Objective. To evaluate the therapeutic effect of big bubble deep anterior lamellar keratoplasty (DALK) in patients with deep fungal keratitis. Methods.Consecutive patients who had DALK for deep fungal keratitis at Shandong Eye Hospital between July 2011 and December 2012 were included. In all patients, the infiltration depth was more than 4/5ths of the corneal thickness. DALK surgery was performed with bare Descemet membrane (DM) using the big bubble technique. Corrected distance visual acuity (CDVA), graft status, and intraoperative and postoperative complications were monitored. Results. Big bubble DALK was performed in 23 patients (23 eyes). Intraoperative perforation of the DM occurred in two eyes (8.7%) during stromal dissection. The patients received lamellar keratoplasty with an air bubble injected into the anterior chamber. Double anterior chamber formed in 3 eyes (13.0%). Mean CDVA of the patients without cataract, amblyopia, and fungal recurrence was improved from preoperative HM/20 cm−1.0 (LogMAR) to 0.23 ± 0.13 (LogMAR) at the last followup (P < 0.01). Fungal recurrence was found in two patients (8.7%). Corneal stromal graft rejection was noted in one patient (4.3%). Conclusions. DALK using the big bubble technique seems to be effective and safe in the treatment of deep fungal keratitis unresponsive to medication. Fungal keratitis (FK) is a major blinding eye disease in Asia  and is bWhen patients are unresponsive to antifungal medication, surgical treatment should be considered to preserve the eye globe and improve visual acuity , 6, 7. PDeep anterior lamellar keratoplasty (DALK) is currently considered to be the first option by many corneal surgeons for patients with corneal diseases not involving the endothelial layer due to its satisfactory clinical results compared with PK –15. HoweThis study was approved by the ethics committee of Shandong Eye Institute. Medical records of patients who were treated by big bubble DALK for deep FK at Shandong Eye Hospital between July 2011 and December 2012 were reviewed. All patients had antifungal medication for at least 2 weeks. If the infection did not heal, DALK surgery was considered in patients with infection or infiltrates penetrating greater than 4/5ths of the corneal thickness in the deepest area as observed by slit-lamp microscopy and laser scanning confocal microscopy (Heidelberg Engineering GmbH), respectively. Those with combined perforation were excluded from this study. Informed consent was obtained from the patients involved.μm) on the host cornea, and then the anterior diseased stroma was cut off. A 30-gauge disposable needle attached to a 2 mL syringe and bent at 15–30° was advanced and beveled down into the paracentral corneal stroma. About 1–1.5 mL of sterilized air was injected into the posterior stroma until a big bubble was formed extending to the border of trephination. If the big bubble did not form after the first attempt, the injection was repeated. After the big bubble formation, debulking of the white posterior stroma was performed with a 45° micro knife , leaving a very thin layer of corneal stromal tissue over the air bubble. Thereafter, a peripheral paracentesis was performed to reduce intraocular pressure. A small opening was created in the stromal tissue overlying the air bubble using a 30-gauge disposable needle. After an iris repositor was employed to retract the residual stroma, a 45° blade was used to divide the rest of the corneal stroma into 2 parts. The stroma was then held using toothed forceps, and the residual stroma was cut off using a 45° blade along the line of the trephination groove to bare the Descemet membrane (DM). The recipient bed was ready.All surgeries were performed by a single surgeon (H. G.) under peribulbar anesthesia (2% lignocaine hydrochloride and 1% ropivacaine) using the big bubble technique . BrieflyFull-thickness donor corneal tissues stored in D-X medium at 4°C or in glycerin at −20°C were used for transplantation. The donor cornea was punched from the endothelial side using the Barron punch  and was oversized by 0.25 mm. The donor DM and endothelium were gently stripped off using 0.12 mm untoothed forceps, which could prevent wrinkling of the donor DM at the interface. After the donor cornea was sutured to the recipient with 16 interrupted 10/0 nylon sutures , the tightness of the sutures was adjusted by a Placido disc to reduce postoperative astigmatism when the corneal echogenic ring became relatively round. Finally, 0.2% fluconazole (0.5 mL) was injected subconjunctivally, and 0.3% ofloxacin topical eye ointments  were used.μm) were stained with periodic acid-Schiff (PAS). The presence of hyphae and spores was observed by light microscopy.Partial corneal buttons (anterior and posterior stroma) obtained during DALK were fixed in 4% formalin and embedded in paraffin. Serial slices  and 0.2% fluconazole eye drops . Both antifungal agents were reduced to 4 times daily after surgery. Systemic fluconazole 0.2  was given intravenously every day in patients with hypopyon, and the duration was not longer than 2 weeks.Postoperatively, 1% cyclosporin A eye drops were given 4 times per day. If no recurrence was detected at 3 weeks after DALK surgery, 0.02% fluorometholone eye drops  were used 3-4 times per day for about 6 months and tapered thereafter.Preoperatively, complete ocular examinations were performed, including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), slit-lamp examination, anterior segment optical coherence tomography (AS-OCT), corneal smear, bacterial and fungal cultures, and laser scanning confocal microscopy examination.Postoperative follow-up examinations were scheduled every week for the first month and once a month thereafter. The main outcome measures were the success of the big bubble technique, intra- and postoperative complications or secondary interventions, CDVA, rejection episode, endothelial cell density, and recipient thickness. The endothelial cell density was measured by specular microscopy, and the recipient thickness was measured by AS-OCT.t-test was used to compare the parameters perioperatively. P < 0.05 was considered statistically significant.SPSS 17.0 was used for statistical analysis. The two-sample A total of 23 patients (23 eyes) underwent big bubble DALK during the study period . The mean age was 46.9 ± 11.6 years (range: 24 to 72 years). The mean follow-up time was 12.5 ± 2.5 months (range: 9 to 18 months). All cases had deep FK, including 8 cases (34.8%) with hypopyon of 2.3 ± 0.9 mm (range: 0.5 to 3 mm). The mean size of ulcer and stromal infiltrate was 7.0 ± 0.5 mm × 6.3 ± 0.9 mm. The mean diameter of the trephine was 7.8 ± 0.3 mm in the recipient and 8.1 ± 0.3 mm in the donor . Fusarium, 2 with Aspergillus, 2 with Agonmycetaceae, and 1 with Alternaria Nees.The KOH smear was positive in 21 (91.3%) patients with corneal scrapings, and the laser scanning confocal microscopy was positive in 22 (95.7%) patients before surgery. Hyphal infiltration was not found in the DM by confocal microscopy in any patient. Seventeen (73.9%) patients had positive fungal cultures, including 12 patients withThe hyphae were observed in 21 cases (91.3%) by histopathology examination. Hyphae and spores invaded into the corneal stroma, and about 1/2 to 2/3 of the stroma was involved in most cases. The density of the hyphae and spores was much higher in the anterior stroma than that in the posterior stroma. The posterior stroma was very loosening due to the air injection. No hyphae or spores were seen in the stroma near DM .Intraoperative microperforation of the DM occurred in 2 eyes (8.7%) during stromal dissection. These two patients still received LK with an air bubble injected into the anterior chamber.A double anterior chamber (interface fluid) occurred on postoperative day 1 in 3 patients (13.0%). Among them, one patient had intraoperative DM microperforation and was managed with intracameral injection of air bubble accompanied with pupil dilation. The interface fluid resolved spontaneously within 5 days. In the other two patients, the interface fluid was drained using 0.12 mm blunt forceps to separate the incision or resolved spontaneously within 3 days. Fusarium oxysporum as the causative organism. The other with previous cultures identifying Fusarium moniliforme as the causative organism was cured with subconjunctival injection of fluconazole (2 mg/mL) twice a day for 10 days.The corneal epithelium healed in all cases within 1 week after surgery. Two patients (8.7%) suffered fungal recurrence within postoperative 3 days. One (case number 14) was unresponsive to antifungal treatment and received secondary PK to control the recurrence. This patient had presented with 2 mm of hypopyon before DALK procedure with cultures identifyingCorneal stromal graft rejection occurred in 1 case (4.3%) during the first 3 months after surgery. This patient presented with a decrease in visual acuity. Slit-lamp examination showed conjunctival congestion, subepithelial infiltrates, and mild stromal edema. Topical 1% prednisolone acetate was given hourly for 3 days and tapered off over the next 2 weeks. No secondary glaucoma was observed.P < 0.01) at 6 months postoperatively. Further improvement was seen at the last follow-up visit when the mean LogMAR CDVA was 0.23 ± 0.13 . At the last followup, the CDVA was ≥20/40 in 81.3% of the 16 patients and ≥20/66 in all of them. Moreover, the CDVA in 6 patients with cataract and/or amblyopia was improved to 20/200-20/63. The patient with secondary PK after fungal recurrence achieved a CDVA of 20/20. Mean spherical equivalent was −0.84 ± 3.2 D, and mean astigmatism was −2.64 ± 2.40 D (range: −0.5 to −4.25) at 6 months in all patients.The mean preoperative CDVA was HM/20 cm to 1.0 (LogMAR). The patients (16 cases) without cataract, amblyopia, and fungal recurrence had a mean LogMAR CDVA improvement of 0.34 ± 0.17  as measured by AS-OCT. The grafts and recipients matched well, and the interfaces were hardly noticeable by slit-lamp microscopy and AS-OCT examination. The mean endothelial cell density in the central area of 22 patients who accepted DALK successfully was 2120 ± 461 (range: 1359 to 2994) cells/mm2 (2 (2 months postoperatively) to 1145 cells/mm2 (18 months postoperatively).The entire graft was clear in all patients at the last follow-up visit. The mean recipient bed thickness was 22.5 ± 3.64 ells/mm2 . The endAccording to the World Health Organization, infectious corneal diseases are a major cause of blindness worldwide, second only to cataract in overall prevalence. Among severe infective corneal ulcers, FK is most common in many developing countries like China, India, Ghana, and Nepal , 16, 17.Due to limited options of commercially available antifungal drugs and low drug sensitivity in some patients, surgical treatment is required to preserve the patient's eyeball and restore useful vision in severe cases. This is especially true when antifungal therapy fails to control the infection , 18.In the early stage, most ophthalmologists thought that fungal hyphae in the stroma grew perpendicular to the corneal stromal collagen, and penetration of the hyphae to the corneal endothelium may result in perforation. In such instances, LK is not adequate to completely remove the infected tissue, and PK may be the only option to control the fungal infection. Sedghipour et al.  and SaidWith further understanding of FK and advances in microsurgical techniques, LK has been found to be effective in the treatment of FK before the hyphae penetrate the full-thickness cornea, with a decreased risk of immune rejection and graft dehiscence . But for Acanthamoeba keratitis, finding that DALK can result in better graft survival and visual outcomes [Big bubble DALK was first introduced by Anwar and Teichmann in 2002 . Keratocoutcomes . ConsideIn DALK, the pathologic corneal stroma is replaced, while the healthy endothelium of the host is preserved. This helps to retain all the advantages of anterior lamellar keratoplasty over full-thickness keratoplasty, providing a clearer interface. In this study, 81.3% of the patients had a final CDVA of ≥20/40 after DALK, which is similar to the results of PK in the treatment of infectious keratitis , 26 and Intraoperative perforation of DM is one of the most common complications during DALK surgery, with a rate of 9% to 23% , 28. In Double anterior chamber is another common complication after the DALK surgery , 29. ThiIn conclusion, DALK using the big bubble technique appears to be effective in the treatment of deep FK that is unresponsive to antifungal treatment. This approach can not only decrease the risk of rejection episodes, but also provide a clear interface between the recipient and the graft, achieving satisfactory visual acuities.


