No Difference in the Phenotypic Expression of Frailty among Elderly Patients Recently Diagnosed with Cancer Vs Cancer Free Patients.

OBJECTIVES: To examine frailty determinants differences in patients with a recent diagnosis of cancer compared to non-cancer patients among older adult. Revealing those differences will allow us to individualize the exact frailty management in those patients diagnosed with cancer. DESIGN: This is an observational cross-sectional, monocentric study. SETTING: Patients were evaluated at the Geriatric Frailty Clinic (GFC), in the Toulouse University Hospital, France, between October 2011 and February 2016. PARTICIPANTS: 1996 patients aged 65 and older were included (1578 patients without cancer and 418 patients with solid and hematological cancer recently diagnosed). MEASUREMENTS: Frailty was established according to the frailty phenotype. The frailty phenotype measures five components of frailty: weight loss, exhaustion, low physical activity, weakness and slow gait. Frailty phenotype was categorized as robust, pre-frail and frail. RESULTS: In a multinomial logistic regression, cancer, compared to the non-cancer group, is not associated with an increased likelihood of being classified as pre frail (RRR 0.9, 95% CI [0.5 ; 1.6 ], p 0.9) or frail (RRR 1.2, 95% CI [0.7 ; 2.0], p 0.4) rather than robust. When considering each Fried criterion, a significant higher odd of weight loss was observed in older patients with cancer compared to the non-cancer patients (OR 2.3, 95% CI [1.8; 3.0], p <0.001) but no statistically significant differences was found among the four other Fried criteria. Sensitivity analysis on the frailty index showed that cancer was not associated with a higher FI score compared to non-cancer (ß 0.002, 95%CI [-0.009; 0.01], p 0.6). CONCLUSION: In this real-life study evaluating elderly patients with and without cancer, we didn't confirm our hypothesis, in fact we found that cancer was not associated with frailty severity using both a phenotypic model and a deficit accumulation approach. Cancer may contribute, at least additively, to the development of frailty, like any other comorbidity, rather than a global underlying condition of vulnerability.

Defining Vitality Using Physical and Mental Well-Being Measures in Nursing Homes: A Prospective Study.

OBJECTIVES: To propose an objective definition of vitality and to evaluate its predictive value regarding the evolution of functional ability, as well as the risk of hospitalization and mortality in very old NH residents. DESIGN: Observational study. SETTINGS: Nursing homes. PARTICIPANTS: 541 participants. MEASUREMENTS: We operationalized tree definitions of vitality (binary variables discriminating vital from non-vital individuals): Mental vitality, assessed using three items of the geriatric depression scale; Physical vitality measured through hand grip strength test; and combined vitality, which combined mental and physical vitality definitions. Outcome measures were the 1-year evolution of functional ability as measured by a scale of activities of daily living (ADL) (score from 0 to 6) and the incidence of hospitalizations and mortality (time-to-event). RESULTS: First, 204 (37.7%) residents were defined as mentally vital. Second, 139 (27.5%) residents were defined as physically vital. And 52 (9.6%) were defined as vital when combining physical and. Combined vitality was associated with a reduced risk of hospitalization compared to combined non-vitality. Physically vital residents were associated with a reduced risk of mortality. No prospective associations were found between vital and non-vital individuals on the evolution of ADL scores across the three vitality definitions. But mentally vital individuals were associated with a worsening of ADL score. CONCLUSIONS: Better combined vitality seems to be associated with a reduced risk for hospitalizations, but more studies are needed to confirm a valid measurement of vitality in people living in NH in regards to ADL and mortality.

Omental flap for treatment of spondylodiscitis with lumbosacral dehiscence: A case report.

We report a case of pedicled omental flap use together with osteosynthesis treatment of a chronic L4-L5 spondylodiscitis due to a large sacral eschar. The 43-years-old patient was paraplegic and had depleted regional flaps solutions due to multiple previous surgeries. The procedure was carried out in supine position then in prone position whereby the dissected flap was recovered through the spine. The surgery was performed by a multidisciplinary team. First, we used an anterior approach for spine osteosynthesis with a metal implant and flap harvest. Then, in a prone position, we completed the vertebral reconstruction by an L3 athrodesis to the pelvis. The flap was recovered through the spine defect, on the side of the implant. It was a right sided pedicled. Complete wound healing was 120 days. The omental flap proved to be a reliable solution in the absence of recipient vessels for free flap transfer and depleted regional flap solutions. It also spared the latissimus dorsi muscle required for a wheelchair user as in our case. The omental flap is still performed in spine surgery especially in oncologic context to prevent wound dehiscence and for spondylodiscitis coverage. The anterior approach allows for both spine osteosynthesis and flap dissection.

