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Supplemental Digital Content is Available in the Text.Geriatric hip fractures are complicated by increased morbidity and mortality, and their incidence continues to rise around the world. Frequent considerations in treating geriatric hip fractures include optimal time to surgery, need for preoperative cardiac clearance, risks of operating through anticoagulation, utilization of regional anesthesia, and collaborative care between treatment teams. This article aims to summarize these factors as well as to provide some tips and tricks that can be helpful in their surgical management.

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Purpose: The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) is a self-report questionnaire that was developed in English to assess prostate cancer (PCa)-related anxiety. The aim of this study was to perform a cultural adaptation for the tool to be used in a population of Italian men on active surveillance (AS).Methods: A total of 222 patients with localized PCa who were recruited for the Prostate Cancer Research International: Active Surveillance (PRIAS) protocol completed the MAX-PC. Psychometric analysis was performed to assess reliability indexes. A Spearman rank correlation was used to test the association between MAX-PC scales and other questionnaires and was used for longitudinal analysis.Results: Cronbach coefficients and item to total correlation demonstrated good internal consistency. Some items related to the repetition of the PSA test showed a large floor effect and thus were poorly effective in measuring anxiety for PSA testing in patients on AS. Confirmatory factor analysis partly failed to reproduce the structure of the original version. A modified version of MAX-PC, excluding the items with a large floor effect, was thus considered for AS patients. Factor analysis on this version demonstrated considerable consistency with the presence of 3 subscales: anxiety related to PCa, anxiety related to PSA testing, and anxiety related to the fear of tumor progression. Longitudinal analysis showed an acceptable validity over time. The MAX-PC was correlated with the anxious preoccupation subscale of the Mini-Mental Adjustment to Cancer scale.Conclusions: A slightly modified version of the MAX-PC was developed for use in Italian men on AS. This instrument appears to be a valid and reliable tool that measures anxiety in men with PCa who are enrolled in AS programs.

Purpose To evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification.Methods In 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0.2 ng/mL/cm3(PRIAS). Switching to active treatment was advised for a worsening of GPS, increased positive cores, or PSA doubling time <3 years. Active treatment-free survival (ATFS) was assessed using the ­Kaplan-Meier method. Factors associated with ATFS were evaluated with a multivariate Cox proportional hazards model.Results A total of 818 patients were included: 200 in SAINT, 530 in PRIAS, and 88 in personalized AS monitoring. Active treatment-free survival was 50% after a median follow-up of 60 months. A total of 404/818 patients (49.4%) discontinued AS: 274 for biopsy-related reclassification, 121/404 (30%) for off-protocol reasons, 9/404 (2.2%) because of anxiety. Biopsy reclassification was associated with PSA density (hazard ratio [HR] 1.8), maximum percentage of core involvement (HR 1.5), positive cores at diagnostic biopsy (HR 1.6), older age (HR 1.5), and prostate volume (HR 0.6) (all p<0.01). Patients from SAINT were significantly more likely to discontinue AS than were the patients from PRIAS (HR 1.65, p<0.0001).Conclusions Five years after diagnosis, 50% of patients with early PCa were spared from active treatment. Wide inclusion criteria are associated with lower ATFS. However, at preliminary analysis, this does not seem to affect the probability of unfavorable pathology.

The Essex-Lopresti lesion, or radioulnar longitudinal dissociation, results from an axial load to the forearm with lesion to the radial head, interosseous membrane and distal radioulnar joint. The lesion is rarely diagnosed early, therefore treatment is often subacute or chronic. In these cases, procedures such as radial head replacement, ulnar shortening and/or wafer procedures should be combined with reconstruction of the interosseous membrane central band to restore longitudinal stability of the forearm. In the technique described, we use a folded fascia lata allograft fixed with specific device throughout transulnar and transradial tunnels passed through dorsal soft tissue access. The graft tension is progressively addressed with the help of fixation device. It seems an easily surgical technique without donor site morbidity.

