Purpose

Craniosynostosis is a common cranial malformation occurring in 1 per 2,000-2,500 births. Isolated defects (nonsyndromic) occur in ~75% of cases and are thought to have multifactorial etiology. It is believed that each suture synostosis is a distinct disease, with varying phenotypes and recurrence rates.

Methods

We analyzed family histories of 660 mutation-negative nonsyndromic craniosynostosis patients and symptoms in 189 of these patients.

Results

The incidence rate of craniosynostosis was highest for first-degree relatives of probands with metopic craniosynostosis (6.4%), followed by those with complex craniosynostosis (4.9%), sagittal craniosynostosis (3.8%), lambdoid craniosynostosis (3.9%), and coronal craniosynostosis (0.7%). Across all suture types, siblings had a greater craniosynostosis incidence rate than parents (7.5 vs. 2.3%). In phenotype comparisons, patients with complex craniosynostosis had the highest frequency of reported symptoms and those with sagittal craniosynostosis had the lowest. Ear infections, palate abnormalities, and hearing problems were more common in complex craniosynostosis patients. Visual problems were more common in coronal craniosynostosis, and metopic craniosynostosis patients noted increased frequency of chronic cough.

Conclusion

Our data suggest that the genetic component of nonsyndromic craniosynostosis appears to be suture specific. The incidence rate of craniosynostosis among first-degree relatives varies by suture and family member. Additionally, the phenotype of each suture synostosis shows both unique and shared features.

Autosomal Dominant Optic Atrophy (ADOA) is a neuro-ophthalmic disease characterized by progressive bilateral vision loss, pallor of the optic disc, central vision loss, and impairment of color vision. Additionally, a small percentage of patients experience hearing loss and ataxia, while recent studies suggest disruption of cardiac and neuromuscular functions. In order to obtain a better understanding of the genotype-phenotype correlation of the various mutations in the optic atrophy 1 (OPA1) gene, we obtained both clinical and genetic information of ADOA patients from published reports. We conducted a systematic review of published OPA1 literature and identified 408 individuals with confirmed OPA1 mutations, 120 of whom reported extra-ocular (ADOA 'plus') manifestations through their descriptions of visual and multi-systemic symptoms. Our results show that there is a significant variation in frequency of the specific exons involved between the ADOA classic and ADOA 'plus' patients. Classic ADOA groups were more likely to have mutations in exon 8 and 9, while ADOA 'plus' groups were more likely to have mutations in exons 14, 15 and 17. Additional comparisons revealed significant differences between mutation types/domains and specific ADOA 'plus' manifestations. We also found that individuals with maternally inherited OPA1 mutations were significantly more likely to develop 'plus' manifestations than those with paternally inherited mutations. Overall, this study provides novel information regarding genotype-phenotype correlations of ADOA which warrants additional recommendations added to the current clinical management of ADOA patients.

AbstractBackground and Purpose

Recent advances in distal sensor technologies have made distal sensor ureteroscopes both commercially and technically feasible. We evaluated performance characteristics and optics of a new generation distal sensor Flex-X^C (X^C) and a standard flexible fiberoptic ureteroscope Flex-X² (X²), both from Karl Storz, Tuttlingen, Germany.

Materials and Methods

The ureteroscopes were compared for active deflection, irrigation flow, and optical characteristics. Each ureteroscope was evaluated with an empty working channel and with various accessories. Optical characteristics (resolution, grayscale imaging, and color representation) were measured using United States Air Force test targets. We digitally recorded a renal porcine ureteroscopy and laser ablation of a stone with the X² and with the X^C. Edited footage of the recorded procedure was shown to different expert surgeons (n=8) on a high-definition monitor for evaluation by questionnaire for image quality and performance.

Results

The X^C had a higher resolution than the X² at 20 and 10 mm 3.17 lines/mm vs 1.41 lines/mm, 10.1 vs 3.56, respectively (P=0.003, P=0.002). Color representation was better in the X^C. There was no difference in contrast quality between the two ureteroscopes. For each individual ureteroscope, the upward deflection was greater than the downward deflection both with and without accessories. When compared with the X², the X^C manifested superior deflection and flow (P<0.0005, P<0.05) with and without accessory present in the working channel. Observers deemed the distal sensor ureteroscope superior in visualization in clear and bloody fields, as well as for illumination (P=0.0005, P=0.002, P=0.0125).

Conclusions

In this in vitro and porcine evaluation, the distal sensor ureteroscope provided significantly improved resolution, color representation, and visualization in the upper urinary tract compared with a standard fiberoptic ureteroscope. The overall deflection was also better in the X^C, and deflection as well as flow rate was less impaired by the various accessories.

Objective

To estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions.

Methods

All patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000 person-years were calculated.

Results

Of 56,692 patients, the majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7% had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow-up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years, respectively. Age-standardized rates (per 100,000 person-years) of ovarian or peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28).

Conclusions

The removal of both ovaries decreases the incidence of ovarian and peritoneal cancers. Removal of one ovary might also decrease the incidence of ovarian cancer but warrants further investigation.

Level of evidence

II.

