Adequate assessment yields appropriate care-the role of geriatric assessment and management in older adults with cancer: a position paper from the ESMO/SIOG Cancer in the Elderly Working Group.

With the aging population, older adults constitute a growing proportion of the new cancer cases. Given the heterogeneous health status among older adults and their susceptibility to aging-related vulnerabilities, understanding their diversity and its implications becomes increasingly crucial for prognostication and guiding diagnostics, treatment decisions, and follow-up, as well as informing supportive care interventions. Geriatric assessment and management (GAM) refers to the comprehensive evaluation of an older individual's health status with subsequent management plans focusing on both oncologic and non-oncologic interventions. In 2019, the European Society for Medical Oncology (ESMO) and the International Society of Geriatric Oncology (SIOG) established the ESMO/SIOG Cancer in the Elderly Working Group. This position paper reflects the recommendations of the working group. Our paper summarizes the existing evidence with a focus on recent key trials and based on this, we propose several recommendations and future directions.

Low Dietary Protein Intakes and Associated Dietary Patterns and Functional Limitations in an Aging Population: A NHANES analysis.

OBJECTIVE: To investigate protein intakes across demographic characteristics in relation to dietary patterns and functional outcomes in older adults. DESIGN: Observational and cross-sectional study. SETTING: Non-institutionalized participants from the 2005-2014 National Health and Nutrition Examination Survey. PARTICIPANTS: Data from 11,680 adults were categorized into 51-60 years (n= 4,016), 61-70 years (n=3,854), and 71 years and older (n=3,810) for analysis. MEASUREMENTS: Adults were stratified by meeting or not meeting the protein recommendation (0.8 g/kg/d) to compare demographics, diet quality with Healthy Eating Index-2015, functional limitations, and other dietary intakes. Dietary recalls were collected using the multiple pass method. Data analyses were weighted to create a nationally-representative sample. RESULTS: Dietary protein intakes were significantly lower in older age groups, with up to 46% of the oldest adults not meeting the protein intake recommendation. Participants consuming protein below the recommended intake level had significantly poorer diet quality across all age groups (P<0.01), however, overall diet quality was better in older adults. Those not meeting the protein recommendation were more likely to have intakes of other nutrients below recommended levels. Those below the protein recommendation had significantly more functional limitations across all age groups, while grip strength was significantly lower in those over 70 years old. CONCLUSION: Lower protein intakes, and lower diet quality and physical functioning are related in an aging population. Meeting the protein recommendation was linked to better overall diet quality and may be protective of lean mass; therefore, evaluation of individual characteristics which may affect protein intakes is crucial in supporting older adults to meet their protein needs.

Prospective associations of C-reactive protein (CRP) levels and CRP genetic risk scores with risk of total knee and hip replacement for osteoarthritis in a diverse cohort.

OBJECTIVE: To examine associations of high-sensitivity C-reactive protein (CRP) levels and polygenic CRP genetic risk scores (GRS) with risk of end-stage hip or knee osteoarthritis (OA), defined as incident total hip (THR) or knee replacement (TKR) for OA. DESIGN: This study included a cohort of postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. Women were followed from baseline to date of THR or TKR, death, or December 31, 2014. Medicare claims data identified THR and TKR. Hs-CRP and genotyping data were collected at baseline. Three CRP GRS were constructed: 1) a 4-SNP GRS comprised of genetic variants representing variation in the CRP gene among European populations; 2) a multilocus 18-SNP GRS of genetic variants significantly associated with CRP levels in a meta-analysis of genome-wide association studies; and 3) a 5-SNP GRS of genetic variants significantly associated with CRP levels among African American women. RESULTS: In analyses conducted separately among each race and ethnic group, there were no significant associations of ln hs-CRP with risk of THR or TKR, after adjusting for age, body mass index, lifestyle characteristics, chronic diseases, hormone therapy use, and non-steroidal anti-inflammatory drug use. CRP GRS were not associated with risk of THR or TKR in any ethnic group. CONCLUSIONS: Serum levels of ln hs-CRP and genetically-predicted CRP levels were not associated with risk of THR or TKR for OA among a diverse cohort of women.

