Supplemental Digital Content is available in the text FT program (FT) is a multimodal approach used to enhance postoperative rehabilitation and accelerate recovery. It was 1st described in open heart surgery, then modified and applied successfully in colorectal surgery. FT program was described in liver resection for the 1st time in 2008. Although the program has become widely accepted, it has not yet been considered the standard of care in liver surgery.we performed this systematic review and meta-analysis to evaluate the impact of using the FT program compared to the traditional care (TC), on the main clinical and surgical outcomes for patients who underwent elective liver resection.I2 was used to assess the heterogeneity across studies.PubMed/Medline, Scopus, and Cochran databases were searched to identify eligible articles that compared FT with TC in elective liver resection to be included in this study. Subgroup meta-analysis between laparoscopic and open surgical approaches to liver resection was also conducted. Quality assessment was performed for all the included studies. Odds ratios (ORs) and mean differences (MDs) were considered as a summary measure of evaluating the association in this meta-analysis for dichotomous and continuous data, respectively. A 95% confidence interval (CI) was reported for both measures. P < 0.00001). The reduced LoS was accompanied by accelerated functional recovery (P = 0.0008) and decreased hospital costs, with no increase in readmission, morbidity, or mortality rates. Moreover, significant results were found within the FT group such as reduced operative time (P = 0.03), lower intensive care unit admission rate (P < 0.00001), early bowel opening (P ≤ 0.00001), and rapid normal diet restoration (P ≤ 0.00001).From 2008 to 2015, 3 randomized controlled trials (RCTs) and 5 cohort studies were identified, including 394 and 416 patients in the FT and TC groups, respectively. The length of hospital stay (LoS) was markedly shortened in both the open and laparoscopic approaches within the FT program (FT program is safe, feasible, and can be applied successfully in liver resection. Future RCTs on controversial issues such as multimodal analgesia and adherence rate are needed. Specific FT guidelines should be developed for liver resection. Major abdominal surgical procedures such as liver resections cause a considerable surgical stress reaction and possible disturbance of metabolic functions. In addition, liver resection has its specific complications, such as postoperative hemorrhage, biliary leakage, and even liver failure.Fast track (FT) program, recently referred to as the enhanced recovery after surgery program, is considered one of the modern protocols used to reduce morbidity and accelerate convalescence. FT combines various approaches that are used in the care of patients who undergo elective operations. These approaches include preoperative information and education of the patients, avoiding bowel preparation and prolonged fasting, using short-acting anesthesia, keeping normal body temperature, choosing minimally invasive techniques, optimizing perioperative fluid therapy, avoiding insertion of nasogastric tubes and peritoneal drains, pain control, and aggressive postoperative rehabilitation, including early ambulation and enteral nutrition combined with nutritional supplements. The core principle of the FT program lies in the combination of these approaches, aiming for reducing the surgical stress response and organ dysfunction, thereby markedly shortening the time required for a full recovery.Before the introduction of the FT program, no institutions had a written or agreed perioperative care pathway. There were no specific multimodal measures to avoid prolonged perioperative fasting, nasogastric decompression, excessive use of intravenous fluids, prophylactic abdominal drains, and postoperative immobilization. The postoperative traditional care (TC) emphasized prolonged rest for both the patient and the gastrointestinal tract. described the “accelerated recovery” program, which was successfully used to achieve better outcomes in patients who underwent open heart surgery. This program was later termed “fast track” by Engelman et al in 1994. Kehlet modified the program in 1997 and developed a multimodal approach to be applied to different types of interventions. Subsequently, it was applied successfully to colonic surgery in 1999. The program has become widely accepted, and several components of the program are increasingly being implemented in modern operative care worldwide. Despite this, FT program has not yet been accepted as the standard of care in many fields, including liver surgery. van Dam et al described the use of the FT program in liver resection for the 1st time in 2008.In 1990, Krohn et alTo be implemented, the FT program requires cooperative teamwork from surgeons, anesthesiologists, physical therapists, nurses, and radiologists.We performed this systematic review and meta-analysis to evaluate the impact of using the FT program compared to TC, on the main clinical and surgical outcomes for patients who underwent elective liver resection.2 Ethical approval was not necessary because this study was a systematic review and meta-analysis. Therefore, our data were based on published studies only.This meta-analysis was conducted according to the preferred reporting items for systematic review and meta-analysis statement.2.1www.crd.york.ac.uk/prospero) with registration number CRD42015020830.The protocol for this systematic review and meta-analysis was registered into the PROSPERO database  AND (“Liver” OR “Hepatic” OR “Hepatectomy” OR “Hepatectomies” OR “Hepatobiliary” OR “Hepato-Biliary”). For all databases, the last search was completed on May 25, 2015.2.4Two authors  independently screened the titles and abstracts of the primary studies that were identified in the electronic search. Then, the bibliographies of relevant articles were manually reviewed to identify additional trials. Duplicate studies were excluded. Discrepancies between the 2 reviewers were resolved by a 3rd expert reviewer (MV).2.5The following parameters were extracted from each study by 2 authors  independently: name of the first author and his/her affiliation, year of publication, study design, the number of patients in each arm, patient characteristics, and study quality.All relevant texts, tables, and figures were reviewed for data extraction; whenever further information was required, the corresponding author of the paper was contacted by e-mail.To evaluate the impact of the FT program in liver resection compared to the TC, the following outcomes were studied: operative time, blood loss, the need for blood transfusion, and conversion rate in the laparoscopic resection. In addition, postoperative events were studied such as length of hospital stay (LoS), functional recovery, intensive care unit (ICU) admission, 1st bowel opening, restoration of oral fluid and normal diet, morbidity and mortality rates, pain score, C-reactive protein (CRP) level, hospital cost, readmission rate, and quality of life (QoL). The primary outcomes of this analysis were postoperative LoS and functional recovery, whereas the others were considered secondary outcomes.Hospital stay was defined as the interval from the day of surgery to the day of actual discharge from the hospital. Functional recovery was determined by the number of days to reach a certain criteria of recovery, which included good pain control with oral analgesia, tolerance of solid food, normal body temperature, independent mobilization, normal or decreasing the serum bilirubin level, and willingness of the patients to be discharged. Readmission was defined as any hospital readmission within 30 days after discharge.Operative time was defined as the interval from the incision to the suturing of the skin. The 1st bowel opening was determined by the 1st passage from the bowel of either stool or flatus while pain score was evaluated by using a visual analog scale (VAS) ranging from 0 to 10. Postoperative mortality was defined as the occurrence of death during hospitalization or within 30 days after surgery, while postoperative morbidity included the complication rate from the time of surgery to 90 days after discharge. was used. Repeated EQ-5D measurements were obtained in the postoperative period, and differences between groups in health-related QoL were calculated by using the area under the curve method. Alternatively, QoL could be assessed by completing the general comfort questionnaire (GCQ) based on the Kolcaba comfort line which is determined on hospital discharge.For assessment of the QoL, European quality of life-five dimensions model (EQ-5D)2.6 This tool analyzes the following criteria: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias. For each entry based on the risk of bias assessment guidelines, we made a judgment . All disagreements were resolved by discussion until a consensus agreement was achieved.The quality of the retrospective studies were assessed according to the Newcastle–Ottawa Scale that scores patient selection, comparability between the 2 study groups, and assessment of outcomes. Studies that achieved ≥7 points were defined as “good” quality. The quality of the randomized controlled trials (RCTs) was assessed according to the Cochrane Collaboration tool for assessing risk of bias.2.7 The fixed-effect model was used when no heterogeneity was detected among studies, while the random-effects model was preferred when variance existed. Statistical heterogeneity was evaluated by using the I2 statistic. I2 values of 0% to 25%, 25% to 50%, and >50% were considered indicative of homogeneity, moderate heterogeneity, and high heterogeneity, respectively. Forest plots were constructed and all data were considered statistically significant for P ≤ 0.05.The meta-analysis was performed by using Review Manager . Odds ratios (ORs) with Mantel–Haenszel method were used as a summary measure of efficacy for dichotomous data while mean differences (MDs) with inverse variance method were applied for continuous variables. A 95% confidence interval (CI) was reported for both measures. If the study provided medians and ranges instead of means and standard deviations, the means and standard deviations were imputed, as described by Hozo et al.In this meta-analysis, we pooled the results from all the included studies in regards to the primary and secondary outcomes. In addition, we meta-analyzed the RCTs separately for each outcome; the results were only discussed if a difference was found compared to the pooled meta-analysis.2.8Assessment of the risk of publication bias across series for all outcome measures will be conducted according to the guidelines established by the Cochrane Handbook for Systematic Reviews.2.9Due to the variability of surgical approaches to liver resection (by either laparoscopy or open surgery), we will include a meta-analysis of subgroups for outcomes affected by this technical difference, such as operative outcomes, postoperative LoS, and morbidity and mortality rates.33.1,15–23 8 did not include a TC control group,–31 1 was a commentary, and 1 was only a protocol description.The preferred reporting items for systematic review and meta-analysis flow diagram of the systematic literature search are shown in Fig. ,8,34–40 The abstract for one of the articles was available but the full-text could not be found in any database, despite after 6 weeks of dedicated searching. The corresponding author of the article was contacted through e-mail but we did not receive a response. Therefore, a final total of 8 studies was included in the quantitative synthesis.Nine comparative studies published between 2008 and 2015 matched our inclusion and exclusion criteria and were selected for inclusion in our systematic review and meta-analysis.3.2The characteristics