved ACP vs. BGI. Both implants had similar surgical failures and complication rates. Final IOP was similar in both groups, but ACP achieved lower medication number. Diplopia was significantly associated with the use of 350 mm2 model of either implant. Neither tube type nor plate size were significant predictors of surgical failure. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Patient Satisfaction with Oral Testosterone Undecanoate in Men Who Received Prior Testosterone Therapy: An Open-Label, Single-Center Clinical Trial.

PURPOSE: To evaluate patient satisfaction and symptom control in hypogonadal men transitioning from other testosterone therapies to oral testosterone undecanoate (TU). MATERIALS AND METHODS: In this open-label clinical trial, men aged 18 to 75 years with hypogonadism were switched to oral TU after a sufficient washout of previous testosterone therapies. Treatment satisfaction and symptom control were primarily measured using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) and quantitative androgen deficiency in aging males (qADAM) questionnaires, respectively. Secondary outcomes included changes in serum testosterone (T), estradiol (E2), hematocrit (HCT), and prostate-specific antigen (PSA) levels. RESULTS: Forty-one men participated, with significant improvements in all TSQM-9 scores observed over 6 months. Symptom control as measured by qADAM remained consistent. There was a significant increase in serum T and E2 levels, but HCT and PSA levels remained stable. CONCLUSIONS: Switching to oral TU from other testosterone therapies is associated with increased patient satisfaction and stable hypogonadal symptom control.

Clinical utility of serum 17-hydroxyprogesterone as a marker for medical therapy for male infertility: recommendations based on clinical scenarios.

Traditional serum hormone testing in the evaluation of male infertility consists of testosterone, follicle-stimulating hormone, luteinizing hormone, and estradiol. Based on these values, medical therapy is often initiated in an attempt to increase intratesticular testosterone levels and, in turn, promote spermatogenesis. While this hormone panel provides serum testosterone levels, it does not evaluate intratesticular testosterone, obviously an important factor that is critical for spermatogenesis. 17-hydroxyprogesterone (17-OHP) is an intermediate in the steroidal pathway of cholesterol to testosterone conversion that has recently demonstrated promise as an accurate serum biomarker for intratesticular testosterone. At present, 17-OHP has not been widely adopted as a clinical tool in the evaluation of male infertility, which likely stems, in part, from a lack of concrete indications for its use. In this review, we present five commonly encountered scenarios of male infertility where the utilization of 17-OHP has aided in the management and provided a more personalized approach to treatment.

A Comparative Analysis of Ergonomic Risk Utilizing the 4K-3D Exoscope Versus Standard Operating Microscope for Male Fertility Microsurgery.

OBJECTIVE: To stratify ergonomic risk in a urologic microsurgeon using the 4K-3D exoscope versus the operating microscope (OM) with wearable technology. METHODS: The surgeon was calibrated with wearable sensor inertial measurement units (IMUs) on the head and upper arms. Each inertial measurement units contained an accelerometer, magnetometer, and gyroscope to measure surgeon joint angle change during microscopic procedures for male fertility. The validated modified rapid upper limb assessment was used to determine the proportion of time spent in ranges of risk. Categories 1-4 were assigned for the head and upper extremities (4= highest ergonomic risk). Chi-squared analysis was used to analyze differences in proportions. RESULTS: A total of 500 and 479 minutes from 4K-3D exoscope and OM guided surgeries were analyzed. The 4K-3D exoscope significantly favored upper arm category 1 positioning compared to the OM (56.2% vs 37.7%; P < .0001). The OM exposed the surgeon to higher category 3 positioning (14.6% vs 1.6%; P <.0001). More time was spent with the neck "extended" using the 4K-3D exoscope (51.8% vs 19.5%; P < .0001) with 67% of neck extension between 0-10° (category 1). Overall, more time was spent with the neck in risk group 1-2 with the OM (P < .0001). CONCLUSION: The 4K-3D exoscope offers favorable ergonomic positioning for the upper extremities which may reduce work stress-related injury. More operative time was spent with the neck in mild extension with 4K-3D exoscope utilization. However, the OM favored longer operative times in low-risk neck ergonomic positions.

Patient Satisfaction After Switching to Jatenzo (Oral Testosterone Undecanoate): Update on an Open-label, Single-arm Clinical Trial.

This is the first study investigating patient satisfaction among men receiving oral testosterone decanoate (TU) who were previously using other forms of testosterone therapy. Oral TU appeared to lead to greater patient satisfaction in comparison to previous modalities and similar improvements in hypogonadal symptoms. TU represents a favorable and viable option for hypogonadal individuals who are unhappy with existing treatment options.

Comparison of Intratesticular Testosterone between Men Receiving Nasal, Intramuscular, and Subcutaneous Pellet Testosterone Therapy: Evaluation of Data from Two Single-Center Randomized Clinical Trials.