An air-liquid interphase approach for modeling the early embryo-maternal contact zone.

We developed an air-liquid interphase culture procedure for mammalian oviduct epithelial cells leading to the formation of functional epithelial tissues, which generate oviduct fluid surrogates. These in vitro oviduct epithelia can be co-cultured with living zygotes and enable embryonic development up to the blastocyst stage without addition of embryo culture medium. The described strategy is broadly applicable to analyze early embryo-maternal interactions under standardized in vitro conditions.

Bovine oviductal epithelial cells: long term culture characterization and impact of insulin on cell morphology.

In vitro models that resemble cell function in vivo are needed to understand oviduct physiology. This study aimed to assess cell functions and insulin effects on bovine oviductal epithelial cells (BOECs) cultured in an air-liquid interface. BOECs (n=6) were grown in conditioned Ham's F12, DMEM or Ham's F12/DMEM with 10% fetal calf serum (FCS) for 3 weeks. After selecting the most suitable medium (Ham's F12), increasing insulin concentrations (1 ng/mL, 20 ng/mL and 5 µg/mL) were applied, and cell morphology and trans-epithelial electrical resistance (TEER; n=4) were evaluated after 3 and 6 weeks. Keratin immunohistochemistry and mRNA expression of oviductal glycoprotein 1 (OVGP1) and progesterone receptor (PGR) were conducted (n=4) to assess cell differentiation. BOECs grown without insulin supplementation or with 1 ng/mL of insulin displayed polarization and secretory activity. However, cells exhibited only 50% of the height of their in vivo counterparts. Cultures supplemented with 20 ng/mL insulin showed the highest quality, but the 5 µg/mL concentration induced massive growth. TEER correlated negatively with insulin concentration (r=-0.459; p=0.009). OVGP1 and PGR transcripts were still detectable after 3 and 6 weeks. Cellular localization of keratins closely resembled that of BOECs in vivo. Cultures showed heterogeneous expression of PGR and OVGP1 in response to estradiol (10 pg/mL). In summary, BOECs grown for long term in an air-liquid interface expressed markers of cell differentiation. Additionally, insulin supplementation (20 ng/mL) improved the cell morphology in vitro.

Initial characterization of an outbreed mouse model for male factor (in)fertility.

We analysed an outbreed mouse line which was selected for the phenotype 'high fertility' for 158 generations. During this selection period the mouse strain increased the number of offspring per litter from 10.4 to 17.1 and the total litter weight up to ~160%. In this study, we initially characterize the reproductive phenotype of high fertility males. Surprisingly, male bucks of the fertility line (FL1) show reduced percentage of motile and progressive motile spermatozoa; however, other sperm motility characteristics (e.g. velocity parameters) are improved compared with an unselected control line. Cytometrical investigation of the testicular cell-type composition indicated a significant increased concentration of diploid cells by a concomitant reduction in haploid cells in the testicular parenchyma of FL1. Furthermore, total testosterone concentrations in blood are dramatically increased in FL1 (>20 ng/mL). In line with increased testosterone levels, we observed increased expression rates of steroidogenic key enzymes Cyp11 and Cyp17 from FL1 testis samples. These data indicate that FL1 males have a manifest 'high fertility phenotype'. Diallelic crosses imply that male-only contribution largely determines the reproductive outcome in cross-breeding experiments. FL1 therefore is a promising model for future investigations on male factor (in)fertility. Our observation might also offer valuable cues for human reproductive medicine.

Analysis of Sertoli cell efficiency allows the differentiation between two fundamentally different forms of feline teratospermia.