[Breast reconstruction with profunda artery perforator flap: A prospective study of 30 consecutive cases]. / Reconstruction mammaire par profunda artery perforator flap : étude prospective des 30 premiers cas consécutifs.

INTRODUCTION: Many flaps have been described in autologous breast reconstruction, the most common being the deep inferior epigastric perforator (DIEP) flap. This flap cannot be harvested in a certain range of patients. The profunda artery perforator (PAP) flap, based on perforators from profunda femoral artery, is therefore a good option. OBJECTIVE: The goal was to highlight technical tips, particularities, and complications of our series of the 30 first PAP flaps for breast reconstruction in our department. PATIENTS AND METHOD: We did a prospective study of all PAP flaps for breast reconstruction between November 2014 and October 2015. Thirty patients were included. We used 2 different types of skin design: classical or with vertical extension. The following parameters were recorded: pedicle length, flap weight, surgery duration, complications on donor or recipient site and type of recipient vessels. RESULTS: Seventy-seven percent of the cases were delayed breast reconstruction, 23% were immediate. Twenty-five flaps were with classical skin design, and 5 with vertical extension. Mean flap weight was 301g (195-700g). Mean pedicle length was 9.88cm (8.2-12.5cm). Internal mammary vessels were the recipient vessels for 90% of the patients, versus 10% for circumflex scapular vessels. Mean surgery duration was 328min (195-610min). We had two total flap failures. The complications on the donor-site were 2 seroma, and 4 late healing scars. No lymphoedema occurred. CONCLUSION: PAP flap is a good option when abdominal flap harvesting is not possible. The donor-site is well tolerated, with low morbidity. The indication is for patients with small to medium breast volume.

[Breast reconstruction with Profunda Artery Perforator flap in lithotomy position. Surgical technique]. / Reconstruction mammaire par Profunda Artery Perforator flap prélevé en position gynécologique. Technique chirurgicale.

Autologous breast reconstruction provides great cosmetic, functional and sustainable incomes. Various flaps have been described in autologous breast reconstruction, Deep Inferior Epigastric Perforator flap (DIEP) being the most frequent. For patients with a non-sufficient abdomen for a DIEP based breast reconstruction, the Profunda Artery Perforator Flap (PAP), based on profunda arteris perforators, is a current trend, but few publications detailed the flap harvest. Comparing with a TUG flap, the morbidity linked to the muscle harvest is decreased. Usually the dissection is done in prone or in "frog leg" position. The aim is to describe a technical option: we propose a different position, with a harvest of the PAP in lithotomy position. It offers additional comfort and security for the surgeon and decreases the operative time. The pedicle had an average of 7cm in length; the artery diameter was 2.2mm and the vein 2.5mm. The cosmetic incomes are very good six months postoperative.

[Lactation after breast plastic surgery: literature review]. / Montée laiteuse après chirurgie plastique du sein: revue de la littérature.

The occurrence of lactation is a rare complication of breast plastic surgery. During the course of his practice, the plastic surgeon will probably encounter this complication. The goal of this article is to carry out a literature review of all published galactorrhea and/or galactocele cases following a breast-reduction or a breast-augmentation, representing a total of 34 cases reported in 21 articles. The physiopathology of this complication is linked to an inappropriate secretion of prolactin in a surgical context. The factors favoring this complication would be the number of pregnancies, a history of recent and extensive nursing, and the intake of certain medicines such as an oestro-progestative pill. The main symptom of this complication is the occurrence of a uni- or bilateral galactorrhea, on average 12.6 days after the surgery. The main differential diagnosis is a postoperative infection. The explorations presented a hyperprolactinemia in 69% of cases. No biological inflammatory syndrome was reported. A fluid collection evoking a galactocele was visible on the ultrasound in 65% of cases. One case of prolactin-secreting pituitary adenoma was reported. Depending on the case, the treatment varied from a simple surveillance to the association of a dopamine agonist, an antibiotic therapy, and a surgical revision. A diagnostic and therapeutic management strategy is proposed.

Oral health status and treatment needs among school children in Sana'a City, Yemen.