of these studies are summarized in Table The indications and extent of liver resection are shown in Table, Supplemental digital Content 1. A detailed FT program, including the most frequently described elements in each study and the respective adherence rate (if reported), is summarized in Table ,36,38 and 5 cohort studies.,34,39,40 Three studies were conducted by laparoscopy,39,40 and 5 by open surgery.,34,36,38The final selected articles included 3 RCTs3.3 while the remaining 4 cohort studies were scored 8.,34,39,40 Consequently, the quality of these studies was considered good, according to the Newcastle–Ottawa Scale.All included RCTs are of high quality as summarized in Fig. 3.43.4.1,34,36,38 and a highly statistically significant result between the FT and TC groups was found, in favor of the FT group , with marked heterogeneity (I2 = 71%). LoS was also reported in all studies of laparoscopic liver resection,,39,40 and the findings demonstrated a significant result in favor of the FT group , with marked heterogeneity (I2 = 70%). Overall, these results demonstrated a highly statistically significant difference between the FT and TC groups, in favor of the FT group . However, marked heterogeneity between these studies was observed; I2 = 73% , with marked heterogeneity (I2 = 88%). On the other hand, 3 studies of laparoscopic liver resection reported the data for the operative time,39,40 and showed that the difference between the FT and TC groups was not statistically significant , with I2 = 66%. Overall, the differences in outcome were significant statistically in favor of the FT group , with marked heterogeneity between studies; I2 = 81% .Studies that reported the intraoperative blood loss during open3.5.3,36,38 and 3 studies of laparoscopic liver resection,39,40 reported the need for blood transfusion data and showed not statistically significant results .Three studies of open liver resection3.5.4,39,40 and showed no statistically significant differences between both groups .The conversion rate from laparoscopic into open liver resection was reported in all studies of laparoscopic liver resection3.5.5,38,39 2 reported the percentages of ICU admission of patients,,39 and there were fewer admitted FT group patients with high statistical difference than TC group patients, .Three studies reported the data regarding ICU admission and stay;3.5.6,38 and showed that differences in the results between the FT and TC groups were statistically significant, where there was earlier bowel activity in the FT group  and flatus passed earlier (P = 0.008) in the FT group, but these data were not included in the meta-analysis because there were, only the P values.Jones et al3.5.7 reported that in nearly all patients in both the FT and TC groups, oral fluid intake was resumed within the 1st 24 hours after surgery , and there was no statistically significant difference between the 2 groups (P = 0.86). Jones et al reported that patients in the FT group resumed oral intake earlier after surgery than those in the TC group  and drank more fluids in the 1st 24 hours . However, these data had no range, so it was not possible to include them in our meta-analysis. van Dam et al also described that fluid intake was resumed 4 hours after surgery in 56 patients (92%) in the FT group.Stoot et al,40 and showed a highly significant difference between the FT and TC groups, in favor of the FT group .All of the selected studies reported these outcomes.3.5.9 and it showed that there were no differences between the FT and TC groups except on the 2nd postoperative day (POD), where VAS was significantly lower in the FT than the TC group .One RCT reported data for the pain score,3.5.10 reported the serum CRP level on POD 1, 3, and 5; its level in the FT group was significantly lower than the TC group .One RCT3.5.11 showed that the average hospital costs were 9470 ± 1540 Renminbi (Chinese yuan) (RMB) between the TC group and only 7742 ± 1200 RMB in the FT group (P = 0.03). Lin et al reported that the median of charges (without range) during hospital stay was 21,004 RMB for the FT group, which is significantly less than the 26,626 RMB for the TC group (P < 0.05). Sanchez-Perez et al reported that the use of the FT program reduced hospital costs by about 30%; the study did not include any other cumulative data that could be used in our meta-analysis.Two studies reported data for hospital costs; He et al3.5.12–36,39,40 and showed that there were no statistically significant results between the FT and TC groups .Seven studies reported the readmission rate3.5.13,36 reported it according to EQ-5D and described significant changes in QoL scores for the FT group over time. In both the FT and TC groups, the QoL measures after surgery showed an initial decrease from baseline. Over the 1st month after surgery, QoL improved considerably in the FT group. The median area under the curve was higher in the FT group than the TC group, as reported by He et al  and Jones et al .The 3 RCTs reported this outcome; 2 of them described QoL according to GCQ and found that the mean of its measures in the FT group was higher than the TC group , which is statistically significant in favor of the FT group.The 3rd trial3.6According to the Cochran handbook for systematic reviews, the test for publication bias is unreliable when less than 10 studies are included in a meta-analysis. Therefore, funnel plots were not constructed in this study.4,6Major surgery is still associated with many undesirable consequences such as pain, cardiopulmonary, gastrointestinal, infectious, and thromboembolic complications associated with a prolonged convalescent period. The key pathogenic factor in postoperative morbidities, excluding failures of surgical and anesthetic techniques, is the surgical stress response and the subsequent increased demand for organ function, especially if it is associated with preoperative risk factors and comorbidities.,6FT program aims to reduce morbidity and accelerate convalescence through preoperative information and education of the patients, stress reduction, optimizing pain control, and aggressive postoperative rehabilitation, including early enteral nutrition and ambulation associated with nutritional supplements.,30 Using short-acting anesthesia and regional anesthesia and analgesia, avoiding hypothermia, and choosing minimally invasive techniques were essentials. In particular, some authors suggested that laparoscopic liver resection could improve postoperative recovery, decrease morbidity, and therefore, may enhance the results of FT program.,41,42 Goal-directed fluid therapy based on individual optimization of stroke volume has been demonstrated to improve outcomes in liver surgery through keeping lower central venous pressure (CVP) during the resection procedure and enhancing gastrointestinal and pulmonary function postoperatively.,43–45 Routine drainage of the peritoneal cavity and insertion of nasogastric tube are not recommended within the FT program.Stress reduction can be obtained by avoiding preoperative bowel preparation and prolonged fasting; patients were allowed to eat and drink until 6 hours, with clear fluids permitted until 2 hours before surgery.,6,8,36 This reduces postoperative nausea and vomiting and allows for early ambulation that is recommended 8 hours after surgery or maximum delayed to the 1st POD. It also facilitates early enteral nutrition; patients within the FT program are encouraged to drink oral fluids 4 to 6 hours after surgery and eat normal food on the 1st POD.,34,35Optimal management of postoperative pain is a prerequisite for FT surgery and it should be a balanced multimodal analgesia. pointed out potential problems with the FT program and suggested that there were adverse effects on the quality of care. He also claimed that hospitals wanted to discharge patients more quickly despite their poorer health state, to decrease their expenses. Moreover, due to the complexity of the FT program and its multiple elements, many barriers to the implementation of the program have arisen, including institutional barriers such as lack of experienced medical and nursing staff. In addition, there were intervention-specific barriers due to limited or weak supporting evidence for several elements of the program. Individual barriers arose from perioperative teams who resisted the change of traditional methods, and poor collaboration between team members.,48 Therefore, TC still prevails in many centers as the preferred choice of many surgeons.However, Anders,18–20,23 2 of them with meta-analyses,20 and 3 discussed upper abdominal surgeries, including liver resections.,19,23 None of these reviews investigated the effect of a laparoscopic approach compared with the open one within the FT program in liver resection. Moreover, none of the publications assessed the QoL, pain score, and ICU admission rate after liver resection in regards to the FT program. In addition, insufficient data about functional recovery, hospital costs, and assessment of protocol adherence were reported. In our present study, we discussed 16 outcomes and aimed to properly assess the FT program compared to the TC program in liver resection.This argument about the FT program resulted in a few published reports that compared the FT and TC programs, particularly in liver resection. The systematic search found 6 previous systematic reviews,A meta-analysis, as a quantitative method for therapeutic evaluation, may be used when controversy persists in order to clarify the results of different studies by developing supporting evidence and recommendations. It was possible to include 8 studies in this meta-analysis, which in total contained 810 patients; 3 studies were RCTs and 5 were cohort studies.P < 0.00001). Moreover, functional recovery was accelerated by the program (P = 0.0008). Currently, functional recovery is considered to be more accurate than LoS in describing the actual time needed for complete recovery, as it is not affected by other social or psychological events. Despite its importance, it was reported by only 3 of the included studies.,38,40In regards to the postoperative outcomes in this meta-analysis, LoS, which is a primary outcome was markedly shortened in both open and laparoscopic liver resections within the FT program. LoS ranged from 2.5 to 7 days compared with the TC group, which ranged from 7.25 to 11 days (P < 0.00001) and markedly reduced hospital costs, with no increase in the readmission, morbidity, or mortality rates. When including only RCTs in the meta-analysis, a significant decrease in morbidity rate was noticed in the FT group (P = 0.02), in concordance with the results of 2 previous meta-analyses.,20 Decreased perioperative fasting periods, restricted fluid infusion, and hypothermia prevention could be the causes of these advantages in the FT group. Maintaining perioperative normal blood glucose level prevents the sense of thirst, hunger, and anxiety. In addition, restricting over-hydration prevents delayed gastrointestinal function and reduces interstitial edema, lung compliance, and cardiac overload. Therefore, amelioration of the overall surgical stress response was resulted, associated with a successive decrease in the complication rate and enhanced recovery.The reduced LoS and accelerated functional recovery in the FT group are accompanied by a lower ICU admission rate (P < .00001) was observed. Oral fluid intake was resumed within the 1st 24 hours after surgery nearly in all patients of the FT group, but the results were not statistically significant between the FT and TC groups. In the FT program, normal diet was restored successfully on the 1st POD compared to the TC group (P < 0.00001). These results may be due to the restriction of perioperative over-hydration, early ambulation, and good pain control.A significant result in favor of the FT group in