Purpose To investigate the presence of regret in patients about having followed an active surveillance (AS) protocol. The secondary aim was to identify variables that influence regret.Methods From February 2006 to May 2014, 204 patients discontinued the AS protocols and were invited to enter the study. Sociodemographic variables were collected at AS enrollment, together with health-related quality of life (Functional Assessment of Cancer Therapy-Prostate version [FACT-P]) and coping (Mini-Mental Adjustment to Cancer). Patients were asked to complete a Treatment Regret Scale as well as the FACT-P questionnaire. Clinical data were gathered, as well as time of stay within the AS protocol, reason for discontinuing AS, kind of post-AS treatment, and time elapsed since AS discontinuation. Questionnaires were completed by 105 patients (51.5% of those who had been invited to enter the study).Results Most of the patients had a low or null degree of regret on the Treatment Regret Scale from 0 to 100 (82/105 patients [78.1%] obtained a score <30, and about 30% of the sample had a score equal to zero). Only 5 patients (4.7%) scored 60 or more, indicating some degree of regret. None of the statistical tests between regret scores and a number of analyzed variables reached significance.Conclusions These results show that the degree of regret about following an AS protocol and after its discontinuation because of entering active treatment was very low. The regret after AS was not related to sociodemographic or clinical factors.

The original Burton-Pellegrini technique used to treat trapeziometacarpal joint osteoarthritis suggests the use of half of the flexor carpi radialis (FCR) width to reconstruct the ligament and perform the tendon interposition arthroplasty. In our study, unlike the original technique, we used the full thickness of the FCR and evaluated a sample of 100 thumbs (95 patients) preoperatively and postoperatively, with a mean follow-up of 36 months. According to the Eaton classification, 1 thumb was grade II, 81 were grade III, and 18 were grade IV. The mean patient age at the time of surgery was 62.4 years. The finger-tip pinch improved by 46.3%, the key pinch improved by 34.5%, the grip strength improved by 50.8%, and the Kapandji test improved by 7.4%. Pain measured with visual analog score improved by 78.8%. The self-administrated questionnaires DASH and PRWHE were completed postoperatively from 2006 to 2012, because the Italian version of PRWHE was not yet validated: the postoperative DASH and PRWHE were, respectively, 9.9 and 10.5. No complications such as metacarpal subluxation of the thumb, impingement, fracture of the first metacarpal base, or a decrease in the wrist function were found in our population after surgical treatment. Therefore, according to our series, this variation of the original Burton-Pellegini surgical technique provides pain relief, stability, and mobility of the thumb without any morbidity caused by the full harvest of the FCR tendon.

There is conflicting evidence regarding the potential benefit of minimally invasive surgery for total hip arthroplasty (THA), especially during the ‘learning curve’ of individual surgeons.Sixty patients who underwent THA between January and December 2010 were evaluated. The aim was to assess the anterior mini-invasive (MI) approach performed in 30 patients during the learning curve of a single experienced hip surgeon compared with the results of 30 patients operated upon through a standard lateral approach by the same surgeon.Operation and hospitalisation times, blood loss, number of transfusions, peri-operative complications and femoral/acetabular component placement were monitored.Harris Hip Score (HHS) and Hip Disability and Osteoarthritis Outcome Score (HOOS) were analysed before and 12 months after surgery. Pain Visual Analogue Scale (VAS) was also recorded 1 week and 1 month after surgery.Hospitalisation, blood loss, number of transfusions and VAS score 1 week postoperatively were significantly lower and operative time was significantly longer in the anterior MI approach. Similar functional outcomes 1 year after surgery, component positioning and complication rates were observed in both groups.The results suggest that anterior MI approach is a safe procedure during the learning curve of an experienced hip surgeon.

