Gadus macrocephalus is a demersal, economically important fish in the family Gadidae. Population genetic differentiation of Pacific cod was examined across its northwestern Pacific range by screening variation of eight microsatellite loci in the present study. All four populations exhibited high genetic diversity. Pairwise fixation index (Fst) suggested a moderate to high level of genetic differentiation among populations. Population of the Yellow Sea (YS) showed higher genetic difference compared to the other three populations based on the results of pairwise Fst, three-dimensional factorial correspondence analysis (3D-FCA) and STRUCTURE, which implied restricted gene flow among them. Wilcoxon signed rank tests suggested no significant heterozygosity excess and no recent genetic bottleneck events were detected. Microsatellite DNA is an effective molecular marker for detecting the phylogeographic pattern of Pacific cod, and these Pacific cod populations should be three management units.The Pacific cod  Gadus macrocephalus is a demersal, economically important fish in the family Gadidae. It is mainly distributed in the North Pacific, from the Yellow Sea of China through the Sea of Japan, Okhotsk and Bering Seas to California in the eastern North Pacific [The Pacific cod  Pacific ,2. As an Pacific . Low tem Pacific ,4,5. The Pacific . Could tet al. [et al. [et al. and the current distribution pattern represents groups previously isolated during glaciations that are now in secondary contact [Studies on population genetics have attracted much attention because such information is important for understanding the pattern of biogeography and sustainable utilization of fishery resources . If we iet al.  detectedet al. . However [et al.  examined contact .et al. [These studies suggested different sensitivities of three molecular markers for detecting the genetic structure and diversity of the Pacific cod. Compared with mitochondrial DNA and allozyme markers, microsatellite DNA is a type of nuclear genetic marker that has been proven to be more sensitive in detecting population genetic structure ,15,16. Iet al. . The resA), observed heterozygosity (Ho), expected heterozygosity (He) and polymorphism information content (PIC) are shown in He) ranged from 0.496 ) to 0.957 ), and the observed heterozygosity ranged from 0.435  to 1.000 ). The PIC values ranged from 0.472–0.933, which suggested high genetic diversity of this species (PIC > 0.5) [Clear and unambiguous bands were identified by denaturing polyacrylamide gel electrophoresis. All eight microsatellite markers were highly polymorphic and the number of alleles per locus varied from eight to 24 . The numC > 0.5) . Five deFst ranged from 0.0204–0.0618 and p-values were adjusted using the sequential Bonferroni procedure . Genetic differences between population YS and the other three populations were larger and statistically significant after sequential Bonferroni correction. The Mantel test indicated no significant relationship between pairwise estimates of Fst/(1 − Fst) and geographic distance    . In orde > 0.05) . The fir > 0.05) .2 genetic distance was calculated according to the allele frequency and the results showed that population YS exhibited the larger genetic distance from the other three populations, which was in accordance with the result of the pairwise Fst. However, the (δμ)2 genetic distance between populations SJ and EH was the smallest, not between populations SJ and OS. The topology of the unweighted pair-group method analysis (UPGMA) tree based on (δμ)2 genetic distance showed the relationship of the four populations more intuitively (The (δμ)uitively .l-shaped distribution of allele frequencies as expected for a stable population under mutation-drift equilibrium.Wilcoxon signed rank tests under the three mutational models ; stepwise mutation model (SMM); two-phase mutation model (TPM)) were not significant, which suggested that no significant heterozygosity excess was detected . In addiK = 2 explained the data in a satisfactory manner, as this model resulted in the highest ΔK value currents ,19. Thoucurrents . Populatcurrents . The res [et al. .et al. [et al. [K = 3 was performed, which was supported by the results of (δμ)2 genetic distance and 3D-FCA. The topology of the UPGMA tree based on (δμ)2 genetic distance showed that populations from the Japanese coast clustered with each other at first, and then with population OS. The pairwise Fst was calculated based on the haplotype frequency, and genetic distance was based on the difference of alleles. There are alleles that may cause this difference between the two methods.The strong genetic differentiation between populations from the Sea of Japan and the Okhotsk Sea determined with mitochondrial DNA by Liu et al.  was in c [et al.  examinedHe) of Pacific cod was higher than the average values of marine fish [et al. [The conservation of genetic diversity is very important for the long-term interest of any species . Studiesine fish , and mos [et al. . Moreove [et al. ,15,16,27et al. [et al. [However, low genetic diversity of this species was detected by allozyme and mitochondrial DNA, which was in contrast with our results and Cunningham et al. . Especia [et al. . The all [et al. ,29. Prev [et al. ,30,31. TIn conclusion, microsatellite DNA is an effective molecular marker for detecting the phylogeographic pattern of Pacific cod. The results of the present study suggested these Pacific cod populations should be considered as three management units and population YS should be paid more attention because of its uniqueness.Samples from four locations across the northwestern Pacific Ocean were used in the present study , Table 6Genomic DNA was isolated from muscle tissue by proteinase K digestion followed by a standard phenol-chloroform method. Eight polymorphic microsatellite markers were employed for this study ,33 Tabl.2. The PCR amplification was carried out in a thermal cycler  under the following conditions: 5 min initial denaturation at 92 °C, and then followed by 25 cycles of 30 s at 92 °C, 30 s at annealing temperature 62–57 °C, 30 s at 72 °C and final extending for 30 min at 72 °C. We used 8% non-denaturing vertical polyacrylamide gel electrophoresis to separated PCR products and visualized by silver staining [Polymerase chain reaction (PCR) was carried out in 10 μL volumes containing 0.5 U Taq DNA polymerase , 100 ng template DNA, 0.15 μM of each forward and reverse primers, 0.2 mM each deoxy-ribonucleoside triphosphate (dNTPs), 10 mM Tris (pH 8.3), 50 mM KCl, 3.0 mM MgClstaining . A sizinA), observed heterozygosity (Ho), expected heterozygosity (He) and Polymorphism Information Content (PIC) were obtained by Microsoft Excel tools [Fst were calculated by FSTAT 2.9.3 [Fst measures were subjected to multidimensional scaling (MDS) and plotted in two dimensions , data not shown). The relationship between genetic distances and geographic distances was assessed using Reduced Major Axis (RMA) regression and Mantel tests using IBDWS [2 genetic distance by POPULATION 1.2 [2 genetic distance by MEGA 5 [K values ranged from 1 to 10 . Ten independent runs were implemented for each specific K-value in order to verify the consistency of the results. The ad hoc estimated likelihood of K (ΔK) was used to determine the most likely number of populations (K) based on the rate of change in the log probability of the data (Ln P(D)) [Deviations from the Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium of each locus within each site were checked by GENEPOP 3.4 . The numel tools . The nulel tools . The valAT 2.9.3 . BottlenAT 2.9.3  was usedAT 2.9.3 . We alsoAT 2.9.3 . ARLEQUIAT 2.9.3 , and AMOng IBDWS ,43. We cTION 1.2  and consy MEGA 5 . Three-dy MEGA 5 . The posy MEGA 5 . Markov Ln P(D)) .


Of the 21 patients, nine patients (43%) could not fulfill the dose constraints. In all these patients, the distance between the planning target volume (PTV) of ENI (PTVeni) and the PTV of SBRT (PTVsrt) was ≤2.0 cm. Of the three patients who developed regional metastasis, two patients had isolated lymph node failure, and the lymph node metastasis was included within the ENI field. When the distance between the PTVeni and PTVsrt is >2.0 cm, SBRT with selective ENI may therefore dosimetrically feasible.More than 10% of all patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer develop regional lymph node recurrence. We evaluated the dosimetric feasibility of SBRT with lobe-specific selective elective nodal irradiation (ENI) on dose–volume histograms. A total of 21 patients were treated with SBRT for Stage I primary lung cancer between January 2010 and June 2012 at our institution. The extents of lobe-specific selective ENI fields were determined with reference to prior surgical reports. The ENI fields included lymph node stations (LNS) 3 + 4 + 11 for the right upper lobe tumors, LNS 7 + 11 for the right middle or lower lobe tumors, LNS 5 + 11 for the left upper lobe tumors, and LNS 7 + 11 for the left lower lobe tumors. A composite plan was generated by combining the ENI plan and the SBRT plan and recalculating for biologically equivalent doses of 2 Gy per fraction, using a linear quadratic model. The V Stage I non–small cell lung cancer (NSCLC) is a potentially curable disease, with the standard treatment being lobectomy with systemic mediastinal lymph node dissection. Unfortunately, up to 25% of patients with Stage I NSCLC are not candidates for lobectomy because of medical problems. Stereotactic body radiotherapy (SBRT) is an alternative treatment option for these patients , 2. SBRT18F-2-fluoro-deoxy-D-glucose (FDG) imaging is a useful diagnostic modality for detecting lymph node metastasis, its ability to detect lymph node metastasis ≤1 cm or lymph node metastasis from adenocarcinoma is limited [According to a recent systemic review , 10% of  limited .On the other hand, a previous surgical study demonstrated the incidence of lymph node metastasis to be associated with the histological type or primary tumor size, and that regardless of the histological type, lymph node failure was not negligible in cases with a primary tumor size ≥2 cm . TherefoThe present study was approved by the Institutional Review Board of our hospital No. 13R-091). The patients included in this study had clinically diagnosed Stage I primary lung cancer, as defined by the Union International Contre le Cancer (UICC). Between January 2010 and June 2012, 24 patients were treated with SBRT for Stage I primary lung cancer in our institution. Of these patients, three were