Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma

Background Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. Methods We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan–Meier method and compared by the Log Rank test. Results Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039). Conclusion Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies (AU)

Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma.

BACKGROUND: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. METHODS: We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan-Meier method and compared by the Log Rank test. RESULTS: Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039). CONCLUSION: Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies.

Outcomes of extraskeletal vs. skeletal Ewing sarcoma patients treated with standard chemotherapy protocol.

PURPOSE: To compare the outcomes of extraskeletal and skeletal Ewing sarcomas treated with standard chemotherapy protocol. METHODS: We retrospectively collected data on primary localized skeletal and extraskeletal ES patients. Demographics and disease characteristics were compared between the two groups. The influence of presentation (skeletal vs. extraskeletal) on overall survival (OS) and local recurrence-free survival (LRFS) was assessed and compared by the log-rank test. RESULTS: A total of 120 patients were included; 29 (24%) had extraskeletal and 91 (76%) had skeletal ES. All patients received vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE) chemotherapy, with a plan for local control at week 12. At a median follow-up of 38 months, there was no difference in OS between skeletal and extraskeletal ES; 5-year OS 70% and 67% respectively, p = 0.96. Patients with extraskeletal ES had inferior 5-year LRFS compared to skeletal ES; 74% vs. 83%; p = 0.042. Local recurrence occurred at a higher frequency in the extraskeletal group; 28% vs. 11%, p = 0.034, although more extraskeletal patients received adjuvant radiotherapy; 73% vs. 36%, p = 0.01. Among patients who underwent surgery (n = 76), there was no difference in R0 resection rate (skeletal: 89%, extraskeletal: 86%, p = 0.52, or good ( ≥ 90%) tumor necrosis; skeletal: 54%, extraskeletal: 38%, p = 0.31. CONCLUSION: Patients with localized extraskeletal ES have comparable OS outcomes to patients with skeletal ES utilizing the standard VDC-IE chemotherapy. However, extraskeletal patients are at significantly higher risk for local recurrence.

Impact of Ramadan Focused Education Program on medications adjustment for patients with type 2 diabetes in a primary health care institution in Saudi Arabia.

AIMS: To examine the impact of Ramadan Focused Education Program (RFEP) on medications adjustment in type 2 diabetes patients in Ramadan. METHODS: This is a controlled, intervention based study. It was run on three phases: before, during, and after Ramadan on 262 type 2 diabetes patients. The intervention group (n = 140) received RFEP on medications doses & timing adjustment before and after Ramadan, while the control group (n = 122) received standard care. RESULTS: The dose of insulin glargine was reduced from 42.51 ±â€¯22.16 at the baseline to 40.11 ±â€¯18.51-units during Ramadan (p = 0.002) in the intervention group while it remained the same in the control group before Ramadan and during Ramadan (38.51 ±â€¯18.63 and 38.14 ±â€¯18.46, P = 0.428, respectively). The hypoglycemia score was 14.2 ± (8.5) pre-Ramadan in the intervention and reduced to 6.36 ±â€¯6.17 during Ramadan (p < 0.001) while in the control group, no significant changes were noted before and during Ramadan (14.01 ±â€¯5.10 versus 13.46 ±â€¯5.30). CONCLUSIONS: Ramadan Focused Education Program done at a primary healthcare setting had a positive impact on medication adjustment for dose and timing during fasting in Ramadan in diabetic patients, and it can be a useful tool to achieve better outcomes; less hypoglycemia and safe fasting among T2D patients during Ramadan.

Equine piroplasmosis in Kelantan, Malaysia: Clinicohemato-biochemical alterations in subclinically and clinically infected equids.

