The retrotransposon - derived capsid genes PNMA1 and PNMA4 maintain reproductive capacity.

The human genome contains 24 gag -like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that the gag -like genes PNMA1 and PNMA4 support reproductive capacity. Six-week-old mice lacking either Pnma1 or Pnma4 are indistinguishable from wild-type littermates, but by six months the mutant mice become prematurely subfertile, with precipitous drops in sex hormone levels, gonadal atrophy, and abdominal obesity; overall they produce markedly fewer offspring than controls. Analysis of donated human ovaries shows that expression of both genes declines normally with aging, while several PNMA1 and PNMA4 variants identified in genome-wide association studies are causally associated with low testosterone, altered puberty onset, or obesity. These findings expand our understanding of factors that maintain human reproductive health and lend insight into the domestication of retrotransposon-derived genes.

Problems in Fish-to-Tetrapod Transition: Genetic Expeditions Into Old Specimens.

The fish-to-tetrapod transition is one of the fundamental problems in evolutionary biology. A significant amount of paleontological data has revealed the morphological trajectories of skeletons, such as those of the skull, vertebrae, and appendages in vertebrate history. Shifts in bone differentiation, from dermal to endochondral bones, are key to explaining skeletal transformations during the transition from water to land. However, the genetic underpinnings underlying the evolution of dermal and endochondral bones are largely missing. Recent genetic approaches utilizing model organisms-zebrafish, frogs, chickens, and mice-reveal the molecular mechanisms underlying vertebrate skeletal development and provide new insights for how the skeletal system has evolved. Currently, our experimental horizons to test evolutionary hypotheses are being expanded to non-model organisms with state-of-the-art techniques in molecular biology and imaging. An integration of functional genomics, developmental genetics, and high-resolution CT scanning into evolutionary inquiries allows us to reevaluate our understanding of old specimens. Here, we summarize the current perspectives in genetic programs underlying the development and evolution of the dermal skull roof, shoulder girdle, and appendages. The ratio shifts of dermal and endochondral bones, and its underlying mechanisms, during the fish-to-tetrapod transition are particularly emphasized. Recent studies have suggested the novel cell origins of dermal bones, and the interchangeability between dermal and endochondral bones, obscuring the ontogenetic distinction of these two types of bones. Assimilation of ontogenetic knowledge of dermal and endochondral bones from different structures demands revisions of the prevalent consensus in the evolutionary mechanisms of vertebrate skeletal shifts.

Financial Benefits of a Hepatopancreaticobiliary Program.

Financial implications of developing a hepatopancreaticobiliary (HPB) center have not been considered. We undertook this study to determine hospital income associated with a new HPB center and to gauge the opportunity cost associated with such a center. Operations included were based on the HPB fellowship curriculum and the six most commonly undertaken general surgery operations. The income with "core" HPB operations (n = 93) and the six most frequently undertaken general surgery operations (n = 583) at one hospital from June 2012 to June 2013 were determined. Patients were not screened based on the ability to pay. Data are reported as mean ± standard deviation. Per operation, hospital income with HPB operations and general surgery operations were $15,583.20 ± $45,909.41 and $5,162.22 ± $33,679.10 (P < 0.005), respectively. Accordingly, net incomes of $1,449,238.04 (n = 93) and $3,009,572.78 (n = 583) were observed. Although general surgery operations are ubiquitous, HPB centers are uncommonly pursued at most hospitals, in part due to the patient volumes necessary to meet the expertise required. A "core" HPB operation produces triple the net income of a general surgery operation. Accordingly, significant financial benefit is achievable with the development of an HPB center when adequate volume is realized.

High-Volume Hospitals with High-Volume and Low-Volume Surgeons: Is There a "Field Effect" for Pancreaticoduodenectomy?

Since the Leapfrog Group established hospital volume criteria for pancreaticoduodenectomy (PD), the importance of surgeon volume versus hospital volume in obtaining superior outcomes has been debated. This study was undertaken to determine whether low-volume surgeons attain the same outcomes after PD as high-volume surgeons at high-volume hospitals. PDs undertaken from 2010 to 2012 were obtained from the Florida Agency for Health Care Administration. High-volume hospitals were identified. Surgeon volumes within were determined; postoperative length of stay (LOS), in-hospital mortality, discharge status, and hospital charges were examined relative to surgeon volume. Six high-volume hospitals were identified. Each hospital had at least one surgeon undertaking ≥ 12 PDs per year and at least one surgeon undertaking < 12 PDs per year. Within these six hospitals, there were 10 "high-volume" surgeons undertaking 714 PDs over the three-year period (average of 24 PDs per surgeon per year), and 33 "low-volume" surgeons undertaking 225 PDs over the three-year period (average of two PDs per surgeon per year). For all surgeons, the frequency with which surgeons undertook PD did not predict LOS, in-hospital mortality, discharge status, or hospital charges. At the six high-volume hospitals examined from 2010 to 2012, low-volume surgeons undertaking PD did not have different patient outcomes from their high-volume counterparts with respect to patient LOS, in-hospital mortality, patient discharge status, or hospital charges. Although the discussion of volume for complex operations has shifted toward surgeon volume, hospital volume must remain part of the discussion as there seems to be a hospital "field effect."