P = 0.05). Metastatic disease was most common in the youngest patients (P = 0.07), and it was 2.5 times more frequent among patients with local recurrence (26.3%) than in those without (10.8%) (P = 0.003). Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary and the site of metastasis. Metastasis to distal bone was the most rapid to develop and had the worst prognosis.Chordoma is a rare, slow-growing malignant tumor arising from notochordal remnants. A retrospective review of patient records at two major referral centers was undertaken to assess the incidence, location, and prognostic factors of metastatic disease from chordoma. 219 patients with chordoma (1962–2009) were identified. 39 patients (17.8%) developed metastatic disease, most frequently to lung (>50%). Median survival from the time of initial diagnosis was 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not ( Chordoma is a rare, slow-growing, malignant tumor arising from notochordal remnants. Chordoma accounts for 1–4% of primary bone tumors  and has Since its description 150 years ago there has been relatively sparse clinical data collected on chordoma. The few studies describing metastatic disease in chordoma report an estimated frequency of metastasis ranging from 3 to 48% . MetastaA retrospective review of all cases of chordoma diagnosed from November 1962 to October 2009 at two major US referral centers, Mass General Hospital, Boston, MA, and University of Miami, Miami, FL, was undertaken. Patient characteristics were recorded and charts, radiographs, and histological slides were reviewed for sites of primary and metastatic lesions. Bone scans, MRI, chest radiographs, and/or CT scans were also reviewed. The following data were obtained or defined: patient age, gender, site of primary tumor, local recurrence, metastasis, site of primary metastasis, presence of multiple metastasis, site of secondary metastasis, and survival. Due to the rare incidence of chordoma and lack of published large scale retrospective studies, we focused only on the prognostic factors of the disease and did not include the effects of treatment or cause of patient death.Frequencies and descriptive statistics were obtained for analysis; categorical variables were examined using chi-square and Fisher's exact tests, where appropriate. Kaplan-Meier survival curves with log rank analysis were performed for survival, time from onset to metastasis, and time from metastasis to death. Survival was defined as time from diagnosis to date of death. Patients surviving beyond the study cutoff date were censored. There was sufficient data to analyse 219 patients, yet only 177 cases of primary chordoma could be used for survival analysis see . Exclude219 patients with chordoma presented to the Orthopaedics Services at two major referral centers in a 46-year span . There wP = 0.06). The youngest patients (Q1: 3–24 yrs old) tended to have atypical primary tumor locations, with chordoma appearing in the cervical spine  more frequently than the sacrum  and clivus . The remaining age quartiles (Q2–Q4: >25 yrs old) were more likely to have involvement in the typical/classical sacrococcygeal region (62.5–64.4%) than in the lumbar (12.5–21.4%), cervical (6.7–14.6%), thoracic spine (7.1–8.9%), and clivus (0.9–2.2%). Patients with youngest age of presentation (Q1) were more likely to be female (56% F : 44% M) as compared to older quartiles Q2–Q4 where males predominated (Q2–Q4 = 27–38% F : 60–73% M). Additionally, patients with primary tumors of the cervical spine were more likely to be female as well (54.4% F : 45.5% M). Clival chordomas were found to occur equally among the genders, with sacral, thoracic, and lumbar chordoma more frequently occurring in males (64.4–68.8% M : 31.3–35.6% F).Chordoma location at initial presentation trended toward a dependence on patient age  . The durP = 0.05)   lower (1 = 0.05) .P = 0.07) and 2.5 times more frequent among patients with local recurrence (26.3%) than without (10.8%) (P = 0.003). Tumors presenting in the cervical spine rarely became metastatic (1 [4.5%] of 22), whereas tumors in the remainder of the mobile spine demonstrated metastatic rates ranging from 17 to 32% (P ≤ 0.001) and progressed more slowly from the diagnosis of metastasis to death (22.1 months) than disease that was directly metastatic (4.5 months).Of the 39 (17.8%) patients who developed metastatic disease, lung was most frequently involved (53.8%). Other sites of primary metastasis include distal bone (20.5%), soft tissue (15.4%), and liver (7.7%) . Metasta7 to 32% . Through7 to 32% , with luP = 0.013). The shortest duration from onset to metastasis was found among patients with primary tumors located in the cervical spine (16.0 months). Time to metastasis of primary tumors located in the thoracic spine, lumbar spine, and sacrum was 22.0 months, 49.2 months, and 58.3 months, respectively. The longest time to metastasis was 120.1 months, which was observed in a patient with a primary clival chordoma.The time from onset to metastasis was found to differ significantly, depending on the site of presentation (P = 0.05) (n = 1), followed by tumors of the thoracic spine , lumbar spine , and sacrum   . Patient n = 16) .P = 0.01)  Tables .In agreement with previous studies, individuals presenting with the typical sacrococcygeal chordoma tended to be males in the 6th and 7th decades of life, with a relatively good prognosis. Our data demonstrate, also in agreement with previous studies, that patients over 25 years of age were more likely to be male and to present with chordoma in the sacral, thoracic, or lumbar spine , 14. TheIn concordance with prior literature, nearly half of the individuals in the present study had local recurrence during the course of their disease. As in the literature, we found a significant correlation between the presence of local recurrence and the subsequent development of metastasis , 6, 9. IThere is a paucity of data in the chordoma literature describing the expected time to metastasis. One study addressed this issue, reporting times to metastasis ranging from 0.2 to 13.3 years . In our Although initially contested, recent literature identifies lung to be the most common site for chordoma metastasis . In our P = 0.07), and it was 2.5 times more frequent among patients with local recurrence (26.3%) than in those without (10.8%) (P = 0.003). Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary chordoma and the site of metastasis. But overall, metastatic disease is a poor prognosticator. The median survival from the time of initial diagnosis is 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not (P = 0.05). Metastasis to distal bone was the most rapid to develop and had the worst prognosis.Our large retrospective study pooled data from two major cancer centers to characterize the incidence, location, and prognostic factors of metastatic disease in patients with primary chordoma. Lung is the favored site for metastasis (>50%). Metastatic disease most commonly occurred in the youngest patients (<25 years old) (


Domestic cats can be infested by a large range of parasite species. Parasitic infestations may cause very different clinical signs. Endoparasites and ectoparasites are rarely explored in the same study and therefore multiparasitism is poorly documented. The present survey aimed to improve knowledge of the prevalence and risk factors associated with ecto- and endoparasite infestations in owned cats in Europe.From March 2012 to May 2013, 1519 owned cats were included in a multicenter study conducted in 9 veterinary faculties throughout Europe . For each cat, ectoparasites were checked by combing of the coat surface associated with otoscopic evaluation and microscopy on cerumen samples. Endoparasites were identified by standard coproscopical examinations performed on fresh faecal samples. Risk factors and their influence on parasitism were evaluated by univariate analysis followed by a multivariate statistical analysis  with logistic regression models.95 27.3-32.0%). Otodectes cynotis was the most frequently identified species (17.4%), followed by fleas (15.5%). Endoparasites were identified in 35.1% of the cats (CI95 32.7-35.7%), including gastro-intestinal helminths in 25.7% (CI95 23.5-28.0), respiratory nematodes in 5.5% (CI95 4.2-7.0%) and protozoans in 13.5% (CI95 11.8-15.3%). Toxocara cati was the most commonly diagnosed endoparasite . Co-infestation with endoparasites and ectoparasites was found in 14.0% of the cats, and 11.9% harbored both ectoparasites and gastro-intestinal helminths.Overall, 50.7% of cats resulted positive for at least one internal or one external parasite species. Ectoparasites were found in 29.6% of cats (CIAge, outdoor access, living with other pets, and anthelmintic or insecticide treatments were significantly associated with the prevalence of various parasites.This survey demonstrates that parasitism is not a rare event in European owned cat populations. The prevalence of multi-parasitism is significantly greater than expected by chance and hence there is tendency for some individual cats to be more prone to infestation by both endo- and ectoparasites due to common risk factors. Toxocara cati and Ancylostoma tubaeformae, which are responsible for human visceral/ocular and cutaneous larva migrans, respectively [Dipylidium caninum or Echinococcus multilocularis[Toxoplasma gondii is of major importance in public health, nevertheless, it is recognized that the main source of infection for humans is related to consumption of meat and less to the occysts [Bartonella henselae, the causative agent of cat-scratch disease [In Europe, domestic cats can be infested by a wide range of endo- and ectoparasites. Depending on the parasite species and its abundance, infestations may cause varying clinical signs in cats, from mild gastro-intestinal disorders and failure to thrive, to anemia or anorexia in the more severe cases, particularly in kittens with heavy parasitic burdens . In addiectively -5. Humanlocularis-6. Among occysts -9. Ectop disease ,11.Parasites of cats are thus a threat for both animal and human health. However, there is much less data available on parasitism in cats compared to dogs.Toxocara cati is usually the most common helminth diagnosed, with infestation rates ranging from 4% to 35% [Toxascaris leonina is generally found with considerably lower prevalence, rarely exceeding 1% [Overall, the prevalence of endoparasites of cats in Europe has been found to vary between 20 and 40% -18. Almo% to 35% -18,20-24eding 1% ,24,25.A. tubaeformae was found to range from 0.3-0.4% [The prevalence of 0.3-0.4% ,16,22 to0.3-0.4% ,14,18,250.3-0.4% , in Hung0.3-0.4%  and in P0.3-0.4% .D. caninum infestation has been found to range from 0.1% to 1% [Tapeworms are rarely found during general endoparasite faecal examinations, but this low prevalence is likely to be related to the poor sensitivity of coproscopy for the detection of cestodes . Indeed,1% to 1% ,15-17.Giardia cysts [Giardia have been recorded when using copro-antigen ELISA: 12.6% in Germany [Giardia (20.3%) recorded in a 2005–2006 survey on 4214 cats conducted in 7 European countries  [Based on coproscopical examination, around 1% of cats have been estimated to shed ia cysts ,17. Howe Germany , 27.9% id Italy) .Cystoisospora spp. ranged usually between 4 to 8% [C. rivolta in Portugal in stray cats [Toxoplasma gondii, the oocyst shedding is considered to be very low in owned cats. The most recent study, including 24106 cats, found 0.11% of cats with Toxoplasma gondii oocyst, and 0.09% for Hammondia  [Few data are available on the