PURPOSE: Testosterone replacement therapy (TRT) can potentially cause decreased spermatogenesis and subsequent infertility. Recent studies have suggested that 17-hydroxyprogesterone (17-OHP) is a reliable surrogate for intratesticular testosterone (ITT) that is essential for spermatogenesis. We evaluated data from two ongoing open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous testosterone pellets (TP) and (Trial II) intranasal testosterone (NT) or intramuscular testosterone cypionate (TC). MATERIALS AND METHODS: Seventy-five symptomatic hypogonadal men (2 serum testosterone <300 ng/dL) were randomized into open label randomized clinical trials. Eligible subjects received 800 mg TP, 11 mg TID NT or 200 mg ×2 weeks TC. 17-OHP and Serum testosterone were evaluated at baseline and follow-up. The primary outcome was changes in 17-OHP. Secondary outcome was changes in serum testosterone. Data was analyzed by two-sample and single-sample t-tests, and determination of equal or unequal variances was computed using F-tests. RESULTS: Median participant age was 45 years old, with overall baseline 17-OHP of 46 and serum testosterone of 223.5 ng/dL. 17-OHP significantly decreased in subjects prescribed long-acting TP or TC. The 4-month change in 17-OHP in the NT group (-33.3% from baseline) was less than the change seen in TC (-65.3% from baseline) or TP (-44% from baseline) (p=0.005). All testosterone formulations increased serum testosterone levels at follow-up, with the largest increase seen in TC (+157.6%), followed by NT (+114.3%) and TP (+79.6%) (p=0.005). CONCLUSIONS: Short-acting nasal testosterone appear to have no impact on serum 17-OHP especially in comparison to long-acting testosterone formulations. All modalities saw significant increases in serum testosterone levels at follow-up. NT and other short acting testosterone formulations may better preserve ITT and be beneficial for hypogonadal men seeking to maintain fertility potential while on TRT.

Prevalence of secondary erythrocytosis in men receiving testosterone therapy A matched-cohort analysis of intranasal gel, injections, and pellets.

INTRODUCTION: Increased hematocrit (HCT) is a common adverse effect in men on testosterone therapy (TTh). We aimed to uncover differences in HCT changes among men receiving different forms of TTh. METHODS: We conducted a single-center, retrospective, matched-cohort study of patients treated for testosterone deficiency (TD) to investigate the effect of three TTh regimens on HCT. We included men who received intranasal testosterone (NT), intramuscular testosterone (TC), or subcutaneous testosterone pellet (TP) regimens between January 2011 and December 2020. We matched treatment cohorts 1:1:1 for age, body mass index (BMI), and history of obstructive sleep apnea (OSA). Those taking TTh for <16 weeks were excluded. Comparison between groups was performed with Mann-Whitney U test, Student's t-test, ANOVA, or Kruskal-Wallis test as appropriate. RESULTS: Seventy-eight matched-cohort individuals with TD received either NT, TC, or TP. The most common TD symptoms prior to initiation of TTh were erectile dysfunction (38%), low libido (22%), and lack of energy (17%). Baseline serum testosterone and HCT were higher in NT recipients (p<0.05). As expected, all men receiving TTh were found to have increased serum testosterone levels at followup (p<0.001). Relative to their respective baselines, men receiving TC experienced the greatest increase in serum testosterone (240.8 ng/dL to 585.5 ng/dL), followed by NT (230.3 ng/dL to 493.5 ng/dL) and TP (210.8 ng/dL to 360.5 ng/dL) (all p<0.001). TC and TP were associated with significant increases in HCT (4.4% and 1.7%) while NT was associated with a decrease in HCT (-0.8%) at 16-week followup. CONCLUSIONS: When controlled for age, BMI, and OSA, men receiving NT experienced decreased HCT compared to TC or TP at 16-week followup. Intranasal testosterone, while able to increase serum testosterone levels to reference range, does not appear to have a significant impact on HCT compared to the longer-acting forms of TTh.

Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial.

Background: Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients. Aim: To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively. Methods: This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg). Outcomes: We evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen. Results: After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to <300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300 ng/dL, with similar rates between the groups in the study. Clinical Implications: Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD. Strengths and Limitations: Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort. Conclusion: E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.

Mortality of COVID-19 in patients with hematological malignancies versus solid tumors: a systematic literature review and meta-analysis.

Cancer patients are more vulnerable to COVID-19 compared to the general population, but it remains unclear which types of cancer have the highest risk of COVID-19-related mortality. This study examines mortality rates for those with hematological malignancies (Hem) versus solid tumors (Tumor). PubMed and Embase were systematically searched for relevant articles using Nested Knowledge software (Nested Knowledge, St Paul, MN). Articles were eligible for inclusion if they reported mortality for Hem or Tumor patients with COVID-19. Articles were excluded if they were not published in English, non-clinical studies, had insufficient population/outcomes reporting, or were irrelevant. Baseline characteristics collected included age, sex, and comorbidities. Primary outcomes were all-cause and COVID-19-related in-hospital mortality. Secondary outcomes included rates of invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission. Effect sizes from each study were computed as logarithmically transformed odds ratios (ORs) with random-effects, Mantel-Haenszel weighting. The between-study variance component of random-effects models was computed using restricted effects maximum likelihood estimation, and 95% confidence intervals (CIs) around pooled effect sizes were calculated using Hartung-Knapp adjustments. In total, 12,057 patients were included in the analysis, with 2,714 (22.5%) patients in the Hem group and 9,343 (77.5%) patients in the Tumor group. The overall unadjusted odds of all-cause mortality were 1.64 times higher in the Hem group compared to the Tumor group (95% CI: 1.30-2.09). This finding was consistent with multivariable models presented in moderate- and high-quality cohort studies, suggestive of a causal effect of cancer type on in-hospital mortality. Additionally, the Hem group had increased odds of COVID-19-related mortality compared to the Tumor group (OR = 1.86 [95% CI: 1.38-2.49]). There was no significant difference in odds of IMV or ICU admission between cancer groups (OR = 1.13 [95% CI: 0.64-2.00] and OR = 1.59 [95% CI: 0.95-2.66], respectively). Cancer is a serious comorbidity associated with severe outcomes in COVID-19 patients, with especially alarming mortality rates in patients with hematological malignancies, which are typically higher compared to patients with solid tumors. A meta-analysis of individual patient data is needed to better assess the impact of specific cancer types on patient outcomes and to identify optimal treatment strategies.