regards to earlier bowel opening (P < 0.05). Also, a 1 study reported that there was no difference in pain score between the FT and TC groups, except on the 2nd POD where the VAS score was significantly lower in the FT group (P = 0.044).Only 1 study reported the serum level of CRP, which is used as a laboratory indicator of the surgical stress response. The study showed that levels of CRP were significantly lower in the FT group compared to the TC group .QoL measures are an important factor in the evaluation of these programs. After surgery, EQ-5D measures showed an initial decrease from baseline in the FT and TC groups. Over the 1st postoperative month, QoL considerably improved in the FT group.P = 0.05). However, no significant difference was noticed between the 2 groups in patients that underwent laparoscopic liver resection. This effect in open hepatectomy with FT may be attributed to the differences in anesthetic agents administered, which may be associated with better hemodynamic stability and less use of vasopressors. This beneficial effect in laparoscopic hepatectomy is mitigated by the technical difficulty of the intervention, which is often time-consuming. Other operative parameters including intraoperative blood loss, blood transfusion, and conversion rate were not significantly different between the FT and TC groups.In regards to the operative outcomes in this meta-analysis, surgical time was significantly reduced in patients that underwent open hepatectomy within the FT program compared to the TC group .,36 In addition, most of these described elements were derived from the colorectal FT program, which may be not suitable for liver surgery.As evidenced by a Cochrane meta-analysis,,36,38 but others used short-term anesthetic agents.,40 The majority of the included studies considered thoracic epidural as the regional anesthesia of choice in the FT program. On the other hand, some authors considered that epidural use is recommended in colorectal surgery, but its use is questionable in liver resection, as it may impair the postoperative recovery and it should be replaced by intrathecal morphine.,50,52,53 Furthermore, Hughes et al reported that a small liver remnant after major resection may be a contraindication to the administration of paracetamol as it may induce liver damage. However, recent evidence recommended that paracetamol is safe in hepatic patients when its maximum dose is reduced to 2 to 3 g/day; nonsteroidal antiinflammatory drugs and opioids are better avoided.,55 As pain control is considered one of the most important elements in the FT program, further evaluation of analgesia with alternative methods in liver surgery is required to establish optimal results.Moreover, the available data about the anesthetic agents used were heterogeneous; some of these studies proposed the standard anesthetic protocol for both groups based on opioids,,57 On the other hand, other reports described many valuable diagnostic and therapeutic benefits of the drain, especially after major liver resection.,59 As the FT program discourages the use of abdominal drains, this element should be revised within the FT program in the context of liver surgery. Perhaps, a protocol for early versus late drain removal or even no drain placement, only in minor liver resection would be applicable.The nonuse of abdominal drains following liver resection is also a matter of debate. Some trials revealed that routine abdominal drainage is unnecessary after elective hepatectomy.,61 and gynecologic/oncology surgeries, and in pancreaticoduodenectomy, cystectomy, and gastrectomy procedures. No guidelines for the implementation of the FT program in liver surgery were identified. As liver surgery is a special entity, we advise the development of well-determined FT program elements specifically for these types of operations to be used as guidelines. This allows for better evaluation and standardization of the FT program in the field of liver surgery.Now, well-established FT program with guidelines was developed in different kinds of surgery, including colorectal/pelvicFinally, this meta-analysis showed significant results in favor of the FT program in regards to LoS, functional recovery, operative time, ICU admission rate, 1st bowel opening, and restoration of a normal diet. No significant differences emerged between the FT program and TC when comparing blood loss, need for blood transfusion and conversion, readmission, and mortality rates. When considering RCTs only, significantly lower morbidity rates were observed in the FT program. None of the analyzed outcomes showed superior results in favor of the TC group.This meta-analysis had several limitations: the majority of the included studies are retrospective in nature and there was a marked heterogeneity between the investigated outcomes. We used the random-effects model as appropriate, but this bias was impossible to overcome. Moreover, there is a marked insufficiency of available data in the literature in regards to the FT program in liver resection, and the comparison of several outcomes such as pain score with multimodal analgesia, hospital costs, the serum level of CRP, duration to 1st bowel opening, and restoration of oral fluid and normal diet. We recommend considering these outcomes in prospective randomized studies so that better judgments can be made for the FT program in liver resection.5LoS was markedly reduced and functional recovery was accelerated when the FT program was implemented, without increasing readmission, morbidity, or mortality rates. Based on our systematic review and meta-analysis, the FT program is safe, feasible, and can be applied successfully in liver resection. Future RCTs focusing on debated issues such as multimodal analgesia and adherence rate are needed. The development of specific FT guidelines in the field of liver resection is strongly recommended.


To evaluate the short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and to observe the safety.A total of 120 elderly patients with trigeminal nerve tumor were divided into a treatment group and a control group by random draw (n=60), and both groups were subjected to resection by stereotactic image-guided endoscopic nasal surgery. Afterwards, the control group was administered with high-dose cytarabine while the treatment group was given low-dose cytarabine for 14 days. Both groups completed treatment, but the effective rate of the treatment group (96.7%) was significantly higher than that of the control group (83.3%) (P < 0.05). The pain scores of the two groups were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 (P < 0.05). During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group (P < 0.05). During three months of follow-up, the appetite, sleep and daily living scores were significantly higher than those of the control group (P < 0.05).Stereotactic image-guided surgery was able to treat trigeminal nerve tumor well, and the effect was enhanced by low-dose cytarabine that improved postoperative outcomes and quality of life by dramatically decreasing complications. It severely affects patients' quality of life by invading adjacent cranial nerves, leading to severe, paroxysmal pain.2 The pathogenesis of trigeminal nerve tumor remains unclear, which has been mostly ascribed to microvascular compression of the trigeminal nerve root. However, the paroxysmal pain cannot be explained.3,4 Besides, trigeminal nerve tumor-induced pain has been related with the impaired inhibitory function of spinal trigeminal nuclei.5Trigeminal nerve tumor, which only accounts for about 0.2%-1% of all intracranial tumors,6 which is mainly realized by radiofrequency ablation, endoscopic surgery, craniotomy for microvascular decompression, peripheral trigeminal nerve avulsion, trigeminal sensory rhizotomy and micro-balloon compression, etc. Particularly, endoscopic approach to the pterygopalatine fossa via the nasal cavity can be conducted directly and minimally invasively, which needs a marker for the anatomical position. To this end, CT and stereotactic image guidance are helpful and thus can remarkably reduce complications owing to accurate surgical procedure and targeted therapeutic effects.7It is now well-established that intervention on pathological nerve conduction exerts satisfactory effects by blocking or mitigating pain,8 On the other hand, cytarabine, as a pyrimidine antimetabolite that mainly targets the S phase of cell cycle, interferes with the proliferation of cells mainly through inhibiting cellular DNA synthesis, thus benefiting the treatment of trigeminal nerve tumor.9 High dose for cytarabine means 1.0-3.0 g/m2 body surface area. However, the adverse reactions of this drug increase with rising dose, so low dose (10 mg/m2) is usually recommended, at which it binds DNA and then kills tumor cells.10In addition, trigeminal nerve tumor-induced pain among elderly patients may be associated with the pathological and physiological changes of peripheral and central nervous systems, such as abnormal impulse of afferent nociceptive neurons. Therefore, additional drug therapy is required.In this study, we aimed to evaluate the short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and to observe the safety.Clinical baseline data: A total of 120 elderly patients with trigeminal nerve tumor treated in our hospital from August 2010 to November 2013 were selected in this study.Inclusion criteria: Diagnosed as trigeminal nerve tumor by history of diseases, physical signs and radiographical data; ≥60 years old; with symptoms such as masticatory muscle weakness, diplopia, facial hypoesthesia and corneal reflex decrease; painful in the dominated area of the maxillary nerve; with written consent.Exclusion criteria: Intolerant or unwilling to accept surgeries; unable to complete surgeries due to mental disorders; with abnormal liver, kidney functions and blood clotting; with secondary trigeminal neuralgia; with psychological and mental disorders that could not be treated by drugs or psychotherapy.The eligible patients were divided into a treatment group and a control group by random draw (n=60), and the two groups had similar gender ratio, age, body mass index, case distribution and disease course (P > 0.05) .Treatment methods: All patients were first subjected to resection by endoscopic nasal surgery after 8 hour of food deprivation and 4 hour of water deprivation. Spiral CT thin-section axial scanning was performed one day before surgery from the supraorbital ridge to the angle of the mandible. The foramen ovale and surrounding important structures were observed and marked, and the angle and distance between the foramen ovale and the sphenopalatine foramen were estimated to simulate surgical positioning. During surgery, the patient was subjected to general anesthesia by tracheal intubation in the supine position on a routinely sterilized surgical drape. Then the nasal cavity was examined, and the nasal mucous membrane was sterilized, incised with an electric knife at the posterior edge of the membranous fontanelle of the maxillary sinus until the sphenopalatine foramen, while keeping the maxillary sinus mucosa intact. A part of posterior wall of the maxillary sinus or substance of the posterior ethmoid bone was removed by a rongeur to enter the pterygopalatine fossa. Under the guidance of CT, the periosteum of the pterygopalatine fossa was incised to seek maxillary nerves and the foramen ovale, and nerves adjoining to the foramen ovale were cut off. The patients feeling painful in the branches of the trigeminal nerve were subjected to electronic cutting of the supraorbital nerve. After surgeries, all patients were intravenously infused with antibiotics, and their noses were packed with hemostatic materials.Drug administration: Control group: After surgeries, this group was intravenously infused with high-dose (1.0-3.0 g/m2 body