The tellurium-based immunomodulator, AS101 ameliorates adjuvant-induced arthritis in rats.

Despite undeniable improvement in the management of rheumatoid arthritis (RA), the discovery of more effective, less toxic and, ideally, less immune suppressive drugs are much needed. In the current study, we set to explore the potential anti-rheumatic activity of the non-toxic, tellurium-based immunomodulator, AS101 in an experimental animal model of RA. The effect of AS101 was assessed on adjuvant-induced arthritis (AIA) rats. Clinical signs of arthritis were assessed. Histopathological examination was used to assess inflammation, synovial changes and tissue lesions. Very late antigen-4 (VLA-4)+ cellular infiltration was detected using immunohistochemical staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure circulating anti-cyclic citrullinated-peptide autoantibody (ACPA) and real-time polymerase chain reaction (PCR) was used to measure the in-vitro effect of AS101 on interleukin (IL)-6 and IL-1ß expression in activated primary human fibroblasts. Prophylactic treatment with intraperitoneal AS101 reduced clinical arthritis scores in AIA rats (P < 0·01). AS101 abrogated the migration of active chronic inflammatory immune cells, particularly VLA-4+ cells, into joint cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Compared to phosphate-buffered saline (PBS)-treated AIA rats, histopathological inflammatory scores were significantly reduced (P < 0·05). Furthermore, AS101 resulted in a marked reduction of circulating ACPA in comparison to PBS-treated rats (P < 0·05). Importantly, AS101 significantly reduced mRNA levels of proinflammatory mediators such as IL-6 (P < 0·05) and IL-1ß (P < 0·01) in activated primary human fibroblasts. Taken together, we report the first demonstration of the anti-rheumatic/inflammatory activity of AS101 in experimental RA model, thereby supporting an alternative early therapeutic intervention and identifying a promising agent for therapeutic intervention.

Correlation Between Intraoperative and Pathological Findings for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: This study aimed to examine the correlation between intraoperative and pathological findings for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and to determine their prognostic significance. METHODS: Pathological reports of all colorectal cancer (CRC) patients undergoing CRS/HIPEC between 2009 and 2016 were retrospectively reviewed. Pathological specimens lacking tumor cells were defined as negative pathological specimens (NPS). The intraoperative peritoneal cancer index (PCI) and pathological PCI (excluding NPS) were calculated separately. Receiver operating characteristic (ROC) curves were applied to compare the prognostic value of intraoperative and pathological scoring systems. RESULTS: For 108 CRC patients, 113 CRS/HIPEC procedures were performed. Of 959 pathological specimens examined, 178 (18.6%) were NPS. Overall, 78 procedures (69%) showed NPS. In 52 procedures (46%), the pathological PCI differed from the intraoperative PCI (∆PCI > 0). The ROC areas for intraoperative PCI and pathological PCI were similar in predicting 1-year overall survival (OS), 2-year OS, and 1-year disease-free survival (all p values not significant). However, for the patients with NPS, the number of positive specimens (containing tumor tissue) was superior to intraoperative PCI in predicting 2-year OS (ROC under the curve areas, 0.69 vs. 0.58, respectively; p = 0.012). In addition, a subgroup of 15 patients with a high ∆PCI (≥ 3) had a more favorable median OS than a matched group of 30 patients with similar intraoperative PCI and a ∆PCI of 0 (median survival not reached vs. 21.6 months, respectively; p = 0.05). CONCLUSIONS: In the majority of CRC CRS/HIPEC procedures, NPS may be found. Among patients with NPS, pathological correlation may have a prognostic significance.

Ten-year reduction in thoracic injury-related mortality among Israel Defense Forces soldiers.