prevalence of coccidia in cats in Europe. Figures for  4 to 8% ,17,29,30 4 to 8% ,25 and uray cats . ConcernAelurostrongylus abstrusus, seems to be more common than might be expected. In previous records from endoparasite surveys, estimated prevalence in Europe varied between 0.5% and 3% [Troglostrongylus brevior and Troglostrongylus subcrenatus have also been recently reported as causative agents of respiratory infestation in domestic cats in Spain and Italy [A. abstrusus was the most frequently detected , larvae of T. brevior were found in 6.5% (7/107) of samples with two cats (1.9%) being co-infected by both species [Capillaria, with a reported prevalence around 1 to 5% [The cat lungworm, % and 3% ,15,21,23% and 3%  or the f% and 3% ,33. The % and 3% . This is% and 3%  and 17.6% and 3%  or in Po% and 3% ,37. The % and 3% . Other mnd Italy -41. Howend Italy ,43. In a species . Some ot 1 to 5% -15,17,18Ctenocephalides felis, C. canis and Pulex irritans, with a preponderance of C. felis felis, which is identified in almost all flea-infested cats [Fleas are a common ectoparasite of cats, with prevalence ranging from 12% up to 70% -47. In sted cats -47,49.Ixodes ricinus was found in 80.1% of the tick-infested cats and the only other tick species found was I. hexagonus (23.4%) [Ixodes and Rhipicephalus genera [Data for tick infestation in cats is rare. In a recent survey in Belgium,  (23.4%) . A surves genera .Otodectes cynotis may be locally frequent in cats in some areas of Europe, especially in kittens and roaming animals. In a survey conducted in Greece, 25.5% of owned cats resulted positive, with age identified as a risk factor [O. cynotis was identified as the primary cause of external otitis in 53.3% of 1087 stray cats examined [Infestation by the ear mite k factor  and 14% k factor . In anotexamined .No previous study explored endoparasites and ectoparasites in the same animal hosts and therefore multiparasitism is poorly documented. The present survey aimed to improve our knowledge on the prevalence of the occurrence of ecto- and endoparasite infections, in household owned cats in Europe and to examine risk factors and their influence on parasitism.From March 2012 to May 2013, a multicenter survey was conducted throughout Europe for parasite infestations in client-owned household cats. Nine veterinary faculties participated: 2 in France , 2 in Italy  and 1 each in Austria (Vienna), Belgium (Liège), Hungary (Budapest), Romania (Cluj-Napoca) and Spain (Madrid).A random sample of cats was included weekly (with an objective of 10 to 20 cats per week) from the consultation services in the Faculty hospitals. Client-owned cats were eligible for participation in the study provided that they were in good health, and were not presented for a medical reason related to any parasitic disease. In addition, cats should not have received an anthelmintic treatment for two months prior to inclusion nor an ectoparasiticide for one month prior to inclusion. Cats that were sick or were difficult to handle for parasite comb counting were excluded from the study. Details of each enrolled cat including demographic data, household accommodation, hunting behaviour and previous parasiticide treatments were recorded on an owner questionnaire form.An informed consent and agreement was obtained from the owners of the cats before enrolment. The examination of cats were conducted with regard to animal welfare.Otodectes. Cats with suspected skin mite infestations were assessed by skin scraping and microscopical observation.Cats were combed for at least 7 minutes and combing continued until no further parasites had been removed for 3 consecutive minutes. The collected fleas or ticks were stored in individual vials containing 60% ethanol for identification of species. The external ear canals of all cats were examined and cerumen sampled for microscopical search of The detection of endoparasites was based on qualitative coprological analyses performed by trained people in expert centers. The techniques and protocol used in each laboratory were those routinely conducted for the diagnosis of parasitical infestation in animals and in accordance with the standard guidelines for parasitological diagnosis. Slight variations in the techniques and protocols used was observed from one laboratory to another. No quantitive analysis was requested and all techniques were considered as reasonably sensitive for an accurate detection (range from 2 to 6 eggs/cysts per gram of faeces) making it possible to rely on the global results and compare results -57.Faecal samples were collected from all cats at the time of consultation or by the owner within 24 hours. Both macroscopic examination  and microscopic examination , were performed. In all laboratories, direct centrifugal flotation techniques were used -57. TheyAll data collected during the study were uploaded electronically to a secure dedicated on line web database.Prevalence rates were recorded as the ratio of the number of positive animals to the total number of examined animals. The 95% confidence intervals were computed with R software , by meanThe model building strategy was that all the factors and their likely interactions entered the logistic regression. The model was then reduced with the function stepAIC in R MASS package for non-nested models. Significance of variables was evaluated, one at a time, by Likelihood Ratio Tests to compare the deviances of nested models. If non-significant, backward eliminations were performed until the most parsimonious model was fitted.The goodness of data fit to the model was assessed graphically by plotting the standard residuals, and by computing the pseudo R-squared (McFadden). Hosmer-Le-Cessie tests or Hosmer-Lemeshow tests were also performed to assess the model. The odds ratios (OR) and their 95% CIs were calculated by exponentiation of the estimates. Significance was set at p < 0.05.A total of 1519 client-owned cats were recruited: 92 in Vienna (Austria), 55 in Liege (Belgium), 96 in Maisons-Alfort (France), 91 in Nantes (France), 300 in Budapest (Hungary), 300 in Bari , 215 in Naples , 300 in Cluj-Napoca (Romania) and 70 in Madrid (Spain). Of the 1519 cats, 57.0% (866) were female (46.5% entire and 53.5% neutered) while 43.0% (653) were male (52.8% entire and 42.2% castrated).Age data were available for 1500 of the cats, ranging from 1 month to 22 years and 5 months, with a mean of 3 years and 5 months and a median of 2 years and 7 months: 223 cats (14.9%) were less than 6 months, 470 cats (31.3%) were between 6 months and 2 years old, and 807 cats (53.8%) were over 2 years old. A minority of cats had infrequent access to the outdoors, whereas 1093 cats (72.0%) had frequent access to the outdoors, including 558 (51.1%) having unlimited access to the outdoors  and 484 (44.3%) having limited access to the outdoors (closed garden).A total of 1147 cats (75.5%) lived in multi-animal households. Among animals living in multi-animal households, 1021 (89.0%) lived with at least one other cat, while 480 (41.8%) lived with at least one dog and 385 (26.0%) lived with at least one cat and one dog. The number of cats living in a house was reported as 1481 cats: 460 cats (31.0%) lived alone (no other cats), while 444 cats (30.0%) lived with 1 or 2 other cats and 577 cats (39.0%) lived with more than 3 other cats.The number of ectoparasiticide treatments given per year was available for 1379 of the cats. This ranged from 0 to 12, with 1131 cats (82.0%) treated less than 3 times a year, and 248 cats (18.0%) treated 4 times or more per year.The number of endoparasiticide treatments given per year was available for 1256 of the cats. This ranged from 0 to 12, with 0 treatments per year for 430 cats (34.2%), 1 or 2 treatment per year for 653 cats (52.0%) and more than 3 treatments per year for 173 cats (13.8%).A total of 50.7% 770/1519) of cats examined in this study were positive for parasites . Ear mites were identified in 17.4% (265/1519) of examined cats, followed by fleas in 15.5% of cats (235/1519), ticks in 1.2% of cats (18/1519) and other ectoparasites in 1.4% of cats (21/1519). Other ectoparasites reported included From macroscopic and microscopic analysis of faecal samples, 35.1% (533/1519) of cats were positive for endoparasites  . One cat was found to excrete Physaloptera spp., Capillaria spp. eggs were identified in 1.0% of the 1519 examined cats.Gastro-intestinal (GI) nematodes were recorded in 20.5% of the examined cats, including Dipylidium caninum in 3.0% and Taeniidae in 1.3% of cats. Cestode proglottids were also observed macroscopically in 52 faecal samples (3.4%).Cestode eggs were detected in 7.0% of cats, including Cystoisospora spp. and Giardia spp., respectively. Other flagellates were found in 4 cats (0.3%), and other coccidians in 9 cats (0.6%). No Toxoplasma like oocyst was observed during this survey.GI protozoans were found in 13.5% of cats: 9.7% and 3.2% of coproscopic samples were positive for A. abstrusus was identified in 4.1% of the 1115 examined cats.The Baermann technique, recommended to separate nematode larvae from faecal material, was not performed in all the examination centers. For the four centers of Bari, Budapest, Cluj-Napoca and Naples having performed this specific search, T. cati, A. abstrusus, C. felis and O. cynotis.Risk factors were specifically analysed only when the rate values made it possible. Therefore, specific analysis was possible for −9), and the number of cats parasitized with both endo and ecto-parasites (213) was more important than expected by chance (158). Infestation with ectoparasites and GI helminths was found in 11.9% (181/1519) of cats while 5.3% (81/1519) harboured both fleas and T. cati. Computed odds ratios for the presence of an external parasite as a risk factor for endoparasite infestation showed that cats harboring external parasites  had a significantly higher risk to also harbor endoparasites  .A total of 305 cats 20.1%) harboured more than two parasite species, and 147 cats (9.7%) harboured more than two endoparasite species, while 14.0% (95% CI 12.3-15.9) of cats were found infested with both external and internal parasites , significant correlations p < 0.05) were found between on Table  and 5. were fouAll these significant risk factors as determined from univariate analysis were entered in the multiple logistic regression model, to address possible confounding factors and to compute adjusted odds ratios Table .T. cati , while cats under 6 months (38.1% positive) were at higher risk .With an age category of 6–24 months (26.6% positive cats) as a reference, cats older than 24 months (10.9% positive) were at lower risk of being infested with T. cati than cats having frequent access (23.0% positive) to the outdoors .Cats with infrequent outdoor access (11.5% positive) were significantly less frequently infested with Compared to the reference center of Budapest (16.7% positive), Naples (34.4%) and Bari (18.7%) presented significant higher frequencies of infestation after adjustment of putative confounding factors . The following examination centers showed no significant differences: Maisons-Alfort (6.3%), Vienna (9.8%), Liège (7.3%), Nantes (12.1%) and Madrid (12.9%).Toxocara positive was significantly higher for cats from households with more than 3 cats .The risk of being Toxocara infestation (23.3%) than cats receiving 1 or 2 treatments per year , while cats receiving more than 3 treatments per year were significantly less infested  than the previous group.Regarding the frequency of anthelmintic treatments, cats receiving no treatment were significantly