Pancreaticoduodenectomy in Florida: do 20-year trends document the salutary benefits of centralization of care?

BACKGROUND: Concentration of care has been promoted as fostering superior outcomes. This study was undertaken to determine if the concentration of care is occurring in Florida for a pancreaticoduodenectomy, and if so, is it having a salutary effect. METHODS: The data for a pancreaticoduodenectomy were obtained from the Florida Agency for Health Care Administration for three 3-year periods:1992-1994, 2001-2003, 2010-2012; data were sorted by surgeon volume of pancreaticoduodenectomy during these periods and correlated with post-operative length of stay (LOS), in-hospital mortality and hospital charges (adjusted to 2012 dollars). RESULTS: Relative to 1992-1994, in 2010-2012 46% fewer surgeons performed 115% more pancreaticoduodenectomies with significant reductions in LOS and in-hospital mortality, and higher charges (P < 0.001 for each). From 1992-1994 to 2010-2012 there was an 18-fold increase in the number of pancreaticoduodenectomies by surgeons completing ≥ 12 per year (n = 45 to n = 806, respectively). During 2010-2012, the more frequently surgeons performed a pancreaticoduodenectomy, the shorter LOS, the lower in-hospital mortality, the greater the likelihood of discharge home and the lower the hospital charges (P < 0.03 for each). CONCLUSIONS: Over the last 20 years, the concentration of care has occurred in Florida with substantially fewer surgeons undertaking many more pancreaticoduodenectomies with dramatic improvements in LOS and in-hospital mortality, albeit with increased hospital charges.

Reoperative Heller myotomy: more pain, less gain.

Heller myotomy provides durable and effective treatment of achalasia. Due to recurrence or persistence of symptoms, a small subset of patients seeks reoperation. This study was undertaken to determine if reoperative Heller myotomy provides salutary amelioration of symptoms. 609 patients undergoing laparoscopic Heller myotomy between 1992 to 2013 were prospectively followed; 38 underwent reoperative myotomy. Patients graded their symptom frequency and severity before and after myotomy on a Likert scale. Median data are reported. Patients undergoing reoperative myotomy, when compared to those undergoing their first myotomy, experienced a higher conversion rate to an "open" myotomy (8% vs 1%, P < 0.05) and a longer length of stay (3 vs 1 day, P < 0.05). Reoperative myotomy led to improvement in symptoms, but the magnitude of improvement in symptoms (e.g., dysphagia, choking, and coughing) was less than for patients undergoing their first myotomy (all P < 0.05). Patients undergoing reoperative Heller myotomy were less likely to report symptoms occurring once per month or less (83% vs 56%, P < 0.01). Patients undergoing reoperative myotomy note improvement in symptoms, although to a lesser extent than patients undergoing their first myotomy. Patients undergoing reoperative Heller myotomy can expect to experience less improvement of symptoms, denoting the importance of the first myotomy.

Distal pancreatectomy and splenectomy: a robotic or LESS approach.

INTRODUCTION: The role and application of robotic surgery are debated, particularly given the expansion of laparoscopy, especially laparoendoscopic single-site (LESS) surgery. This cohort study was undertaken to delineate differences in outcomes between LESS and robotic distal pancreatectomy and splenectomy. METHODS: With Institutional Review Board approval, patients undergoing LESS or robotic distal pancreatectomy and splenectomy from September 1, 2012, through December 31, 2014, were prospectively observed, and data were collected. The results are expressed as the median, with the mean ± SD. RESULTS: Thirty-four patients underwent a minimally invasive distal pancreatectomy and splenectomy: 18 with robotic and 16 with LESS surgery. The patients were similar in sex, age, and body mass index. Conversions to open surgery and estimated blood loss were similar. There were two intraoperative complications in the group that underwent the robotic approach. Time spent in the operating room was significantly longer with the robot (297 vs 254 minutes, P = .03), although operative duration (i.e., incision to closure) was not longer (225 vs 190 minutes; P = .15). Of the operations studied, 79% were undertaken for neoplastic processes. Tumor size was 3.5 cm for both approaches; R0 resections were achieved in all patients. Length of stay was similar in the two study groups (5 vs 4 days). There was one 30-day readmission after robotic surgery. CONCLUSIONS: Patient outcomes are similar with LESS or robotic distal pancreatectomy and splenectomy. Robotic operations require more time in the operating room. Both are safe and efficacious minimally invasive operations that follow similar oncologic principles for similar tumors, and both should be in the surgeon's armamentarium for distal pancreatectomy and splenectomy.