excluded from the study because they were treated with a reduced radiation dose that was different from that of our protocol  due to a violation in the dose constraints of SBRT for at-risk organs. Data from 21 patients were available for this study. The patient characteristics are shown in Table 3R-091. TThe patients were fixed in the supine position on a body support immobilization system  with the upper extremities raised using a vacuum pillow for the dorsal aspect of the thorax and a thermoplastic shell for the ventral aspect of the thorax. Tumor movement was fluoroscopically measured prior to treatment planning. An abdominal compression device, equipped with a body support system to reduce respiratory motion, was used when the tumor moved more than 1 cm due to respiration. Serial CT images for treatment planning were acquired with 2-mm slice thickness in the target area and 5-mm in the remaining area, using a 4-row multi-detector CT scanner , from the neck to the upper abdomen. The gross tumor volume (GTV) was delineated as the visible tumor at the lung window setting (window width 800 Hounsfield units (HU) and window level –600 HU), using a 3D radiation treatment planning system . Two-phase CT images, which consisted of an inspiratory breath-holding phase and an expiratory breath-holding phase, were obtained to determine the range of tumor movement, and a long-scan-time CT with an 8-s scan time in free breathing was also obtained to determine the trajectory of tumor movement. GTVs were contoured on each of the three images to generate the internal GTV from their fusion. The clinical target volume (CTV) for SBRT (CTVsrt) was defined as the internal GTV plus an additional 5–8 mm margin, and the planning target volume (PTV) for SBRT (PTVsrt) was created by a 3-mm expansion of the CTVsrt in all directions. The dose was prescribed at the center of the PTV, and the PTV was covered with an isodose line between 80 and 90% of the prescription dose. The leaf margins were adjusted in an effort to improve conformity. The radiation doses were calculated using an analytical anisotropic algorithm (AAA) implemented in Eclipse 10.0.28 with heterogeneity correction. The calculation grid size was 0.25 × 0.25 × 0.25 cm. All patients were treated using 6-MV X-rays with non-coplanar static fields (ranging from 7 to 9 fields). Radiation treatment was then performed after image verification with 2D matching of the kilovoltage planar image and 3D matching of cone-beam CT acquired with the Varian on-board imaging (OBI) system equipped at the linear accelerator . The dose constraints of our protocol were determined based on the Japan Clinical Oncology Group (JCOG) Phase II clinical trial for Stage IA NSCLC (JCOG 0403 protocol) in consideration of other reports –14. TablIn surgery for cN0 lung cancer, hilar lymph node metastasis plus mediastinal lymph node metastasis is the most common pattern, with a frequency of 39%, followed by hilar lymph node metastasis alone (17%) and mediastinal lymph node metastasis alone (17%). The frequency of intrapulmonary lymph node metastasis is low (7.4%) .et al. [Oda et al.  performeIt was found that 72–73% of micrometastases cases demonstrated metastasis to a single station, in which the range of metastasis was localized, and the prognosis was better than that of metastasis to multiple stations .et al. [In several surgical reports –23, a reet al. , we alsoA search using the PubMed electronic database was conducted using the words ‘non–small cell lung cancer’, ‘lymph node metastasis’ and ‘Stage I’ to determine the optimal selective ENI fields. The criteria by which we selected articles were: a sufficient number of cases, pathological findings, and reference to the frequency and location of lymph node metastasis according to primary sites. We found 10 articles that met the above criteria and provided useful information for our study. A summary of these articles is as follows.et al. [et al. [Referring to the summary of the above reports on mediastinal metastasis of lung cancer, we set mediastinal ENI fields at lymph node stations with a probability of mediastinal lymph node metastasis of 20% or higher with the aim of inhibiting single station lymph node metastasis. Finally, lobe-specific selective ENI fields were set at the lymph node regions with a 20% or higher frequency of lymph node metastasis according to reports by Asamura and Ichinose et al. , 22, who [et al. , who invright upper lobe (RUL): lymph node stations #3, #4, #11right middle lobe and right lower lobe (RML-RLL): lymph node stations #7, #11left upper lobe (LUL): lymph node stations #5, #11left lower lobe (LLL): lymph node stations #7, #11.et al. [The CTVeni, which indicates the CTV of the selective ENI field, was delineated according to the CT atlas of the lymph node stations clearly defined by Chapet et al.  . Contouring of these organs was performed according to the atlas presented by Kong et al. . The traN is the number of fractions of SBRT and d is the dose per fraction adopted in SBRT.To evaluate the total biological dose of the two treatment plans comprising SBRT and the additional ENI plan, we used biologically equivalent doses of 2 Gy per fraction (EQD2) from the linear quadratic (LQ) formula with an α/β of 3 for late-responding tissues  and an α/β of 2 for the spinal cord using the following equation for the SBRT plan:20, which indicates the percentage of volume that received ≥20 Gy. The esophagus was estimated from the D31cm, which indicates the minimal radiation doses for the most irradiated volume of 1 cm3, and the D310cm, which indicates the minimal radiation doses for the most irradiated volume of 10 cm3. The spinal cord was estimated from the D31cm, and the tracheobronchial wall was estimated from the D310cm.We recalculated the SBRT plan into the EQD2 plan by changing the prescription, namely 4 × 12 Gy into 72 × 2 Gy, 5 × 10 Gy into 65 × 2 Gy, and 7 × 8 Gy into 61 × 2 Gy, to evaluate the lung, esophagus and tracheobronchial wall, and also converted 4 × 12 Gy into 84 × 2 Gy, 5 × 10 Gy into 75 × 2 Gy, and 7 × 8 Gy into 70 × 2 Gy, to evaluate the spinal cord. Composite plans were then generated by combining the EQD2 plan of the SBRT and ENI plans, and total dosimetric data for each organ were obtained from these to estimate the feasibility on dose–volume histograms (DVH). The lung as an OAR was defined as the total lung minus the GTV and was estimated from the V20 of the lung was ≤30% [31cm of the spinal cord was ≤50 Gy. D31cm and D310cm of the esophagus were ≤70 Gy and ≤60 Gy, respectively [310cm of the tracheobronchial wall was ≤70 Gy [To define the dose constraints of OARs, we searched for studies using the PubMed database regarding radiation-induced toxicity and the tolerance dose for OARs. Although the number of available studies was limited because of sporadic reports, we determined the dose constraints of the composite plan for OARs as follows. The Vwas ≤30% , 30. D1cectively –33, and s ≤70 Gy –36. Becas ≤70 Gy .20 of the lung in all patients increased from a median value of 13.2% (range: 8.3–31.8%) to a median value of 24.4% (range: 17.6–33.6%) after adding the ENI plan. Figure 20 according to the primary site. The addition of ENI increased the median V20 from 12.6% (range: 8.3–17.1%) to 25.9% (range: 24.2–29.1%) in patients with RUL primary lesions, from 16.8% (13.2–31.8%) to 24.1% (23.3–33.6%) in those with RML-RLL primary lesions, from 11.6% (8.5–15.2%) to 19.0% (17.6–20.0%) in those with LUL primary lesions, and from 12.8% (11.5–14.2%) to 19.8% (17.7–22.0%) in those with LLL primary lesions. Figure 31cm from 14.3 Gy (range: 0.5–46.8 Gy) to 45.7 Gy (range: 30.6–86.4 Gy), and the median D310cm from 1.6 Gy (0.2–19.3 Gy) to 11.2 Gy (1.3–52.6 Gy). Both D31cm and D310cm were lower than 60 Gy in most patients, even though ENI was added, while D31cm and D310cm increased to 86.4 and 52.6 Gy, respectively, in one patient. Figure 31cm increased from 14.9 Gy (range: 0.6–41.8 Gy) to 44.6 Gy (range: 2.9–84.5 Gy). Figure 310cm of the tracheobronchial wall. Although, the addition of ENI increased the D310cm, the values were lower than 60 Gy in all patients. Table Of all the 21 patients, nine patients 43%) could not fulfill the dose constraints of the composite plan for the OARs determined in this study. The V% could nThe median follow-up time after SBRT was 26 months (range: 3–38 months). The 2-year overall survival rate was 84%, and the 2-year local control rate was 88%. Grade 2 radiation pneumonitis, according to the common terminology criteria for adverse events (CTCAE) version 4.0, was observed in one patient. Local recurrence was observed in two patients and regional lymph node metastasis was observed in three patients. Three patients developed distant metastasis.Of the three patients who developed regional metastasis, two patients had isolated lymph node failure in a single station as the initial site. The other patient had both hilar node metastasis and local recurrence. Although 11 patients underwent PET-CT before the treatment, none of the three patients with lymph node metastasis did. One of the two patients with isolated lymph node failure had a RUL primary tumor and developed lymph node metastasis in #3 two months after the completion of SBRT. The other patient had a LUL primary tumor and developed lymph node metastasis in #5 four months after the completion of SBRT. The former patient developed further metastasis to the pleura and lung seven months later. In both patients, lymph node metastasis was included within the additional ENI field.The treatment outcome of conventional radiotherapy for Stage I NSCLC has been poor, with a 5-year overall survival rate of 13−27% , 39. In et al. [et al. [et al. [However, even when all patients were staged by FDG-PET, the 5-year regional recurrence rate after SBRT was ∼12.7% , and lymet al.  noted th [et al.  demonstr [et al. . Oda et  [et al.  reportedet al. [et al. [Parashar et al.  estimate [et al.  showed tet al. [et al. [There were several limitations associated with this study. One limitation was the use of the LQ model for evaluations. Although Gay et al.  also cal [et al. , 48 demoIn conclusion, the addition of lobe-specific selective ENI to SBRT for patients with clinical Stage I lung cancer is therefore considered to be feasible on a DVH evaluation, when the distance between the 2 PTVs was more than 2 cm. Further clinical studies are therefore needed to confirm the feasibility of SBRT with ENI.Funding to pay the Open Access publication charges for this article was provided by Tokai University.