UNLABELLED: Data on the oral health status and treatment needs among Yemeni children are lacking. OBJECTIVES: To assess caries prevalence, treatment needs and gingival health status among school children in Sana'a City and to examine how these are affected by age, gender and khat chewing. METHODS: 1489 children (6- to 14-year old) were randomly selected from 27 schools representing all nine districts of Sana'a City. Dental caries and treatment needs were evaluated using standard WHO oral survey methods. The plaque index (PI), calculus index (CI) and the gingival index (GI), recorded at the six Ramfjord's teeth, were used to assess gingival health status. RESULTS: 4.1% of the study subjects were caries-free. Prevalence of these was significantly higher among the males. Overall, mean dmfs, dmft, DMFS and DMFT scores were 8.45, 4.16, 3.59 and 2.25 respectively. The decayed component accounted for >85% of the scores. The highest dmfs/dmft means were found among the 6-8 years age group, while the highest DMFS/DMFT means were scored by the 12-14 years age group. The need for restorative treatment and extractions was high; the former was significantly higher among the females. All subjects had gingivitis; the mean PI, CI and GI were 1.25, 0.3 and 1.36 respectively. Khat chewing did not affect caries experience; however, it was significantly associated with higher PI, CI and GI scores. CONCLUSIONS: The prevalence of caries, gingivitis and treatment needs among children in Sana'a city is high. More surveys in other Yemeni cities to generate comprehensive data are required.

Frequent gain of the human telomerase gene TERC at 3q26 in cervical adenocarcinomas.

The level of genomic amplification of the human telomerase gene TERC, which maps to chromosome band 3q26, was determined in primary cervical adenocarcinomas. Interphase nuclei prepared from archival material of 12 primary cervical adenocarcinomas, eight of which were human papillomavirus positive, were hybridised with a triple colour probe set specific for centromeres of chromosomes 3 and 7 and the TERC gene. We observed high proportions of nuclei with increased absolute copy numbers for TERC in all tumours (mean 3.3; range 2.3-5.2). Amplification of the human telomerase gene TERC is a consistent aberration in cervical adenocarcinomas. Therefore, application of our probe set may provide an objective genetic test for the assessment of glandular cells in Pap smears and hence for the diagnosis of cervical adenocarcinomas.

Gain of chromosome 3q is an early and consistent genetic aberration in carcinomas of the vulva.

The aim was to determine whether specific gains of chromosome 3q and laminin-5gamma2-chain expression can improve early detection of invasive capacity in precancerous and squamous cell carcinoma of the vulva (VSCC). Six VSCC and three precancerous lesions were studied. Multicolor fluorescence in situ hybridization (FISH) probe sets were applied to nuclei suspensions prepared from archival material using the Hedley method. The probe panel consists of the centromers of chromosome 7, chromosome 3, and the TERC gene residing on the long arm of chromosome 3. Laminin-5gamma2-chain immunohistochemical analysis was performed on corresponding specimens and was expressed only in the VSCC. The genome-specific FISH analysis revealed 3q amplification in 43% of the nuclei analyzed for the VSCC and 22% of the nuclei for the precancerous lesions. Low-level 3q amplifications were found in precancerous lesions with an average fold increase of 1.15 for 3q. The invasive lesions showed higher average fold increases for 3q, averaging 1.32. Laminin-5gamma2-chain protein was expressed only in VSCC, whereas 3q gains were observed both in precancerous lesions and in VSCC, indicating that gain of chromosome 3q is an early and consistent event during carcinogenesis of VSCC.

[Interphase cytogenetics with DNA-probes for chromosome 8 to detect circulating tumor cells in breast cancer patients]. / Interphasezytogenetik mit DNA-Sonden für Chromosom 8 zur Detektion zirkulierender Tumorzellen beim Mammakarzinom.

