Direct conversion from long-acting testosterone replacement therapy to Natesto allows for spermatogenesis resumption: Proof of concept.

Long-acting testosterone replacement therapy (TRT) suppresses spermatogenesis. A short-acting TRT, Natesto, maintains spermatogenesis in some men. This study evaluated hormonal and semen parameters converting men from long-acting TRT to Natesto. Baseline hormones, again on long-acting TRT and 1 month after converting to Natesto, as well as semen parameters 3 months after converting to Natesto were assessed. Twenty-seven men were directly converted from long-acting forms of TRT to Natesto. Mean duration on long-acting TRT was 24.3 ± 19 months. Testosterone levels were similar on long-acting forms of TRT and Natesto, however; E2 levels were significantly lower on Natesto. Ten men had semen analyses demonstrating azoospermia while on long-acting TRT, the remainder were presumed to be azoospermic or severely oligospermic which has been well established as an effect of long-acting TRT. All 27 men had resumption of spermatogenesis with a mean sperm concentration of 50.7 million/ml after converting to Natesto, considered within the fertile range. One couple achieved a pregnancy 4 months after converting to Natesto. Hypogonadal men on long-acting TRT interested in resumption of spermatogenesis may convert directly to Natesto for an opportunity to do so while remaining on a form of TRT and achieving lower E2 levels.

The expression of pregnancy-associated plasma protein-A (PAPP-A) in human blastocoel fluid-conditioned media: a proof of concept study.

PURPOSE: The aim of this study was to determine if pregnancy-associated plasma protein-A (PAPP-A), typically measured in maternal serum and a potential predictor of adverse maternal and fetal outcomes such as spontaneous miscarriage, pre-eclampsia, and stillbirth, is expressed in blastocoel fluid-conditioned media (BFCM) at the embryonic blastocyst stage. DESIGN: This is an in vitro study. METHODS: BFCM samples from trophectoderm-tested euploid blastocysts (n = 80) from in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were analyzed for PAPP-A mRNA. BFCM was obtained from blastocyst stage embryos in 20 uL drops. Blastocysts underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy prior to blastocyst vitrification and BFCM collection for snap freezing. cfDNA was synthesized using BFCM collected from 80 individual euploid blastocysts. Next, real-time qPCR was performed to detect expression of PAPP-A with GAPDH for normalization of expression in each sample. RESULTS: PAPP-A mRNA was detected in 45 of 80 BFCM samples (56.3%), with varying levels of expression across samples. CONCLUSION: Our study demonstrates the expression of PAPP-A in BFCM. To our knowledge, this is the first study to report detection of PAPP-A mRNA in BFCM. Further studies are required and underway to investigate a greater number of BFCM samples as well as the possible correlation of PAPP-A expression with pregnancy outcomes of transferred euploid blastocysts. If found to predict IVF and obstetric outcomes, PAPP-A may provide additional information along with embryonic euploidy for the selection of the optimal blastocyst for embryo transfer.

Pre-treatment estradiol does not predict testosterone response to clomiphene citrate.