surface area) cytarabine for 14 consecutive days (bid). Treatment group: After surgeries, this group was intravenously infused with low-dose (10 mg/m2 body surface area) cytarabine for 14 consecutive days (bid).Observation indices: Standards for therapeutic effects: Markedly effective: Main clinical symptoms basically disappeared, and pain was moderately relieved . Improved: Main clinical symptoms were partly alleviated, and pain was slightly relieved (by 1/4-1/2). Ineffective: Neither main clinical symptoms nor pains were relieved or even aggravated.Pain grading: Pain was graded before (T0) and 1 h (T1) and 14 d (T2) after surgeries by using visual analogue scale, with 0 being painless and 10 being extremely painful.Safety observation: The complications of patients, including headache, vomiting, vision impairment, nausea and local swelling, were observed during treatment.Investigation on quality of life: All patients were followed up for 3 months and investigated in the dimensions of appetite, sleep, daily living, social life and interest in life. A higher score meant better quality of life.Statistical analysis: All data were analyzed by SPSS19.0. The categorical data were expressed as mean ± standard deviation (x ± s), and inter-group and intra-group comparisons were performed by t test and repeated measures analysis of variance respectively. The numerical data were compared by Chi-square test. P < 0.05 was considered statistically significant.Therapeutic effects:  Both groups completed treatment, but the effective rate of the treatment group (96.7%) was significantly higher than that of the control group (83.3%) (P < 0.05) ( < 0.05) .Pain scores: The pain scores of the two groups were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 (P < 0.05) ( < 0.05) .Complications: During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group (P < 0.05) ( < 0.05) .Quality of life: During three months of follow-up, the appetite, sleep and daily living scores were significantly higher than those of the control group (P < 0.05) ( < 0.05) .11 that is clinically manifested as intermittent, intolerant, extreme pain, involving at least two branches.Trigeminal nerve tumor rarely occurs and cannot be found early until it grows to trigger trigeminal neuralgia. Firstly, the posterior sensory root of the trigeminal nerve was involved and damaged, or the facial nerve was compressed. With enlarging tumor, the auditory nerve, the facial nerve and the trigeminal nerve are injured, which are accompanied by cerebellar damage and compression-induced brainstem shift. Of all the symptoms, trigeminal neuralgia is most common12 The surgical protocol, which targets the superior maxillary nerve by enlarging the sphenopalatine foramen under endoscopic control and by opening the posterior wall of the maxillary sinus until the foramen ovale, provides a constant positioning marker, thus being more visible and minimally invasive. In the meantime, the maxillary sinus mucosa, which is exposed by endoscopy, is well protected.13 The stereotactic positioning used herein allowed accurate and successful surgeries by imaging a clear foramen ovale. As a result, key basicranial structures were protected and the lesions were reached via the shortest route, which minimized the injuries to crucial structures and tissues. In other words, the method was analgesic as well as safe.14 All the patients in this study managed to complete the treatment and did not have severe complications. At present, trigeminal nerve tumor is treated mainly by surgical resection to ensure survival. Ideal surgical protocols should be minimally invasive and easily acceptable, being able to relive pain rapidly and entirely without giving rise to complications.15 Extracted from the broth of streptomyces and prepared by chemical synthesis, cytarabine is a purine nucleoside antiviral agent, together with its metabolites, can block the synthesis of viral DNA by inhibiting DNA polymerase. This drug moderately inhibits pain by effectively suppressing the synthesis and aggregation of cellular DNA but not those of RNA and proteins.16 The pain scores of the two groups herein were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 (P < 0.05).In general, trigeminal neuralgia results from excessive synthesis of nerve branch that then transmits pain by decreasing the pain threshold, thus inducing severe, paroxysmal pain. Long-term neurogenic inflammation disorders the release of monoamine neurotransmitters by the central nervous system, which produces noxious stimuli even in the presence of slight maxillofacial tactile stimulation and also leads to sharp pain.17 In contrast, low-dose cytarabine, which is as effective as standard-dose therapy, is more conducive to the recovery of elderly, critically ill patients owing to milder toxic reactions and shorter hospital stay. In this study, the effective rate of the treatment group (96.7%) was significantly higher than that of the control group (83.3%) (P < 0.05).High-dose cytarabine is not always preferential because of the aggravated adverse reactions that restrict therapeutic effects and extend remission.18 During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group (P < 0.05). During three months of follow-up, the appetite, sleep and daily living scores significantly exceeded those of the control group (P < 0.05). Meanwhile, low-dose cytarabine can induce the apoptosis of malignant clone cells, inhibit their proliferation, regulate intercellular adhesion molecules, and eventually facilitate the recovery of patients with tumor.Although this surgical method is easily operable, a series of complications  may occur because of complex anatomical structures around the foramen ovale. Administration of high-dose drug is bound to increase the risks of headache, nausea and vomiting, so the postoperative quality of life is affected.In summary, stereotactic image-guided surgery successfully treated trigeminal nerve tumor, with its effect boosted by low-dose cytarabine that improved postoperative outcomes and quality of life by significantly decreasing complications.XSL&BZJ conceived, designed and did statistical analysis & editing of manuscript.XSL, WLY, FZS, GJG & JWM did data collection and manuscript writing.BZJ did review and final approval of manuscript.BZJ takes the responsibility and is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


Kawasaki disease is an acute necrotising vasculitis of the medium- and small-sized vessels, occurring mainly in Japanese and Korean babies and children, aged 6 months to 5 years. Its main complication is damage of coronary arteries, which has the potential to be fatal. Here we report a rare case of Kawasaki disease that occurred in a 20-year-old Greek adult.A 20-year-old Greek man presented with high fever, appetite loss, nausea and vomiting, headache and significant malaise. He had an erythema of the palms and strikingly red lips and conjunctiva. As he did not respond to broad-spectrum antibiotics and after having excluded other possible diagnoses, the diagnosis of Kawasaki disease was set. He was treated with intravenous immunoglobulin and oral aspirin on the 10th day since the onset of the illness. His clinico-laboratory response was excellent and no coronary artery aneurysms were detected in coronary artery computed tomography performed 1 month later.This report of an adult case of European Kawasaki disease may be of benefit to physicians of various specialties, including primary care doctors, hospital internists, intensivists and cardiologists. It demonstrates that a case of prolonged fever, unresponsive to antibiotics, in the absence of other diagnoses may be an incident of Kawasaki disease. It is worth stressing that such a diagnosis should be considered, even if the patient is adult and not of Asian lineage. Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute necrotising vasculitis of the medium- and small-sized vessels. It was first described by Tomisaki Kawasaki in 1967. It occurs most often in babies and children, aged 6 months to 5 years and the male-to-female ratio ranges from 1.5–1.8 to 1. KD is most prevalent in Japan, while Korea holds the second place as to the number of patients. Its incidence in Japanese and Korean children living in the USA and following a Western lifestyle is higher than in Caucasian children. Since the disease is not common in adults, especially in Europe, it is very often misdiagnosed . AccordiTHRIL, a long noncoding ribonucleic acid involved in tumour necrosis factor (TNF) α regulation [Lactobacillus casei cell wall extract [The pathogenesis of KD is to a very large extent unknown. A passive protection by maternal antibodies could possibly explain the rarity of the illness during the first months of life of an individual. An infectious cause might be possible, since seasonal outbreaks, national epidemics, associations with tropospheric wind patterns  and a segulation . Also of extract .ITPKC [CASP3 [FCGR2A, HLA, BLK and CD40 have also been suggested as susceptibility candidates by means of genome-wide association studies [A genetic predisposition hypothesis is supported by: i) noticeable differences in incidence rates among people of various ethnic groups along with ii) a higher incidence of KD among siblings of a patient compared to the general population. Nevertheless, the genetic background of KD remains mostly unclear. A series of polymorphisms in a number of genes have been linked with increased susceptibility for KD, with the most notable ones being in ITPKC  and CASPC [CASP3 . Finally studies -23.KD diagnosis is absolutely clinical since no specific diagnostic tests are available , althougITPKC [IL-10 [TGFBR2 [DC-SIGN [KCNN2 [Coronary artery damage is the main and sometimes fatal complication of the disease, being expressed as aneurysm, calcification or stenosis ,26. CoroITPKC , IL-10 [C [IL-10 , TGFBR2  [TGFBR2 , DC-SIGN[DC-SIGN  and KCNNN [KCNN2 . ArterieN [KCNN2 , a left N [KCNN2 , a proxiN [KCNN2  are descSystemic inflammation of many organs can occur. Inflammation of the central nervous system would cause typical meningitis  or just Clinical and laboratory findings concerning liver inflammation are jaundice ,40,48,49Mild renal failure, dysuria , as wellThe upper and lower respiratory system may also be affected. Reddened pharynx ,47-49,54The upper and lower intestinal tract are involved in KD as well. Nausea ,55,56,58The musculoskeletal system participates in the inflammatory process with various clinical representations: arthralgia of the big joints ,51,55,58Lymphadenopathy is often observed in KD. It may be mainly cervical -52,55-58Skin and mucous membranes express a variety of abnormalities: skin rash ,52-56,58Eye problems are frequent and of great variety: conjunctivitis ,55,57-59Adult KD seems to occur more frequently in patients with human immunodeficiency virus ,42,50,58Ideal treatment for KD should be immediate administration, no later than on the 10th day of the disease onset, of both immunoglobulin at 2g/kg once and aspirin at 50 to 100mg/kg for as long as the inflammation is present ,49,52,56Individuals who do not respond to the dual treatment ,12,42,61The long-term outcome of adults with a history of KD without CAA is excellent -49,55,56A 20-year-old Greek man presented to our hospital in late May of 2010 because of high fever , appetite loss, nausea and vomiting, persistent headache and a feeling of significant malaise for 5 days. He was diagnosed at a provincial hospital with an atypical infection and had received azithromycin for 3 days, without any improvement.He had not travelled recently either within the country or abroad. He denied intravenous drug use, new sexual partners or tattoos. He had no animal exposure. He did not use tobacco products or alcohol and had not taken any medication. He was previously healthy. According to his medical history, he