P-cresol,a uremic toxin,decreases endothelial cell response to inflammatory cytokines

BACKGROUND: Infectious diseases are among the most morbid events in uremia. The uremic toxin p-cresol may play a role in the immunodeficiency of uremia by depressing phagocyte functional capacity. Leukocyte adhesion to endothelium, a key event in the immune response, is mediated by endothelial adhesion molecules. These include intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, which are induced by various inflammatory cytokines. We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta). Thereafter, the endothelial molecules ICAM-1, VCAM-1, and E-selectin were quantitated and the monocyte (THP-1) adhesion to HUVEC measured. RESULTS: P-cresol decreased cytokine-induced protein and mRNA expression of ICAM-1 and VCAM-1. In addition, p-cresol significantly decreased the adhesion of THP-1 to cytokine-stimulated HUVEC. CONCLUSIONS: P-cresol may play a role in the immune defect of uremic patients by inhibiting cytokine-induced endothelial adhesion molecule expression and endothelium/monocyte adhesion.     

The Impact of Financial Conflict of Interest on Surgical Research: An Observational Study of Published Manuscripts

Background

Substantial discrepancies exist between industry-reported and self-reported conflicts of interest (COI). Although authors with relevant, self-reported financial COI are more likely to write studies favorable to industry sponsors, it is unknown whether undisclosed COI have the same effect. We hypothesized that surgeons who fail to disclose COI are more likely to publish findings that are favorable to industry than surgeons with no COI.

Methods

PubMed was searched for articles in multiple surgical specialties. Financial COI reported by surgeons and industry were compared. COI were considered to be relevant if they were associated with the product(s) mentioned by an article. Primary outcome was favorability, which was defined as an impression favorable to the product(s) discussed by an article and was determined by 3 independent, blinded clinicians for each article. Primary analysis compared incomplete self-disclosure to no COI. Ordered logistic multivariable regression modeling was used to assess factors associated with favorability.

Results

Overall, 337 articles were reviewed. There was a high rate of discordance in the reporting of COI (70.3%). When surgeons failed to disclose COI, their conclusions were significantly more likely to favor industry than surgeons without COI (RR 1.2, 95% CI 1.1–1.4, p < 0.001). On multivariable analysis, any COI (regardless of relevance, disclosure, or monetary amount) were significantly associated with favorability.

Conclusions

Any financial COI (disclosed or undisclosed, relevant or not relevant) significantly influence whether studies report findings favorable to industry. More attention must be paid to improving research design, maximizing transparency in medical research, and insisting that surgeons disclose all COI, regardless of perceived relevance.

     

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 μm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis.     

Emergency Presenting Colon Cancer Is an Independent Predictor of Adverse Disease-Free Survival

Twenty percent of colon cancers present as an emergency. However, the association between emergency presentation and disease-free survival (DFS) remains uncertain. Consecutive patients who underwent elective (CC) and emergent (eCC) resection for colon cancer were included in the analysis. Survival outcomes were compared between the 2 groups in univariate/multivariate analyses. A total of 439 patients underwent colonic resection for colon cancer during the interval 2000−2010; 97 (22.1%) presented as an emergency. eCC tumors were more often located at the splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group displayed features of more advanced disease with a higher proportion of T4 (P = 0.009), N2 tumors (P < 0.01) and lymphovascular invasion (P< 0.01). eCC was associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P < 0.01 ) on univariate analysis. eCC remained an independent predictor of adverse locoregional recurrence (HR 1.86, 95% CI 1.50–3.30, P = 0.03) and DFS (HR 1.30, 95% CI 0.88–1.92, P = 0.05) on multivariate analysis. eCC was not associated with adverse overall survival and systemic recurrence. eCC is an independent predictor of adverse locoregional recurrence and DFS.Key words: Emergency presentation, Colon cancer, Disease free survival, Locoregional recurrenceColorectal cancer (CRC) is a significant cause of mortality, with over 40,000 new cases diagnosed annually in the UK contributing to over 16,000 deaths (Bowel Cancer UK).^1,2 Up to 20% of colon cancers (CC) present as an emergency (eCC) necessitating emergent surgery.^3,4 Although eCC has been shown to be associated with poorer overall survival (OS), much discrepancy exists in the literature regarding its association with disease-free survival (DFS).⁵⁻⁷Studies reporting the oncologic outcomes of CRC presenting as an emergency consist of heterogeneous populations of patients with colon and rectal cancers.^3,5 Colon and rectal cancers are 2 distinct entities with different molecular, clinical, pathologic, and biologic characteristics and treatment modalities.^8,4,9−11 Since the incorporation of combined multimodal treatment and total mesorectal excision the disparity in OS and DFS between colon and rectal cancer has increased.¹²⁻¹⁷ Rectal cancer patients may alter the impression of outcomes in emergency presenting colon cancer. Consequently, previous studies assessing outcomes in eCC may be flawed. Furthermore, the negative impact of eCC has previously been attributed to immediate postoperative complications with an inpatient hospital mortality of approximately 15%. Inclusion of such cases in studies assessing long-term outcomes may have overestimated the negative impact of eCC.¹⁸The aim of the current study was to determine the association between eCC and disease-free/overall survival.     