Teratospermia is a common phenomenon within felid species and has been attributed to reduction in genetic diversity. Testes from teratospermic domestic cats show enhanced spermatogenesis accompanied by remarkably reduced germ cell apoptosis. In the present study we investigated whether free-range teratospermic tom cats exhibit a similar testicular phenotype as proven permanently teratospermic males. Randomly collected teratospermic cats were compared with normal (normospermic; >60% morphologically normal sperm per ejaculate) and a well-characterized population of permanently teratospermic domestic cats, with respect to their spermatogenic potential. Histomorphologic assessment of testes from randomly collected teratospermic cats revealed no differences compared with normospermic donors. These two groups, however, were both different from permanently teratospermic cats, which exhibit fewer Sertoli cells and increased numbers of round spermatids per tubule cross-section resulting in a remarkably increased Sertoli cell efficiency (ratio of round spermatids to Sertoli cells). In conclusion, we can distinguish at least two fundamentally different forms of feline teratospermia. One subtype, found in most of the randomly collected tom cats, but not associated with altered quantitative spermatogenic parameters. Another subtype, found in all permanently teratospermic felids, is manifested by an impairment of Sertoli cell efficiency. We suggest that spermatogenic output should be analyzed before using random source domestic cats to study the phenomenon of teratospermia.

Feline gonads exhibit tissue specific alternative splicing of oestrogen receptor alpha (ESR1).

Male felids frequently show teratospermia. At least in the domestic cat model, teratospermia is accompanied by impaired regulation of testicular apoptosis. We hypothesize that this phenomenon is caused by dysregulations in oestrogen signalling pathways. Both classical oestrogen receptors (ESR1 and 2) are expressed in species and/or tissue-specific manners and display different variants, inter alia, caused by alternative splicing. In vitro studies showed that exon deleted transcripts are translated into proteins and that some of the variants modify the effects of the full-length ERs. It has been proposed that some of the functional and morphological dysregulations, for example, during spermatogenesis, could directly derive from this phenomenon. In the present basic study, we investigated the expression pattern of ESR1 splicing variants in the gonads of domestic cats. Testicular, epididymal as well as ovarian tissue samples were collected from routine castrations. ESR1 variants were detected by means of RT-PCR using primers spanning one to three exons. We detected the variants Δ4 and Δ7 in all tissue samples investigated. Additionally, the testicular parenchyma expressed the variant Δ6 and double exon deletions of ESR1 (Δ4/6 and Δ6/7). Using an antiserum recognizing all previously identified ESR1 splicing variants, we revealed ESR1 proteins being expressed in nearly all cells of the testicular and ovarian parenchyma. ESR1 Δ6 protein, however, detected by an antiserum specifically raised against the Δ6 variant, was predominantly located in Sertoli cells. As the exon deletion variants are significantly expressed and show a distinct expression pattern, they could specifically modulate the cellular responsiveness to hormonal stimuli within the gonads.

Modelling the porcine oviduct epithelium: a polarized in vitro system suitable for long-term cultivation.

For exploring the processes leading to successful reproduction, differentiated long-term in vitro systems modelling the mammalian oviduct are needed. Therefore, in the present study culture conditions for primary porcine oviductal epithelial cells were optimized with regard to morphological differentiation and usability for extended cultivation periods. To evaluate different growth media for the primary cells, we used morphological criteria as well as real-time impedance measurement. After an initial media testing, the cells were grown on hanging membranes and the culture settings (conventionally cultured, serum gradient over the membrane and air-liquid interface) were assessed by histology and electron microscopy. We proved long-term expression of an oviduct specific marker (oviductal glycoprotein 1) and showed a hormone responsiveness of the culture system by means of quantitative reverse transcription-PCR. Differentiated epithelial cells could reproducibly be cultured up to 6 weeks in an air-liquid interface. After 3 weeks of culturing, the cells were clearly polarized and exhibited cilia. The model maintains physiological properties such as morphological features (mixed cell population of ciliated and secretory cells, apical cell-cell contacts typical for columnar epithelial cells) and oviduct-specific markers showing hormone responsiveness. We established a polarized long-term in vitro-system of the porcine oviductal epithelium preserving detailed features of the porcine oviduct. Therefore, we provide a useful tool to elucidate unsolved scientific questions concerning reproductive physiology.

Cognitive function after sevoflurane- vs propofol-based anaesthesia for on-pump cardiac surgery: a randomized controlled trial.