Introduction. Differentiated thyroid cancer (DTC) is rare and confers good prognosis. Long-term health related quality of life (HRQoL) and pregnancy outcomes are not well known in subjects treated during adolescence and young adulthood. Methods. Cross-sectional analysis of HRQoL and global self-esteem, using SF-36 and ISP-25 surveys, and of pregnancy outcomes in female survivors of DTC treated by total thyroidectomy and I131 before age of 25 years. Results. Forty-five of 61 patients (74%) responded to the survey. Cumulative I131 activity was ≤3.85 GBq in 18 subjects and >3.85 GBq in 27 subjects. Mean time from diagnosis was 7.6 ± 5.2 years for the group ≤ 3.85 GBq versus 16.9 ± 11.6 years for the group > 3.85 GBq (P < 0.05). No significant alteration in long-term HRQoL and global self-esteem was observed. Thirty pregnancies after I131 were noted in patients from the group > 3.85 GBq and 10 in patients from the group ≤ 3.85 GBq. Frequency of miscarriages was of 17% (group > 3.85 GBq) and 10% (group ≤ 3.85 GBq) with 9 and 24 live births, respectively. No congenital malformations or first year mortality was noted. Conclusion. Long-term HRQoL, global self-esteem, and pregnancy outcomes are not affected in young female survivors of DTC. Differentiated thyroid cancer (DTC) is rare and its incidence in Europe in 2012 has been estimated as 6.3 per 100 000 with a mortality rate of 0.4 per 100 000 , 6. One Up till now, existing studies report short-term HRQoL of patients with DTC , 10, 12.131 prior to pregnancy of 3.7 GBq, with range of 2.96–28.86 GBq. Thirty-five children (72%), 5 (10%) miscarriages, and 9 (18%) induced abortions were noted. There were no congenital malformation and first year mortality. A higher therapeutic dose (>3.7 GBq) did not have a significant impact on pregnancy outcomes. Similarly, in the largest French study fluoro-D-glucose whole body positron emission tomography/computed tomography (18F FDG-PET/CT), received 3.7 GBq (100 mCi) of I131. TNM staging was performed according to the criteria of the American Joint Committee on Cancer 2009.All patients underwent total thyroidectomy followed by radioactive iodine (RAI) ablation by IHealth related quality of life was evaluated using the self-administered Short Form-36 version 2 (SF-36 v2) , 19. TheTo evaluate fertility and reproductive outcomes a four-part self-administered instrument was developed by investigators after consideration of the relevant data available in the literature. The questionnaire was sent to participants by mail and took approximately 30 to 45 minutes to complete. All responses were kept confidential. The survey addressed the following domains. The first domain provided information on the self and familial medical history, treatment, tobacco and alcohol consumption of responders, weight, and size (11 items). The second domain concerned demographic data (5 items). The third domain of the questionnaire focused on gynaecological history (12 items). The fourth domain recorded data concerning reproductive and fertility outcomes . Subjects were invited to add free comments at the end of the questionnaire.n = 3, and Ewing sarcoma, n = 1) and were excluded from the study. Finally, out of 61 subjects who received the questionnaire, 45 returned the questionnaire, for a survey response rate of 74%. Flow chart of study participants is detailed in Of 90 subjects who were eligible to participate, 61 received questionnaire between December 2014 and June 2015. Twenty-eight subjects could not be contacted because of the missing data (incomplete address) in the medical records and 1 patient refused to participate. Four females presented a history of another malignancy preceding diagnosis of thyroid cancer  and second, higher dose (>3.85 GBq). The mean age at diagnosis of DTC was similar for both groups. Compared to the patients from the lower dose group, the patients from the higher dose group had a significantly longer mean follow-up period, 7.6 ± 5.2 versus 16.9 ± 11.6 years, respectively (P < 0.05). Four patients presented with pulmonary metastases and 1 patient presented with bone metastases at diagnosis. Mean cumulative dose of I131 was 3.5 versus 8.3 GBq for the first and second group, respectively. Total dose was unknown for 6 females from the second group, but it was superior to 3.85 GBq. Characteristics of the participants are detailed in The patients were divided into two groups according to the cumulative dose of IThe components of the SF-36 and ISP-25 questionnaires are detailed in 131 administered prior to pregnancy was 3.74 GBq for the first group and 7.88 GBq for the second group  to our survey reflects interest of subjects and ongoing health concern despite having completed the cancer therapy. Interestingly, information-seeking behavior in cancer survivors and desire to receive additional health related information has been observed [Herein, we evaluated a long-term health related quality of life and pregnancy outcomes in young female thyroid cancer survivors from the region of Lorraine in France. Our study highlights that long-term quality of life and global self-esteem are not affected. Up till now, little has been published on a long-term HRQoL in patients with DTC. The Swedish SF-36 survey has shown no alteration of mental and physical quality of life in 77 patients of all ages who underwent total thyroidectomy and RAI for DTC . Recentlobserved . Thus, iobserved –22. Moreobserved .131 were observed: 30 in patients who received cumulative dose of I131 > 3.85 GBq and 10 in patients who received ≤3.85 GBq. Frequency of miscarriages was of 17% in females from the group > 3.85 GBq and 10% in patients with cumulative I131 dose ≤ 3.85 GBq. Our observations are consistent with the data for the French general population [131 activity < 0.37 GBq and 21% miscarriages out of 178 pregnancies and cumulative I131 activity ≥ 3.70 GBq) [http://www.has-sante.fr/portail/upload/docs/application/pdf/2010-07/ald_30_gm_cancer__thyroide_web.pdf) avoiding pregnancy for 6 months after I131 treatment is suggested. The effects of other factors such as thyroid hormone status on the pregnancy outcomes were not investigated and this topic is out of the scope of this paper.In terms of pregnancy outcomes, to our knowledge, the here presented study is the first to be addressed specifically to the population of long-term DTC survivors diagnosed and treated during adolescence or young adult age. Forty pregnancies after administration of Ipulation  and with.70 GBq) . Based oThe conclusions of this study should be applied with caution since its sample population is not truly a reflection of the total French population of female patients diagnosed with DTC at adolescent age and young adulthood. However, the high response rate to this study represents less serious potential for a nonresponse bias. Furthermore, majority of the study participants were still in their reproductive age and report their real-life experience.Altogether our results suggest that quality of life of young female thyroid cancer survivors is not affected. The results allowed us to evaluate the quality of life over a longer time period and incite new questions regarding information strategies for patients who underwent active thyroid cancer treatment especially at young age.


Satisfaction evaluation is a good way to assess hospital conditions. In Health Care System, parentscan be also as children's main supporters, thus they may act as patient's viewpoints' representatives.This study aimed to evaluate mother’s satisfaction of hospital care in hematology – oncology ward in Dr Sheikh hospital.  A Cross-sectional descriptive analytic study was conducted using Pediatric Family Satisfaction (PFS) questionnaire and interviewing with 164 mothers duringMarchto February2013. The obtained data were analyzed using SPSS -16 software and descriptive statistics.The mean age of mothers and children was31.2±5.8, and 7.95 4/66 years.The children were 64 % male and 36 % femael. A large number of mothers  reported their satisfaction about nursing care at very high level and(36.5 %) reported satisfaction about welfare services at high level(59%)and describe overall satisfaction at very high level . The totals mean of mothers’ satisfaction ratewas 121.8 ± 10.8. The mean of medical care, nursing care, welfare services was 2.9±34.1,4.6±50 and4.8± 32.9 respectively. Overall satisfaction with medical, nursing and welfare staff was acceptable. For more satisfaction, it is widely recommended to improve veinipuncture by nurses, Physicians should inform parents about the tests results, and finally disturbance in ward with noise should be controled. New movement in health industries have been initiated towards continuous quality improvement and this phenomenhas gained momentum since 1990 .According to Donabedian's declaration for incorporating patient perception into quality assessment, healthcare managers incorporate patient centered care as a major component in the healthcare mission. In 1996A Cross-sectional descriptive analytic study was conducted using Pediatric Family Satisfaction (PFS) questionnaire and interviewing with 164 mothers during 2013. The interview was done after discharging from the hospital.Questionnaire: The questions reflected 3 dimensions: medical care (9 items), nursing care (11 items), and welfare services (8 items). For each item, the parents were asked to assess what they found most important on a 5-point Likert scale, from excellent to not applicable. The questionnaire also included items on mother characteristics: age and education. The pilot studywasdone and had a pretest of questionnaire in 15 parents.For reliability we use internal consistency. The Cronbach α score for 3 dimensions was 0.9. The distribution ofthe responses were normal.To describe Motherssatisfaction Rate from hospital cares, the mean score of each item was calculated using scores from 1 to 5 on the rating scale. Statistical analysis was carried out using SPSS 16 statistical software . Statistical significance was set at P<.05.We also used Anova and t- test. The mean age of mothers and children were 31.2±5.8 and 7.95 4.66 years, respectively. The children were 64 % male and 36 % female. A large number of mothers about nursing care at very high level, and(36.5 %) about welfare services at high level(59%)and very high level about all aspect. The total mean of Mothers’ Satisfaction Rate was 121.8 ± 10.8 .The mean of medical care, nursing care, and welfare services were2.9 ± 34.1 406±50and4.8± 2.9, respectively.Regarding medical care The main points, evaluated weakly, in order of importance included as follows: to inform parents about the tests results (29.9 %), regarding nursing care :doing veinipuncture (4.9%) and in regard to welfare services: disturbance in ward with noise(1.8%). There is a negative relationship between mother's education and mother's satisfaction .Hosseinian and et al in their research about Mothers satisfaction of hospital care in the pediatric ward of Kashan reported mothers were dissatisfied with doctors for not being available on time and their failure to notify the results of their chidern’stests. They were also dissatisfied with nurses for the lack of education about their chidern’streatment and also the lack of post-discharge care. The mothers were also dissatisfied with welfare services (e.g. providing an appropriate play room for children (71.4%) Average satisfaction scores for the medical, nursing,and welfare staff were 22.25±6.19, 29.05±6.88,:and 26.68±6.93,respectively. A significant relationship was observed between child's disease and mothers satisfaction (P<0.0001) , regarding nursing care: to aware parents about medical care and post-charge care 10.5%) and then in regard to welfare services: availability of playing conditions for children in the ward (56.5%). Overall mean score for welfare, nursing,and medical care were 32.01±4.58, 47.32±7.43and 38.36±6.13respectively  and disturbance in ward with noise(1.8%). veinipuncturein oncology ward is a important role of nurses and it should be done by expert nurses because most of the children havedamaged vein caused by chemotherapy.Noise disrupts the peace of mothers and their children and since psychological state of them is not stable, the noise can make bad Situation for them. ; therefore, noise control is essential in the ward. In this study, overall satisfaction in children with mother's education with bachelor's degree was lower .The obtained findings revealed thatThere is a negative relationship between mother's education and mother's satisfaction.Pourmovahed and etal in their researchshowed the same) .Overall satisfaction reported excellent in oncologic ward of this hospital.To satisfy mothers and improve their satisfactionit is necessaryto inform parents about the tests results, veinipuncture should be done by expert nurses and thenoiseshould be control in ward. There is a growing interest in mother's satisfaction as an outcome of care and as an indicator of the quality of care. Interest in mother's satisfaction with pediatric care is not new, but research in this field is limited.