INTRODUCTION: This study aims to describe injury patterns, prehospital interventions and mortality rates of combat-related thoracic injuries during the past decade among Israel Defense Forces (IDF) soldiers before and after implementation of the 2012 IDF-Military Corps 'My Brother's Keeper' plan which included the publication of clinical practice guidelines (CPGs) for thoracic injuries, emphasis on adequate torso protection, introduction of modern life-saving procedures and encouragement of rapid evacuation. METHODS: The IDF prehospital trauma registry was reviewed to identify all patients who sustained thoracic injuries from January 2006 to December 2017. IDF soldiers who were injured, died of wounds or killed in action (KIA) were included. These were cross-referenced with the Israel National Trauma Registry. The periods before and after the plan were compared. RESULTS: 458 (12.3%) of 3733 IDF soldiers wounded on the battlefield sustained combat-related thoracic injuries. The overall mortality was 44.3% before the CPG and 17.3% after (p<0.001). Most were KIA: 97% (95 of 98) died by 30 June 2012, and 83% (20 of 24) after (p<0.001). Casualties treated with needle thoracostomy before and after CPG were 6.3% and 18.3%, respectively (p=0.002). More tube thoracostomies were performed after June 2012 (16.1% vs 5.4%, p=0.001). Evacuation was faster after June 2012 (119.4 min vs 560.8 min, p<0.001), but the rates of casualties evacuated within 60 min were similar (21.1% vs 25%, p=0.617). CONCLUSIONS: Among military casualties with thoracic injuries, the rate of life-saving interventions increased, evacuation time decreased and mortality dropped following the implementation of My Brother's Keeper plan.

Sexual cyclicity in captive lowland gorillas.

Oppositely sexed pairs of gorillas exhibit some behavior indicative of higher cognitive functioning, such as individual partner preferences and varied copulatory positions, but also mate in a cyclic manner closely related to the degree of female genital swelling. The latter finding is contrary to predictions based on their advanced position in phylogeny.

Robotics in urologic surgery.

Robotic surgery is becoming rapidly integrated in urology. Nearly every open or laparoscopic procedure has been described with robotic assistance. While the da Vinci robot is recently applied to the upper urinary tract, it has become widely adopted for performing radical prostatectomy. Benefits of robotics include 3-D vision, blood-less field from pneumoperitoneum, and ease of intracorporeal suturing. Disadvantages include cost, lack of haptic feedback, surgical learning curve and longer operative times. Here, the authors describe the state of the art applications and outcomes of robotics in urologic surgery.

Systematic review and meta-analysis of the association between frailty and outcome in surgical patients.

INTRODUCTION: Frailty is becoming increasingly prevalent in the elderly population although a lack of consensus regarding a clinical definition hampers comparison of clinical studies. More elderly patients are being assessed for surgical intervention but the effect of frailty on surgical related outcomes is still not clear. METHODS: A systematic literature search for studies prospectively reporting frailty and postoperative outcomes in patients undergoing surgical intervention was performed with data collated from a total of 12 studies. Random effects meta-analysis modelling was undertaken to estimate the association between frailty and mortality rates (in-hospital and one-year), length of hospital stay and the need for step-down care for further rehabilitation/nursing home placement. RESULTS: Frailty was associated with a higher in-hospital mortality rate (pooled odds ratio [OR]: 2.77, 95% confidence interval [CI]: 1.62-4.73), a higher one-year mortality rate (pooled OR: 1.99, 95% CI: 1.49-2.66), a longer hospital stay (pooled mean difference: 1.05 days, 95% CI: 0.02-2.07 days) and a higher discharge rate to further rehabilitation/step-down care (pooled OR: 5.71, 95% CI: 3.41-9.55). CONCLUSIONS: The presence of frailty in patients undergoing surgical intervention is associated with poorer outcomes with regard to mortality and return to independence. Further in-depth studies are required to identify factors that can be optimised to reduce the burden of frailty in surgical patients.

Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma.

Condyloma acuminata (CA) is a common sexually transmitted disease caused by Human Papilloma Virus (HPV) infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC) arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

Primitive neuroectodermal tumor of the kidney--another enigma: a pathologic, immunohistochemical, and molecular diagnostic study.