Equine piroplasmosis (EP) is global disease of equids affect the international movement of horses and their industry. This work was conducted on a random collection of blood samples from a total of 306 equids (horses and ponies) comprising both clinically healthy (n=276) and clinically suspected animals (n=30) for EP from 53 stables in eight districts at Kelantan, Malaysia. Competitive-inhibition enzyme linked immunosorbent test (cELISA) was applied to detect the antibodies for Theileria equi and Babesia caballi and their titers in the serum. Hemato-biochemical parameters were analyzed from blood and serum samples from clinical and subclinical cases in comparison to healthy animals (n=25) a control group. The overall prevalence of EP infections (T. equi, B. caballi and both infections) in subclinical and clinical infected equids was 70.26 and 9.80 per cent, respectively. The subclinical infection in equids was statistically higher than that of clinical infection (P<0.05). Higher titration of T. equi antibodies in clinical infected cases ranged from 1/160 to 1/1280 in (n=27), whereas in B. caballi the titres ranged from 1/160 to 1/640 (n=26). Manifestation in clinical cases was the acute onset of the disease, with significant Hemato-biochemical changes. Whereas, equids with subclinical infection appeared healthy with absence of clinical signs and non-significant Hemato-biochemical alterations were seen as compared to clinical cases and healthy control groups.

Equine piroplasmosis in Kelantan, Malaysia: Clinicohemato-biochemical alterations in subclinically and clinically infected equids

Equine piroplasmosis (EP) is global disease of equids affect the international movement of horses and their industry. This work was conducted on a random collection of blood samples from a total of 306 equids (horses and ponies) comprising both clinically healthy (n=276) and clinically suspected animals (n=30) for EP from 53 stables in eight districts at Kelantan, Malaysia. Competitive-inhibition enzyme linked immunosorbent test (cELISA) was applied to detect the antibodies for Theileria equi and Babesia caballi and their titers in the serum. Hemato-biochemical parameters were analyzed from blood and serum samples from clinical and subclinical cases in comparison to healthy animals (n=25) a control group. The overall prevalence of EP infections (T. equi, B. caballi and both infections) in subclinical and clinical infected equids was 70.26 and 9.80 per cent, respectively. The subclinical infection in equids was statistically higher than that of clinical infection (P<0.05). Higher titration of T. equi antibodies in clinical infected cases ranged from 1/160 to 1/1280 in (n=27), whereas in B. caballi the titres ranged from 1/160 to 1/640 (n=26). Manifestation in clinical cases was the acute onset of the disease, with significant Hemato-biochemical changes. Whereas, equids with subclinical infection appeared healthy with absence of clinical signs and non-significant Hemato-biochemical alterations were seen as compared to clinical cases and healthy control groups.

Constructing a question bank based on script concordance approach as a novel assessment methodology in surgical education.

BACKGROUND: Script Concordance Test (SCT) is a new assessment tool that reliably assesses clinical reasoning skills. Previous descriptions of developing SCT-question banks were merely subjective. This study addresses two gaps in the literature: 1) conducting the first phase of a multistep validation process of SCT in Plastic Surgery, and 2) providing an objective methodology to construct a question bank based on SCT. METHODS: After developing a test blueprint, 52 test items were written. Five validation questions were developed and a validation survey was established online. Seven reviewers were asked to answer this survey. They were recruited from two countries, Saudi Arabia and Canada, to improve the test's external validity. Their ratings were transformed into percentages. Analysis was performed to compare reviewers' ratings by looking at correlations, ranges, means, medians, and overall scores. RESULTS: Scores of reviewers' ratings were between 76% and 95% (mean 86% ± 5). We found poor correlations between reviewers (Pearson's: +0.38 to -0.22). Ratings of individual validation questions ranged between 0 and 4 (on a scale 1-5). Means and medians of these ranges were computed for each test item (mean: 0.8 to 2.4; median: 1 to 3). A subset of test items comprising 27 items was generated based on a set of inclusion and exclusion criteria. CONCLUSION: This study proposes an objective methodology for validation of SCT-question bank. Analysis of validation survey is done from all angles, i.e., reviewers, validation questions, and test items. Finally, a subset of test items is generated based on a set of criteria.

Radiological findings in gliosarcoma. A single institution experience.

Gliosarcomas are rare tumors with a poor prognosis composed of intermingled malignant glial and sarcoma elements with an estimated incidence of 1.8-8.0% of all malignant astrocytic neoplasms. We aimed to review the imaging findings in eight patients with gliosarcoma who were treated in our center between 2002 and 2010. The diagnosis was confirmed by morphological and immunohistochemical stains. This study, to the best of our knowledge, is the largest describing the imaging manifestations of this tumor. Although our study revealed no unique radiological features for gliosarcoma, it is important to note that they all demonstrated either dural or ependymal involvement or both. Calcification, hemorrhage or cystic components are described with a tendency for a ring enhancement pattern. Interestingly pre-existing benign looking lesions and associated remotely located small meningiomas are also described.

