Recent Publications by CFE Educators

PURPOSE

Approximately 10% to 20% of patients will have a recurrence after urethroplasty. Initial management of these recurrences is often by urethral dilation or direct vision internal urethrotomy. In the current study we describe the outcomes of endoscopic management of stricture recurrence after bulbar urethroplasty.

MATERIALS AND METHODS

We retrospectively reviewed bulbar urethroplasty data from 5 surgeons in the TURNS (Trauma and Urologic Reconstruction Network of Surgeons). Men who underwent urethral dilation or direct vision internal urethrotomy for urethroplasty recurrence were identified. Recurrence was defined as the inability to pass a 17Fr cystoscope through the area of reconstruction. The primary outcome was the success rate of recurrence management. Comparisons were made between urethral dilation and direct vision internal urethrotomy, and then between endoscopic management of recurrences after excision and primary anastomosis urethroplasty vs substitutional repairs using time to event statistics.

RESULTS

In 53 men recurrence was initially managed endoscopically. Median time to urethral stricture recurrence after urethroplasty was 5 months. At a median followup of 5 months the overall success rate was 42%. Success after urethral dilation was significantly less than after direct vision internal urethrotomy (1 of 10 patients or 10% vs 21 of 43 or 49%, p 0.001) with a failure HR of 3.15 (p = 0.03). Direct vision internal urethrotomy was more effective after substitutional failure than after excision and primary anastomosis urethroplasty (53% vs 13%, p = 0.005).

CONCLUSIONS

Direct vision internal urethrotomy was more successful than urethral dilation in the management of stricture recurrence after bulbar urethroplasty. Direct vision internal urethrotomy was more successful in patients with recurrence after substitution urethroplasty compared to after excision and primary anastomosis urethroplasty. Perhaps this indicates a different mechanism of recurrence for excision and primary anastomosis urethroplasty (ischemic) vs substitution urethroplasty (nonischemic).

BACKGROUND

Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population.

METHODS

A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively).

RESULTS

Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p  0.05). No significant enrichment in copy-number abnormalities at del13q14, del11q, del17p or trisomy12 was identified in UR-CLL compared to other groups. Type of work performed in the Chornobyl zone, age at exposure and at diagnosis, calendar time, and Rai stage were significant predictors of total genetic lesions (all p  0.05). Tumor telomere length was significantly longer in UR-CLL than in UN-CLL (p = 0.009) and was associated with the POT1 mutation and survival.

CONCLUSIONS

No significant enrichment in copy-number abnormalities at CLL-associated genes was identified in UR-CLL compared to other groups. The novel associations between radiation exposure, telomere maintenance and CLL prognosis identified in this unique case series provide suggestive, though limited data and merit further investigation.

OBJECTIVE The authors' institution is in the top 5th percentile for hospital cost in the nation, and the neurointensive care unit (NICU) is one of the costliest units. The NICU is more expensive than other units because of lower staff/patient ratio and because of the equipment necessary to monitor patient care. The cost differential between the NICU and Neuro transitional care unit (NTCU) is $1504 per day. The goal of this study was to evaluate and to pilot a program to improve efficiency and lower cost by modifying the postoperative care of patients who have undergone a craniotomy, sending them to the NTCU as opposed to the NICU. Implementation of the pilot will expand and utilize neurosurgery beds available on the NTCU and reduce the burden on NICU beds for critically ill patient admissions. METHODS Ten patients who underwent craniotomy to treat supratentorial brain tumors were included. Prior to implementation of the pilot, inclusion criteria were designed for patient selection. Patients included were less than 65 years of age, had no comorbid conditions requiring postoperative intensive care unit (ICU) care, had a supratentorial meningioma less than 3 cm in size, had no intraoperative events, had routine extubation, and underwent surgery lasting fewer than 5 hours and had blood loss less than 500 ml. The Safe Transitions Pathway (STP) was started in August 2016. RESULTS Ten tumor patients have utilized the STP (5 convexity meningiomas, 2 metastatic tumors, 3 gliomas). Patients' ages ranged from 29 to 75 years (median 49 years; an exception to the age limit of 65 years was made for one 75-year-old patient). Discharge from the hospital averaged 2.2 days postoperative, with 1 discharged on postoperative day (POD) 1, 7 discharged on POD 2, 1 discharged on POD 3, and 1 discharged on POD 4. Preliminary data indicate that quality and safety for patients following the STP (moving from the operating room [OR] to the neuro transitional care unit [OR-NTCU]) are no different from those of patients following the traditional OR-NICU pathway. No patients required escalation in level of nursing care, and there were no readmissions. This group has been followed for greater than 1 month, and there were no morbidities. CONCLUSIONS The STP is a new and efficient pathway for the postoperative care of neurosurgery patients. The STP has reduced hospital cost by $22,560 for the first 10 patients, and there were no morbidities. Since this pilot, the authors have expanded the pathway to include other surgical cases and now routinely schedule craniotomy patients for the (OR-NTCU) pathway. The potential cost reduction in one year could reach $500,000 if we reach our potential of 20 patients per month.

Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a "post-test" criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT. This was a multicenter retrospective cohort study. Patients were over 18 years in age, underwent serologic testing for HIT, and received alternative anticoagulation treatment for HIT. Classification of each patient's likelihood of having HIT was based on an empiric, pre-hoc combination of the 4T score and serology results. The primary outcome for this study was a platelet count response after initiation of direct thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were analyzed. The sensitivity and specificity of having an immediate platelet rise of at least 10,000/µL by day 2 after starting treatment among high-likelihood for HIT patients were 0.71 (95% CI 0.55-0.84) and 0.64 (95% CI 0.5-0.76), respectively. The negative predictive value of no platelet rise was 75.5% (95% CI 0.61-0.86). A prompt platelet count rise may be appropriate to consider along with other known criteria for the clinical diagnosis of HIT. The rise should be immediate following discontinuation of heparin and initiation of recommended treatment, with an upward rise within 48 h.

Organ fibrosis, including idiopathic pulmonary fibrosis, is associated with significant morbidity and mortality. Because currently available therapies have limited effect, there is a need to better understand the mechanisms by which organ fibrosis occurs. We have recently reported that transforming growth factor (TGF)-β, a key cytokine that promotes fibrogenesis, induces the expression of the enzymes of the de novo serine and glycine synthesis pathway in human lung fibroblasts, and that phosphoglycerate dehydrogenase (PHGDH; the first and rate-limiting enzyme of the pathway) is required to promote collagen protein synthesis downstream of TGF-β. In this study, we investigated whether inhibition of de novo serine and glycine synthesis attenuates lung fibrosis in vivo. We found that TGF-β induces mRNA and protein expression of PHGDH in murine fibroblasts. Similarly, intratracheal administration of bleomycin resulted in increased expression of PHGDH in mouse lungs, localized to fibrotic regions. Using a newly developed small molecule inhibitor of PHGDH (NCT-503), we tested whether pharmacologic inhibition of PHGDH could inhibit fibrogenesis both in vitro and in vivo. Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF-β-induced collagen protein synthesis. Mice treated with the PHGDH inhibitor beginning 7 days after intratracheal instillation of bleomycin had attenuation of lung fibrosis. These results indicate that the de novo serine and glycine synthesis pathway is necessary for TGF-β-induced collagen synthesis and bleomycin-induced pulmonary fibrosis. PHGDH and other enzymes in the de novo serine and glycine synthesis pathway may be a therapeutic target for treatment of fibrotic diseases, including idiopathic pulmonary fibrosis.

BACKGROUND

Rising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only 2 data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time.

METHODS

Our cohort included 336 patients undergoing LT with Model for End Stage Liver Disease exception for HCC within Milan criteria from 2003 to 2013. Most (98%) had pre-LT locoregional therapy. AFP slope was estimated by fitting a regression line to the AFP levels over time.