Objectives

There is intense interest in lung volume reduction surgery (LVRS) for treatment of severe symptomatic emphysema. LVRS results in objective and subjective improvement in lung function in selected patients. However, LVRS is complicated by substantial morbidity, including prolonged pulmonary air leak associated with resection of emphysematous lung tissue. In this study, we investigated the use of a novel implanted silicone elastomer device that reduces lung volume without surgical resection, in a previously reported emphysematous animal model. The purpose of this investigation was to determine the applicability, physiologic effects, complications, and air-leak results of this lung volume reducer (LVR) approach.

Design

Controlled, randomized, prospective animal study. Emphysema was induced in 20 New Zealand white rabbits with three nebulizations of 10,000 U of porcine elastase. After 6 weeks, the animals were randomized to control sham surgery (n = 10) vs implanted silicone elastomer LVR (n = 10) treatment groups. Lung function, including helium-dilution lung volumes, static respiratory system compliance curves, and diffusion capacity of the lung for carbon monoxide (DLCO), was measured at baseline, following emphysema induction (week 6), and when the animals were killed (1 week after LVR or sham surgery). Histologic evaluation was performed in all lung specimens after fixation.

Results

Moderate emphysema developed after elastase nebulization, assessed by lung function and postmortem histology. Functional residual capacity (FRC) and an upward shift of lung compliance curves was observed with development of emphysema at 6 weeks (p < 0.05). Following LVR, FRC decreased (p = 0.005) and compliance curves shifted back downward (p = 0.002), without reduction in DLCO. There was no change in control sham animals. DLCO did not change in either group.

Conclusions

In this short-term, randomized, controlled animal model study, the implantable LVR approach produced safe and effective lung volume reduction without tissue resection in the treated animals. The implant procedure produced minimal morbidity, no mortality, and no observed air-leak complications in the treated animals. Limitations include the short-term follow-up and moderate degree of emphysema in this animal model. Further research is required to assess long-term effects and complications of this method for lung volume reduction.

Purpose

Survivors of cervical cancer experience quality-of-life (QOL) disruptions that persist years after treatment. This study examines the effect of a psychosocial telephone counseling (PTC) intervention on QOL domains and associations with biomarkers.

Patients and methods

We conducted a randomized clinical trial in survivors of cervical cancer, who were ≥ 9 and less than 30 months from diagnosis (n = 204), to compare PTC to usual care (UC). PTC included five weekly sessions and a 1-month booster. Patient-reported outcomes (PROs) and biospecimens were collected at baseline and 4 and 9 months after enrollment. Changes in PROs over time and associations with longitudinal change in cytokines as categorical variables were analyzed using multivariable analysis of variance for repeated measures.

Results

Participant mean age was 43 years; 40% of women were Hispanic, and 51% were non-Hispanic white. Adjusting for age and baseline scores, participants receiving PTC had significantly improved depression and improved gynecologic and cancer-specific concerns at 4 months compared with UC participants (all P < .05); significant differences in gynecologic and cancer-specific concerns (P < .05) were sustained at 9 months. Longitudinal change in overall QOL and anxiety did not reach statistical significance. Participants with decreasing interleukin (IL) -4, IL-5, IL-10, and IL-13 had significantly greater improvement in QOL than those with increasing cytokine levels.

Conclusion

This trial confirms that PTC benefits mood and QOL cancer-specific and gynecologic concerns for a multiethnic underserved population of survivors of cancer. The improvement in PROs with decreases in T-helper type 2 and counter-regulatory cytokines supports a potential biobehavioral pathway relevant to cancer survivorship.

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry.

Objective

To assist in preoperative counseling by assessing long-term changes in American Urological Association symptom scores (AUAss) and lower urinary tract symptom (LUTS)-related quality of life (QOL) in patients undergoing robot-assisted radical prostatectomy (RARP).

Materials and methods

RARP was performed on 666 men by one surgeon from 2002 to 2007 at a single institution. AUAss and QOL were queried preoperatively and at 3, 9, 15, 24-48, 60-84, and 96+ months postoperatively. LUTS subgroups were compared pre-/postsurgery using univariate and multivariate statistics.

Results

The mean and median follow-up for all responders was 3.0 and 2.4 years. Pad-free continence at 12 months was 89%. A subset of 174 men reported preoperative and long-term responses; average follow-up was 5.8 years (range 4.0-10.3 years). AUAss for all men declined from baseline to 5 years by 3.7 (8.6 to 4.8) whereas QOL/Bother scores decreased by 0.5 (1.7 to 1.2) (all P < .05). Men with baseline mild LUTS remained clinically unchanged with long-term AUAss. Individuals with moderate and severe preoperative LUTS had marked improvements in AUA and QOL scores (all P ≤ .05).

Conclusion

Men with mild LUTS have short-term increases in AUAss but most return to baseline and are stable at 5 years. Benefits were found for men with preoperative moderate and severe LUTS in that 63% had significant QOL improvements and 68% reduced their AUAss to mild LUTS, persisting years after RARP. This study suggests that certain patients with preoperative urinary symptoms and bother may experience improvements in LUTS and associated QOL after RARP.