The substantial decline of eastern oyster (Crassostrea virginica) stocks along the east coast of the United States has prompted the growth of many types of restoration and enhancement efforts. One of the most recent types is oyster gardening. Oysters grown in floating structures are subsequently planted in bays, where they Continue to live, grow, and spawn; filter the water; contribute to the larval pool; and provide habitat. Our study is one of the first evaluations of habitat value provided by floating oyster gardens in a degraded mid-Atlantic estuary. Oyster growth and survival within the floats was monitored in a eutrophic, turbid, periodically hypoxic, soft-bottom coastal lagoon system. We examined the abundance and diversity of fishes and invertebrates with respect to 3 replicated treatments: live oyster clusters, disarticulated oyster shell, and a float with no shells or oysters. We also studied the effects of 2 cleaning frequencies (biweekly and monthly) on species assemblages, and the growth and survival of oysters, and monitored basic water quality parameters. The species assemblages in floats with oyster clusters were very similar to those with loose shell but considerably different than that of empty floats. Cleaning frequency (biweekly and monthly) did not affect the growth or survival of oysters. Location of floats within the canal system, however, was a large determinant of oyster vital rates as well as community structure. Forty-nine species of fishes and invertebrates, and 8 species of macroalgae were collected from floating oyster gardens, including 9 commercial or recreational fishery species, many of which are likely habitat limited in the Inland Bays because of the loss of tidal wetlands, oyster reefs, and seagrass beds. Newly settled juvenile oysters have been found for the first time within the floating oyster gear in the manmade, residential canal systems. Our results will be used to gauge the success of enhancement efforts and to improve our understanding of the effects oyster gardens on the Inland Bays ecosystem. [ABSTRACT FROM AUTHOR]

Aims and background A retrospective analysis was conducted to evaluate the tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and radiation therapy on total CMF dose and dose intensity.Methods The medical records of 59 patients who had received conservative or radical surgery for breast cancer were analyzed. All patients had been assigned to 6 cycles of “1,8 CMF” adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and dose intensity were calculated. Toxicity was recorded scored according to WHO criteria.Results A total of 355 cycles was administered. Fifty of 59 patients received at least 85% of the programmed chemotherapy total dose, the median value being 100% (range, 42-100). The median relative dose intensity was 0.97 (range, 0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20 febrile neutropenia) and 29 (49%) required G-CSF support.Conclusions This retrospective analysis showed that it is possible to give concurrent CMF and breast radiation while ensuring adequate chemotherapy total doses and dose intensities to most patients. However, G-CSF support is required in a significant proportion of patients.

GPCRs are one of the most popular classes of therapeutic drug targets. It is therefore important to design specific assay formats to readily identify ligands at these receptors. CypHer 5 technology utilizes the general ability of GPCRs to be internalized into the endosomal pathway of a cell in response to agonist ligands. The CypHer 5 dye is fluorescent in acidic environments, but nonfluorescent at neutral pH. When CypHer 5 is bound to a receptor on the extracellular surface of the cell, it is essentially nonfluorescent. On internalization into a cell, it displays a significant increase in fluorescence. Here we demonstrate the detection of agonist activation of two GPCRs in stably transfected live cells using CypHer 5 technology. The Gq-coupled TRHR-1 and the Gs-coupled β2-adrenoceptor were both N-terminally tagged with VSV-G. Following addition of CypHer 5-labeled anti-VSV-G antibodies to HEK 293 cells stably expressing the β2-adrenoceptor or CHO-K1 cells stably expressing the TRHR-1, the cells were treated with agonists and then imaged on Amersham Biosciences' IN Cell Analyzer 3000. Data were quantified using a granularity analysis module. Concentration-response curves were obtained with signal-to-background ratios of 7:1 for both receptors. An EC50of 0.52 nMwas observed on TRH stimulation of the TRHR-1, and an EC50of 30 nMwas obtained on isoprenaline stimulation of the β2-adrenoceptor. These results demonstrated that the CypHer technology was capable of measuring high-potency agonist responses. The β2-adrenoceptor antagonist, alprenolol, competed for isoprenaline with an IC50of 30 nM, indicating that a high-potency antagonist inhibition curve could also be observed using CypHer. CypHer 5 provides a generic tool to measure GPCR activation in a live cell, homogeneous assay format, and may be equally suitable for detecting activation of other classes of cell surface receptors.