Method. Patients data of 20 years was collected and evaluated in the “Shahid Modarres Hospital”—a tertiary university hospital—Tehran, Iran. Results. 42 patients with cardiac myxoma  were included in study, 17 males and 25 females, age difference: 13 to 76 years (mean 50.6). Most of patients were in functional classes I, II. 35 patients complained of dyspnea and 3 patients had embolic events. 97.6% of tumors were primary (41 patients) and one tumor was recurrent (2.4%), 85.7% of tumors (36 cases) were located in LA, and 88.1% of tumors (37 cases) were pediculated. 40 patients (95%) had one tumor. In 22 patients (52.3%) after tumor resection septal defects were repaired primarily while in 18 patients (42.8%) the defects were repaired with pericardial patch and In one patient, tumor resected without any septal defect. Mean tumor size was about 5.22 cm (range of 2.2 to 8.2 cm). Postoperatively, 33 patients discharged from hospital without any complication. Discussion. The research reveals that patients' age and gender were similar to that of other studies in other countries while tumor's incidence seems to be higher. 3 patients were diagnosed after remote embolic event and one patient was diagnosed after MI reflecting relatively high tumor complications and late diagnosis. Conclusion. In our study mean time from diagnosis to operation was too long. The patients had more preoperative embolic events and complication. However, size of myxoma and location of that was as same as its rate in the other literature. As recommendation we suggested that in all patients with vague chest pain or remote embolic events cardiac myxomas should be ruled out.Although cardiac tumors are not common they may vary in terms of race and surgical approach in different countries.  Primary cardiac tumors are rare ones. Their annual incidence is 5 per million among people of 30 to 60 years old . They coCrafoord reported first cardiac myxoma diagnosis and successful operation by CPB in 1955 . Tumors This study is descriptive and has been conducted by collecting data of patients admitted in Tehran's Shahid Modarres Hospital—a tertiary university hospital—with diagnosis of cardiac myxoma from 1994 to 2014. Patients' data then got categorized according to their age, gender, clinical manifestations, diagnostic modalities, preoperative functional class, preoperative and postoperative arrhythmia, serologic abnormalities, waiting time to operation, hospital stay, operative findings, concurrent operations, complications, and patients' outcome.44 patients with cardiac myxoma underwent operation in 20 years . Two patients were excluded from study due to lack of data and finally 42 cases were included in the study. 17 (40.4%) and 25 (59.6%) were male and female cases, respectively, and patients' mean age was 50.6 ± 17 (rang of 13 to 76) .Mean time from diagnosis to operation was 5.8 days (range from 1 to 48 days) and mean postoperative hospital stay was 12.7 days (range 5 to 32 days). Patients' most common complaints were dyspnea in 23 patients (54.8%), dyspnea with palpitation in 12 cases (28.5%), palpitation in 5 patients (11.9%), weight loss in 9 patients (21.4%), and 3 patients admitted in hospital with embolic events .Six patients were in NYHA class I (14.3%), 17 patients in class II (40.5%), 14 patients in class III (33.3%), and 4 patients in NYHA class IV (9.5%). Three patients had a history of cerebral emboli (CVA or TIA) .Transthoracic echocardiography (TTE) was the primary diagnostic modality in all patients; indeed in 22 patients (52.4%) TTE was the only diagnostic tool but in 5 patients (11.9%) transoesophageal echocardiography (TEE) was used as well. In 19 patients (45.23%) coronary angiography was used to rule out concurrent coronary artery disease . In addiLaboratory findings were charted as mean WBC: 8294 ± 280 , mean HCT: 38.56 ± 5.38% ; ESR and CRP were also checked; however, in some patients these data had not been checked, so to analyze these data was out of value.Almost all tumors were primary  compared to one recurrent case (2.4%) .Tumors were primary in 41 patients (97.6%) and recurrent in one patient (2.4%) . Tumors'After tumor removal, septal defect was repaired primarily in 22 cases (52.4%) while for 18 cases (42.8%) pericardial patch was applied. In one patient, tumor was resected without any residual defect in septum. Also, for one case tumor had been located in right ventricular outflow tract with extension into pulmonary valve leaflets for which in addition to the tumor right ventricular septal partially resected and pulmonary valve was repaired.Along with tumor removal mitral valve replacement was performed in two patients . Mitral annuloplasty was done in two patients as well (due to severe MR) and one patient underwent CABG concurrent with tumor resection.Patients were followed up for a mean time of 48.8 months (range 1–82 months).there was post-CPR loss of vision in ICU in one patient (after cardiac arrest);there was heart block in two cases, a complete and a partial one which were managed with and without pacemaker, respectively;because of huge tumor size and chronic illness one patient experienced congestive heart failure;secondary to tumor emboli two patients developed cerebral complications (hemiplegia and aphasia);in one patient that postembolic coma was developed having many late complications including low LOC, prolonged mechanical ventilation, tracheotomy, blue toe, and bed sore;one month after discharging from hospital one patient died due to noncardiac problems ;Preoperative CVA and pneumonia resulted in postoperative death in one case .33 patients (78.4%) were discharged postoperatively from hospital without any complication. Postoperative complications wereDischarging from hospital 33 patients (78.4%) had NSR . On the other hand, some others suffered from different dysrhythmia. AF: 4 patients, partial heart block: 3 patients, PAT with heart block: 1 patient and one patient had complete heart block.Mean tumors' size was 5.22 ± 1.6 cm (range of 2.2 to 8.2 cm).Cardiac myxoma is the most important cardiac tumor. Its annual incidence is 5 in one million people. Each cardiac surgery center encounters one to two of this rare disease in year .There were 42 cardiac myxomas in our hospital in last 20 years (incidence rate: 2.1 per year). Meanwhile in Middle East no precise statistic records about this tumor prevalence are at hand. However, there is a report of 35 cases in 5-year period (7 cases in each year) in Tabriz [Zheng et al. reported 66 cardiac myxoma cases within 26 years in China (2.5 cases per year) . So far,All referral literatures emphasize female predominance , 8 and iThese recent trends show a change in gender predominance which necessitates further study. According to many literatures disease clinical manifestations are evident in 3rd to 6th decades of life . In our In our study mean time from diagnosis to operation was 5.83 days (range of 1 to 48 days) and most operations were performed in one or two days after diagnosis.Since the disease is naturally lethal and it requires urgent cardiac operation, there was no report of waiting time to operation in most cardiac surgical centers (8–10% of patients die while waiting for operation) , 5.Common causes of delay in operation are patients' fear of operation, waiting for more diagnostic modalities such as coronary angiography, CT scan and TEE, and finally long waiting list in public hospitals . In our Most common clinical symptoms in this study were dyspnea, dyspnea with palpitation and chest pain which were similar to other studies –6. AlthoIn all patients primary diagnostic modality was TTE. For 5 of them additionally TEE was conducted as well. Depending on patient's age, coronary angiography was applied to evaluate atherosclerosis (in 19 patients) leading to one concurrent CABG and myxoma operation. Although TEE can diagnose small tumors of 1–3 mm diameter, waiting for TEE can delay operation up to two weeks. So, it is not clear whether delay for TEE is beneficial for patient or not; also it is not certain if this delay favors or changes operation method.Except one recurrent case (2.4%) who had a familial cancer history all myxomas were primary. Nearly 5% of myxomas are familial , they are mainly younger patients, and there is not gender predominance in this group , 10.In 20% of them , tumor originates from atrium and ventricle. This group have abnormal DNA chromosomal genotype pattern , 6, 8. IThere is no general agreement about repairing septal defect after tumor resection. Many surgeons repair it with artificial patches such as Dacron , 14, 15 We prefer to repair septal defect with pericardial patch. In our center, septal defects were repaired with pericardial patch in 42.8% and with primary approach in 52.4% of cases. In one case with myxoma located on ventricular septum tumor was excised with partial septal resection .In some occasions other cardiac operations are concurrently essential. We experienced a concurrent CABG, one pulmonary valve repair, two mitral valve repairs, and two mitral valve replacements. There are reports of concurrent CABG  and CABGLike other literatures, we witnessed postoperative arrhythmia after septal removal (21.42%) , 5, 13.While average hospital mortality is around 5% , 5, 10 wMyxoma tumors' prevalence in Iran was the same as that in other countries in the Middle East; however, its rate is less than that in East of Asia and more than that in Europe. These recent results indicate a change gender predominance, mean time from diagnosis to operation was too long. The patients had more preoperative embolic events and preoperative complications. In terms of size and location it was approximately parallel to other literatures.AS vague chest pain and remote embolic events can raise doubt about myxoma existence. We recommended that in all patients with these findings myxoma should be ruled out.


Aging is associated with structural and functional changes in the immune system which may be responsible for a higher incidence of infection in the elderly.The aim of the study was to assess the prevalence of infections among elderly students of the Academy of Healthy Ageing and to establish factors associated with frequent infections.The questionnaire including questions about infections, medication, comorbidities and socio-economic background was filled by 157 students  of Academy of Healthy Ageing, one of the initiatives of the Healthy Ageing Research Centre. Univariate and multivariate logistic regression analysis was used to establish factors associated with frequent respiratory, urinary and cutaneous infections.At least one infections of respiratory system during last year were reported by 71% of elderly students. The mean number of infections was 3.2 per patient. Herpes simplex infection was reported by 40% of students (mean number 0.9) and 32% study participants had urinary tract infections (mean number 0.74). Frequent respiratory, urinary and cutaneous infections were reported by of 45.2%, 10.2% and 14% of students respectively. 37% of elderly were treated with antibiotics at least once during past year, and only 2% of study subjects were hospitalized due to infection.The risk factors for frequent (defined as more than 3 per year) respiratory infections in multivariate analysis were inflammatory arthritides  OR=1.64 (CI95% 1.01-2.67) and polytherapy (more than 5 prescription drugs) (OR=1.93 (CI95% 1.11-3.36). Multivariate analysis did not reveal the risk factors for frequent infections of urinary tract or Herpes simplex infection. In univariate analysis frequent urinary tract infections were associated with diabetes (OR=2.32 (CI95% 1.26-4.27)) and anti-diabetic treatment (OR=2.35(CI95%1.21-4.6)).Frequent infections among elderly students of the Academy of Healthy Ageing are associated with certain comorbidities and medications used.


