Emergencies in patients with advanced cancer followed at home.

Abstract CONTEXT: Patients with advanced cancer stay at home for most of their time, and acute problems may occur during home care. Caregivers may call medical services for an emergency, which can result in patients being admitted to the hospital. No data exist on emergencies in patients followed by a home care team. OBJECTIVES: The aim of this multicenter prospective study was to assess the frequency, reasons for, and subsequent course of emergency calls for patients followed at home by a palliative care team. METHODS: A consecutive sample of patients admitted to home care programs was surveyed for a period of seven months. Epidemiological data, and characteristics of emergency calls and outcomes, as well as environmental situations were recorded. RESULTS: Six hundred eighty-nine patients were surveyed; 118 patients (17.1% of the total number of patients surveyed) made one emergency call, 23 made two calls, and four made three calls for a total number of 176 emergency calls. The mean age was 71 years (standard deviation [SD] 13), and the mean Karnofsky status the day before the emergency call was 38 (SD 14). The mean time from admission to the first emergency call was 38.4 days (SD 67), and the mean time from the first emergency call to death was 17.5 days (SD 41.5). No differences were found for age, diagnosis, gender, duration of assistance, and survival between patients making emergency calls and those who did not make a call during an emergency. Twenty-three patients were managed by phone, and 122 were visited at home for the emergency. Calls were prevalently recorded on weekdays and were primarily made by relatives. The most frequent reasons for calling were dyspnea, pain, delirium, and loss of consciousness. Calls were considered justified by home care physicians in most cases. The mean number of relatives present during the emergency home visit was 2.2 (SD 1.5). The intervention was mainly pharmacological and considered satisfactory in the majority of cases. CONCLUSION: Emergency calls are relatively frequent in patients followed at home by a palliative care team. Phone consultation or intervention at home may avoid inappropriate hospital admission

One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy

Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >\u201310%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: 120.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance

Identification of a unique form of protein C in the ovine fetus: developmentally linked transition to the adult form

To investigate fetal development of protein C, a pregnant ovine model was used. Protein C was isolated from ovine plasma, and a polyclonal antibody was raised. Citrated plasma was obtained from undisturbed chronically catheterized fetal lambs. On Western blot, nonreduced adult ovine protein C had a molecular mass of 70 kD. Fetal ovine protein C was determined to have a molecular mass of 4 to 6 kD larger than the adult molecule. Crossed immunoelectrophoresis demonstrated slightly increased anodal migration of the fetal form. Isoelectric focusing demonstrated a decreased pI of the fetal molecule (4.45 versus 4.6). The ovine protein C molecules were deglycosylated with N-glycanase. Deglycosylated fetal protein C migrated more similarly to the adult form, although a portion of the fetal form persisted. These experiments demonstrate the first example of a unique fetal form of a vitamin K-dependent protein and are compatible with increased glycosylation of fetal ovine protein C. It is speculated that altered posttranslational processing may exist as a general process by which certain coagulation proteins are modified during fetal development. mRNA was isolated from maternal and fetal hepatic tissue and analyzed by Northern hybridization. Fetal plasma concentration and hepatic mRNA for protein C were both 40% of normal maternal values from midgestation onward. At term, protein C mRNA increased to adult range (p < 0.025), although plasma protein C concentration decreased slightly (p < 0.001). A transition from fetal to adult protein C form was found beginning 6 d before term birth, with a doubling time of 24 h. These data are compatible with a gestationally determined maturation of ovine protein C.(ABSTRACT TRUNCATED AT 250 WORDS

Zoledronic acid in a mouse model of human fibrous dysplasia: ineffectiveness on tissue pathology, formation of “giant osteoclasts” and pathogenetic implications

We compared the effects of a nitrogen-containing bisphosphonate (N-BP), zoledronic acid (ZA), and an anti-mouse RANKL antibody (anti-mRANKL Ab) on the bone tissue pathology of a transgenic mouse model of human fibrous dysplasia (FD). For comparison, we also reviewed the histological samples of a child with McCune–Albright syndrome (MAS) treated with Pamidronate for 3&nbsp;years. EF1α-GsαR201C mice with FD-like lesions in the tail vertebrae were treated with either 0.2&nbsp;mg/kg of ZA at day 0, 7, and 14 or with 300&nbsp;μg/mouse of anti-mRANKL Ab at day 0 and 21. All mice were monitored by Faxitron and histological analysis was performed at day 42. ZA did not affect the progression of the radiographic phenotype in EF1α-GsαR201C mice. FD-like lesions in the ZA group showed the persistence of osteoclasts, easily detectable osteoclast apoptotic activity and numerous “giant osteoclasts”. In contrast, in the anti-mRANKL Ab-treated mice, osteoclasts were markedly reduced/absent, the radiographic phenotype reverted and the FD-like lesions were extensively replaced by newly formed bone. Numerous “giant osteoclasts” were also detected in the samples of the child with MAS. This study supports the hypothesis that osteoclasts per se, independently of their resorptive activity, are essential for development and expansion of FD lesions

Microbiota control acute arterial inflammation and neointimal hyperplasia development after arterial injury

Background: The microbiome has a functional role in a number of inflammatory processes and disease states. While neointimal hyperplasia development has been linked to inflammation, a direct role of the microbiota in neointimal hyperplasia has not yet been established. Germ-free (GF) mice are an invaluable model for studying causative links between commensal organisms and the host. We hypothesized that GF mice would exhibit altered neointimal hyperplasia following carotid ligation compared to conventionally raised (CONV-R) mice. Methods: Twenty-week-old male C57BL/6 GF mice underwent left carotid ligation under sterile conditions. Maintenance of sterility was assessed by cultivation and 16S rRNA qPCR of stool. Neointimal hyperplasia was assessed by morphometric and histologic analysis of arterial sections after 28 days. Local arterial cell proliferation and inflammation was assessed by immunofluorescence for Ki67 and inflammatory cell markers at five days. Systemic inflammation was assessed by multiplex immunoassays of serum. CONV-R mice treated in the same manner served as the control cohort. GF and CONV-R mice were compared using standard statistical methods. Results: All GF mice remained sterile during the entire study period. Twenty-eight days after carotid ligation, CONV-R mice had significantly more neointimal hyperplasia development compared to GF mice, as assessed by intima area, media area, intima+media area, and intima area/(intima+media) area. The collagen content of the neointimal lesions appeared qualitatively similar on Masson’s trichrome staining. There was significantly reduced Ki67 immunoreactivity in the media and adventitia of GF carotid arteries 5 days after ligation. GF mice also had increased arterial infiltration of anti-inflammatory M2 macrophages compared to CONV-R mouse arteries and a reduced proportion of mature neutrophils. GF mice had significantly reduced serum IFN-γ-inducible protein (IP)-10 and MIP-2 5 days after carotid ligation, suggesting a reduced systemic inflammatory response. Conclusions: GF mice have attenuated neointimal hyperplasia development compared to CONV-R mice, which is likely related to altered kinetics of wound healing and acute inflammation. Recognizing the role of commensals in the regulation of arterial remodeling will provide a deeper understanding of the pathophysiology of restenosis and support strategies to treat or reduce restenosis risk by manipulating microbiota.</p