G protein-coupled receptors (GPCRs) are the largest family of proteins involved in transmembrane signal transduction and are actively studied because of their suitability as therapeutic small-molecule drug targets. Agonist activation of GPCRs almost invariably results in the receptor being desensitized. One of the key events in receptor desensitization is the sequestration of the receptor from the cell surface into acidic intracellular endosomes. Therefore, a convenient, generic, and noninvasive monitor of this process is desirable.A novel, pH-sensitive, red-excited fluorescent dye, CypHerTM5, was synthesized. This dye is non-fluorescent at neutral pH and is fluorescent at acidic pH. Anti-epitope antibodies labeled with this dye were internalized in an agonist concentration- and time-dependent manner, following binding on live cells to a range of GPCRs that had been modified to incorporate the epitope tags in their extracellular N-terminal domain. This resulted in a large signal increase over background.When protonated, the red fluorescence of CypHer 5 provides a generic reagent suitable for monitoring the internalization of GPCRs into acidic vesicles. This approach should be amenable to the study of many other classes of cell surface receptors that also internalize following stimulation.

Aims and Background The purpose of this study was to review our experience with the combination of circadian chronomodulated 5-fluorouracil infusion in association with cisplatin in patients with locally advanced or metastatic cancer of the cervix in order to assess the activity and tolerability of the combination.Methods Twenty patients with locally advanced disease and 21 patients with metastatic or recurrent disease were treated from January 1995 to May 1999. 5-fluorouracil (600 mg/m2, days 1 to 5) was administered by a continuous circadian-shaped infusion employing an external programmable portable pump; cisplatinum (20 mg/m2) was infused days 1 through 5 iv over a 2-hr period. Response to treatment was evaluated after 3 and 6 cycles of therapy. Patients with locally advanced disease who achieved a clinical shrinkage of their tumor or were at least stable were submitted to surgery; pelvic radiotherapy was administered to patients with disease progression.Results Seven patients with locally advanced disease achieved a partial clinical response (overall response, 35%; 95% Cl, 15.4-59.2), and 12 of 20 patients were submitted to surgery. Median progression-free and overall survival were 17 months and 36 months, respectively. Objective responses were observed in 9 of 21 patients with metastatic/recurrent disease (7 partial plus 2 minor responses: overall response 43%; 95% Cl, 21.8-65.9). Median time to progression and overall survival were 5 and 17 months, respectively.Conclusions Cisplatinum plus 5-fluorouracil chronomodulated infusion showed a moderate but definite activity and was well tolerated in both groups of patients. In consideration of clinical results comparable to more toxic and expensive regimens reported in the literature, the combination appears to be a reasonable option especially for women with metastatic/recurrent cervical carcinoma and a promising treatment in combination with definitive radiotherapy in patients with locally advanced disease.

Women affected by gross cystic disease of the breast have an increased risk of breast cancer. We report here the incidence of breast cancer by cyst type and intracystic epidermal growth factor (EGF) concentration. Our retrospective study included 504 women who had at least 1 cyst aspiration between 1985 and 1993. Cyst fluids were processed for electrolyte concentration (n = 378), EGF concentration (n = 347) or both (n = 337). Age-standardized incidence ratios (SIRs) were estimated using the population of the Genoa Cancer Registry. A multivariate Poisson regression model was used to estimate relative risks (RRs) when the study groups were compared directly. By June 1999, 19 invasive breast cancers had developed in the cohort of women. The age SIR of breast cancer calculated for the whole cohort was 3.32 (95% confidence interval 2.00–5.18). The ratio was not affected by age and was only moderately increased in women with a positive family history of breast cancer and type I cysts (i.e., those with a Na⁺/K⁺ ratio &lt;3). However, it was significantly increased in women with high EGF concentrations. Direct comparisons confirmed that age, cyst type and family history only moderately increased the RR, whereas EGF concentration was a strong predictor of risk. Our results confirm that women affected by palpable cysts have an increased risk of developing breast cancer and suggest that the risk is higher in women with high intracystic EGF concentrations. © 2001 Wiley-Liss, Inc.