Deficiencies of terminal components of complement have been described in patients affected by meningococcal meningitis. The need of routine investigation has to be established. We evaluated patients with confirmed meningitis due to N. meningitides looking for complement system evaluation.Prospective study in which data and blood samples of patients with confirmed meningococcal meningitis were collected. Hemolytic assays, CH50 and APH50, for classical and alternative pathways respectively, ELISA for properdin and mannose binding lectin (MBL) were performed. Specific components were evaluated after confirmed impairment of complement system.A hundred and twenty nine patients (69M:60F) were included in the study. The age of the patients ranged from 2 months (m) up to 64 years old . The following serogroups were identified: type C, 36.4%; B, 20.2%; W135, 1.5% and 41.9% had no serogroup identified. CH50 and AP50 values were below the reference levels in 48 patients (37.2%) and 97 patients (75.2%), and the activity was undetectable in 5 and 15 patients, respectively. Levels of CH50 and AP50 were both low in 46 patients (33.65%) and in 8 were both undetectable. Properdin levels were performed in patients with low AP50 (n = 44) and 43.2% had decreased properdin value. MBL values were below 50 micrograms in 2/26 patients evaluated. One patient was diagnosed with C6 deficiency after the second meningitis.Although high number of patients had low levels of complement evaluation, it probably represents activation of the system due to meningitis. The study suggests the need of complement evaluation but a period after the acute infection would be more reliable to establish real complement defect.


Fonsecaea nubica was described in 2010 as a molecular sibling of F. monophora, an established agent of the human skin disease chomoblastomycosis in tropical zones. Genome analysis of these pathogens is mandatory to identify genes involved in the interaction with host and virulence.On the basis of multilocus phylogenetic data,  Fonsecaea comprises anamorph members in the Chaetothyriales, an ascomycete order of black yeasts and filamentous relatives covering numerous opportunistic pathogens on humans  method with phenol-chloroform/isoamyl alcohol. Total DNA was purified with the microbial DNA UltraClean kit. DNA of F. nubica was used for library construction using the Ion Plus Fragment library kit  and Nextera XT (Illumina) following the manufacturer’s instructions. The libraries were sequenced on an Ion Proton  for single-end reads and in Miseq (Illumina) for paired-end reads. The quality of the reads was assessed by means of FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc). The reads were assembled de novo using SPADES v3.6.2 (Strain S v3.6.2 . The draS v3.6.2 . AnnotatS v3.6.2  and InteS v3.6.2  comparisS v3.6.2 .Information about the genome sequence of this black yeast might provide a better understanding of the basic mechanisms of adaptation to requirements of the environmental habitat, and of pathogenicity and virulence.LVCJ00000000. The version described in this paper is version LVCJ01000000.This whole-genome shotgun project has been deposited in DDBJ/ENA/GenBank under accession number


To analyze the contribution of multiparametric MRI and PCA3 assay, pre- decision of initial biopsy in PSA level between 3-10 ng/mL patients with normal digital rectal examination(DRE). PSA level 3-10 ng/mL ,patients, with normal DRE results and no previous prostate biopsy history, were included in this study. Each patient underwent multiparametric MRI one week before biopsy. Urine sample taking for PCA3 examination preceded the biopsy. Systematic and targeted biopsies were conducted. Patients with high PSA levels were seperated into two groups as: high PCA3 scored and low PCA3 scored. Then each group was divided into two sub-groups as: MRI lesion positive and negative. Tumor incidence, positive predictive values(PPV) and negative predictive values(NPV) were calculated. 53 patients were included between February 2013 and March 2014.Mean age 61.22 ± 1.06. Mean PSA value 5.13 ± 0.19 ng / mL. Mean PCA3 score 98.01 ± 23.13 and mean prostate size was 48.96 ± 2.67 grams. Fourty nine patients had both PCA3 score and multiparametric MRI. The PCA3’s PPV value was 58.33%. If multiparametric MRI lesions are added to high PCA3 scores , the PPV appears to elevate to 91.66%. NPV of PCA3 was 96%. NPV was 95% when there was no lesion in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% , specificity was 95% respectively. Adding multimetric MRI can also support biopsy decision for patients with high PCA3 value. When PCA3 value is low, patients can be survailled without any need to take a MRI. Prostate cancer (CaP) is the most commonly diagnosed cancer in men . CaP diaIn our study, we investigated the collective benefits of PCA3 and multiparametric MRI for grey area patients whose DRE are normal and serum PSA values are between 3-10ng/mL before initial biopsy decision.The study was planned as a prospective and single-centered. Consent of the local ethics committee for this study was taken with B.30.2.IST.0.30.90.00/16077 numbered decree of Dean of the Cerrahpasa Faculty of Medicine Clinical Research Ethics Committee in 8 June 2012. Serum PSA level 3-10ng/mL patients with normal digital rectal examination scheduled for initial prostate biopsy were included in the study between February 2013 and March 2014. Each patient underwent multiparametric MRI a week before biopsy. After 3-minute prostate massage 20-30mL initial urine sample for PCA3 examination were taken pre-biopsy.Although biopsy was performed schematically, additional cores were taken from lesions shown in the multiparametric MRI.Each patient underwent multiparametric MRI evaluation one week before biopsy. Siemens Avanto 1.5 Tesla MRI equipment was used. T2 sequence MRI, diffusion MRI, dynamic contrast-enhanced MRI and MRI spectroscopy were evaluated in multiparametric MRI. Intensity loss regions in T2 sequence MRI, diffusion loss zones in diffusion MRI, contrast involvement and after the early wash-out common areas in dynamic contrast-enhanced MRI, (choline+creatine)/citrate>3SD (this ratio is above 0.86) regions in spectroscopic MRI were considered to be significant. Biopsies were directed to these regions, described and accepted as significant by at least two MRI methods and multiparametric MRI.Initial 20-30cc urine sample after 3 minutes prostatic massage was taken from each patient before the biopsy. Massage from lateral to medial and from baseline through the apex was conducted. After urine was centrifuged within 15 minutes, supernatant section was discarded and RNA preservative was added for later work. The mix was stored at-80ºC. PCA3 study was done with real time multiplex PCR posteriorly (PCA3 mRNA copy number/PSA mRNA copy number) X 1000 formula was used for PCA3 score calculation  patients. Tumor detected mean cores was 3.21±0.45. ASAP was found in two patients, Gleason 3+3 PCa in thirteen patients and Gleason 3+4 PCa in four patients. None of the patients had Gleason 4+3 or above tumor grade. Two patients’ second biopsy conducted after two months was reported as benign, whose first biopsies were ASAP. As the second biopsies were benign, these two patient’s results were accepted as benign for further evaluation.Fifty patient’s urine samples were suitable for PCA3 evaluation. Prostate cancer was detected in 15 of them. PCA3 scores were over 35 in 25 patients. In 14 (56%) of these 25 patients tumor was detected. PCA3 score was low in 25 patients. In 1 (4%) of these 25 patients, tumor was detected. Tumor of this patient was present in 1 core and Gleason score was 3+3.In patients with high PCA3 score tumor detection rate was high and statistically significant (p=0.0001) .In our survey PCA3’s sensitivity was 93.33%, specificity 68.57% for the threshold of PCA3 of 35. PCA3’ s positive predictive value was 56%, and negative predictive value was 96%. PCA3 score was not related to prostate volume and patient’s age .PCA3 score was not significantly different between Gleason score 3+3 and 3+4 tumors .Multiparametric MRI lesions were detected in 18 patients (when seen at least in two MRI they were accepted as multiparametric MRI lesion). Twelve tumors were screened in 18 lesions (66.6%). Twenty nine lesion negative patients among 34 had no tumor (85.2%).Significantly more tumors were found in the MRI lesion positive patients than MRI lesion negative patients (p=0.0001) . SensitiPatients with both PCA3 score and multiparametric MRI available totaled 49. There were 24 patients with high PCA3 scores. Fourteen of these patients had tumors. Accordingly, the PCA3’s positive predictive value detected was 58.33%. Twelve patients had both high PCA3 score and multiparametric MRI lesion and tumor was detected in 11 of these. Our study revealed that if multiparametric MRI lesions are added to high PCA3 scores, the positive predictive value appears to increase to 91.66%.There were 25 patients with normal PCA3 scores and only one patient had tumor whereas 24 patients didn’t. Accordingly, the negative predictive value of PCA3 was calculated as 96%. In 20 of these 25 patients, any MRI lesion was observed. Of these patients, tumor was detected in only one patient. Negative predictive value was calculated as 95% when no lesion existed in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% and specificity was 95% respectively .The systematic TRUS-guided prostate biopsy still continue to be the standard method when cancer is suspected . HoweverNowadays PCA3 is usually used to decide on second biopsy in patients with continuous PSA elevation whose first biopsies were reported as benign . ConsideIn our survey PCA3’s sensitivity was 93.33% and specificity was 68.57% for the threshold of PCA3 35. PCA3’ s positive predictive value was 56%, and negative predictive value was 96%. In the literature, it’s stated that sensitivity was 47-69%, and specificity ranged from 72 to 79% , 15. In Also PCA3 wasn’t related with age and prostate volume . This can represent that PCA3 is superior to PSA. In our study, detected tumor’s Gleason scores were 6 and 7. No difference was detected between the Gleason scores for PCA3 . There was also no difference between the high grade tumors and low grade tumors for PCA3 in Leyten and his colleague’s study . Unlike MRI can be used in several areas of prostate cancer diagnosis and treatment. MRI can be used in patients with ongoing high PSA whose previous biopsy resulted benign, before the second biopsy, to increase the success, to preoperative evaluation of the tumor relationship neurovascular bundles, radiotherapy planning, in focal treatment planning, and for patients undergoing active surveillance .In addition to these areas, today MRI is used before the initial biopsy decision to increase the biopsy success. Although various MRI methods are used, the most sensitive and specific method is multiparametric MRI which is a combination of several multiparametric MRI methods . In our There is no study which determines combined benefits of PCA3 score and multiparametric MRI in this patient group in the literature. Fourty nine patients had both PCA3 score and multiparametric MRI available. There were 24 patients with high PCA3 score and fourteen of these patients (58.3%) had tumors. Twelve patients had both high PCA3 score and multiparametric MRI lesion. Tumor was detected in 11 of 12 patients. Our study showed that if multiparametric MRI lesions are added to high PCA3 scores, the positive predictive value appears to increase to 91.66%. There were 25 patients with a normal PCA3 score. Of these 25 patients, only one patient had tumor. Accordingly, the negative predictive value of PCA3 was calculated as 96%. Fradet and colleagues stated that PCA3 positive predictive value was 75% and negative predictive value 84% . In TinzNo lesion was observed in MRI of 20 of 25 patients with normal PCA3 score. Among these patients, tumor was detected only in one patient. Negative predictive value was calculated 95% (no lesion in multiparametric MRI with low PCA3 scores). Sensitivity was 91.66% and specificity 95%.Our study revealed that using only PSA score for tumor detection, accuracy rate is 35.9%, but this rate raised to 58.33% by adding PCA3. PCA3 score, along with multiparametric MRI findings, elevated this rate to 91.66%. Likewise, in this study we observed that NPV was calculated as 96% using the PCA3 score (<35). There wasn’t any increase in the NPV when we added absence of lesions in the multiparametric MRI. Thus, our data suggest that when patient’s PCA3 is low (<35), we can affirm there is no tumor with 96% of accuracy without MRI study.In patients with PSA level between 3-10ng/mL and normal DRE, PCA3 score and multiparametric MRI seems to provide additional contributions to first biopsy decision for the detection of prostate cancer. When these methods and approaches are combined used, PPV is significantly increased for predicting tumor presence.