more at risk of T. cati infestation than the average .Cats over 24 months old and with infrequent outdoor access were significantly less at risk of A. abstrusus infestation. Age was not significantly related to lungworm infestation.From univariate analysis, significant correlations were found between outdoor access (p = 0.018), location (p <0.001) and 95 0.06-0.55).The risk factors were included all together in a logistic regression model Table . Age was−6), multipet household (p <0.001) and location (p <10−15). No statistical difference was found at the 5% level for O. cynotis infestation with the three age categories. These risk factors were included as explanatory variables in the logistic regression model. In agreement with the results of the univariate analysis, no significant difference was found regarding the risk factor age. Nevertheless, this variable was retained in the regression model since the Likelihood Ratio Tests estimated a significant reduction of the deviance of the model by keeping it , cats from the following sites were significantly less infested with ear mites: Maisons-Alfort (4.2%), Vienna (4.3%), Liège (3.6%), Nantes (2.2%) and Cluj-Napoca (8.7%), while cats from Bari (40.3%) and Naples (21.9%) were significantly more infested. Madrid center (8.6%) was not significantly different from Budapest.95 1.92-15.23).Outdoor access was identified as a risk factor, cats with infrequent outdoor access (9.4% positive) being less at risk than cats with frequent outdoor access (20.6% positive) . Cats under 6 months old and living alone were significantly less at risk than other cats  or outdoor access (p < 0.0001). No significant relationship was found between flea infestation and age or multipet household.From the univariate analysis (contingency tables and χ² tests), significant correlations (p < 0.05) were found between flea infestation and the location (p <1095 0.64-2.36). Nevertheless cats older than 24 months and living in single animal household appeared significantly less at risk for flea infestation .These risk factors were entered into a regression model. The Vienna center, due to the low number of animals with fleas (n = 2) was responsible for a poor goodness of fit, and was therefore excluded from the regression model. Following this, cats with frequent outdoor access (18.0% positive) were found to be more at risk for flea infestation than cats with infrequent outdoor access . Flea infestation did not differ significantly between cats living alone and cats living with other pets, even after adjustment of confounding factors .Cats treated more than 4 times a year (11.7% positive) were significantly less at risk for flea infestation than cats receiving fewer treatments per year , cats from the following centers were significantly more frequently infested with fleas: Liege (34.5%), Nantes (26.4%) and Naples (31.6%), while cats from Bari (3.7%) were significantly less frequently infested. The centers of Maisons-Alfort (13.5%), Cluj-Napoca (15.7%) or Madrid (4.3%) did not significantly differ from the Budapest center, after adjustment of confounding factors .The present survey offers the first large scale overview on parasite infestation of the European owned cat population. It demonstrates that more than half (50.7%) of the owned cat population carry at least one parasite at a given time with a high level of co-infestations.Prevalence values in the present survey were estimated for healthy cats that were not presented to veterinary consultation for a medical reason related to parasitic disease. The real prevalence of parasites may be much higher, as many potentially parasitic conditions were excluded from the study. Regarding internal parasites, a study in Spain found a significantly higher prevalence in stray cats (32.9%) than in household cats (16.5%) . PreviouThe observations were performed at a single time-point for each cat, therefore, due to the natural lifecycle of parasites, which include intermittent egg/cyst shedding, this may have underestimated the observed prevalence.Giardia cysts). However, this factor was taken into consideration at the setup of the study and several considerations allowed consideration of the comparisons as valid.The discrepancies between the different locations may have been related to the fact that different techniques and technicians performed the examinations, with specific local expertise  [Aelurostrongylus abstrusus in the present survey may include lungworms of the genus Troglostrongylus, due to the morphological similarities of the first stage larvae and the consequently low specificity of diagnosis by non-specialists [The overall prevalence of endoparasites found in cats in this study 35.1%) is close to that found in previous epidemiological surveys in Europe -15,17. Tthan 3%) ,18,23,25than 3%) ,35 and h.1% is clthan 3%) . It shoucialists .Toxoplasma gondii like oocyst was found during this survey. It gives a CI50 of 0–0.24%. A coproscopy survey conducted throughout Europe in 2008 found a prevalence of 0.11% for Toxoplasma and 0.09% for Hammondia, based on 24106 owned cats, which gives 0.20% of Toxoplasma like oocysts [Toxoplasma oocysts in a parallel analysis of 153 stray cats in Madrid (unpublished). The infection rate is significantly higher in young cats, stray cats, than owned cats eating dried food, as demonstrated in a serological survey conducted in Portugal [No Portugal . A studyMixed infestations with more than two endoparasites were found in 15-18% of cats in Hungary and Romania ,17 and 2−9). This significant association should be related to similar risk factors considering the mode of life of the cats and probably not to a parasitic effect. Moreover, cats with the presence of an external parasite were more likely to harbour internal parasites than cats without ectoparasites (Odds Ratio 2.10 CI95 1.68-2.64).The present survey shows that 14.0% of cats were co-infested with at least an external and an internal ectoparasite . The number of cats with both endo-and ecto-parasites (213) was more important than expected by chance .This supports the fact that an endo and ecto- parasite checking and management should be handled in parallel. The observed co-infestations were mainly with external parasites and gastro-intestinal worms with 11.9% of cats (i.e. protozoans and lungworms excluded), here again significantly higher than expected by chance . Meanwhile infestations of hookworms, lungworms, whipworms and taeniid cestodes seem to be mainly prevalent in older cats [Toxocara infestation, higher prevalence rates are commonly recorded in young cats, with 26.5% of cats under one year being infested compared to 13.8% for adult ones in a study in Hungary [T. cati in our survey while cats under 6 months were at higher risk. Nevertheless, it should be highlighted that cats over 6 years where found infested by T. cati, meaning that the immunity is not absolute and that veterinarians should not be surprised to see ascarids in adults or even old cats. Hookworms were more prevalent in cats older than 2 years  than in cats from 6 months to 2 years , themselves being more infested than cats under 6 months , however χ² tests performed were not significant due to low frequencies for Ancylostoma spp. and Uncinaria spp. The age was not a significant risk factor for A. abstrusus, O. cynotis nor flea infestation, from both univariate and multivariate analysis.In several studies, young cats are estimated to be much more frequently infested with digestive parasites especially with ascarids and protozoans  were significantly more at risk than cats over 1 year old (10.8% positive), when adjusted with outdoor access and presence of symptoms [Regarding symptoms . The reaOtodectes infestation was not found to be linked to the age of cats in the present study: indeed, a systematic search was performed, regardless of clinical signs. We can hypothesize that, although otodectic mange may be considered mainly as a kitten-infestation (young cats being the ones developing otitis due to the parasites), adult cats are probably subclinical carriers and reservoirs for other domestic carnivores in the house [he house .T. cati, A. abstrusus, O. cynotis and fleas. Outdoor access was also seen to have a significant influence on T. cati infestation in previous studies [T. cati is not only circulating through a mother-to-kitten transmission during lactation, but that egg persistence in the outdoor environment as well as paratenic hosts play an important role in its transmission [A. abstrusus, Traversa (2008) also found that 38 out of the 40 infested cats had outdoor access, which was estimated as significant after multivariate analysis [Outdoor access was identified as a risk factor in our study for all parasites studied. Cats with infrequent outdoor access were found to be significantly less frequently infested than cats with frequent outdoor access for  studies . This masmission . Regardianalysis . This isT. cati being a cat-specific parasite, the influence of a multi-cat household as a risk factor was assessed. Cats living with one or two other cats were not significantly more infested than cats living alone, but for higher densities of cat populations (more than 3 other cats in the house), the risk for Toxocara infestation was significantly more important. Multi-pet households  were found to be a significant risk factor for ear mite infestation from univariate analysis with cats living alone (11.6% positive), being less infested than cats living in multipet household (19.4% infested). However, after multivariate analysis, this factor was no longer significant. It can be supposed that the power of the test was decreased due to the other factors. Knowing the biology of the parasite and its direct transmission [smission , we can Living with other pets was not a relevant risk factor for flea infestation. This could be explained by the fact that close-contact is not needed for flea transmission. The main source of infestation are pupae, which are able to survive for several months in contaminated environments . TherefoT. cati infestation than cats receiving one or two treatments per year, themselves being significantly more frequently infested than cats receiving more than 3 treatments per year.A recent study in Hungary showed that cats whose owners claim the use of an anthelmintic were significantly less frequently helminth-positive than cats that were not dewormed . This isThe frequency of anti-flea treatment was also evaluated by multivariate analysis for flea infestation. Cats treated with an anti-flea product more than 4 times a year were significantly less at risk for flea infestation than cats receiving less than 3 treatments a year. Most of the commonly used anti-flea products have a persistent effectiveness of one month, but no data were analyzed in regards to the way treatments were applied, i.e. once every 3 months, or consecutively during the flea season, which is more probable. Cats treated more than 4 times a year probably receive better veterinary care than others, and regular anti-flea treatments may have an impact on flea infestation in the long term ,62.The results of this study highlight the fact that both ecto- and endoparasites are still common in cats throughout Europe. Given the zoonotic consideration and the clinical importance, it is strongly advisable to promote effective and regular parasite control in cats, with adequate frequencies of treatment for both internal and external parasites.The author’s declare that they have no competing interests.To include: All authors read and approved the final version of the manuscript.


