Wensink MJ, Lu Y, Tian L et al: Preconception antidiabetic drugs in men and birth defects in offspring: a nationwide cohort study. Ann Intern Med 2022; 175: 665–673.

Special thanks to Drs. Kareim Khalafalla and Samuel Ohlander at the University of Illinois at Chicago.

For pregnant women, diabetes is related to risks in pregnancy and to developmental and neonatal malformations in the fetus. Consequently, diabetes is aggressively treated in women during pregnancy. But men don’t carry offspring, and a compelling question is whether to treat diabetes with medication as vigorously for the male attempting to conceive with his partner.

Over 1 million live births from mothers without diabetes or hypertension and who were younger than 35 years old over a 20-year period were studied from the Denmark nationwide birth registry. Offspring were counted as exposed if the father had been prescribed any diabetic medication during the development of the fertilized sperm, defined as 3 months before conception. Over 36,000 offspring were observed to have 1 or more major birth defects, out of which somewhat over 7,000 were exposed to diabetic medications for the father, including insulin, metformin, sulfonylurea and a handful of others. In the metformin-exposed group, birth defects were statistically increased, with an odds ratio of 1.4 compared to insulin-exposed groups, unexposed siblings or offspring of fathers filling a metformin prescription before or after the fertilized sperm period. Out of all birth defects, genital anomalies were found to be more prominent in those with fathers treated with metformin and exclusively in boys, with an odds ratio of 3.4.

Metformin is a well-established first-line therapy for diabetes. This study presents compelling evidence that using it during the 3 months prior to conception in fathers substantially increases the risk of major birth defects and especially genital anomalies in baby boys. While this observation needs to be replicated in other studies, it certainly gives pause to using metformin to treat diabetes in fathers in the preconception period.

Ory J, Nackeeran S, Balaji NC et al: Secondary polycythemia in men receiving testosterone therapy increases risk of major adverse cardiovascular events and venous thromboembolism in the first year of therapy. J Urol 2022; 207: 1295–1301.

Special thanks to Drs. Susan Talamini and Samuel Ohlander at the University of Illinois at Chicago.

Between 2003 and 2013, the use of testosterone replacement therapy increased 3- to 4-fold in the United States. Given the ubiquitous marketing, availability and consumer awareness of this therapy, its use is expected to continue to grow. Consequently, research into potential adverse events and factors that predispose to problems is crucial for patient safety. This multi-institutional retrospective cohort study investigated the risk of major adverse cardiovascular and thromboembolic events associated with polycythemia secondary to testosterone therapy.

After matching for comorbidities, 2 comparison groups were established, those who had a pretreatment testosterone less than 350 ng/ml and who developed an elevated hematocrit, defined as greater than 52% within 1 year of testosterone therapy, and those for whom a high hematocrit didn’t occur. There were nearly 6,000 men in each group.

The authors observed the risk of a major adverse cardiovascular or thromboembolic event to be 5.2% in men who developed polycythemia compared to 3.9% in those men who did not, with an odds ratio of 1.35. When parsing different hematocrit levels, the odds of an event remained higher in the polycythemia group when defined as a hematocrit greater than 54%, but no difference was observed between groups if the hematocrit threshold was defined as greater than 50%. The authors did not find a difference in major adverse events in hypogonadal men on therapy versus those not on therapy when hematocrit levels remained below 52%. This finding supports that it is the adverse response that increases risk rather than purely the use of testosterone.

The authors conclude that the appearance of polycythemia during treatment with testosterone therapy is an independent risk factor for major adverse cardiovascular or thromboembolic events in the first year of therapy and stress the importance of considering the level of the hematocrit as an independent variable.

Catto JWF, Khetrapal P, Ricciardi F et al: Effect of robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy on 90-day morbidity and mortality among patients with bladder cancer: a randomized clinical trial. JAMA 2022; 327: 2092–2103.

Special thanks to Drs. Hari Vigneswaran and Simone Crivellaro at the University of Illinois at Chicago.

With its challenging location in the bony pelvis and care to be taken sparing delicate nerves and creating a continent urethral anastomosis, and a medical specialty in urology replete with technophiles, radical prostatectomy quickly established itself as the “killer app” for the surgical robot. For other urological surgeries such as bladder cancer, the jury is still out.

The iROC trial was an investigator-initiated, phase 3, multicentered, randomized study conducted at 9 high-volume centers in the United Kingdom comparing open radical cystectomy to robotic-assisted laparoscopic radical cystectomy for nonmetastatic bladder cancer with less than or equal to N1 disease. Importantly, all robotic cystectomies were followed by intracorporeal reconstruction, distinguishing iROC from the recent landmark RAZOR trial. Approximately 300 patients were randomized 1:1 to each arm, with the primary endpoint of days outside a hospital and alive within 90 days from surgery, along with secondary outcomes including quality of life and survival.

Most patients had good functional status with ECOG 0-1, and approximately one-third of the patients received neoadjuvant chemotherapy. The median number of days outside the hospital within 90 days of surgery was statistically improved for the robotic arm by 2 days, at 82 versus 80 days. There was no difference in survival. Length of stay, at 7 versus 8 days, thromboembolic events, at 2% versus 8%, and wound complications, at 6% versus 16%, favored robotic surgery.

While not a slam dunk in survival, this well-conducted study seems to favor using the surgical robot in radical cystectomy in length of stay, thromboembolism and wound complications.