The detection of micrometastases in the bone marrow or peripheral blood of cancer patients is increasingly used for a more sensitive tumor staging and prognostication. The potential value of the currently used techniques for the detection of epithelial antigens by RT-PCR or immunohistochemistry in respect of specificity is currently controversially discussed. In the present study we demonstrate a new approach which enables the direct visualization of the tumor specific alteration of chromosome 8 in circulating tumor cells. We have therefore studied breast cancer patients with various tumor stages and tried to determine the frequency of circulating tumor cells in the peripheral blood by using interphase cytogenetics for chromosome 7 and 8. Imprints of primary breast cancers and cytospins with circulating tumor cells of corresponding patients were studied in a blinded fashion. The blood samples were generated by immunomagnetic enrichment of circulating tumor cells from peripheral blood by ferrofluid and centrifugation onto cover slips. These cytospins were then hybridized with centromer probes 7 and 8. After analyzing 27 patients with benign as well as malignant breast tumors we can demonstrate that the chromosomal pattern between malignant tumor and corresponding circulating tumor cells is identical. Furthermore, the detection of circulating tumor cells directly correlates with the primary tumor stage. We did not find any cells with chromosome 8 alterations in the patients with benign disease. Surprisingly, even in early breast cancers (T1N0) interphase cytogenetics identified circulating tumor cells in 2 out of 4 patients. In conclusion, interphase cytogenetics represent a non-invasive, sensitive and specific assay for the direct visualization of circulating tumor cells in the peripheral blood. The prognostic value of these findings remains to be further evaluated in larger prospective studies.

Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms.

Jumping translocations (JTs) and segmental jumping translocations (SJTs) are unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to multiple recipient chromosomes. In leukemia, where JTs have been predominantly observed, the donor segment (usually 1q) preferentially fuses to the telomere regions of recipient chromosomes. In this study, spectral karyotyping (SKY) and FISH analysis revealed 188 JTs and SJTs in 10 cell lines derived from carcinomas of the bladder, prostate, breast, cervix, and pancreas. Multiple JTs and SJTs were detected in each cell line and contributed to recurrent unbalanced whole-arm translocations involving chromosome arms 5p, 14q, 15q, 20q, and 21q. Sixty percent (113/188) of JT breakpoints occurred within centromere or pericentromeric regions of the recipient chromosomes, whereas only 12% of the breakpoints were located in the telomere regions. JT breakpoints of both donor and recipient chromosomes coincided with numerous fragile sites as well as viral integration sites for human DNA viruses. The JTs within each tumor cell line promoted clonal progression, leading to the acquisition of extra copies of the donated chromosome segments that often contained oncogenes (MYC, ABL, HER2/NEU, etc.), consequently resulting in tumor-specific genomic imbalances. Published 2001 Wiley-Liss, Inc.

Unusual 1H NMR chemical shifts support (His) C(epsilon) 1...O==C H-bond: proposal for reaction-driven ring flip mechanism in serine protease catalysis.

13C-selective NMR, combined with inhibitor perturbation experiments, shows that the C(epsilon)(1)H proton of the catalytic histidine in resting alpha-lytic protease and subtilisin BPN' resonates, when protonated, at 9.22 ppm and 9.18 ppm, respectively, which is outside the normal range for such protons and approximately 0.6 to 0.8 ppm further downfield than previously reported. They also show that the previous alpha-lytic protease assignments [Markley, J. L., Neves, D. E., Westler, W. M., Ibanez, I. B., Porubcan, M. A. & Baillargeon, M. W. (1980) Front. Protein Chem. 10, 31-61] were to signals from inactive or denatured protein. Simulations of linewidth vs. pH demonstrate that the true signal is more difficult to detect than corresponding signals from inactive derivatives, owing to higher imidazole pK(a) values and larger chemical shift differences between protonated and neutral forms. A compilation and analysis of available NMR data indicates that the true C(epsilon)(1)H signals from other serine proteases are similarly displaced downfield, with past assignments to more upfield signals probably in error. The downfield displacement of these proton resonances is shown to be consistent with an H-bond involving the histidine C(epsilon)(1)H as donor, confirming the original hypothesis of Derewenda et al. [Derewenda, Z. S., Derewenda, U. & Kobos, P. M. (1994) J. Mol. Biol. 241, 83-93], which was based on an analysis of literature x-ray crystal structures of serine hydrolases. The invariability of this H-bond among enzymes containing Asp-His-Ser triads indicates functional importance. Here, we propose that it enables a reaction-driven imidazole ring flip mechanism, overcoming a major dilemma inherent in all previous mechanisms, namely how these enzymes catalyze both the formation and productive breakdown of tetrahedral intermediates.

Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation.