The aim of this study was to evaluate the benefit of a combined treatment, surgery followed by adjuvant hypofractionated stereotactic radiosurgery (HSRS) on the tumor bed, in oligometastatic patients with single, large brain metastasis (BM).Fom January 2011 to March 2015, 69 patients underwent complete surgical resection followed by HSRS with a total dose of 30Gy in 3 daily fractions. Clinical outcome was evaluated by neurological examination and MRI 2 months after radiotherapy and then every 3 months. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume, and brain distant progression as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Surgical morbidity and radiation-therapy toxicity, local control (LC), brain distant progression (BDP), and overall survival (OS) were evaluated.3 (range 4.1–64.2cm3) and 3.6cm (range 2.1-5-4cm); the median CTV was 29.0cm3 (range 4.1–203.1cm3) and median PTV was 55.2cm3 (range 17.2–282.9cm3). The median follow-up time was 24 months (range 4–33 months). The 1-and 2-year LC in site of treatment was 100%; the median, 1-and 2-year BDP was 11.9 months, 19.6% and 33.0%; the median, 1-and 2-year OS was 24 months (range 4–33 months), 91.3% and 73.0%. No severe postoperative morbidity or radiation therapy toxicity occurred in our series.The median preoperative volume and maximum diameter of BM was 18.5cmMultimodal approach, surgery followed by HSRS, can be an effective treatment option for selected patients with single, large brain metastases from different solid tumors. In careported . Hypofrareported ,17–22. I10 = 60Gy). The plan objective for OARs was to minimize as much as possible the dose to normal brain tissue. The constraint for the mean dose to the brain was 4 Gy, but for the majority of the plans the mean dose was much lower. The dose constraints used for brainstem, optic apparatus, and lenses were D1% ≤ 20 Gy, D1% ≤ 15 Gy, and D1%< 10 Gy, respectively. All plans were optimized on PTV aiming to achieve a PTV coverage of D95%>95%, with an homogeneous dose distribution [The present retrospective study includes patients with single, large BMs treated with surgery plus HSRS on the resection cavity. All patients were treated in agreement with the Helsinki declaration. This study was based on a retrospective analysis of treatment charts and received approval by the Humanitas Cancer Center Ethical Committee. All patients signed at admission a consent to the use of their data for scientific scope. To define the appropriate therapy, each patient has been evaluated by a multidisciplinary team including neurosurgeons, neuro-oncologists and radiation oncologists. The inclusion criteria for surgery were: 1) KPS ≥70, 2) controlled primary tumor and extracranial metastases, 3) RPA class I-II, 4) evidence of single BMs ≥2.1 cm or < 2 cm when located close to critical structures and/or conditioning neurological symptoms unresponsive to medical treatments. Surgical resection was performed with the aid of intraoperative neurophysiological monitoring and brain mapping techniques with the aim to maximize resection and preserving functions. All patient received a “supramarginal resection” according with functional boundaries, defined as a microsurgical tumor excision with an extension larger at least 5 mm than enhancing T1 weighted MRI sequences borders, as shown in ribution . All plaClinical outcome was evaluated by neurological examination and brain MRI performed two months after RT and then every 3 months. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume on serial MR imaging, and BDP as the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. Radionecrosis (RN) was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion-MRI. RN was considered as the presence of central hypointensity and peripheral enhancement on T1-weighted post-contrast imaging, with edema on T2-weighted sequences and a clear lack of perfusion without any nodular highly vascularized area within the contrast enhanced lesion on perfusion MRI.Standard descriptive statistics  were used to describe the data general behavior. Survival and recurrence time observations were plotted according to the method of Kaplan and Meier, starting from the date of surgery. The log-rank test was used to carry out the univariate analysis, in order to investigate the prognostic role of individual variables. For the analysis, variables analyzed were age, gender, KPS, histology of primary tumor, recursive partitioning analysis (RPA) class, diagnosis-specific Graded Prognostic Assessment (DS-GPA), and maximum diameter of BMs. Groups were defined according to discrete volume of each variable. For age the analysis was dichotomized according to 65 years threshold. For BMs size 3 groups were considered: 2.1–3 cm; 3.1–5 cm; >5 cm Multivariate Cox model was used as a method to estimate the independent association of a variable set with OS, LC, and incidence of BDP. Statistical software used was STATA v. 13.13 (range 4.1–64.2 cm3) and 3.6 cm (range 2.1-5-4 cm); the median CTV was 29.0 cm3 (range 4.1–203.1 cm3) and median PTV was 55.2 cm3 (range 17.2–282.9 cm3).From January 2011 to March 2015, among patients referred to our institution for BMs, 69 patients with single, large lesion underwent surgical resection followed by HSRS. Of these patients, 42 (61%) were female and 27 (39%) male, with a median age of 51 years (range 33–77 years). The most common primary cancers were breast cancer and NSCLC. BMs were present at diagnosis of primary tumor in 24 patients (35%); whereas BMs developed in 45 (65%) patients after a median time of 38 months (range 8–216 months) from the primary tumor treatment. At the time of BMs diagnosis, 51 patients (74%) had only a single BM and 18 (26%) had also additional controlled extracranial metastatic localizations at any site. Based on RPA class  which coIn all patients no residual tumor was recorded on MRI acquired within 48–72 hours postoperatively. At a median follow-up time of 24 months (range 4–33 months) no local progression in site of multimodal treatment occurred. The 1 and 2-year LC rate was 100%. Twenty-four (35%) patients had new brain metastases at distant brain site and in 18 (26%) progressive extracranial disease was present too. The median time for developing new BMs in other sites was 11.9 months, and the 1 and 2-year rate of BDP were 19.6% and 33.0%, respectively. The median survival time was 24 months (range 4–33 months), and the 1 and 2-year OS rates were 91.3% and 73.0% respectively. Peri-operative complications occurred in 7 (10%) patients, consisting in hemianopsia in 6 and aphasia in 1. Patient affected by aphasia recovered within 1 month. No perioperative mortality occurred. All patients completed the scheduled RT planning. No toxicity was recorded during treatment and neurological examination scores remained stable. Steroids dependency occurred in 6 (9%) after treatment in relation to and increase edema at control MRI during follow up. At the last observation time no symptomatic or progressive RN that requires surgical resection has been reported.Among 24 patients with BDP, 21 underwent further treatment consisting of SRS for 12 patients and WBRT for 9. All these patients are alive at the last follow-up.10Gy >10.5 cm3 or V12Gy >7.9 cm3 hypofractionated rather than single-fraction radiosurgery have to be considered to minimize the risk of symptomatic RN. Eaton [3, a gross total resection was performed in all patients; this data showed that extended surgical resection is feasible; the use of intraoperative techniques has proved to be able to perform surgery according to functional boundaries minimizing the post-operative morbidity and/or permanent neurological deficits. The lack of severe morbidity or neurological deficit after surgery allowed to perform adjuvant HSRS within 1 month from surgery in all patients. No severe grade III-IV toxicity or symptomatic radionecrosis such as to require surgical resection was observed. Many are the open questions about the optimal HSRS strategies. Firstly, if and how to define margins around the surgical cavities. Several reported series apply margins to delineate the target volume [10 on the tumor bed greater than 54 Gy for an adequate local control of large BMs. At a median follow-up time of 24 months no relapse in site of treatment occurred. We are aware that our analyses has the limit of a retrospective study but the multimodal treatment performed has proven to be a feasible and effective therapeutic approach. In addition, ours is highly selected series, including only oligometastatic patients, with good KPS (80–100), in RPA class I or II, controlled extracranial disease, and single BM. These inclusion criteria can partially explain the good results recorded in terms of OS . Anyway, in our experience, a strict selection of patients, to be subjected to an aggressive treatment approach, is essential to provide the best therapeutic result without compromising the patient QoL.The main treatment option for oligometastatic patients with single, large BMs is represented by surgery, if feasible. The role of surgical resection is not clearly defined yet and it is a topic of debate. Few data are available about the better surgical strategies, nevertheless the surgical methodology used could be a critical point. On the one hand, an aggressive surgery could compromise patients quality of live (QoL) making adjuvant treatments less tolerable, on the other hand an incomplete surgical resection might result in a higher rate of local brain relapse. Literature data showed that a gross total removal preserving neurological functions, is essential to achieve optimal clinical conditions for applying adjuvant treatment and potentially to affect tumor LC and patient survival ,9,26. CoN. Eaton  evaluateN. Eaton . Wang anN. Eaton . In the N. Eaton . In our t volume ,18,21,22t volume ,27,28. TSurgical resection followed by HSRS can be an effective treatment option for selected patients with large brain metastases from different solid tumors. In patients with good performance status, controlled extracranial disease, breast histology and single brain metastases an aggressive local approach can improve the outcome and quality of life.All patients were treated in agreement with the Helsinki declaration. This study was based on a retrospective analysis of treatment charts and received approval by the Humanitas Cancer Center Ethical Committee. All patients signed at admission a consent to the use of their data for scientific scope.