Primitive neuroectodermal tumor (PNET), the second most common type of sarcoma in the first two decades of life, rarely presents as an organ-based neoplasm. Rather, it is seen typically in the soft tissues of the chest wall and paraspinal region. We report a case of primary PNET of the kidney in a 17-year-old girl who presented with abdominal pain, hematuria, and an abdominal mass. Nodules and sheets of monotonous-appearing primitive round cells and the formation of rosettes focally were the principal microscopic features. The tumor cells were uniformly immunoreactive for vimentin, cytokeratin, neuron-specific enolase, and 013 (CD99). In addition, the characteristic translocation of PNET and Ewing sarcoma, t(11;22)(q24;q12), was detected by polymerase chain reaction (PCR). Eight previous examples of renal PNET have been reported in the literature in the past 2 years, but only three of these cases have had complete immunohistochemical evaluation with the demonstration of 013 positivity. To our knowledge the present case is the only one to date demonstrating the recurrent translocation t(11;22)(q24;q12) by PCR. Assuming that the previous cases in the literature are bona fide examples of PNET, the kidney may be another site of predilection for this usual soft-tissue neoplasm. We are once again confronted with the dilemma about the nature of the progenitor cell.

Serum and urinary concentrations of sex hormones and genital swelling during the menstrual cycle of the gibbon.

The relationship between sex hormone concentrations and female genital swelling during the menstrual cycle in the monogamous gibbon was comparable with that of polygamous female primates, such as the chimpanzee, which live in multimale groups and have larger swellings. The data, therefore, support the hypothesis proposed by C. R. Carpenter more than 50 years ago, that the gibbon's genital swelling, like that of other female primates, reflects basic physiological processes associated with progress of the menstrual cycle. Genital swelling increased during the follicular phase with increasing concentrations of oestradiol and oestrone glucuronide, reached maximal swelling in association with the mid-cycle peaks in the oestrogens and LH and began detumescence with the initial increases in progesterone during the luteal phase. The data also suggest that the menstrual cycle of the gibbon is shorter than previously reported, since cycles of 19-22 days exhibited hormone patterns that are consistent with ovulation. The genital swelling of the female gibbon is a useful marker for monitoring progress of the menstrual cycle and the presumptive time of ovulation.

Sexual aggression in the great apes.

Species-typical frequencies of copulation during the menstrual cycle differ among common chimpanzee, orang-utan, and gorilla, but all three species exhibit a midcycle enhancement associated with estrus. Thus, in the natural habitat, chimpanzees mate for 10-14 days, orang-utans for 5-6 days, and gorillas for 2-3 days. In traditional laboratory pair-tests, however, conducted in a single cage with both animals freely accessible to each other, all three species of great apes copulate more frequently than the species-typical pattern. In all three species, moreover, the increased copulation appears to result from increased male sexual initiative (aggression), male dominance over females, and the inability of the female to avoid or escape from the male within the limited spatial conditions of the free-access test. This interpretation is supported by studies using restricted-access tests in which females control sexual access. These data suggest that male sexual aggression in our closest biological affiliates commonly occurs when females are rendered vulnerable to the male by the absence of the normal social constraints and spatial prerogatives typical of the natural habitat. The possible implications of this interpretation for a biological perspective on human sexual aggression are considered.

Delayed infection of a pelvic lymphocele following pelvic lymphadenectomy.

Pelvic lymphocele is an infrequent complication of pelvic surgery, usually presenting shortly after surgery. We report a case of an infected pelvic lymphocele presenting more than 1 year after a staging pelvic lymphadenectomy for adenocarcinoma of the prostate. This case illustrates that late infection of pelvic lymphoceles can occur following a pelvic lymphadenectomy and radical prostatectomy.

Fascial closure of laparoscopic port sites: a new technique.

The laparoscopic operative procedure is not complete until the port sites are closed with a fascial suture. Herein, we report a simple new technique that uses a venous catheter for suture placement and direct laparoscopic visualization to secure the abdominal wall fascia and peritoneum.

Who is best benefited by radical prostatectomy?

The last few years have taught us much about prostate cancer. We now recognize that prostate cancer, even if it is of low stage and low grade, is a relentlessly progressive disease, especially if found in men with prolonged (greater than 15 years) life expectancy. We now know that serum PSA is a valid endpoint after radical prostatectomy to definitively assess its ability to eradicate prostate cancer. We are learning better how to use a variety of clinical parameters to predict pathologic stage, and we are in the process of developing other markers that may be exploited to predict which patients with early-stage prostate cancer have surgically curable lesions. From these observations it is reasonable to conclude that the best candidates for radical prostatectomy are young men (those with 10 to 20 years of life expectancy) with impalpable, clinically organ-confined low- or moderate-grade prostate cancers.