BACKGROUND: Cognitive dysfunction is a frequent complication after cardiac surgery and has been found to be associated with decreases in cerebral oxygen saturation measured with near-infrared spectroscopy. Sevoflurane has neuroprotective properties in vitro and in animal models. This study was designed to determine cognitive and clinical outcomes after sevoflurane- compared with propofol-based anaesthesia for on-pump cardiac surgery and the impact of decreases in under different anaesthesia regimens. METHODS: One hundred and twenty-eight patients were randomly assigned to either i.v. anaesthesia with propofol- (PROP) or sevoflurane-based anaesthesia (SEVO). An intraoperative was defined as desaturation. The Abbreviated Mental Test, Stroop Test, Trail-Making Test, Word Lists, and mood-assessment tests were performed before, 2, 4, and 6 days after cardiac surgery. Markers of general outcome were obtained. RESULTS: The analysis groups had differences in baseline cognitive performance. Analysis of variance for repeated measures (incorporating covariance of baseline scores) showed that in three of four cognitive tests, patients with cerebral desaturation showed worse results than patients without desaturation. Patients assigned to sevoflurane-based anaesthesia showed better results in all cognitive tests than patients after propofol. Interactions between the anaesthetic regimen and desaturation were found in all four cognitive tests. There were no differences in markers of organ dysfunction or general clinical outcome. CONCLUSIONS: Patients with impaired cognitive performance before operation may be at particular risk for intraoperative cerebral insult. A sevoflurane-based anaesthesia was associated with better short-term postoperative cognitive performance than propofol.

Establishment and characterization of an adherent pure epithelial cell line derived from the bovine oviduct.

The oviduct in vivo has to perform various tasks: maturation and transport of the gametes, milieu preparation for fertilization and embryonic development, and transport of the embryo. The complex arrangement of endocrine and paracrine signals being exchanged between the early embryo and the inner cell layers of the oviduct is barely understood. Therefore, a reproducible, well-characterized oviduct epithelial cell line as well as an optimized transfection protocol for DNA vectors and siRNA for this cell line has been established. A bovine oviduct primary cell culture system has been optimized using a selection medium permitting the survival of only epithelial cells. From this we established an adherent bovine oviduct pure epithelial cell line (aBOPEC-1). This cell line maintains some important characteristics of the primary cells such as the expression of estrogen receptors and p450 aromatase but it lacks some characteristics due to the selection and dedifferentiation processes (cilia, expression of progesterone receptor and oviduct specific glycoprotein-1). Optimization of the transfection protocols finally revealed a suitable DNA-transfection procedure yielding transfection efficiencies of over 50%. Additionally, siRNA transfection efficiency reached more than 90%. This new cell line builds an essential basis especially for future functional studies in the oviduct epithelium using distinct knock down experiments.

Major mesh-related complications following hernia repair: events reported to the Food and Drug Administration.

Mesh material affects complications following hernia repair. Medical device reports on the use of surgical mesh for hernia repair were reviewed from the Food and Drug Administration's (FDA) Manufacturer User Facility Device Experience Database from January 1996 to September 2004. We analyzed 252 adverse event reports related to the use of surgical mesh for hernia repair. Adverse events included infection (42%, 107 reports), mechanical failure (18%, 46), pain (9%, 23), reaction (8%, 20), intestinal complications (7%, 18), adhesions (6%, 14), seroma (4%, 9), erosion (2%, 6), and other (4%, 9). Compared to all other mesh types, Sepra/polypropylene mesh had more mechanical failures (80 vs 14%, p < 0.05), biomaterial mesh had more reactions (57 vs 7%, p < 0.05), polytetrafluoroethylene (PTFE)/polypropylene mesh had more intestinal complications (14 vs 7%, p < 0.05), and PTFE mesh tended to have more infections (75 vs 41% all other, p = 0.07). Death occurred in 2% (5). We conclude that specific mesh materials are related to specific complications.

The combined use of two endosteal implants and iliac crest onlay grafts in the severely atrophic mandible by a modified surgical approach.