The transition of normal epithelium to invasive carcinoma occurs sequentially. In colorectal and cervical carcinogenesis, this transition is reflected by histomorphologically defined grades of increasing dysplasia that untreated may progress to invasive disease. In an attempt to understand the role of chromosomal aberrations during tumorigenesis we have applied comparative genomic hybridization using DNA extracted from defined stages of colorectal and cervical tumors, from low- and high-grade astrocytic tumors and from diploid and aneuploid breast carcinomas. Genetic instability, as measured by the number of chromosomal copy alterations per case, increases significantly at the transition from precursor lesions to invasive carcinomas and continues to increase with tumor stage. Aggressive tumors have a higher number of copy alterations per case. High-level copy number changes (amplifications) become more prevalent in advanced-stage disease. Subtractive karyograms of chromosomal gains and losses were used to map tumor stage-specific chromosomal aberrations and clearly showed that nonrandom chromosomal aberrations occur during disease progression. In colorectal and cervical tumors, chromosomal copy number changes were correlated with nuclear DNA content, proliferative activity, expression levels of the tumor suppressor gene TP53, and the cyclin-dependent kinase inhibitor p21/WAF1, as well as the presence of viral genomes. Here we summarize and review the results of this comprehensive phenotype/genotype correlation and discuss the relevance of stage-specific chromosomal aberrations with respect to diagnostic applications.

Increasing the effectiveness of resource deployment in healthcare organizations.

This article suggests ways to enhance the effectiveness with which healthcare organizations deploy their resources. Specifically, the article: (1) reviews research findings from the academic literature that managers often continue, or even increase, resource allocation to unprofitable courses of action; (2) reports the results of a case study with hospital administrations that suggests that this tendency may exist in healthcare organizations; and (3) suggests ways for healthcare organizations to control the occurrence of such suboptimal actions, thereby increasing the effectiveness and timeliness of their resource deployment.

The balanced scorecard: a potent tool for energizing and focusing healthcare organization management.

The current environment for healthcare organizations contains many forces demanding unprecedented levels of change. These forces include changing demographics, increased customer expectations, increased competition, and intensified governmental pressure. Meeting these challenges will require healthcare organizations to undergo fundamental changes and to continuously seek new ways to create future value. This article provides explanation of a potent new management tool-the balanced scorecard-that can be used by healthcare organizations to meet these challenges. The article also presents the opinions of many high-level healthcare administrators that the balanced scorecard can be highly beneficial to healthcare organizations. It also summarizes these administrators' suggestions regarding the goals and measures that can make up an effective scorecard for a hospital as a whole, as well as for a specific subunit of a hospital. Interestingly, while no published report of balanced scorecard implementations in healthcare organizations exists, a number of administrators stated that they had fully implemented systems similar to the scorecard. These actions can be considered support for the scorecard's potential usefulness; at the same time, they suggest that some sharing of experiences will likely be available in the future. As all administrators are well aware, moving from concept to practice is often difficult. While the article includes some suggestions for scorecard development and implementation, each organization must engage in the full range of activities, from defining its mission to the selection of goals and strategies, and develop its own unique scorecard to assist progress toward the selected goals. As a starting point, Table 3 provides a timeline of some general events that may be common to all organizations during this process.

Voluntary purchasing pools: a market model for improving access, quality, and cost in health care. American College of Physicians.

States and small businesses have been rapidly establishing voluntary health care purchasing pools during the past few years. Purchasing pools can decrease health care costs, improve access for some small businesses and individual persons, allow greater choice among health care plans, and provide continuity of care. Purchasing pools also help to even the balance of power in the health care marketplace, which has come increasingly under the control of huge proprietary managed care corporations. This position paper of the American College of Physicians discusses how a system of well-designed voluntary purchasing pools can help protect the integrity of health care in the emerging managed care marketplace.

Polyreactive autoimmune response induced by PC 12 cell grafts into rat striatum.

In order to better characterize the autoantibodies induced by PC12 cells grafted into rat brain, we have tested sera from these animals by immunoblotting with several preparations, including phosphorylated and dephosphorylated neurofilaments, keratins, PC12 cells and proteins from various rat tissues, and by immunofluorescence of rat spinal cord neurons in culture. Sera from grafted rats reacted with several antigens present in all tissues tested and stained in cultured neurons not only NF but also cell bodies and membranous granular structures. These observations suggest either the polyreactivity of autoantibodies or the induction of a polyclonal B cell activation consecutive to the release of central nervous system antigens into the blood stream. These results are discussed with regard to the role of NF autoantibodies in neurodegenerative diseases.