AbstractPlectranthusbarbatus (Lamiaceae), a medicinal plant, were investigated using a cytogenetic approach and flow cytometry (FCM). Here, we describe for the first time details of the karyotype including chromosome morphology, physical mapping of GC rich bands (CMA3 banding), as well as the mapping of 45S and 5S rDNA sites. All accessions studied showed karyotypes with 2n = 30 small metacentric and submetacentric chromosomes. The CMA3 banding and fluorescent in situ hybridization techniques revealed coincidence between CMA3 bands and 45S rDNA sites  while for the 5S rDNA were observed 4 subterminal marks no coincident with CMA3 marks. For nuclear genome size measurement, the FCM procedure provided histograms with G0/G1 peaks exhibiting CV between 2.0–4.9 and the mean values obtained for the species was 2C = 2.78 pg, with AT% = 61.08 and GC% = 38.92. The cytogenetic data obtained here present new and important information which enables the characterization of Plectranthusbarbatus.Accessions of  Plectranthus L' Herit. (Lamiaceae) contains nearly 300 species distributed in tropical Africa, Asia, Australia and Brazil  H. L. Maass., Plectranthusgrandis (Cramer) R. H. Willemse, Coleusforskohlii Briq., Coleuskilimandschari Gürke ex Engl., Coleuscoerulescens Gürke, Coleuscomosus A. Rich., and Coleusbarbatus (Andr.) Benth  Benth .Plectranthusbarbatus is mainly used for liver disturbance, respiratory disorders, heart diseases and certain central nervous system disorders, being also used as hypotensive and antispasmodic  at room temperature for 7h and then fixed in ethanol and acetic acid (3:1 v/v) for 24h at -20 °C. Root meristems were submitted to enzymatic maceration (4% Celullase: 40% Pectinase) for 5h at 37 °C. The slides was prepared according to Chromosome length, short and long arms and ratio between chromosome arms (AR) were measured on 5 well-spread metaphases for each accession using the CellSens software . Chromosome classification was done according to in situ hybridization (FISH) was performed using the probe pTA71 from Triticumaestivum, which contain a 9kb EcoRI fragment including the 18S – 5.8S – 25S rRNA gene and intergenic spacer regions (rDNA) , kindly provided by Dr. J. Jiang. Each probe was labeled with digoxigenin by nick translation and then hybridized according to PageBreakslides were mounted in Vectashield , and some samples were rehybridized after discoloration in 100% ethanol for 24h. Good metaphases were captured in an Olympus DP72 digital camera and images with DAPI, 45S and 5S signals were merged using CellSens software . Chromosomes were observed using an epifluorescence microscope (Olympus BX 51) with appropriate filter set .Fluorescence s (rDNA)  and 5S p3 (0.5 mg/mL) for 1 h, dystamicyn (0.1 mg/mL) for 30 min and 2-4 diamidino-2-phenylindole (2 µg/mL) for 30 min. The slides were mounted in Mcllvaine’s pH 7.0 buffer-glycerol (1:1 v/v). For this analysis five metaphases of each accession were observed and captured in an Olympus DP72 digital camera. The chromosomes were observed using an epifluorescence microscope (Olympus BX 51) with appropriate filter set.The chromosome banding was performed according Plectranthusbarbatus and the same amount of young foliar tissue of standard references Zeamays CE-777 were chopped on ice with 1 mL of OTTO I lysis buffer solution  buffers. The sample were homogenized and stained with 50 µg mL–1of propidium iodide (PI) to determine the total DNA content. AT/GC composition was determined by adding DAPI  4 µg mL–1 to the samples. At least 10,000 nuclei were analyzed per sample in a FACSCantoII (BectonDickinson) flow cytometer. The histograms were analyzed using Flowing 2.5.1 software (http://www.flowingsoftware.com).Nuclear DNA content was determined according to the method of solution  supplemeZeamays 5.43). Each accession was measured three times following the equation (The DNA nuclear amount (pg) of each sample was estimated by the relative fluorescence intensity of the sample and the internal reference standard  = 3 for DAPI dye . The perThe accessions showed symmetrical karyotype, all with 2n = 30. Fourteen chromosomes showed centromeres at the median m, AR = 1–1.7) and one of them at submedian region   Fig. , while 53 revealed bands on three chromosome pairs, which were also DAPI negative. Heterochromatin blocks correspond to 0.37% of the total haploid complement. The observed bands showed similar size and bright, all of them at terminal regions and coincident with 45S rDNA marks, on the short arm of chromosome 6 and 10, respectively, and on the long arm of chromosome 11  possess 2714.148 Mpb  technique provided high quality histograms with Gpg Table , and comPlectranthusbarbatus. The percentage of base was 61.08% for AT and 38.92% for GC. The representative histograms of DNA content and base composition can be seen in Figure In addition, PI and DAPI fluorochromes index allowed, for the first time, the estimation of base composition of the genome of PageBreakPageBreakPageBreakPlechtrantus has a great variability of chromosome numbers. Although the basic chromosome number for most of the species is x = 7, and 2n chromosome number is 28, some species show secondary basic chromosome numbers (6 and 8) (Plechtrantusassurgens (Baker) J. K. Morton and Plechtrantusglandulosus Hook, 2n = 28 and 30 for Plechtrantustenuicaulis (Hook. f.) J. K. Morton, while for Plechtrantusamboinicus (Lour.) Spreng, The genus 6 and 8) . AdditioPlectranthusbarbatus can be cytologicaly considered as a species with different cytotypes that include a possible aneuploid series with 2n = 28, 30, 32 and 34 described so far , for example, it was observed karyotypic variations in different populations although the individuals showed the same chromosome number  cytotypes  reinforcing the hypothesis that chromosome structural rearrangements such as duplication, transytotypes . The obsytotypes .Plectranthusbarbatus. Several authors have been discussed the stability of 45S and 5S rDNA  in the cytotypes formation. Lippiaalba (Verbenaceae) and suggested that 45S rDNA sites are very variable . On the other hand, taking the monoploid number of sites as reference, the 5S rDNA was more stable following the expected number according to the ploidy level. In the common bean Phaseolusvulgaris L. (Fabaceae), Alternatively, additional chromosomes  may also explain the number of 45S rDNA sites here observed for Plectranthusbarbatus genome size is relatively small comparing with other Lamiaceae species. Taking all estimations described so far from 25 genera, the 1C value ranged from 0.28 to 6.24 pg.  corresponds to the bright blocks of CMA3 constitutive heterochromatin. This is also the first report of chromosome banding data for the genus.Although there are several estimations of plant genome sizes, few of them reported the AT/GC genome composition, being the most detailed studies performed by Meister and Martin (2007) and f dicots . It was Lippiaalba (Mill.) N. E. Brown (Verbenaceae), an important PageBreakmedicinal plant in Brazil, it was observed that different chemotypes, but morphologically similar, showed different major component of the essential oil (In addition to understand the biology and the evolution of plant species, the characterization of chromosome number and DNA content can be very interesting, especially when different cytotypes had been described for a medicinal species. Studying different accessions of tial oil . While dtial oil .Plecthrantus and of the Lamiaceae family should be investigated once no detailed cytogenetic data is available. The increase in the number of taxa will be very important for a better understanding of the biology and the evolutionary relationship within this important medicinal plant group. Other cytotypes and possible chemotypes of Plectranthusbarbatus are up to know under-characterized.In addition to the new data here described more species of the genus