p56lckis a lymphocyte-specific tyrosine kinase that plays an important role in both T-cell maturation and activation. We have developed a homogeneous assay in which p56lckcatalyzes the transfer of the γ-phosphate group from [γ-33P]ATP to a biotinylated peptide substrate. The labeled peptide is then captured on a streptavidin-coated scintillation proximity assay (SPA) bead or imaging proximity bead. The SPA is counted in a microplate scintillation counter and the imaging proximity assay is counted in a charge-coupled device-based imaging system called LEAD-seeker™, recently launched as a homogeneous imaging system by Amersham Pharmacia Biotech. We show, via time-dependence assays and inhibitor studies, that this assay can be performed in 1536-well microplate format using imaging proximity as the method of detection. The results compare favorably with the same assay performed in 384-well microplate format using both SPA and imaging proximity as the detection methods. From this study, we conclude that a kinase assay can be performed in 384- and 1536-well format using imaging as the detection method, with significant time savings over standard scintillation counting. In addition, we show cost saving advantages of 1536- over 384-well format in terms of reagent usage, higher throughput, and waste disposal.

p56lckis a lymphocyte-specific tyrosine kinase that plays an important role in both T-cell maturation and activation. We have developed a homogeneous assay in which p56lckcatalyzes the transfer of the γ-phosphate group from [γ-33P]ATP to a biotinylated peptide substrate. The labeled peptide is then captured on a streptavidin-coated scintillation proximity assay (SPA) bead or imaging proximity bead. The SPA is counted in a microplate scintillation counter and the imaging proximity assay is counted in a charge-coupled device–based imaging system called LEAD-seeker™, recently launched as a homogeneous imaging system by Amersham Pharmacia Biotech. We show, via time-dependence assays and inhibitor studies, that this assay can be performed in 1536-well microplate format using imaging proximity as the method of detection. The results compare favorably with the same assay performed in 384-well microplate format using both SPA and imaging proximity as the detection methods. From this study, we conclude that a kinase assay can be performed in 384- and 1536-well format using imaging as the detection method, with significant time savings over standard scintillation counting. In addition, we show cost saving advantages of 1536- over 384-well format in terms of reagent usage, higher throughput, and waste disposal.

Using breath hydrogen analysis after an oral lactose load (2 g/kg; maximum 50 g), we investigated the prevalence of lactose malabsorption in 61 healthy Italian children aged 6–13 years. We also examined the relationship between symptoms and small bowel transit time and the degree of sugar malabsorption. Three of 61 subjects produced no H2after both lactose and lactulose load and thus were eliminated at the outset. Lactose malabsorption was defined as excretion of >20 ppm H2. Lactose intolerance was classified as mild (colicky pain, flatulence, abdominal distension, borborygmi) or severe (diarrhea). The frequency of lactose malabsorption in the children aged 6–8 years (group I) was 25; in the children aged 8–11 years (group II), it was 35, and in the children aged 11–13 years (group III) 56. The differences in frequency between the first and the third groups were significant (p = 0.05). Three of 20 (15) in group I, two of 20 (10) in group II, and three of 18 (17) in group III were classified not only as lactose malabsorbing, but also as lactose intolerant, with symptoms during and after the test. We found no difference in the small bowel transit times or in the quantities of malabsorbed lactose in symptomatic and asymptomatic malabsorbing subjects. Other factors that may play a role in symptom production are discussed.

We report our experience in the treatment of infected pseudarthrosis of the inferior limb with pulsing electromagnetic fields (PEMFs) in 16 patients. The problems arising from the treatment of the infected pseudarthrosis, in which skin lesion, bone non-union and draining infection must be faced at the same time, will be discussed. Twelve patients healed in an average stimulation time of 5.6 months. The results of PEMFs stimulation were satisfactory because of the high percentage of success (75%), and the fact that a surgical operation was avoided in most of the patients. In the failed patients, PEMF stimulation had a positive effect on the local conditions of the pseudarthroses.