Seventeen patients, who received an iliac crest onlay bone graft augmentation to their severely atrophic mandible with simultaneous placement of two endosteal implants by a modified surgical approach, were studied retrospectively. Follow-up ranged from 0.5 to 7.9 years after implant loading with an average follow-up of 4.3 years. Frequency of wound dehiscences and other postoperative complications, the extend of resorption of the initial graft, and the implant success rate were assessed. Two patients, who had a previous history of preprosthetic and implantological procedures at the surgical site, developed a serious wound dehiscence with loss of two implants in one patient and need for antibiotic treatment and sequestrectomy in the other patient. One implant was lost in two other patients with a negative surgical history, resulting in an implant success rate of 88.2%. The average resorption at the last follow up visit was 15% of the initial graft. Damage of the mental nerve was seen in 14.7% of nerves. Our preliminary data indicate that the procedure presented provides a reliable and predictable method for the construction of an implant-bearing overdenture in patients with a severely atrophic mandible. This one-step procedure can not be recommended for patients with a history of surgery in the anterior mandible.

Shear stress-induced nitric oxide release triggers the liver regeneration cascade.

The trigger of the liver regeneration cascade is currently unknown and has been the subject of debate. We hypothesize that, following 2/3 partial hepatectomy (PHX), an increase in the blood flow-to-liver mass ratio results in shear stress-induced nitric oxide (NO) release, which triggers the liver regeneration cascade. Portal venous pressure (PVP), reflecting shear stress in the liver, increased to the same extent following PHX and selective portal vein branch ligation (PVL), a hemodynamic model of PHX, suggesting similar amounts of shear stress in both models. Two indices of the initiation of the liver regeneration cascade were used: proliferative factor (PF) activity in blood 4 h after PHX or PVL and hepatic c-fos mRNA expression 15 min. after PHX or PVL. PF activity and c-fos mRNA expression were increased to similar extents after PHX and PVL, suggesting a similar stimulus in both models. PF activity and c-fos mRNA expression were inhibited by administration of the nitric oxide synthase antagonist, l-NAME, and the NO donor, SIN-1, reversed the inhibition in both models. These results provide support for the hypothesis that a hemodynamic change results in increased shear stress in the liver causing generation of NO, which then triggers the liver regeneration cascade.

A new bioabsorbable interference screw: preliminary results of a prospective, multicenter, randomized clinical trial.

SUMMARY: A randomized clinical trial was conducted to compare a bioabsorbable polyglyconate screw (Endo-Fix; Smith & Nephew, Andover, MA) to a metal screw in anterior cruciate ligament reconstruction. A total of 124 patients were operated on and 113 assessed up to 1 year postoperatively. Assessments included a history and physical examination, the IKDC evaluation, and knee arthrometry measurements. No significant differences were found between the groups with respect to any of the IKDC problem areas at 1 year. The IKDC final evaluation was normal or nearly normal in 92% of polyglyconate patients and 90% of controls. The incidence of postoperative complications was similar in the 2 groups. One polyglyconate patient developed a subcutaneous cyst that may have been related to breakdown of the screw. This resolved without treatment and the patient had an excellent clinical outcome. This study shows that the polyglyconate screw is an effective alternative to metal in endoscopic reconstruction of the ACL.

A NMR study of parasitized Tenebrio molitor and Hymenolepis diminuta cysticercoids.

In vivo NMR spectra of uninfected and Hymenolepis diminuta-infected Tenebrio molitor fed D-(1-13C)glucose showed that infected beetles of both sexes had a significantly higher ratio for (glycogen C1/lipid (CH2)n) than the corresponding controls. Quantitative metabolic profiles and the per cent 13C-label in metabolites, based on NMR of perchloric acid extracts, are presented for control and infected beetles fed D-(1-13C)glucose and for H. diminuta cysticercoids. Female beetles, both control and infected, contained more glycogen than their male counterparts and infected beetles of both sexes possessed less glycerophos-phocholine, but more glycogen and a higher percentage label in glucose and trehalose than their respective controls. Label was also incorporated into glycogen, succinate, acetate, alanine and lactate. Extracts of cysticercoids from beetles fed D-(1-13C)glucose contained the following labelled compounds, in order of decreasing per cent 13C label: glucose, trehalose, alanine, succinate, lactate, glycogen and acetate. In vitro cultivation experiments, employing D-(1-13C)glucose, revealed that trehalose found in cysticercoids was of parasite, and not beetle, origin.