Background. Metabolic control is an important factor in growth of children with type I diabetes. This study assessed the relationship between growth and metabolic control in such children. Materials and Methods. 83 children with diabetes were studied. They were examined for weight and height gain and HbA1C was quantified every 3 months for one year. The growth process was studied in patients who were divided into 3 groups according to their HbA1C amounts, consisting of good, intermediate, and poor metabolic control. Results. Mean age of cases was 7.6 ± 2. The presenting sign at the onset of disease was diabetic ketoacidosis in 44.6%. The average HbA1C amount was 8.89%. The average weight SDS at diagnosis was −0.18 and at the end of the study was 0.45 (P<0.001). The average height SDS at diagnosis was −0.04 and at the end of the study was −0.07 (P=0.64). A significant difference in weight SDS changes was only seen between patients with good and poor metabolic control (P=0.04). Conclusion. Poor metabolic control can decrease height growth but has minimal influence on weight. Metabolic control was not the only predictive factor of physical growth in children with diabetes. Diabetes is one of the main problems in health systems in the world . DiabeteBMI = (weight in kilograms/square of height in meters).Height SDS = [2 × (50 height percentile − patients height)/(50 percentile height − 3 percentile height)]. In this study HbA1C was measured in laboratory of diabetes research center of Ahvaz Jundishapur University of Medical Sciences. Values between 6 and 7.9% were considered as good metabolic control, values within 8–9.9% were considered as intermediate, and values of 10% or higher were considered as poor metabolic control. Seventeen patients were excluded from our study  and 83 patients were finally included and each patient was followed for one year. The patients used three types of insulin therapy. In the first method, fixed doses of NPH and regular insulin were used in the morning and evening. In the second method a fixed dose of NPH insulin was used in the morning and evening and doses of regular insulin were adjusted according to blood glucose levels obtained by glucometers and injected three times a day . In the third method, long-acting insulin was used at bedtime and short-acting insulin was administered before meals. Data analysis was performed by chi-square, repeated measure, ANOVA, and Pearson's correlation coefficient tests. P value less than 0.05 was considered as significant.Children with diabetes who were referred to diabetic clinic in Ahvaz Golestan Hospital from 2010 were included in the study. A written consent was obtained from the participants' parents. This study was approved by ethical committee of Ahvaz Jundishapur University of Medical Sciences. Inclusion criteria were age of 1–15 years and signing the informed consent by their parents. Exclusion criteria were hypothyroidism, celiac disease, thalassemia, and other diseases that have effect on growth. Age, height, and weight at the time of diagnosis and follow-up visits were recorded. Events of ketoacidosis were recorded. Patients were followed every 3 months. A detailed history and complete physical examination were performed. Exact measurements of height and weight, number of admissions with ketoacidosis, type of insulin, and its dosage were also recorded. Standing height without shoes (with Seca height meter) and weight without jackets and blazers were measured with standard scales, in the clinic. NCHS percentile for height and weight was determined based on standard curves. Based on height and weight, BMI and height SDS were calculated according to the following formulas:P = 0.21 and 0.3, resp.). Based on metabolic control 20.5% of patients were in the poor metabolic control group (HbA1c: 10% or higher). 42.2% of subjects were placed in moderate metabolic control group (HbA1c: 8–9.9%) and 37.3% were placed in good metabolic control group (HbA1c: 6–7.9%). No significant difference was observed between the metabolic control and sex and age  (P < 0.001). Average weight SDS at diagnosis was −0.18 and at the end of the study was 0.45 (P < 0.001). The increase of weight SDS was significant in both gender groups and in all patients under 10 years old. Average height SDS at diagnosis was −0.04 and at the end of the study was −0.07 (P = 0.64). The decrease in height SDS in both genders and in all age groups was not significant. When the average weight SDS of each group was compared with the two other groups of metabolic control (one-way ANOVA and Tukey's test) a significant increase was seen between average weight SDS of patients with good metabolic control compared to patients with poor metabolic control (P = 0.04) (P = 0.017). This significant increase was also seen in the analysis of comparison between poor-intermediate and poor-good metabolic control groups by Tukey's test (P < 0.04) (P = 0.29) (P = 0.58). The frequency of menarche based on metabolic control in this study was assessed using the Kruskal-Wallis test which was not significant (P = 0.96). A significant relationship was found between reduced height SDS and repeated ketoacidosis by t-test (P = 0.03). A significant relationship was not found between changes in height SDS, disease duration, and type of insulin therapy.In this study, 83 patients  were studied. Mean age of cases was 7.6 ± 2.9 (range: 2.5–13.5). Duration of DM was < 1 year in 61.4% and > 1 year in 38.6% of cases. Diabetic ketoacidosis was the diagnostic key in 44.6% of subjects (52.3% of girls and 35.9% of boys). Diabetic ketoacidosis was seen one time in 14.5% and repeated two times in 1.2% of subjects; however 70% of the participants did not experience diabetic ketoacidosis during this study. Age range of menarche was 11–13.83 years. The average age of onset of menarche in girls was 12.8 years. Nine patients had experienced menarche before the study. Of all patients 54.4% have used a fixed dose of NPH and regular insulin twice a day, 21.7% have used the second method, and 22.9% used the third method of insulin therapy. Gender and age groups did not significantly influence the types of insulin regimens. The mean HbA1c level in patients was 8.89, ranging from 5.85 to 14.25. The mean HbA1c was 9.07 in girls and 8.70 in boys. Average HbA1c level at ages younger than 5 years was 8.67, for ages 5 to 10 years was 8.70, and in ages 10 years and older was 9.50. Differences in mean HbA1c levels based on age and sex were not statistically significant  . To dete = 0.04) . A signi < 0.04)   . To dete = 0.29) . There wP < 0.001) during the study. Changes in mean height SDS between the onset and end of the study indicate that height SDS was higher at the onset compared to height SDS after treatment which can be seen in both genders and in all ages. Such an outcome was also obtained by Salardi et al. [P = 0.04) and a decrease in height SDS was noticeable in patients who had endured ketoacidosis. Many studies have found similar results to our study [P = 0.58), clinically, good metabolic control had a higher prevalence in the 5–10-year age group and poor metabolic control was seen the most in the 10-year and older age group. In this study there was no significant relationship method of insulin therapy and height SDS scores. Donaghue and colleagues demonstrated a relationship between less frequent insulin injections and a reduction in height SDS [The aim of this study was to determine the relationship of metabolic control and growth in children with DM. In this study 83 patients were studied. The mean age at onset of menarche in girls was 12.8 years which is two months later than mean age of Iranian girls (12.6) , 25. Sali et al. . Anotheri et al. . In thisur study , 26–31. ight SDS , 33. In ight SDS .According to this study the only determinant of growth is not metabolic control; however poor metabolic control may reduce growth. Weight is less affected by metabolic control in comparison to height growth.


Pay-for-performance programs and economic constraints call for solutions improving the quality of healthcare without increasing costs. Many studies have shown decreased morbidity in major surgery when perioperative goal-directed therapy (PGDT) is used. We assessed the clinical and economic burden of postsurgical complications in the University HealthSystem Consortium (UHC) in order to predict potential savings with PGDT.Data from adults who had 10 major surgical procedures in 2011 were screened in the UHC database. Thirteen postsurgical complications were tabulated. In-hospital mortality, hospital length of stay and costs from patients with and without complications were compared. The risk ratios reported by the most recent meta-analysis were used to estimate the potential reduction in postsurgical morbidity with PGDT. Potential cost savings were calculated from the actual and anticipated morbidity rates.P < 0.001), mean hospital length of stay was 20.48 ± 20.09 days and 8.5 ± 7.11 days (P < 0.001), and mean direct cost was $47,284 ± 49,170 and $17,408 ± 15,612 (P < 0.001) in patients with and without complications, respectively. With PGDT, morbidity rate was projected to decrease to 6.5 to 9.0%, yielding gross costs savings of $50 million to 151 million for the study population or $670 to $1,406 per patient.A total of 75,140 patients met the search criteria. In total, 8,421 patients developed one or more postsurgical complications (morbidity rate 11.2%). In-hospital mortality was 12.42% and 1.39% (Postsurgical complications have a dramatic impact on mortality, hospital length of stay and costs. Potential cost savings resulting from PGDT are substantial. PGDT may be recommended to improve quality of care and decrease costs.