RESULTS

The 1- and 5-year post-LT survivals were 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (hazard ratio [HR], 13.1; P0.001), tumor grade (HR, 1.8; P0.001), pathologic stage >Milan criteria (HR, 8.9; P0.001), 3 tumor nodules (HR, 5.5; P=0.002), AFP slope greater than 7.5 ng/mL per month (HR, 3.9; P=0.005), and female sex (HR, 2.3; P=0.01). In multivariable analysis of factors known before LT, 3 tumor nodules (HR, 7.6; P0.001), female sex (HR, 2.5; P=0.01), and AFP slope >7.5 (HR, 3.0; P=0.03) were significantly associated with HCC recurrence. AFP slope greater than 7.5 was also associated with microvascular invasion (odds ratio, 6.8; P=0.008).

CONCLUSIONS

AFP slope increasing greater than 7.5 ng/mL per month despite locoregional therapy is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT.

Background High stress and depression during pregnancy are risk factors for worsened health trajectories for both mother and offspring. This is also true for pre-pregnancy obesity and excessive gestational weight gain. Reducing stress and depression may be one path to prevent excessive caloric intake and gestational weight gain. Study Purpose We tested the feasibility of two novel interventions aimed at reducing stress and overeating during pregnancy. Reflecting different theoretical underpinnings, the interventions target different mechanisms. Mindful Moms Training (MMT) uses mindfulness to improve awareness and acceptance of experiences and promote conscious rather than automatic behavior choices. Emotional Brain Training (EBT) uses active coping to change perceptions of negative experience and promote positive affective states. Methods Forty-six overweight/obese low-income women were assigned to either MMT (n = 24) or EBT (n = 22) for an 8-week feasibility study. Pre-post changes in perceived stress, eating and presumed mechanisms were assessed. Results Women reported high levels of stress at baseline. Both interventions were well attended and demonstrated clinically significant pre-post reductions in stress, depressive symptoms, and improved eating behaviors. MMT significantly decreased experiential avoidance, whereas EBT significantly increased positive reappraisal; these changes were marginally significantly different by group. Conclusions This feasibility study found that both interventions promoted meaningful reductions in stress and depressive symptoms and improved reported eating behaviors in a high-risk group of pregnant women. Each intervention has a potentially different pathway-acceptance for MMT and reappraisal for EBT. Larger studies are needed to test efficacy on longer term reductions in stress and overeating.

BACKGROUND

Female genital self-image is an important aspect of psychosocial and sexual health. The Female Genital Self-Image Scale (FGSIS) is a validated instrument that has been used to characterize women's level of genital dissatisfaction.

AIM

In this report, we assess genital dissatisfaction using the FGSIS in a nationally representative sample of U.S. women.

METHODS

We conducted a nationally representative survey of non-institutionalized adults aged 18-65 years residing in the United States. The survey included questions about demographics, sexual behavior, and the FGSIS.

OUTCOMES

Demographic characteristics were found to significantly correlate to women's perceived genital dissatisfaction.

RESULTS

In total, 3,372 women completed the survey and 3,143 (93.2%) completed the FGSIS. The mean age was 46 years, and there was broad representation across the United States in terms of age, education, and location. On bivariate analysis, women's genital dissatisfaction was significantly correlated to their age, race, location, and education. Women who were sexually active were less likely to report genital dissatisfaction than women who were not sexually active (76% vs 62%, respectively, P .001). The frequency of sexual activity was negatively correlated with genital dissatisfaction (P = .002). Women who reported genital dissatisfaction were less likely than those who reported satisfaction to engage in receptive vaginal sex (83% vs 88%, respectively, P = .03). There were no other significant associations between genital dissatisfaction and types of sexual activity. On multivariate analysis, women were less likely to report genital dissatisfaction if they were older, of black race, had an education level of high school or above, and/or lived in the Northeastern or Midwestern United States. There was no association between genital dissatisfaction and relationship status or gender of sexual partner.

CLINICAL TRANSLATION

Female genital dissatisfaction may be related to age, race, education, and geography.

CONCLUSIONS

This is the first nationally representative sample of U.S. women focusing on genital and self-image and dissatisfaction. These data may not apply outside the United States. These data may help providers who provide information for women and manage concerns related to genital self-image. Rowen TS, Gaither TW, Shindel AW, et al. Characteristics of Genital Dissatisfaction Among a Nationally Representative Sample of U.S. Women. J Sex Med 2018;15:698-704.