The role of CD4+CD25+ T regulatory cells (Tregs) in immune tolerance in experimental transplantation is very important but the clinical significance of circulating Tregs in the peripheral blood is undetermined. We evaluated the association between the frequency of T cell activation markers CD25 and CD71 and clinical parameters that may affect the level of these T cell markers.1) anti-thymocyte globulin (THYMO) group (n =29) and Basiliximab (BSX) group (n=10).In 47peditric kidney transplant (KT) recipients and 20 healthy controls, the frequency of T cell activation markers, CD25 and CD71 was measured with flow cytometry after transplantation. Two clinical protocols of induction immunosuppression were used:  decreased the frequency of CD25 but mammalian target rapamycin (mTOR) inhibitor did not. The proportion of CD25 significantly decreased in THYMO group during the first year after transplantation.The frequency of circulating T cell activation marker CD25 in pediatric KT recipients is strongly affected by CNIs, and a high frequency of CD25 is associated with acute rejection during the early posttransplant period. The measurement of T cell activation markers, may become a useful immune monitoring tool after kidney transplantation. Maintaining long-term allograft survival is a main role in organ transplantation. Transplant tolerance might be a way, to both reduce rejection and minimize immunosuppressive side effects, therefore improving graft outcome. A better understanding of basic tolerogenic mechanisms  as well as the capital role that T cells play during transplant rejection has resulted in different strategies trying to induce tolerance –4; namelTreg have been described as specialized T lymphocytes that are able to suppress immune responses to self- and nonself-antigens. Multiple populations of Treg have been described , includiSubsequently, Treg were also shown to play an important role in the development and maintenance of transplantation tolerance in experimental models . In humae.g., in heart transplant recipients experiencing acute rejection (AR)  .After trion (AR) , 18. Treion (AR) , 20; howet al -related nephrotoxicity, and transplant glomerulopathy . In ordeet al  showed tet al . The maiTotal of 47 consecutive pediatric kidney transplant (KTx) recipients were studied. As controls, 20 healthy controls  were included. All transplant recipients received an allograft at the Center of Pediatric Nephrology and Transplantation (CPNT), Children’s Hospital, Cairo University, Egypt. Healthy children were recruited from the Pediatric Clinic of the National Research Centre (NRC). The time elapsed from the time of transplantation to the point of the study is 2.39 ± 0.97 yrs (range 0.5-4.5 yrs). Peripheral blood samples were obtained in HC and KT recipients. In kidney transplantation, blood sample was withdrawn after transplantation. In patients having episodes of acute rejection, the samples were taken during the period of rejection.All of the patients gave informed written consent before participating in the study, which was read and approved by the Ethics Committee of NRC in Egypt.All children received intravenous methylprednisolone (12.5-30 mg per day) on the first month of transplantation, and then oral prednisolone was tapered down to 2.5-7.5 mg/day on the first year of transplantation. We divided the KT patients into 4 groups according to their clinical status and immunosuppression: 1-FK group n=24) stable patients ; they w stable pInitial CsA dose was 10 mg/kg per day by oral route (100-400 mg/day), and target trough levels were ranged from 66 to154 ng/mL in the CsA based immunosuppression. Initial FK506 dose was 0.16 mg/kg per day by oral route (1.5-6 mg/day), and target trough levels were 3-14 ng/mL in the first 3 months and 4.5 ng/mL in the FK506/everolimus group. Initial dose of MMF was 360-1000mg/day, and dose was modified based on adverse effects such as diarrhea or leucopenia. IL-2 receptor blocking antibody  , was given to 10 patients (BSX group) (CsA or FK506 based immunesuppression) 4 hrs before and 3 days after renal transplantation (two 20-mg doses). Anti-thymocyte globulin (ATG)  was given to 29 patients (THYMO group) (CsA or FK506 based immunesuppression) from days 0 to 3 , Everolimus was administered 2 mg per day and sirolimus was loaded 6 mg per day and then adjusted dose of 2 mg/day was maintained with target trough level of 5-15 ng/mL.vs. unrelated), subclinical acute rejection (AR), episode of cytomegalovirus (CMV) infection), graft function and cyclosporine/FK506 serum concentrations were evaluated. The diagnosis of CMV infection was made when copy number of by real time polymerase chain reaction (RT-PCR) is more than 2,000 copies/mL or with tissue biopsy.The potential factors which may affect surface markers CD25 and CD71were included. The number of HLA mismatch, the living donor  with monoclonal antibodies were incubated 20’ in the room temperature in the dark. Samples were lysed with 0.5 ml lysing solution Optilyse C  10’ the room temperature in the dark. Lysing reaction was stopped with 1 ml Cell Wash (optimized PBS) , the pellet suspended in PBS and kept in dark between 2-8°C. Samples were measured on a FC 500 flow cytometer .Gating strategy: As described before , 27 cellp value of < 0.05 was considered statistically significant.Statistical package for social science (SPSS) program version 16.0 was used for analysis of data. Data were summarized as mean ± SD, range or percentage. Histograms and normality plots were used for evaluating the normality of data. For those data with skewed distribution, log transformation was performed before a t-test. Data were valuated between the experimental groups by One-Way Analysis of Variance (ANOVA) or by independent t-test. A Clinical Characteristics. The demographics of the 47 KTx are summarized in Table P=0.66). Also when analyzing the various study groups, the percentage of CD71 between the patients groups was not statistically different (p=0.82).For patients with CAN (n=3): the mean recipient age at transplant was10.67 ± 3.10 yrs., while the donor age was37.00 ± 4.36 yrs. The donor organ source was 2 (66.67%), living, related and 1(33.33%) living, unrelated. The number of HLA mismatch was 2.67 ± 0.58. The immunosuppression at the time of the study was FK506, MMF and prednisone . No significant difference was found between KTx children and healthy controls as regard to percentage of the other T-cell activation marker, ie, CD71  as compared with the 20 healthy controls  . Similar finding was observed in the CsA group (p=0.02). The 2 cases that received the FK/ mTORi IS regimen had 24.00 ± 1.41% of circulating CD25 with 95% confidence interval from -23.68 to 6.51. However, they did not show any significant difference in the circulating CD25 percentage as regards to controls (p=0.26). For the 3 patients with CAN the percentage of CD25 was 26.27 ± 6.11% and was also not statistically significant as compared to control (p=0.33).Figure vs 24.68 ± 10.08%, p=0.20)  , CsA and FK506, affected the circulating CD25 percentage. The children with CsA high levels (≥100 ng/mL) had insignificantly lower levels of CD25 than those with low CsAlevels (<100 ng/mL) (17.98 ± 6.24% ) Figure ; however) Figure .p=0.04)  Fig. . So we a04) Fig. . There wFigure Thirty-nine patients were enrolled, all receiving a first kidney transplant.1) THYMO group (n=29) and BSX group (n=10). When analyzing the two study groups, the percentage of CD25 between patients groups was not statistically different; they were found to represent 22.73 ± 9.70% in THYMO group and 23.42 ± 9.64% in BSX group (P=0.75). Of note, the THYMO group had significantly lower values as compared to controls (p=0.005), while CD25 values in BSX group was not statistically different as compared to controls (p=0.06).Two clinical protocols were used: . The results of our study demonstrate that the frequency of circulating CD25 during the posttransplant period in pediatric renal transplant recipients is affected by the type of immunosuppressant treatment and associated with acute rejection. This finding suggests that circulating CD25 expression may be used as a surrogate marker for assessing immune status of renal transplant recipients during the early posttransplant period.We found that the overall percentages of CD25 T-cells were significantly lower in all KTx to a comparable extent when compared to the controls values. The activation of Tregs depends on the engagement of the T-cell receptor and the presence of IL-2 signaling , 29. Thein vivo , infectious factors  and allograft function . The results of our study revealed that the frequency of circulating CD25 has no significant association with these clinical parameters except acute rejection which showed high percentage of T cell activation marker i.e.CD25. During acute rejection of kidney allografts, an augmented FOXP3 gene expression as well as increased CD4g others . Overallet al.  may be useful in the diagnosis of graft rejection as well as during the so-called IS minimization strategies.In summary, monitoring of circulating T cell activation marker i.e. CD25 in peripheral blood is helpful for evaluating the immune status of kidney transplant recipients during the early posttransplant period. We demonstrated that expression of CD 25 on peripheral blood T cells correlates closely with the presence of acute graft rejection in renal allograft pediatric recipients. Measurement of this surface marker may provide a rapid, noninvasive, and accurate means by which graft rejection can be identified. The data presented here provide the scientific basis for implementing the monitoring of T cell activation marker CD25 in large prospective clinical studies. Prospective monitoring of T cell activation marker CD25 (