To assess clinical characteristics, treatment and survival of patients with uveal melanoma in China.The retrospective study included all patients with malignant uveal melanoma who were consecutively examined in the study period from January 2005 and June 2015 in the Beijing Tongren hospital.P = 0.017), tumor location in the nasal meridian(P = 0.004), smaller tumor size (P<0.001), hemispheric tumor shape (P = 0.025), histological tumor cell type , and type of treatment  were significantly associated with the overall survival in univariate analysis, while in multivariate analysis only smaller tumor size was significantly  associated with better overall survival.The mean age of the 582 patients (295(50.7%) women) was 44.6±12.6 years (range:5–77 years). The tumors were located most often in the superior temporal region (in 117(21.5%) patients) and least common in the inferior region (in 31(5.7%) patients). In 548(94.2%) patients, the tumors were located in the choroid, in 33(5.7%) patients in the ciliary body, and in one (0.2%) patient in the iris. Treatment included episcleral brachytherapy (415(71.3%) patients), local tumor resection (48(8.2%) patients) and primary enucleation (119(20.4%) patients). In 53 individuals out of the 415 patients with primary brachytherapy, episcleral brachytherapy was followed by enucleation, due to an increasing tumor size or due to uncontrolled neovascular glaucoma. Median follow-up time was of 30 months . Overall survival rate at 5 and 10 years was of 92.7% and 85.1%. Younger age (In this study on clinical characteristics of uveal melanoma of a larger group of patients from China, the onset age was considerably younger and survival rate better than in studies from Western countries. Tumor size was the most significant factor for survival. Uveal melanoma is the most frequent primary malignant intraocular tumor in adults with an estimated incidence of 4–5 patients per million inhabitants and year in the United States and of 5–7.4 cases in European studies –4. In a Although uveal malignant melanoma is the most common primary intraocular malignancy and despite the large population of China, there has been a scarcity of studies on patients with uveal melanoma from China. We therefore conducted this study to analyze the clinical characteristics, types of treatment and the survival rate of patients diagnosed with uveal melanoma within a period of 10 years, and to compare the results with those published from other populations.The retrospective hospital-based study included all patients who were consecutively diagnosed with primary uveal melanoma in the study period from January 2005 to June 2015 in the Beijing Tongren Hospital by the same surgeon (WBW). The study was approved by the Medical Ethics Committee of the Beijing Tongren Hospital, followed the tenets of the Declaration of Helsinki. Informed written consent was obtained from every study participant. All patients underwent a complete ocular examination including measurement of best corrected visual acuity, anterior biomicroscopy, tonometry, ophthalmoscopy, fluorescein angiography, and echography for measurement of the tumor dimensions. At six month intervals during the first two years and subsequently once per year, patients who received treatment of the uveal malignant melanoma additionally underwent sonography of the liver and biochemical blood analysis for liver-related enzymes. Imaging techniques additionally applied included magnetic resonance imaging, abdominal sonography and X-ray examination. Some patients also underwent abdominal computer tomography and/or positron emission tomography.The classification based on size of uveal malignant melanoma was based on the criteria published by the Collaborative Ocular Melanoma Study (COMS) . The tot125 was applied for medium-sized tumors or for small tumor with documented tumor growth. Brachytherapy was also indicated for large tumors in which the patient rejected enucleation. Enucleation was performed for large tumors, if it appeared unlikely to recover visual function, for tumors with optic nerve invasion or extraocular extension, for tumors with a flat large infiltration of the choroid, or when the patient refused brachytherapy. The patients treated with brachytherapy and enucleation were re-examined at one month and three months after surgery, and after that once per half year. All enucleated globes were examined by the same pathologist. Parameters assessed were tumor cell type, basal tumor diameter and height, tumor location and position and tumor shape. Results of the histo-pathological examinations were available for those patients who underwent local resection or enucleation.All patients were treated by the same surgeon (WBW). The type of therapy depended on the size and characteristics of the tumors. Small tumors which did not show signs of activity or tumors of patients who rejected treatment were observed without intervention. Brachytherapy using IP-value smaller than 0.05 was considered to be statistically significant.We used a statistical analysis program  for the statistical analysis of the data. The Kaplan-Meier method was applied to assess survival curves and the log-rank test was used for the univariate analysis of associations. The survival time was defined as the interval (measured in months) between the date of the initial therapy or supportive care and the date of death or the date of the last follow-up. Parameters which were significantly associated with the survival rate in the univariate analysis were included in the multivariate survival analysis using the Cox proportional hazards model. A The study included 582 patients (295 (50.7%) women; 293 right eyes, 289 left eyes) with a mean age of 44.6 ± 12.6 years . Visual acuity in the affected eye was equal to or better than 0.80 in 70 (16.9%) patients, ranged between 0.50 and less than 0.80 in 66 (15.9%) patients, was between 0.10 and less than 0.50 in 165 (39.8%) patients, and it was lower than 0.10 in 114 (27.5%) patients. For 167 patients, visual acuity measurements were not reliable. Intraocular pressure was within the normal range of 10 to 21 mm Hg in 357 (86.9%) patients, while it was lower than 10 mmHg in 49 (11.9%) patients and higher than 21 mm Hg in 5 (1.2%) patients. For 171 patients, intraocular pressure measurements were not reliable. A retinal detachment was detected in 245 (71.6%) patients at the time of the diagnosis of the uveal melanoma.The tumors were most often located in the superior temporal region (in 117 (21.5%) patients), followed by the temporal region (111 (20.4%) patients), the inferior temporal region (98 (18.0%) patients), the nasal region (62 (11.4%) patients), the superior nasal region (46 (8.4%) patients), the inferior nasal region (36 (6.6%) patients), the superior region (35 (6.4%) patients), and finally the inferior region (in 31 (5.7%) patients). In 9 (1.7%) patients, the tumor had extended over several regions. For 37 patients, the information on the location of the tumor was not sufficiently descriptive. In 548 (94.2%) patients, the tumors were located in the choroid, in 33 (5.7%) patients in the ciliary body, and in one (0.2%) patient the tumor was located in the iris. An optic disc involvement was detected in 13 (2.2%) patients.Using the criteria of the COMS, there were 6 (1.1%) small tumors, 416 (77.9%) medium-sized tumors, and 112 (21.0%) large tumors. For 48 patients, the information on tumor size was not clear enough to allow a classification. With respect to the tumor form, the tumors had a mushroom-like shape in 117 (27.9%) patients, a mostly flat configuration in 11 (2.6%) patients, a hemispheric shape in 256 (61.1%) patients, and an irregular form in 35 (8.4%) patients. For 163 patients, the tumor shape was not sufficiently described to allow a clear allocation to a group.Among the 159 patients for whom a histologic examination of a tissue specimen was possible and performed, 114 (71.7%) patients showed a spindle cell-type tumor, 17 (10.7%) patients had an epitheloid cell-type tumor, and 28 (17.6%) patients exhibited a mixed cell type tumor.Treatment included episcleral brachytherapy in 415 (71.3%) patients, local tumor resection in 48 (8.2%) patients and primary enucleation in 119 (20.4%) patients. In 53 individuals out of the 415 patients with primary brachytherapy, episcleral brachytherapy was followed by enucleation, due to an increasing tumor size or due to uncontrolled neovascular glaucoma.The median follow-up time was of 30 months . Follow-up was less than one year for 103 (17.7%) patients, more than one year and equal to or less than 3 years for 254 (43.6%) patients, more than three years and equal to or less than 5 years for 126 (21.6%) patients, more than five years and equal to or less than 10 years for 98 (16.8%) patients, and longer than 10 years for one (0.2%) patient.Within the study period from January 2005 to June 2015, 32 patients (5.5%) died, among them 29 patients died due to a melanoma-related metastasis; one patient developed a second tumor, and two patients died due to pulmonary embolism and myocardial infarction . A metasP = 0.017), location of the tumor in the nasal meridian (P = 0.004), smaller tumor size (P<0.001), hemispheric tumor shape (P = 0.025), histological tumor cell type (spindle-cell type versus mixed cell type versus epitheloid cell type) (P = 0.014), and type of treatment  were significantly associated with higher overall survival. Survival was not significantly associated with gender (P = 0.55), right eye or left eye (P = 0.58), visual acuity (P = 0.50), intraocular pressure (P = 0.44), retinal detachment (P = 0.62), tumor location in the choroid or in the ciliary body (P = 0.90), and optic nerve head involvement (P = 0.37)   Fig 1)..P = 0.01P<0.001; RR: 4.75; 95% confidence interval: 2.11, 10.7) associated with the overall survival , and the type of treatment  . In the P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), tumor pigmentation (P = 0.001), subretinal fluid or retinal detachment (P = 0.001), intraocular hemorrhage (P = 0.045), and extraocular extension (P = 0.036) [An overall survival rate at 5 years was of 92.7%  in the Chinese patients of our study was higher than the 5-year survival rate found in previous studies in Western countries –12. In aIn our study, the medium age at diagnosis of the uveal melanomas was 44 years. A similar age at the time of diagnosis was reported in a study on 103 patients from India with uveal melanoma . This aget al. found in a study of 723 patients with uveal melanoma that men had a worse prognosis with a higher rate of melanoma‑related metastasis and death than women had. In their study, melanoma‑related mortality in the first 10 years was two‑fold higher in men than in women [In our study, gender was not significantly associated with the survival rate, and both sexes had roughly the same proportion on the total study population. Correspondingly, the COMS group did not find significant differences in uveal melanoma-related metastasis and death between men and women . In disain women . In multin women . It was et al. found a significant association between the largest basal diameter of the tumor and a higher melanoma‑related mortality [et al. increasing tumor thickness was associated with an increasing risk for metastasis. Kaplan–Meier estimates of metastasis at 5 years, 10 years and 20 years was 6%, 12%, and 20% for small melanoma (<3 mm tumor thickness), 14%, 26%, and 37% for medium melanoma (3.1–8 mm), and 35%, 49%, and 67% for large melanoma (>8 mm), respectively. Each millimeter increase in tumor thickness was associated with approximately a 5% increase in the risk for metastasis at 10 years and a hazard ratio of 1.08 [Tumor size defined as the largest basal diameter and the largest height of the tumor has been one of the most important clinical prognostic features of uveal melanomas –26. In oortality . In a stTumor cell type has been considered to be an important prognostic factor for the survival of patients with uveal melanomas –33. CallOur results should be interpreted with some limitations in mind. First, the follow up period was relatively short for a major part of the study population. Second, we did not carry a molecular genetic examination of the tumor specimen. Recent studies have shown that the genetic pattern of the uveal melanoma is of high importance for the development of metastasis and survival –37. ThirIn conclusion, in this first study on clinical characteristics of uveal melanomas of a relatively large group of patients from China, the onset age was considerably younger and survival rate better than in studies from Western countries. Tumor size was most significant factor for survival.


Monotherapy with darunavir plus ritonavir (DRV/r) is a good maintenance strategy for suppressed HIV-infected patients. The clinical trials designed to prove the efficacy of PI/r do not include patients with resistance mutation in protease gene ,2. Somet2 test; and during the follow-up by using the Kaplan–Meier test. The statistical analysis was done with SPSS 17.0.We designed an observational cohort study of adults in treatment with DRV/r monotherapy in a tertiary Spanish hospital since 2011 to 2014. Demographic data and clinical outcomes were described. The analysis of efficacy was done according to the snapshot algorithm . We analyzed the difference of efficacy between patients with and without baseline resistance mutations at 48 and 96 weeks by using the χEighty-nine patients were included in the cohort but 14 were excluded because they had not reached more than six months with monotherapy. The cohort was composed mainly by men (78%), the medium age was 51 years (SD±10), 35% were MSM and 19% were former IDU. Twenty-four patients (35%) had a previous diagnosis of AIDS. The mean time taking NRTIs was 10.5 years (SD±5.4). Sixty-four patients (85%) had been treated with PI in the past. Previous failure with PI had been reported in 15 (20%). A resistance mutation test had been done at baseline in 45 patients (51%). Twenty-two patients (29%) had some mutations in protease gene, 10 patients (13%) had major mutations and 1 patient had some mutations of resistance for darunavir (I64V). At 48 weeks, 93% (CI 95% 86–98%) had VL<50 copies/mL, and 79% (CI 95% 67–89%) at 96 weeks. There were not differences between patients with or without resistance mutations (p=0.53). After a median follow-up of 70 weeks, 88% of patients remain free of virological failure and there were not differences between both groups.According to these data, previous resistance mutations in the protease gene, which do not affect darunavir, are not related with the efficacy in patients treated with DRV/r monotherapy.