reported allergic rhinitis and conjunctivitis for his first 5 years of life, chickenpox at the age of 5 years, a streptococcal pneumonia at the age of 6 years, several episodes of tonsillitis until the age of 12 years and a tonsillar abscess at the age of 11 years. He reported no drug allergies. No contacts with similar symptoms were identified. He had no antecedents of Asian origin. The family history was non-contributory and no family members had rheumatic diseases.On admission, his temperature was 38.3°C, blood pressure at 80/50mmHg, pulse was measured at 100 beats per minute and blood oxygen saturation at 92%. A physical examination revealed bilateral conjunctival chemosis, strawberry lips and tongue, dry mucus membranes, a mild skin rash of his trunk, erythema of his thenar and opisthenar regions of both palms, an oedema of palms and soles and tachycardia with S3 and S4 gallop. Results of examinations of his lungs, abdomen, neurological and musculoskeletal systems were normal.3 per cubic millimetre) with neutrophilia (91%) and left shift with segmented neutrophils, anaemia (haematocrit 33%) and normal platelets upon admission, which were later elevated , he was given IVIG at 2000mg/kg once and aspirin at 50mg/kg orally for the first 3 days, and at 100mg per day for another 3 months. His treatment was based on the diagnostic criteria developed for KD in children because there had been no validated criteria for adult cases of KD. Antibiotic treatment was discontinued at this time.Immunoglobulin and aspirin had a striking result, since the patient was afebrile and in better condition on the very next day after the initiation of treatment. During the following days, all clinico-laboratory findings gradually improved and only a reactive thrombocytosis remained. In total, he remained hospitalised for 10 days. A computed tomography coronary angiography performed 1 month later showed no coronary aneurysms. Today, about 5 years later, our patient remains healthy.Our patient developed the disease in late May. Thorough investigation for many infectious agents did not prove an infectious source of the disease . NeverthOur patient did not have some signs and symptoms that are more usual in adult KD, compared to that in children, such as lymphadenopathy and articular involvement. Lymphadenopathy is present in 93% of adult cases of KD, compared to 75% of child cases. Joint problems are observed in 63% of adults with KD, versus 24 to 38% of children with the disease according to a review in 2011 [In contrast, our adult patient had persistent headache that subsided only after the administration of IVIG and ASA. Involvement of the central nervous system takes place more often in children with KD (34%) than in adults (10%) .Our patient’s response to the treatment was astonishing and extremely quick: fever resolved and his general condition ameliorated within hours. Such a response is not usual in the KD literature ,39,40,56Laboratory findings consistent with KD were leucocytosis with neutrophilia, anaemia, late thrombocytosis, elevated ESR and CRP, hypoalbuminemia, hyponatremia, elevated serum transaminases and gamma-glutamyl transpeptidase .Other than a single IVIG administration and high doses of ASA during the acute phase, no supplementary IVIG or even corticosteroids or immunosuppressive agents were given, since no symptoms persisted or relapsed ,62. ASA This case makes the point that a prolonged fever without response to antibiotics should raise the physician's suspicion of a possible KD incident, considering though its rare occurrences in European adults. Prompt diagnosis and timely treatment of this potentially fatal disease are the keys that can save lives, preventing CAA formation.Physicians of various specialties are involved either in recognition or treatment of KD. Primary care doctors, being the first to come across the patients, should transfer them to hospitals at once. Hospital internists should then set the diagnosis, according to the relevant criteria, having first excluded other possible diseases. It is vital that patients receive treatment with IVIG and ASA as soon as possible and no later than 10 days since the onset of symptoms. Cardiac complications and hemodynamic instability may bring the need for transfer to an intensive care unit, relegating treatment to intensive care practitioners. Finally, cardiologists have the responsibility of tracing long-term follow-ups, along with monitoring any arising cardiac issues.Future studies will hopefully shed light on the origins and aetiology of the disease, allowing for more efficient and targeted treatment and follow-up.The data set supporting the results of this article is available in the Figshare repository .Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Background and Aim. p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects. Methods. We evaluated anthropometry, body composition, and p53 polymorphism in 140 women distinguished in NW, NWO, and Preob-Ob. Results. *Arg/*Arg genotype increases sarcopenia risk up to 20% . The risk of being sarcopenic for *Arg/*Arg genotype in NWO and Preob-Ob is 31% higher than NW carriers of *proallele . We developed a model able to predict sarcopenia risk based on age, body fat, and p53 polymorphism. Conclusion. Our study evidences that genotyping TP53 polymorphism could be a useful new genetic approach, in association with body composition evaluations, to assess sarcopenia risk. Interactions between genetic and environmental factors such as diet and lifestyle, particularly overnutrition and sedentary behavior, promote the progression and pathogenesis of polygenic diet-related diseases. Their current prevalence is increasing dramatically to epidemic proportions .Certain single nucleotide polymorphisms (SNPs), occurring within the promoter region of a large number of genes, influence their transcriptional activity, resulting in intraindividual differences in the synthesis of coded proteins. A goal of the new postgenomic era is to uncover correlations between particular polymorphisms and the predisposition to develop certain diseases as a result of complex interaction of genetic, nutritional, and metabolic factors . Once in predictive, preventive, personalized, and participatory [In this context, the mounting influx of global quantitative data from both genetic, blood biomarkers and body composition, with a constant attention to disease and wellness, had led to a necessary transformation of the concept of medicine, intended not only as a curative intervention. It is necessary to transform healthcare to a proactive P4 medicine, that iscipatory . This apcipatory . To applRecent literature focuses attention on new roles for tumor protein p53 (TP53) beyond cancer progression, in processes such as metabolic syndrome, insulin resistance, adipose tissue inflammation, obesity, and skeletal muscle differentiation and homeostasis .In fact, in response to different genotoxic stimuli and depending on the degree of activation, p53 can promote transcriptional programs and protein-protein interactions which orchestrate DNA repair, cell cycle arrest, cellular stress responses, cell cycle regulation and differentiation , and sen TP53, encoding p53, has a common sequence polymorphism in exon 4 of codon 72 characterized by a G to C substitution that determines the change of Arginine (Arg) to Proline (Pro) in the protein thereby coding for p53 variant R72P. The amino acidic change affects biochemical and functional properties of p53 protein. In fact, this polymorphism occurs in the Proline-rich domain of p53 protein, which is necessary for the protein to fully induce apoptosis. The Arg variant is a stronger apoptosis inducer, while the Pro variant is a stronger transcriptional activator [The gene,ctivator .Moreover, a putative role of TP53 was proposed in the severe and rapid skeletal muscle atrophy, which represents a hallmark of cachexia and of sarcopenia when the muscle atrophy occurs during aging . HoweverVarious conditions leading to muscle wasting involve different pathways of intracellular signaling that trigger (i) programmed cell death (apoptosis); (ii) increased protein degradation through autophagy, calcium-dependent proteases , and proteasome system; (iii) decreased satellite cell activation, responsible for muscle regeneration . InteresSarcopenia is an “age-related” and “obesity-related” loss of muscle mass leading to muscle weakness, limited mobility, and increased susceptibility to injury; an understanding of the underlying causes of muscle loss is critical for the development of strategies and therapies to preserve muscle mass and function . SarcopeGreater loss of muscle mass leading to sarcopenic obesity in women occurs increasingly with age.DXA-derived total body fat mass (TBFat), total body lean mass (TBLean), and appendicular skeletalmusclemass index (ASMMI) measures reflect the percentage of total body fat (PBF), muscle mass and muscle strength providing a reliable measure for assessment of sarcopenia and obesity .For instance, among subjects with sarcopenic obesity, we found women suffering of normal weight obese (NWO) syndrome, characterized by normal body weight and BMI, but high TBFat accumulation (PBF ≥ 30%) accompanied by TBLean mass deficiency .The key problem for this disease is diagnosis. In order to avoid the risk of sarcopenia in the elderly and to prevent it in the young population, the diagnosis of sarcopenia requires the utilization of various methods, including body composition evaluation and metabolic, functional, and genetic approach. The assessment of the physical status in association with genotype represents very important information to evaluate both the health status and the quality of life. Moreover, while a number of risk factors and diagnostic methodologies are available, it would be very useful to be able to develop additional predictive tools and risk indexes for this pathology.Given the clinical significance of sarcopenia and the involvement of TP53 in muscle differentiation and homeostasis, the purpose of the present study was to investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism and to determine whether this polymorphism is associated with ASMMI in normal weight population (NW with a PBF < 30%), NWO, and preobese-obese (Preob-Ob) subjects, with PBF ≥ 30% –22.We comprehensively analysed anthropometric values, TBFat, and TBLean in a TP53 polymorphism association study. Moreover, we test the possibility to define a function for predicting the risk of sarcopenia due to the simultaneous presence of obesity and TP53 gene polymorphism and provide a simple online tool to apply these calculations.The study was conducted on a sample of 140 Italian Caucasian women (aged 18 to 65 years), recruited from ongoing studies at the Division of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, University of Rome “Tor Vergata” , from May 2013 to February 2014. A completed screening of anthropometry and body composition was assessed using standardized equipment.Participation in the study included a complete medical history to gather information about health status, current medications including supplements of vitamin and mineral, alcohol drinking, smoking, dietary intake, and physical activity (PA). Subjects with acute diseases, severe liver, heart, or kidney dysfunctions, endocrine disorders , cancer, or other conditions capable of altering body composition  were excluded. The use of certain drugs  was also a reason for exclusion. Moreover, individuals that either smoke or take medications were excluded from the study. A complete assessment of anthropometry and body composition was performed.The subjects were categorized according to PBF cutoff point  in (1) w2 and ≥25 kg/m2), into three groups: (1) NW women having a BMI < 25 kg/m2 and PBF < 30%; (2) women with PBF ≥ 30% including NWO women with BMI < 25 