Aim. To determine the prevalence of HIV infection among patients seen at the surgical oncology unit of Donka . Method. We conducted a retrospective and descriptive study of HIV infection in cancer patients from May 2007 to December 2012. Social characteristics  and immune status  were reviewed. Results. Out of 2598 cancer patients, 54 (2.1%) tested positive for HIV. There were 11 (20.4%) defining AIDS and 43 (79.6%) nondefining AIDS cancers. The most frequent cancers were breast (14) (26.0%), non-Hodgkin lymphoma (6) (11.1%), liver (6) (11.1%), eye and annexes (6) (11.1%), and cervical cancer (5) (9.3%). These patients were female in 34 (63.0%) and had a median age of 39 years and body mass index was 20,3 Kg/m2. They were unschooled in 40 (74.1%) and married in 35 (64.8%). CD4 count showed a median of 317 cells/mL. Antiretroviral treatment was performed in 40 (74.1%). Conclusion. HIV prevalence is higher in patients in our unit of surgical oncology. Breast cancer was the most common in this association. A national survey of a large sample is needed to determine the true prevalence and impact of HIV on cancer prognosis.  While opportunistic infections continue to be enameled care of patients infected with acquired immunodeficiency, cancer remains overlooked in the care of these patients in developing countries.According to Center Disease Control (CDC) , the revThe occurrence of malignant tumors in patients with HIV infection currently represents for years to come one of the most difficult and controversial challenges of therapeutic management of these patients . As of 2Indeed, 30 to 40% of patients infected with HIV are likely to develop cancer about their disease .The widespread use of antiretroviral therapy (ARV) in industrialized countries since the mid-1990s led to a dramatic decrease in mortality of patients with HIV infection and incidence of opportunistic infections .However, antiretroviral treatment types HAART also had a significant impact on the natural history of HIV-associated malignancies .A US study found an increase in median survival of AIDS patients from 11.3 months before 1985 to 12.5 months in 1986 to 20.8 months in 1987 for AIDS cases diagnosed in Washington [In France, a study showed that, out of a total of 964 recorded deaths, 149 were attributed to the type of AIDS defining cancers .According to the Regional Office for Africa of WHO, 64% of new cancer cases worldwide are registered in developing countries .Sub-Saharan African countries have experienced nearly 600,000 deaths in 2008 related to tumors. If this epidemiological trend continues due to longer life expectancy and increased exposure to tobacco, Africa will have by 2020 from 800,000 to 1,000,000 new cases of cancer each year , 11.5 inhabitants in West Africa and 90.0 per 105 in Guinea [The cancer incidence rate is estimated at 95.5 cases per 10n Guinea . As in mThere is very little data available on the prevalence of HIV infection in cancer patients in West Africa, especially in our country. It is therefore important to have a first database that will guide future investigations.This study aims to determine the prevalence of HIV infection among patients seen at the surgical oncology unit of Donka.Data from this study were obtained from the hospital and came from surgical oncology unit of Donka national hospital, teaching hospital of Conakry (Guinea).The study involved the records of cancer patients followed with HIV infection from May 2007 to December 2012.The status of HIV infection was determined by the Western blot method. This checkup has become routine for any cancer patient received in our unit since January 2009.CD4 count was requested for HIV positive patients.All patients were referred to antiretroviral treatment center for treatment of immune status.The prevalence has been determined according to the number of patients and pathology subject of consultation or follow-up. Pathologies associated with HIV have been classified into malignant, benign, and inflammatory diseases.Social characteristics  and immune status  were reviewed according malignant tumor pathologies, divided into defining AIDS and nondefining AIDS cancers. Gynecological history  was determined in women with breast cancer.p was less than 0.05.This was descriptive and retrospective study. The qualitative variables were presented and analyzed in percentage. The median with interquartile range (IQR) was calculated for the quantitative variables. Defining AIDS and nondefining AIDS cancers were compared in relation to patient age. ANNOVA test was performed and was significant if Out of 3143 patients received from May 2007 to December 2012, 69 (2.2%) tested positive for HIV in our unit. This proportion was 12 (1.9%) of 625 patients from 2007 to 2008 and 57 (2.3%) of 2518 patients from 2009 to 2012.Of the 64 HIV-infected patients, 54 (78.3%) had a malignant tumor, 8 (11.6%) of benign and 7 (10.1%) of inflammatory tumors .The prevalence of HIV in cancer patients was 54 on 2598 cases (2.1%). Of the 54 cases of cancers associated with HIV, there were 11 (20.4%) defining AIDS and 43 (79.6%) nondefining AIDS.p = 0.007).These patients were female in 34 (63.0%). Cancer patients had a median age of 39 (IQR 31–48) against 32 (IQR 25–38) for noncancer patients. This median age was different about defining AIDS status: 33 (25.0–40.0) versus 39 (IQR 35.7–50.0) (2 (IQR 17.7–21.8). They were unschooled in 40 (74.1%) and married in 35 (64.8%). Tobacco use was found in 13 (24.1%) and alcohol consumption in 14 (20.2%).Their body mass index was 20,4 Kg/mAll patients were infected with HIV type 1. CD4 count, performed in 22 patients, showed a median of 317 cells/mL (IQR 246.2–534.2). Antiretroviral treatment was performed in 40 (74.1%) patients of which it was performed in 39 only after the cancer diagnosis.Breast cancer (6) (11.1%), followed by cancer of the liver (6) (11.1%), and eye and annexes (6) (11.1%) were leading nondefining AIDS cancers.Patients with breast cancer had a median age of 14.0 years (IQR 12.5–15.0) at menarche and 22.0 years (IQR 17.0–25.0) in the first full term pregnancy; and they had 1.0 full pregnancy in term (IQR 0.5–3.0).This preliminary study shows a high prevalence (2.1%) of the HIV infection in patients with cancer in our surgical oncology unit. This prevalence appeared to be higher than in the general population in Guinea (1.5%)  but loweInversely, 30–40% of those HIV-infected patients are at risk of cancer . Risk ofIn this study, non-AIDS defining cancers were more frequent than defining AIDS cancers (77.8% versus 22.2%). This could be explained partly by the decrease in the number of cancer cases defining AIDS since the beginning of antiretroviral therapy as supported by Yanik et al. in the US . Also, KBreast cancer is the most common of nondefining AIDS cancers. This predominance of breast cancer among nondefining AIDS cancers is reported by studies in sub-Saharan Africa , 22. TheWe noted a female predominance and patients were younger. However, cancer patients were older than those who did not have cancer. Conversely, those with AIDS classifying cancer were younger than those who had a non-AIDS defining illness cancer. The female gender and the young age of patients are already reported by several authors , 21. UnsThis study has some limitations related to the CD4 count and ART coverage. This could be related to the irregular availability of reagents for CD4 and antiretroviral despite their free access in our country. CD4 count, carried out for 22 cases out of 54, showed no difference in the depth of immunosuppression that cancer is either AIDS defining or not. For defining AIDS cancers, there is no doubt that the risk is higher in the case of lower CD4 count (<200 cells/mL) , 25. HowThat is why a national prospective study is needed to determine the true prevalence of cancer among people living with HIV. It will also be important to determine whether HIV changes the risk factors, clinicopathological futures, and prognosis of these cancers.HIV prevalence is higher in patients in our unit of surgical oncology. Breast cancer is the most common in this association. A national survey of a large sample is needed to determine the true prevalence and impact of HIV on cancer prognosis.


Purpose. This study evaluated the efficacy of 50% autologous serum eye drops in ocular surface diseases not improved by conventional therapy. Methods. We analyzed two groups: (1) acute eye pathologies  and (2) chronic eye pathologies . The patients were treated for surface instability after conventional therapy. The patients received therapy 5 times a day until stabilization of the framework; they then reduced therapy to 3 times a day for at least 3 months. We analyzed the best corrected visual acuity, epithelial defects, inflammation, corneal opacity, and corneal neovascularization. We also analyzed symptoms such as tearing, burning, sense of foreign body or sand, photophobia, blurred vision, and difficulty opening the eyelids. Results. We enrolled 15 eyes in group 1 and 11 eyes in group 2. The average therapy period was 16 ± 5.86 weeks in group 1 and 30.54 ± 20.33 weeks in group 2. The epithelial defects all resolved. Signs and symptoms improved in both groups. In group 2, the defect recurred after the suspension of therapy in 2 (18%) patients; in group 1, no defects recurred. Conclusions. Autologous serum eye drops effectively stabilize and improve signs and symptoms in eyes previously treated with conventional therapy. The ocular surface is a morphofunctional unit that owes its action to the perfect cooperation of all its structures  . In partβ (TGF-β), which is involved in the epithelial and stromal repair process . We trGroup 2 included patients with chronic diseases that were unresponsive to conventional therapy . The treatment in this group was 5 times a day for 3 months and then was reduced progressively to 3 times a day for 3 months until the absence of symptoms. An antibiotic (moxifloxacin/netilmicin/tobramycin) was administered 4 times a day until the closing of the epithelial defect. No other supportive therapies were used during the treatment period. For each patient, the specialist could modify the therapy whenever necessary. The change was registered and justified.Autologous serum drops were produced in the following manner. A total of 200 mL of blood was procured by venipuncture and collected in a sterile container. The blood was allowed to stand for 24–48 h at 4°C to allow clotting. The blood was centrifuged at 4000 rpm for 10 min. The serum was separated from the blood and diluted with saline to 50% in a laminar flow cabinet. At this point, the product was quarantined until the outcome of the sterility test performed by the Laboratory of Microbiology of the AO Civil Hospital of Brescia . The final product was formed from an average of 288 single-dose eye drops for venipuncture. Single-application packs were packed in bags of 20 and marked with a label plate.At −30°C, the product is preserved for 6 months from the date of withdrawal. From the time of delivery, the product is stored at a destination  at −20°C for a period not exceeding 3 months from the date of delivery and no later than the expiration date stated on the label. If the entire production process is successful, the eye drops are validated, which takes into account negative serology examinations, group control transmitted and validated by the Emonet management system , and negative results of sterility control.Statistical Analysis. The data were recorded on a predesigned pro forma and managed on a spreadsheet using the Microsoft Excel 2013 software . All entries were checked for errors. Appropriate statistical tests were applied to analyze the results. The t-test was used to determine the significance of changes in subjective symptoms, BCVA, epithelial defects, corneal neovascularization, opacity, and inflammation before and after AS eye inoculation therapy in the 2 groups of patients. The significance (p) was defined as a probability of error <0.01.In this study 28 eyes of 28 patients were enrolled. Two patients dropped out of the study because of the impossibility of obtaining blood samples: the first patient was seropositive for the human immunodeficiency virus and the second patient did not have venous access.Of the 26 eyes of the 26 patients treated with AS, 18 patients were men and 8 were women. The mean age was 39.6 ± 16.47 years  in group 1 and 57.63 ± 16.59 years  in group 2 .Group 1 consisted of 15 eyes  injured by chemical agents of different natures. Group 2  consisted of 11 eyes as follows: 6 eyes with neurotrophic keratopathy, 3 eyes with keratoconjunctivitis sicca not Sjögren, and 2 eyes with keratoconjunctivitis sicca, Sjögren-related.The average therapy period was 22.15 ± 15.44 weeks , 16 ± 5.86 weeks in group 1 and 30.54 ± 20.33 weeks in group 2. Two patients, both in group 2, remain under treatment. visual acuity in group 1 went from 2.4/10 ± 1.91/10 (mean ± standard deviation) to 6.25/10 ± 3.25/10 (P < 0.01) after treatment with an average gain of 4 Snellen lines. In group 2, visual acuity went from 2.96/10 ± 2.04/10 to 4.7/10 ± 3.37/10 (P < 0.01) with an average gain of 2 Snellen lines. The visual acuity improved in 100% of patients ; 100% of patients had corneal opacity (grade 3 in 93% of patients and grade 2 in 7% of patients); and 60% of patients had neovascularization (grade 3 in 33% of patients and grade 2 in 27% of patients).In group 2 before treatment, 100% of patients had corneal inflammation (grade 3 in 64% of patients and grade 2 in 36% of patients); 82% of patients had corneal opacity (grade 3 in 60% of patients and grade 2 in 40% of patients); and 55% of patients had corneal neovascularization  .Evolution of the Clinical Data Epithelial Defects. Epithelial defects were completely resolved (grade 1) by the end of followup in all patients. In 2 patients in group 2, the epithelial defect recurred after the suspension of therapy. One patient was administered a new cycle of AS eye drops that resolved the defect. In the second patient, a tarsorrhaphy was necessary owing to the severity of the ocular disease and the impossibility of restarting AS therapy because of the inability to perform blood sampling due to the patient's worsening condition.Inflammation. After treatment in group 1, the inflammation was grade 1  in 87% of patients and grade 2 in 13% of patients with an improvement of 2 degrees in 58% of patients and 1 degree in 42% of patients. In group 2, inflammation was grade 1  in 81% of patients and grade 2 in 19% of patients with an improvement of 2 degrees in 55% of patients and 1 degree in 45% of patients. All patients improved. The average improvement was 1.60 ± 0.49 degrees in group 1 (P < 0.01) and 1.54 ± 0.50 degrees in group 2 (P < 0.01).Opacity. After treatment in group 1, opacity became grade 1 in 60% of patients and grade 2 in the remaining 40% with an improvement of 2 degrees in 35% of patients and 1 degree in 54% of patients. In group 2, opacity became grade 1 in 55% of patients and grade 2 in 45% of patients. The improvement was 2 degrees in 18% of patients and 1 degree in 64% of patients; by contrast, 2 patients remained stable at grade 2 (these were diabetic patients with neurotrophic keratopathy).P < 0.01) and 0.82 degrees ±0.60 in group 2 (P < 0.01).The average improvement was 1.53 degrees ±0.52 in group 1  and 1.17 degrees ±0.75 in group 2 (P < 0.01).The symptoms reported in group 1 were (in decreasing frequency) burning, feeling a foreign body/sand in the eyes, tearing, photophobia, and blurred vision.Tearing was present in 42% of patients at the first visit: 73% of patients had grade 4 and 27% of patients had grade 3.Burning was present in 73% of patients at first visit: 79% of patients had grade 4, 11% of patients had grade 3, and 10% of patients had grade 2.The sense of sand in the eyes was present in 78% of patients at the first visit: 55% of patients had grade 4 and 45% of patients had grade 3.Photophobia was present in 65% of patients at the first visit: 53% of patients had grade 4, 37% of patients had grade 3, and 10% of patients had grade 2.Blurred vision was present in 73% of patients at the first visit: 48% of patients had grade 4, 48% of patients had grade 3, and 4% of patients had grade 2. the eyelids was present in 42% of patients at the first visit: 64% of patients had grade 4, 27% of patients had grade 3, and 9% of patients had grade 2.Difficulty openingThe most severe symptom was eye burning. The symptoms reported in group 2 (in decreasing frequency) were a sense of a foreign body in the eyes, blurred vision, burning, and photophobia. The feeling of sand in the eyes and blurred vision were the most severe symptoms .Evolution of Symptoms. Tearing at the end of followup was grade 1 in 55% of patients and grade 2 in 45% of patients. There was an improvement of 3 degrees in 36% of patients, 2 degrees in 55% of patients, and 1 degree in 9% of patients. All patients improved. The average improvement was 2.43 ± 0.49 degrees in group 1 (P < 0.01) and 2 ± 0.70 degrees in group 2 (P < 0.01).P < 0.01) and 2.28 ± 0.70 degrees in group 2 (P < 0.01).Burning at the end of followup was grade 1 in 74% of patients, grade 2 in 21% of patients, and grade 3 in 5% of patients. There was an improvement of 3 degrees in 53% of patients, 2 degrees in 32% of patients, and 1 degree in 15% of patients . The average improvement was 2.42 ± 0.76 degrees in group 1 (P < 0.01) and 1.89 ± 0.99 degrees in group 2 (P < 0.01).The sense of sand in the eyes at the end of followup was grade 1 in 75% of patients, grade 2 in 15% of patients, and grade 3 in 10% of patients. There was an improvement of 3 degrees in 40% of patients, 2 degrees in 45% of patients, and 1 degree in 10% of patients; however, 1 (5%) patient with neurotrophic keratopathy showed no improvement. The average improvement was 2.45 ± 0.50 degrees in group 1 (Photophobia at the end of followup was grade 1 in 71% of patients and grade 1 in 29% of patients.P < 0.01) and 1.83 ± 037 degrees in group 2 (P < 0.01).There was an improvement of 3 degrees in 35% of patients, 2 degrees in 47% of patients, and 1 degree in 18% of patients . The average improvement was 2.36 ± 0.77 degrees in group 1 (P < 0.01) and 1.87 ± 0.92 degrees in group 2 (P < 0.01).Blurred vision at the end of followup was grade 1 in 63% of patients, grade 2 in 21% of patients, and grade 3 in 16% of patients. There was an improvement of 3 degrees in 32% of patients, 2 degrees in 37% of patients, 1 degree in 21% of patients, and no improvement in only 2 (10%) patients . The average improvement was 1.91 ± 0.99 degrees in group 1 . The average improvement was 2.5 ± 0.76 degrees in group 1 (P < 0.01) and 2.25 ± 0.83 degrees in group 2 (P < 0.01).Difficulty openingAutologous serum eye drops are actually used in the treatment of many ocular diseases, and many studies have demonstrated the effectiveness of AS eye drops in treating different conditions such as superior limbic keratoconjunctivitis , recurreDespite clinical evidence of the efficacy of AS, a shared protocol for the preparation and the administration of this therapy is lacking because of the bureaucratic and technical difficulties of handling biological materials. The European Union (European Parliament and Council) has issued several directives concerning AS eye drops . However, in the European Union, individual countries regulate the manufacture and distribution of pharmaceuticals, and the use of serum eye drops remains an experimental approach . The marIn addition, there have been few reports that show the efficacy of some blood products such as platelet-rich plasma (PRP) in treating chemical burns , 49. Henβ concentration in human serum is approximately 50 ng/mL, which is 5 times higher than the amount in tears, and TGF-β has antiproliferative effects and high concentrations of this molecule may suppress wound healing of the epithelium [We chose to use 50% AS eye drops instead of other concentrations  used in some works in the literature . This deithelium , 52. Jenithelium  say thatithelium . TherefoThe main focus of the study was to show the clinical success of AS eye drops in the treatment of different ocular surface diseases. All collected data were analyzed complexly and subsequently in 2 distinct groups of pathologies—acute eye pathology  and chronic eye pathology —with the aim of understanding the potential and the efficacy of this therapy.The data analysis showed that all patients achieved a significant improvement in symptoms and all patients had excellent compliance with the treatment. No patient in the current study has reported any adverse effects to date; however, some studies have reported adverse effects . In our Best corrected visual acuity improved in all patients, which was in contrast to the study of Ziakas et al.  Figures. The aveIn primary or secondary tear deficiency, the AS supplies the lacking factors and reestablishes a correct ocular surface balance. This is the situation with dry eyes, Sjögren and non-Sjögren-related. For mild dry eyes, artificial tears, when frequently applied, are usually effective since they are able to reduce symptoms and prevent complications and the progression of damage , 54. HowIn our study, the patients with dry eye syndrome started therapy with AS eye drops because the symptom had not resolved with conventional therapy and they had a long history of chronic inflammation and recurrent epithelial defects leading to infection, opacity, and visual capacity damage . All patIn neurotropic keratopathy, a different mechanism occurs . In thisThe patients with ocular burn represent a different framework in which a single traumatic event, the acid burn, leads to an ocular surface injury with an action at term, but persistent damage. Few studies are available in the literature on chemical burns, and used as a treatment PRP , umbilicThe rationale of using AS in chemical burns derives from the fact that it contains antiproteases such as alpha 2 macroglobulin (which reduces collagenase) and vitamin A  , 67. It β, retinoic acid, and nerve growth factor that are able to promote proliferation and differentiation of limbal corneal epithelium cells.In our casuistry, 5–7 days after injury, all patients had evident signs of corneal suffering with epithelial instability and inflammation that was caused by trophic damage on the cornea and conjunctiva, despite limited limbal deficiency. The study of clinical signs showed that in each patient we attained the primary objective, which was the stabilization of the condition in the absence of inflammation, and a complete restitution of epithelial integrity. The regression of neovascularization in most patients may be because of an increase in trophic factors and a decrease in inflammatory factors. In fact, neovascularization that is formed to provide nourishment disappears quickly if the stimulus ceases. Opacity declined because of the reduction of inflammation and because of stromal remodeling supported by serum factors such as EGF, fibronectin, TGF-All our patients obtained these results, although with different timings between acute and chronic diseases. Chemical burns had a shorter average treatment time. This suggests that chemical injury is reversible and the ocular surface stability can be self-maintained if inflammation is properly reduced and growth factors are rebalanced. We suggest that our patients had a limited limbal ischemia with a largely preserved limbus. None of the chemically burned patients remain in therapy and all patients have a healthy ocular surface.A limitation of our study is the lack of a control arm for the acute group patients. A future goal will be to followup with a control arm treated with anti-inflammatory drugs and artificial tears to make direct comparisons between both therapies in chemical injury.In our casuistry, AS eye drops have been effective in improving and stabilizing signs and symptoms in patients who do not improve with conventional therapy. We believe that a reconfirmation of our findings will be desirable in a larger group of patients in a prospective controlled trial setting. Studies aimed at clarifying the beneficial effects and risks of prolonged application of AS drops at different AS concentrations should also be the subject of future investigations.In addition, a future goal will be to conduct examinations, especially in the composition of tears. This can help scientists understand what factors are decreased in the tears of these patients and how they are decreased and how long AS components can effectively remain in tears after therapy.