Anatomical Mapping of the External Obturator Footprint: A Study In Cadavers with Implications for Direct Anterior THA

BackgroundThe external obturator footprint in the trochanteric fossa has been suggested as a potential landmark for stem depth in direct anterior THA. Its upper border can be visualized during surgical exposure of the femur. A recent study reported that the height of the tendon has little variability (6.4 ± 1.4 mm) as measured on CT scans and that the trochanteric fossa is consistently visible on conventional pelvic radiographs. However, it is unclear where exactly the footprint of this tendon should be templated during preoperative planning so that it can be useful intraoperatively.Questions/purposesIn this study, we sought: (1) to provide instructions on exactly where to template the external obturator footprint on a preoperative planning radiograph, and (2) to confirm the small variability in height of the external obturator footprint found on CT scans in a cadaver study.MethodsTwo-dimensional (2-D) and three-dimensional (3-D) imaging was used to map the anatomy of the external obturator footprint. This dual approach was chosen because of their complementarity; conventional 2-D radiographs translate to clinical practice but 3-D navigation-based digitalization combined with CT allows for a better understanding of the cortical lines that comprise the outline of the trochanteric fossa. In 12 (four males, mean age 80 years, range 69 to 88) formalin-treated cadaveric lower extremities including the pelvis, the external obturator tendon was dissected, and the top and bottom end of its footprint marked with two small needles, and calibrated radiographs were taken. For another five (three males, mean age 75.7 years, range 61 to 91) fresh-frozen cadaveric lower extremities, including femoral reflective marker frames, CT scans were obtained and the exact location of the external obturator footprint was recorded using 3-D navigation-based digitalization. Qualitative analysis of both imaging modalities was used to develop instructions on where the external obturator footprint should be templated on a preoperative planning radiograph. Quantitative analysis of the dimensions of the external obturator footprint was performed.ResultsThe lowest point of the external obturator footprint was consistently found (± 1 mm) at the intersection of the vertical line comprised of the lateral wall of the trochanteric fossa and the oblique line formed by the intertrochanteric crest and therefore allows templating of this structure on the preoperative planning radiograph. The median (range) height of the footprint measured 6.4 mm and demonstrated small variability (4.7 to 7.6).ConclusionsWe suggest templating a 6.4-mm circle with its bottom on the intersection described above.Clinical RelevanceThe distance between the templated shoulder of the stem and the top of the circle can be used intraoperatively for guidance. Discrepancy should lead to re-evaluation of stem depth and leg length. Future work will investigate the usability, validity, and reliability of the proposed methodology in daily clinical practice.     

Efficacy and safety of anti-vascular endothelial growth factor therapies in older patients for first line treatment of metastatic renal cell carcinoma

Backgroundimmunotherapy became the first line treatment of metastatic renal cell carcinoma (mRCC). Nevertheless, a better understanding of the specificities of targeted therapies (TT) in the elderly population could be helpful in order to improve the management of mRCC in this population. The aim of this retrospective study was to assess efficacy and safety of sunitinib and sorafenib used as first-line TT in 70 years older patients compared to younger patients.MethodsData were retrospectively collected for all consecutive mRCC patients receiving first line TT treatment by sunitinib or sorafenib for mRCC from January 2006 to November 2017. Patients were divided into two groups according to the age using a cut-off at 70 years old. Median progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared using log-rank test.ResultsIn total, 147 patients were included; 94 (63.9%) were <70 and 53 (36.1%) were 70 years old or more. First line TT used was sunitinib in 123 (83.7%) patients or sorafenib in 24 (16.3%) patients. Median PFS was 8 months for elderly patients vs. 6 in younger group (P=0.68). Median OS were 26 vs. 36 months (P=0.08). Severe induced toxicity was more frequent among elderly patients: 34 (64.2%) vs. 46 patients (48.9%) (P=0.07). Rate of treatment discontinuation due to toxicity was 22 patients (23.4%) in younger group vs. 28 patients (52.8%) in the elderly group (P=0.0005). Results were similar in the 2 groups regarding the type of toxicities.ConclusionsOur results suggest similar efficacy of anti-vascular endothelial growth factor (VEGF) agents as first-line treatment for mRCC among younger and older patients with an age cut-off of 70 years. Safety results suggest that these drugs can be safely used for older patients with a need of caution regarding toxicity prevention.     