kg/m2 and PBF ≥ 30% [2 10 and PBF ≥ 30% [Moreover, we categorized these groups also according to BMI (<25 kg/mBF ≥ 30%  and (3) BF ≥ 30% .Study design was clearly written in lay-person language and provided to each study subject. A written informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the Declaration of Helsinki.NCT01890070.This trial is registered with ClinicalTrials.gov Anthropometric parameters for all participants were performed according to standard methods by trained personnel , with participant wearing only light underwear and without shoes. After a 12-hour overnight fast, all subjects underwent anthropometric evaluation. Anthropometric measurements for all participants according to standard methods were carried out . All theWaist and hip measures were taken using a flexible steel metric tape to the nearest 0.5 cm, with subjects standing with arms relaxed by their side and balanced on both feet. The tape was held tight to the skin but without compression of tissue. Hip circumference was also measured according to International Society for the Advancement of Kinanthropometry protocol , taken aBody weight (kg) was measured to the nearest 0.1 kg, using a balance scale . Height (m) was measured using a stadiometer to the nearest 0.1 cm .2 (kg/m2).Body mass index (BMI) was calculated using the formula: BMI = body weight/heightThe total body composition was assessed by DXA , according to the previously described procedure .The technique combined a total body scanner, an X-ray source, an internal wheel to calibrate the bone mineral compartment, and an external lucite/aluminium phantom to calibrate the fat compartment. Standard DXA quality control and calibration measures were performed prior to each testing session. The subjects were instructed not to exercise within 24 h from the test. The subjects were given complete instructions on the testing procedure. Individuals were asked to remove all clothing except for undergarments including shoes, socks, and metal items prior to being positioned on the DXA table. Scans were performed with individuals in a supine position. The entire body was scanned beginning from the top of the head and moving in a rectilinear pattern down the body to the feet. The average measurement time was 20 min. The effective radiation dose from this procedure is about 0.01 mSv. The coefficient of variation (coefficient of variation = 100 × SD/mean) intra- and intersubjects ranged from 1% to 5%. The coefficient of variation for bone measurements is less than 1%; coefficient of variation on this instrument for five subjects scanned six times over a nine-month period was 2.2% for TBFat and 1.1% for TBLean; total PBF was calculated as TBFat mass divided by total mass of tissues (TBFat + TBLean + TBBone) × 100.Resting metabolic rate (RMR) was calculated according to the previously described procedure .2. Female subject was defined sarcopenic with a relative ASMMI < 5,47 kg/m2 [ASMMI was calculated as follow = appendicular skeletal muscle mass (kg)/height (m)47 kg/m2 .p53 codon 72 genotype was determined according to the method of de La Calle-Martin .PCR Primers. The primer sequences corresponded to the 4th exon of the human p53 gene.Sense oligo 5′-AATGGATGATTTGATGCTGTCCC-3′.Antisense oligo 5′-CGTGCAAGTCACAGACTTGGC-3′.Polymorphism. AccH (CGCG) digest of the amplified fragment identifies two alleles: Al = 259 bp and A2 = 160 bp + 99 bp.Chromosomal Localization. The polymorphic AccH recognition site occurs within the 4th exon of the human p53 locus (17ql3).PCR Conditions. PCRs were carried out in a total volume of 250 μL containing 500 ng of genomic DNA, 50 pmoles of each primer, 2 mM MgCl2, 200 AM dNTPs, 50 mM KCl, 20 mM Tris-pH 8.3, and 0.1% gelatine. The amplification was performed for 35 cycles with an annealing temperature of 62°C. The amplified DNA was digested overnight with a tenfold excess of AccH. DNA fragments were resolved by electrophoresis through a 2% agarose gel and analyzed under a UV source, using the Molecular Imager Gel Doc image analysis system.Data are presented as group median ± standard error (SE) or percentage.χ2 test was also used to evaluate the Hardy-Weinberg equilibrium of the observed genotype frequencies with respect to the general population.The nonparametric Mann-Whitney test was used when comparing two groups. A Pearson's simple correlation was used to study the association between 2 variables. Data were analyzed to check assumptions about the distribution of the measured variables. Three genotype groups were first considered to check differences in considered variables between groups. Because a dominant or recessive effect existed, analysis was repeated comparing *Arg/*Arg genotype versus carriers of *proallele groups. A We further calculated odds ratios (OR) and relative risk (RR) with 95% confidence intervals (CI) for sarcopenia-risk factors with a binary logistic regression model. Population attributable risks (PAR), expressed as percent in the text, were computed using the method described by Bruzzi et al. , which aP ≤ 0.05 for all the procedures.Statistical analysis, OR, and their confidence intervals (CI) were performed using the computer software package SPSS for Windows, version 13.0; SPSS, Chicago, IL. The logistic response model was used to predict the probability associated with each value of the binary response . A stepwThe web calculator was designed with standard html, CSS, and JavaScript for the user interface and PHP for data processing.One hundred forty Caucasian Italian women gave informed consent and were enrolled: 127 women were eligible for the study design according to inclusion criteria. The anthropometric, body composition, and biochemical parameters in the study group were shown in n = 1) were underweight, 44.88% (n = 57) were normal weight (eutrophic), 19.69% (n = 25) were overweight, and 34.64% (n = 44) were obese. Moreover 4.54% of subjects classified as obese by BMI were sarcopenic.Characterization of the nutritional status by BMI revealed that 0.79% .P = 0.0009).Moreover, according to attributable risk (PAR) we found that up to 21% of sarcopenia incidence was dependent on obesity . As expected, all parameters of body composition were significantly different between the Preob-Ob and NW groups (P < 0.05). Preob-Ob women showed higher amount of fat mass, evaluated as PBF and TBFat (P < 0.05) with NW and Preob-Ob women (P < 0.05).No significant differences in W/H ratio and lean arms were observed between the NW and NWO women. BMI, WC, PBF, TBF, and lean legs were significantly different between NW, NWO, and Preob-Ob (P < 0.05).No significant differences of ASMMI were observed between the NW and NWO women. Moreover, Preob-Ob subjects showed higher ASMMI with respect to other groups  had the Arg/Arg genotype with an average age of 37, 64 ± 13, 64 years, 54 women (42.52%) had the Arg/Pro genotype with an average age of 35, 42 ± 11, 73 years, and 6 women had the Pro/Pro genotype with an average age of 37, 82 ± 10, 49 years.No statistical difference in the mean age was observed.In a second step statistical analysis was performed on the study population divided into 2 subgroups, *Arg/*Arg genotype and carriers of *proallele TP53 codon 72 polymorphism (Arg/Pro + Pro/Pro).P < 0.05).In NW subjects, TBL and RMR between *Arg/*Arg genotype and carriers of *proallele were significantly different (P < 0.05). Preob-Ob showed significant differences in BMI, WC, HC, and W/H values with respect to NW and NWO (P < 0.05).Among overall *Argo/*Arg genotype, NWO showed significant differences in PBF, TBFat, lean legs, TBLean, and RMR with respect to NW (P < 0.05). Moreover, significant differences were observed in W/H, lean legs, TBLean, and RMR with respect to Preob-Ob (P < 0.05).Among overall carriers of *proallele, NWO showed significant differences in BMI, WC, HC, PBF, TBFat, and lean arms values with respect to NW (P < 0.05). Moreover, significant differences were observed in ASMMI values between NW and Preob-Ob (P < 0.05).In NW subjects ASMMI between *Arg/*Arg genotype and carriers of *proallele were significantly different  and 33.33% of NWO  were sarcopenic. Moreover, 4.29% of Preob-Ob were sarcopenic and all were *Arg/*Arg genotype.By dividing the women population into sarcopenic and nonsarcopenic individuals, it was observed that *Arg/*Arg genotype increases sarcopenia risk to 20% .P = 0,0079).The risk of being sarcopenic for *Arg/*Arg genotype women, with a PBF ≥ 30%, is 31% higher than women carriers of *proallele with a PBF < 30%  indicates the presence or absence of the TP53 gene polymorphism. In the case of the Arg/Arg genotype the value of X1 = 1 and X2 = X3 = 0. In the case of Arg/Pro genotype the value of X2 = 1, and X1 = X3 = 0. In the case of Pro/Pro genotype the value of X3 = 1 and X1 = X2 = 0. The variable Y is the age of the subject, and Z is the PBF.Furthermore, in this investigation the probability of sarcopenia was modeled; P response variable is as follows: P = 0 means no risk; P = 1 means 100% probability of sarcopenia risk.The http://immuno.bio.uniroma2.it/sarcopenia-p53-calculator/.This equation allows the prediction of individual sarcopenia risk on the base of PBF, age, and TP53 gene polymorphism. We have developed an online tool to apply this equation that is available for public use at In the last years, several genetic studies were performed in order to discover genes involved in the development of obesity susceptibility, osteoporosis, and insulin resistance. More than 300 genes have been putatively identified as involved in these processes . Still, Human aging is characterized by increased levels of physical disability due to, at least in part, loss of muscle strength that depends on both decrease in muscle mass and accumulation of intermuscular adipose tissue (IMAT), contributing to the decline of muscle quality, predicting sarcopenia, and increasing risk of mobility impairment , 31.κB and PI3 K/Akt pathways that are central in controlling muscle size, promoting protein synthesis, and blocking degradation [p53 is a tumour suppressor gene which responds to a variety of stress signals, including DNA damage, resulting in cell cycle arrest, apoptosis, or senescence, and several studies suggest that p53 protein activity plays a role in regulating muscle homeostasis, with an important role in the process of myoblasts differentiation –35. It iradation –41.Considering the great interest toward p53 function in the context of skeletal muscle differentiation and apoptosis and the established difference in activities of Arg and Pro variants, we investigated the possible relationship between the polymorphism at codon 72 of p53 gene, body composition, and ASMMI in NW, NWO, and Preob-Ob women, to highlight a potential connection of these genetic variants with the predisposition to sarcopenia.Aims of our work were to identify which group of women, as a function of the weight, body lean, and fat mass, were at increased risk of reduction of skeletal muscle mass that could lead to sarcopenia and to verify if the codon 72 in exon 4 p53 gene polymorphism could be associated with this condition.Therefore, we used TP53 genotyping as a screening factor for this disease. Finally, we tried to identify a model to predict the risk of sarcopenia, according to age, genotype, and body fat mass. We have initially classified our study population according to BMI and PBF, to identify obese subjects, and to ASMMI, to identify sarcopenic subjects.P < 0.05). According to PBF cutoff classification, only 14.17% of the total were eutrophic and normal weight, while all the others were obese.In the present study, a significant difference in the diagnosis of obesity between BMI and PBF was observed with an error percentage of 40.68% , cardiovascular diseases (CVD), high oxidative stress, and low RMR become necessary to evaluate body composition to assess the risk of