BACKGROUND: Clomiphene citrate (CC) is a selective estrogen receptor modulator (SERM) used to stimulate ovulation in women. CC is used off-label in men to increase levels of endogenous testosterone (T) while potentially improving semen parameters by downregulating the inhibitory feedback of estradiol (E) on the male hypothalamus. Our objective was to determine whether pre-treatment E level is associated with greater total testosterone (TT) response to treatment with CC in men with low T. METHODS: Following IRB approval (The University of Miami IRB No. 20170849), retrospective chart review was performed for all men prescribed CC (25 mg every other day) between January 1, 2015 and December 31, 2018. Age, body mass index (BMI), and prescription date were recorded for all patients. Pre- and post-treatment E, total T (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were recorded for all patients as well. Only men with pretreatment TT <300 ng/dL were included in the analysis in order to focus our study on men with low TT. Univariate linear regression analysis was performed to determinate the percent change in TT following CC treatment (dependent variable) and pre-treatment E and other variables including age, BMI, FSH, and LH (independent variables). RESULTS: A total of 69 men with TT <300 ng/dL received CC 25 mg every other day. Mean age and BMI were 33.3±7.31 years and 35.4±5 kg/m2 respectively. Median pre-treatment E, TT, FSH, and LH were 18 [11.35-24.6] pg/mL, 226 [156-262] ng/dL, 5.1 [2.98-8.05] mIU/mL, and 4.5 [2.6-6.8] mIU/mL respectively. Post-treatment TT was 389 [263-592] ng/dL and TT% change was 102 [45.51-176.75]. Univariate linear regression showed that pre-treatment E (B=-0.595; R2=0.001; P=0.757) did not significantly predict TT% change. TT% change could be significantly predicted by age in years (B=-7.428; R2=0.057; P=0.048), pre-treatment FSH (B=-8.362; R2=0.068; P=0.041), and pre-treatment LH (B=-20.67; R2=0.096; P=0.027). CONCLUSIONS: Pre-treatment E level does not appear to predict treatment response with CC in men with low T.

Implementation of a standardized handoff protocol for post-operative admissions to the surgical intensive care unit.

BACKGROUND: The transfer of critically ill patients from the operating room (OR) to the surgical intensive care unit (SICU) involves handoffs between multiple providers. Incomplete handoffs lead to poor communication, a major contributor to sentinel events. Our aim was to determine whether handoff standardization led to improvements in caregiver involvement and communication. METHODS: A prospective intervention study was designed to observe thirty one patient handoffs from OR to SICU for 49 critical parameters including caregiver presence, peri-operative details, and time required to complete key steps. Following a six month implementation period, thirty one handoffs were observed to determine improvement. RESULTS: A significant improvement in presence of physician providers including intensivists and surgeons was observed (p = 0.0004 and p < 0.0001, respectively). Critical details were communicated more consistently, including procedure performed (p = 0.0048), complications (p < 0.0001), difficult airways (p < 0.0001), ventilator settings (p < 0.0001) and pressor requirements (p = 0.0134). Conversely, handoff duration did not increase significantly (p = 0.22). CONCLUSIONS: Implementation of a standardized protocol for handoffs between OR and SICU significantly improved caregiver involvement and reduced information omission without affecting provider time commitment.

Ex-vivo ureteroscopy of deceased donor kidneys.

INTRODUCTION: When encountered, the ideal management of lithiasis in deceased donor kidneys is not well-defined. With advances in endourological techniques, minimally invasive treatments are becoming an increasingly viable option. We set out to describe our experience performing ex-vivo ureteroscopy on cadaveric donor kidneys, including one in which the procedure was completed on-pump. METHODS: A retrospective chart review was undertaken to identify patients who had undergone ex-vivo ureteroscopy prior to cadaveric renal transplant. Four patients were identified, including one in which the procedure was done with the kidney remaining on-pump. The surgical technique and subsequent data were reviewed. RESULTS: Ex-vivo ureteroscopy was successfully completed in all four instances without intraoperative complication. All kidneys were endoscopically stone-free. Creatinine nadirs ranged from 0.8-1.4. All four patients remained stone-free at a mean followup of 13 months. CONCLUSIONS: Our series provides further evidence as to the safety and efficacy of ex-vivo ureteroscopy prior to transplantation in cadaveric renal transplants and describes a novel technique in the form of on-pump ex-vivo ureteroscopy.

Management of a renal fungal bezoar caused by multidrug-resistant Candida glabrata.

We describe our management of an immunocompetent individual who developed obstructive uropathy and candidemia as a result of a fungal bezoar in the kidney. These sequelae arose from candiduria, provoked after several courses of antibiotics. Successful treatment included therapy with both culture-appropriate intravenous antifungals and operative intervention, including direct irrigation of the affected kidney with amphotericin B, relief of renal obstruction with a ureteral stent, a percutaneous nephrostomy tube, and ultimately endoscopic removal of the fungal bezoar. Our patient was successfully treated as evidenced by negative urine culture and lack of ongoing symptomatology.