Penile erection: a reflection of sexual arousal and arousability in male chimpanzees.

A study was conducted to determine if sexual motivation in male chimpanzees, defined by the two components, sexual arousal and arousability, could be quantified by measuring penile erection during laboratory pair-tests of sexual behavior. Sexual arousal, the momentary level of sexual excitation, was quantified by single measurements on a scale of penile erection. Sexual arousability, the propensity for arousal, was quantified by the rate of approach to full erection and by mean erection scores. Sexual arousability, as defined, was related to the frequency of male courtship displays, copulations, and ejaculations, which were highest at midcycle and positively correlated with a quantitative measure of female anogenital swelling. Sexual arousal was negatively correlated with continued exposure to the female and least variable during midcycle. These operational definitions of sexual motivation in the male chimpanzee facilitate comparative research in which analogous indexes of sexual motivation are required such as when extrapolating from animal to human.

Variations in the use of prostate cancer staging tests: results from one NCCN Institution.

Medical care for prostate cancer accounts for as much as $26 billion in medical expenditures. There is debate about whether urologists who treat a large number of cases of prostate cancer use medical resources more efficiently than do urologists who treat fewer patients. This study focuses on one aspect of this debate by addressing the following issue: Are men with prostate cancer more likely to undergo noninvasive staging tests when they are treated by urologists who have higher caseloads than urologists with lower caseloads? Our study identified variations in patterns of ordering staging tests for prostate cancer. The finding supports the use of guidelines. Adherence to the guidelines is likely to be associated with more efficient use of medical resources by physicians with lower caseloads of prostate cancer.

Sexual behavior of chimpanzees (Pan troglodytes): male versus female regulation.

We investigated the sexual behavior of 13 chimpanzees (Pan troglodytes) in 2 types of pair test in order to clarify the interaction of social variables with female hormonal state. The frequency of copulation in tests in which the partners were freely accessible to each other was related to the male's dominance over the female; copulation was less frequent and was related to social compatibility in tests in which the female controlled access. Copulation was related to female hormonal state in both types of test. The results demonstrate (a) an association between female hormonal state and sexual activity of chimpanzees, (b) the influence of social relationships on sexual interactions, and (c) the importance of focusing on female sexual behavior before copulation, rather than copulation per se, in research on sexual arousability of female primates.

Prostate cancer patients' utilities for health states: how it looks depends on where you stand.

Two versions of the time-tradeoff (TTO) method were compared. In the personal TTO version, 31 prostate cancer patients decided whether they personally would give up some longevity to have perfect health rather than a longer life in a state of poor health associated with prostate cancer. In the impersonal version, 28 patients compared two hypothetical friends, one of whom has perfect health but will live less time than the other who is in poor health, and decided which person they would rather be. All patients evaluated three hypothetical health states. The two TTO methods were assessed by examining 1) how well they distinguished three health states of varying degrees of dysfunction and 2) patients' willingness to trade time for quality of life. Patients using the impersonal TTO version were more likely than those using the personal version to order the three health states appropriately (68% vs 16%, p < 0.0001) and were more willing to trade off length of life for quality of life (p < 0.05).

Surgeon's workshop: antegrade collagen injection: new technique for postprostatectomy stress incontinence.

Intraurethral collagen injection has become a recognized modality to treat stress urinary incontinence. The results of this procedure using the traditional retrograde endoscopic approach have generally been disappointing for men with sphincteric incontinence after radical prostatectomy. We describe a new technique of antegrade collagen injection utilizing suprapubic percutaneous bladder access to achieve simultaneous antegrade and retrograde endoscopic views of the bladder neck. This new injection technique is a promising and simple method of correcting postprostatectomy stress urinary incontinence.

Nephroenteric fistula treated with fulguration of the fistulous tract.

We report the management of a nephroenteric fistula with percutaneous fulguration in a patient with recurrent pyelonephritis and urolithiasis. A nephrostogram at 6 weeks and retrograde pyelogram at 18 weeks after fulguration showed no evidence of a recurrent fistula. We believe this to be the first reported case of a nephroenteric fistula treated successfully with fulguration.