sarcopenia –50. It wMoreover, in the total population, 5.5% of NW, 10.24% of NWO, and 2.36% of Preob-Ob were sarcopenic according to ASMMI values.As previously described, BMI does not take into consideration muscle mass loss, exacerbating misclassifications of sarcopenic obesity . In factMoreover, to assess the relationship between sarcopenia and obesity we calculated the population attributable risk (PAR) and found that up to 20% of sarcopenia incidence could be reduced by appropriate detection and treatment of obesity.By dividing the study population according to genotype and body composition, significant differences in the three study groups, NW, NWO, and Preob-Ob, and intergenotypes were found. Among the same group NW carriers of *Pro have lower weight with respect to *Arg/*Arg genotype; the same results were observed between Preob-Ob. In NWO no significant differences were observed. Moreover, among the same genotype, NW carriers of *proallele have significantly lower weight with respect to NWO and Preob-Ob; on the contrary Preob-Ob carriers of *proallele are the fattest.In NWO women carriers of *proallele, higher values in BMI, but not in weight, were observed.Regarding WC, among the same group, NW carriers of *proallele have lower WC with respect to *Arg/*Arg genotype; on the contrary, in Preob-Ob the lower value was observed in *Arg/*Arg genotype. Among NWO women, carriers of *proallele show the higher value with respect to *Arg/*Arg genotype. WC or waist-to-hip ratio has been used as a proxy measure for body fat distribution when investigating the health risk increased with an increasing ratio. Some studies have suggested that WC, either alone or in combination with BMI, may have a stronger relation to some health outcomes than BMI alone . We consP < 0.05) of RMR between NWO, NW, and Preob-Ob women was observed, independently of genotype. We confirmed, according to our previous results [P < 0.05). According to genotype, the RMR in Preob-Ob carriers of *proallele is significantly higher than *Arg/*Arg genotype. NW carriers of *proallele have significantly lower values than *Arg/*Arg genotype, tending towards a value similar to NWO. The RMR is the lowest due to a reduction in metabolically active fat free mass. Thus, the measurement of energy expenditure normalized to metabolically active mass should provide a tool to identify hyper- and hypometabolic states at an early stage.As reported in  results , a lowerP > 0.05). In the NW groups we found an opposite trend with respect to the Preob-Ob women. For the first time, we highlighted that the NW *proallele carriers have ASMMI values lower than normal cutoff, indicating a sarcopenic predisposition.The NWO groups showed the same trend of the Preob-Ob women in terms of fat mass content and of ASMMI levels .In the present study, we developed a logistic model to assess the sarcopenia risk, based on age, genetic analysis, and body composition, that may be applicable to Italian women ranging widely in age. Note that our study cohort was selected from a population of patients and affiliates of our Division of Clinical Nutrition and Nutrigenomic: although it was not taken at random from the Italian population, this sample can be regarded as representative of women at risk and requiring medical examination.Finally, we mention some limitations of the study. Our cohort is composed of a limited number of subjects and it is population specific. Because the number of included subjects was relatively low, validation of the results in larger, independent cohorts is recommended to confirm our results and exclude the risk of false negative findings.Some reports suggest an increase of inflammatory catabolic signals with age and a reduction of anabolic signals to muscle present in young adulthood, favoring onset of sarcopenia . HoweverFurthermore, we were unable to perform laboratory evaluations for all participants, and we lack muscle function data (strength or performance), thereby sometimes hindering a complete sarcopenia diagnosis.However, our results support the hypothesis that codon 72 p53 gene polymorphism could be associated to sarcopenia, in a way that is independent of BMI.http://immuno.bio.uniroma2.it/sarcopenia-p53-calculator/. The PBF can be either inputted directly or calculated from height, weight, waist circumference, and hip circumference as described in our previous study [Moreover, physicians should take full advantage of the predictive model and simple equation generated by the present study for the assessment of sarcopenia risk. For this reason, we have developed an online tool that provides free access to the calculations for this equation, now accessible at us study .To prevent and manage poor quality of life related to sarcopenia, greater attention and early evaluation should be given to subjects showing a lower ASMMI.The changes in medicine are represented by a new systems approach to studying, understanding, and monitoring fundamental biological and disease processes that will trigger the emergence of personalized medicine focused on the integrated diagnosis and treatment and prevention of disease in individual patients .The key elements of all risk-prediction tools, from baseline risk assessment to analysis of appropriate therapeutics, will benefit from the molecular understanding of the pathogenesis of disease, along with the identification of predictive factors, particularly biomarkers that anticipate or quantify the pathogenic process. Moreover, an integrated approach and the development of new mathematical and computational methods, for extracting maximum information from molecular and genetic information on individuals and from other clinical data and history, as well as integrating all of this information into predictive models, become necessary for the application of the P4 medicine , 59.Since chronic diseases, such as sarcopenia, develop as a consequence of an individual's baseline susceptibility coupled with exposure to environmental factors, including life style, diet, and body composition, personalized risk prediction, and strategic health-care planning will facilitate the “prospective health care,” according to predictive, preventive, and personalized medicine . The preIn conclusion, this study shows that a genetic approach, like genotyping of codon 72 p53 polymorphism, associated with body composition evaluation is highly desirable, in order to prevent and manage the risk of muscle mass loss or ASMMI reduction in women population.http://immuno.bio.uniroma2.it/sarcopenia-p53-calculator/.The developed equation for the calculation of the sarcopenia risk can be accessed online at the following address:


Studies of undervaccinated children of minority/stateless populations have highlighted significant barriers at individual, community, and state levels. These include geography-related difficulties, poverty, and social norms/beliefs.The objective of this study was to assess project outcomes regarding immunization coverage, as well as maternal attitudes and practices toward immunization.The “StatelessVac” project was conducted in Thailand-Myanmar-Laos border areas using cell phone-based mechanisms to increase immunization coverage by incorporating phone-to-phone information sharing for both identification and prevention. With limitation of the study among vulnerable populations in low-resource settings, the pre/post assessments without comparison group were conducted. Immunization coverage was collected from routine monthly reports while behavior-change outcomes were from repeat surveys.This study revealed potential benefits of the initiative for case identification; immunization coverage showed an improved trend. Prevention strategies were successfully integrated into the routine health care workflows of immunization activities at point-of-care. A behavior-change-communication package contributes significantly in raising both concern and awareness in relation to child care.The mobile technology has proven to be an effective mechanism in improving a children’s immunization program among these hard-to-reach populations. Part of the intervention has now been revised for use at health centers across the country. The figures for minority and stateless populations, besides the population of 64 million with citizen identification in Thailand, vary between different reports, depending on the definition of the populations of interest . In 2011Geographically, hilltribe settlements in Thailand are scattered over 20 western and northern border provinces of the country; however, about 90% of them reside in nine upper northern provinces. The highest proportion of the hilltribe population lived in the Chiang Rai Province, Chiang Mai Province, Mae Hong Son Province, Tak Province, and Nan Province. According to the 1995 survey, there are six major distinctive ethnic groups, each of which can be identified by distinctive costumes and languages including: Karen, Hmong, Lahu, Akha, Mein or Yao, and Lisu . AccordiThailand has adopted the Expanded Programme on Immunisation (EPI) as a national policy since 1976 ,17. OverA review of the literature on the epidemiology of undervaccinated children in resource-limited settings -27 revea” and “prevention”. “Identification” refers to valid case registration on the EPI scheme for ethnic-minority and stateless children; “prevention” is proper case management so as to receive fundamental immunizations, plus behavior-change communication measures in relation to seeking out and gaining access to health care services. The main objective of this study was to assess project outcomes regarding EPI coverage, and maternal attitudes and practices toward the immunization of their children.The “StatelessVac” project was developed and implemented in Thailand-Myanmar-Laos border areas in the Chiang-Rai Province, using cell phone-based solutions with the specific purpose to provide an effective mechanism for achieving EPI coverage targets among ethnic hilltribe and stateless populations. Strategies included two system functionalities for phone-to-phone information sharing, for “identificationThe areas for project implementation consisted of all villages under the responsibility of three governmental PHUs, covering Thai citizens and both registered and unregistered highland populations. Each village was populated with a mix of 6 main highland minorities: Karen, Hmong, Mein, Akha, Lahu, and Lisu, with one immigrant minority population of Yunnan Chinese. The distances from each village to its responsible PHU ranged from 1 to 17 kilometers, with a median of 7 kilometers. It should be noted that in Thailand, the Ministry of Public Health has established and maintained 68 provincial hospitals, 759 district hospitals, and 28 referral  hospitals, while providing 9761 primary health care services at the PHUs . The PHUIn response to the call for proposal “Create Low-Cost Cell Phone-Based Solutions for Improved Uptake and Coverage of Childhood Vaccinations” by the Grand Challenges Explorations Round 7, the StatelessVac project was developed ,34. In oMobile technology, particularly the use of smartphone systems, has already been employed as a vehicle for global health care innovation, in terms of facilitating behavior change and improving health care. The benefits of such innovations include: improved access to and quality of care, patient management, and health outcomes among underserved populations . The fouSome novel ideas for case identification include transmitting “picture” and “pronunciation” data using the phone-to-phone system from remote highland areas to lowland PHUs. Specific issues of complexity concerning the registration procedure include noncitizenship, lack of birth certificate, inconsistency of name, and unspecified residential location. Due to changes of a baby’s appearance throughout the 5 year immunization program, the picture of baby was used as a