Dynamic magnetic resonance imaging for grading pelvic organ prolapse according to the international continence society classification: Which line should be used?

AIMS: To assess and compare the reliability of dynamic MRI to quantify pelvic organ prolapse (POP) according to the International Continence Society (ICS) using two different reference lines, and to determine which line gives the best concordance with clinical examination. METHODS: Forty-seven patients with genital prolapse underwent physical examination and dynamic MRI. Five nulliparous, symptom-free female volunteers underwent dynamic MRI as control subjects. Two distinct observers performed the MRI measurements of POP according to the ICS using two distinct reference lines: the mid-pubic line and a new one, the perineal line that provides a better match with the hymen plane. Measurements were repeated twice according to each line. The intra-class coefficient was used to estimate intra-observer and inter-observer reliability; the Altman and Bland plot was used to assess the agreement between MRI and clinical measurements. RESULTS: The intra-observer and inter-observer reliability of MRI measurements were in general excellent. Intra-class coefficients were better for the mid-pubic line than the perineal line. Although the MRI measurements correlate significantly with the physical measurements, the Altman and Bland plot shows an unacceptable magnitude of discrepancy between clinical and MRI examinations. CONCLUSIONS: Although dynamic MRI shows excellent inter- and intra-observer reliability, its agreement with clinical examination is poor whatever the line used.     

Trans-Sinusal Frontal Approach for Olfactory Groove Meningiomas

The authors report on their experience with the trans-sinusal frontal approach in removing olfactory groove meningiomas. Six tumors were operated on by the trans-sinusal frontal approach, using a bicoronal incision; two tumors developed on one side, and there were four bilateral olfactosellar tumors. Osteotomy of the anterior wall of the frontal sinus was performed with an oscillating saw without any burr hole. The posterior wall of the sinus was resected and the tumor was attacked through a real subfrontal route along the plane of the anterior skull base. Ethmoidal blood supply was controlled at the initial stages of the operation, allowing avascular tumor debulking. Olfactory nerves, invaded by the tumor, were removed along with the tumor. Tumor extensions toward the sella and the optic canals were removed without brain retraction, opening of the Sylvian fissure, or dissection of the carotid arteries. All patients made a good neurologic recovery; intellectual impairment disappeared within 1 month, and visual acuity normalized within 2 weeks. Olfactory nets were preserved on the contralateral side in unilateral tumors. The trans-sinusal frontal approach is technically easy and safe to achieve. Osteotomy and replacement of the anterior wall of the frontal sinus are rapidly performed. When the frontal sinus is small, imageguided surgery allows precise deliniation of its limits and the free bone flap, including the calvarial outer layer, tangentially cut from one supraorbital canal to the other. The cosmetic result is perfect, as the normal contour of the forehead is maintained without any scar or visible burr hole. The trans-sinusal frontal approach gives access to the orbital roofs and to the central anterior skull base from the crista galli to the tuberculum sellae and the anterior clinoid processes. The trans-sinusal frontal approach represents an alternative to conventional craniotomies for tumors developed in the central anterior skull base, especially for olfactory groove meningiomas, whatever their size.     

Lepidium meyenii （ Maca ） improved semen parameters in adult men

Aim: The present study was designed to determine the effect of a 4-month oral treatment with tablets of Lepidium meyenii (Maca) on seminal analysis in nine adult normal men aged 24 - 44 years old. Methods: Nine men received tablets of Maca (1500 or 3000 mg/day) for 4 months. Seminal analysis was performed according to guidelines of the World Health Organization (WHO). Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured before and after treatment. Results: Treatment with Maca resulted in increased seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility. Serum hormone levels were not modified with Maca treamaent. Increase of sperm count was not related to dose of Maca. Conclusion: Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.     

Prognosis of lupus membranous nephropathy in children

The occurrence of membranous nephropathy in pediatric series of systemic lupus erythematosus has been reported only rarely, probably due to a very low frequency. One hundred fifty-four children who were seen in 100 French pediatric centers between January 2002 and April 2005 were included. Fifteen (12 girls and three boys) out of the 81 (18.5 %) children with renal involvement presented histological features of membranous nephropathy. Their ages ranged from six to 15 years old (mean=11.3) at the age of SLE diagnosis and 8/15 children were of African origin. Isolated membranous nephropathy was observed in nine patients, of whom five patients displayed a complete recovery following immunosuppressive treatment. Associated proliferative lesions were observed on the first kidney specimen in two patients and in a further renal biopsy in four other patients, leading to a less favorable course of lupus nephropathy.