biometric data. With parental permission, pictures of each infant and its mother, taken via tablet prior to each vaccination visit, were securely transmitted to authorized health care personnel at the responsible PHU. Each hilltribe has its own dialect; most have spoken, but not written languages -14. VariThe case-identification strategy was developed and incorporated into tablet functionality. On a VHV’s tablet, after a baby was registered on the responsible PHU’s database, EPI scheduling was flagged monthly as due and/or overdue immunization(s) for each VHV’s routine home visit. Replacing monthly case management on papers between VHVs and PHU staff, the vaccination history of the infant/child was updated on each VHV’s tablet. Monthly information about EPI schedule, plus additional picture and pronunciation of each child’s name, was routinely transmitted and synchronized between VHV and responsible PHU’s tablet. On the set vaccination dates at the PHU each month, health care personnel employed pictures and pronunciation data obtained from the VHV’s tablets, by presenting the child’s picture on a television screen and calling out the child’s name in the ethnic language from the PHU’s tablet. Behavior change communication (BCC) and advocacy in the community is another preventive measure that was developed. Based on the United Nations Children’s Fund (UNICEF)’s guideline for communication strategy for a development program , the effExpected project outcomes were changes in EPI coverage, and BCC determinants over time. EPI monthly coverage data, by child age and by different type of vaccine, were collected from quarterly reports from the three PHUs to the Ministry of Public Health, submitted from January 2011 to February 2012, and from March 2012 to March 2013, before and after project implementation. BCC outcomes are based on repeat surveys from the same respondents in relation to maternal knowledge, attitudes, and practices (KAP) toward EPI vaccination. As part of the formative project evaluation, surveys were collected at months 6 and 12 after BCC was first launched. The KAP survey content was based on messages delivered via the BCC package. With due consideration of limited literacy among minorities in remote settings, the KAP questionnaire was constructed with minimum critical issues and simplicity of format. The KAP survey composes of 6 items on knowledge, 5 items on attitude, and 6 items on practice. The survey items were developed by consensus among three content experts on immunization and one on hilltribes in the study area. The survey items were piloted and revised in the nearby villages of the study areas and with different ethnics groups participating in this study. The surveys were conducted using individual interview methods by trained, designated VHVs. The VHV interviewer either spoke Thai or translated the items according to the precoded script. The analysis of the data was simply descriptive statistics.Access to EPI management systems and databases is strictly controlled, and only permitted for authorized health care personnel and village health volunteers in charge of case management. Information sharing on tablets as part of the phone-to-phone mechanism maintains all crucial features of data integrity and confidentiality, mirroring the routine paper-based processes at the local health care clinics, and during routine site/home visits.Mothers and/or children who visited the health care clinics signed no written informed consent or assent form, or when meeting with health care personnel during site/home visits; all activities were routine work performed as part of standard health care practices. Data extracted for analysis were all secondary data and summary statistics, and were not identification (ID)-linked. The authors were granted permission to use extracted data for analysis from the authorized person at the Chiang-Rai Provincial Health Office. The study protocol was reviewed and approved by the Ethics Committee, Faculty of Tropical Medicine, Mahidol University.During the study period, a total of 3649 highland children age < 6 years were registered in the three PHUs. Immunizations for tuberculosis (BCG) and hepatitis B (HepB) have been reported at 100%, according to the records that all children were immunized at the hospital at birth. Vaccine coverage for children age 1 year showed a slight improvement after project implementation. Overall immunizations for OPV and DTP increased from 91.7% (483/527) to 94.4% (408/432), while measles increased from 89.2% (470/527) to 89.6% (387/432)  to 86.6% (362/418), while JE increased from 83.9% (380/453) to 87.6% (366/418). However, the minimum-maximum range for monthly immunizations of OPV-DTP changed from 77% (24/31)-94% (31/33) to 60% (12/20)-96% (24/25), and for JE it was 67% (24/36)-93% (27/29) to 68% (21/31)-98% (43/44). Due to a change in the JE vaccine schedule for children age 3 years during the project implementation period, the overall coverage for JE decreased from 80.6% (348/432) to 75.4% (310/411), while the minimum-maximum range changed from 71% (20/28)-91% (20/22) to 68% (21/31)-88% (29/33). Among children age 4 years, the overall coverage for OPV and DTP increased from 73.2% (372/508) to 78.0% (348/446), and the minimum-maximum range for monthly immunizations changed from 54% (13/24)-87% (27/31) to 58% (21/36)-89% (17/19).Repeat KAP surveys were carried out among the 7 highland minority groups, and composed of: 32.5% (104/320) Akha, 25.3% (81/320) Lahu, 15.6% (50/320) Hmong, 11.3% (36/320) Mein, and other groups ; about 7Knowledge scores, measured at months 6 and 12 after the BCC was launched, appeared to increase, but without statistical significance. The percentages of those who scored > 50% correct about a particular disease changed from 82.2% (263/320) to 88.8% (284/320) . RegardiThe technical challenge of applying information sharing between tablets of VHVs and health care personnel staff in remote areas was manageable. The telephone signals in the highland project implementation villages varied, but all data could be transmitted when a telephone signal was available, while other routine activities and data collection during each home visit were conducted offline. This proved that the innovation could be useful in hard-to-reach populations. Other research also suggests this kind of innovation can yield timely information for improving case management, delivering much higher quality, validity, and reliability ,37. In aIn 2011, Thai nationwide statistics indicated that vaccine coverage rates were > 90%: 99% for BCG, DTP, and OPV; and 98% for measles and HepB . But as As suggested in the literature, nonimmunization or lower immunization rates could be partly attributable to the complexity of individual, community, and legal factors involved. The most common explanations about this outcome concern competing priorities in child immunization, working longer hours due to poverty, and being socially and legally alienated ,23,43. SDifferences in culture and beliefs in relation to the health care-seeking behaviors of hilltribe peoples represent an ongoing challenge. The BCC animations with selectable languages have been implemented and accepted by all stakeholders. As part of the development of a selectable language BCC, the script translation into 7 ethnic languages was quite a challenge. While many common and technical words are equivalent to Thai or English, sometimes no words had precisely the same meaning. Moreover, some words have different spellings and pronunciations, even within the same tribe. However, posttesting translations and back-translations and piloting their use among several tribal groups achieved a solution.In analyzing the postlaunch success of BCC in the community, the KAP survey revealed that the mothers had good knowledge, a positive attitude, and employed proper practices at completion of the 6 month survey, and demonstrated even higher levels at the 12 month follow-up. In this study, even though knowledge of diseases under the EPI scheme measured at 2 time points were not statistically significant; the overall percentage of correct answers was higher at 12 months. As shown by studies of factors associated with completing immunization in vulnerable populations, the primary goal of EPI activities and interventions should be strengthening communication and raising awareness in the community; inadequate knowledge regarding the objectives and importance of immunization demonstrably leads to low vaccine coverage ,48. The To meet the challenge of attaining their maternal and child health Millennium Development Goals, the WHO and UNICEF have recommended countries to implement a central strategy of immunizing hard-to-reach infants and other age groups by focusing more on work carried out at district level . This st


To the Editor: New World cutaneous leishmaniasis (CL), a zoonotic disease, is increasingly seen among travelers returning from Latin American countries, particularly from Bolivia, Belize, and French Guiana . We report an outbreak of 7 cases of Among the 7 patients, 6 were male; mean age was 32 ± 5 years. None of the patients were immunocompromised. The scientists stayed in Saül a mean of 17 (range 12–30) days. The mean time to symptom onset after they left Saül was 19 (range 0–50) days. The mean number of CL lesions was 2.3 (range 1–5). Lesions were localized mainly on lower limbs (11/14 lesions) but also appeared on upper limbs (2/14 lesions) and ears (1/14 lesions). CL was associated with nodular lymphangitis, adenitis, and superficial phlebitis of the affected limb in 2, 3, and 1 patient, respectively. No patients had mucosal involvement, fever, or decline in general health. Leishmania species–specific PCR result, or both. L. braziliensis complex was diagnosed by using different molecular techniques, according to the laboratory, and then confirmation of L. braziliensis species was conducted by the French National Reference Center for Leishmaniasis on the basis of a putative translation initiation factor α-subunit gene sequence  in deep forest areas with hot spots of transmission. Favorable environmental conditions in a well-delimited zoonotic microfocus hot spot might have contributed to this high rate of transmission. However the relative genetic diversity of strains we observed among the 5 analyzed patients was unexpected, given the relatively small spatial and temporal scale of the transmission area, and indicates that the reservoirs in this restricted area were infested by distinct genotypes. Development of a peridomestic cycle, perhaps with specific reservoirs (pets) and vectors, cannot be excluded in the Saül area.This outbreak of L. braziliensis parasites cause <10% of CL acquired in French Guiana, this species is noteworthy for its involvement of the mucous membranes of the lips, nose, soft palate, or larynx. Also, L. braziliensis parasites usually fail to respond to pentamidine isethionate, the first-line treatment of L. guyanensis CL in French Guiana; instead, treatment of L. braziliensis infection relies on parenteral meglumine antimoniate or liposomal amphotericin B (This case series suggests that caution should be taken in the diagnosis and treatment of CL in patients returning from the Amazonian rainforest, and a species-specific approach based on molecular identification should be proposed to provide appropriate medical management (L. braziliensis cases in the Guiana ecoregion complex, as observed in the rest of South America, are worrisome, and continuous epidemiologic surveillance is needed. Infection with L. braziliensis, which is emerging and has potential to disseminate, must be considered in cases of CL acquired in this region. These issues have key implications for leishmaniasis treatment, which should be directed to the identified species (In summary, the geographic extension of and numeric increase in