Better be prepared than sorry: what should the New Zealand healthcare system learn from the 2009 Pacific Tsunami?

On the early hours of the 29 September 2009, an earthquake in the Pacific generated a massive tsunami that caused significant destruction and claimed many lives across several Pacific nations. The disaster initiated an international relief operation from New Zealand (NZ), Australia, and the United States. The NZ healthcare response was adequate given the multiple challenges encountered. This article reviews the challenges faced by NZ healthcare responders to the Pacific Tsunami. Furthermore, it presents the lessons learnt from this operation in order to enhance the NZ healthcare system preparedness to respond to future disasters and mass emergencies nationally and internationally.

Infections with the 2009 H1N1 influenza virus among hematopoietic SCT recipients: a single center experience.

We retrospectively reviewed medical records of 39 hematopoietic SCT (HSCT) recipients who presented at our hospital between 1 October 2009 and 31 January 2010 with the 2009 H1N1 influenza infection. The median age at presentation was 13.8 years (range: 3.3-56.9), infections developed at a median of 585 days (range: 0-2316) post transplant, the majority (n=27, 69%) occurred in allogeneic HSCT recipients, 12 (31%) patients were on immunosuppressive therapy and 12 (31%) had GVHD. Lower airway disease was present in 8 patients (21%). In total, 15 patients (39%) were hospitalized with a median duration of 4.5 days (range: 3-27 days) and 3 (8%) required mechanical ventilation; 2 of whom died.

Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators.

BACKGROUND: The survival of retinoblastoma in less-developed countries (LDCs) and the impact of socioeconomic variables on survival are not widely available in the literature. METHODS: A systematic review of publications from LDCs was performed. Articles were from multiple databases and written in seven languages. Results were correlated with socioeconomic indicators. Lower-income countries (LICs) and middle-income countries (MICs) were included in our analyses. RESULTS: An analysis of 164 publications including 14,800 patients from 48 LDCs was performed. Twenty-six per cent of the papers were written in languages other than English. Estimated survival in LICs was 40% (range, 23-70%); in lower MICs, 77% (range, 60-92%) and in upper MICs, 79% (range, 54-93%; p = 0.001).Significant differences were also found in the occurrence of metastasis: in LICs, 32% (range, 12-45); in lower MICs, 12% (range, 3-31) and in upper MICs, 9.5% (range, 3-24; p = 0.04). On multivariate analysis, physician density and human development index were significantly associated with survival and metastasis. Maternal mortality rate and per capita health expenditure were significantly associated with treatment refusal. CONCLUSIONS: Important information from LDCs is not always available in English or in major databases. Indicators of socioeconomic development and maternal and infant health were related with outcome.

Clinical profile of sleep apnea syndrome. A study at a university hospital.

OBJECTIVES: To review a series of patients with sleep apnea syndrome, to promote more awareness and alert local health professionals to early diagnosis and treatment. METHODS: We studied, prospectively, 48 consecutive patients who were managed at the university hospital from 1992 to 1996. RESULTS: The male:female ratio was 1.4:1. The mean interval between onset of symptoms and the diagnosis was 5.5 years (range 0.25 to 30). In over half of the patients the diagnosis was not suspected upon referral. The mean body mass index was 42.8 kg/m2, (range 25 to 76). Daytime hypoxemia was present in 28 patients (58%), while 26 (54%) had Pa CO2 > 45 mmHg, mainly as a result of obesity-hypoventilation syndrome. Significant proportions had systemic and pulmonary hypertension (60% and 23%), and 32% had ischemic heart disease. All patients, but one, tolerated continuous positive airway pressure, but cost of the equipment led some to prefer surgical treatment that is offered free. CONCLUSION: This series shows a bias towards female sex and frequent association with obesity-hypoventilation syndrome. In many cases the diagnosis was not suspected suggesting poor recognition and awareness of sleep apnea syndrome. Monitoring pulse oximetry during sleep was helpful in the diagnosis and titration of continuous positive airway pressure. Ways of providing continuous positive airway pressure under the health system need to be studied.

Mesiodistal crown diameters of permanent teeth in Jordanians.

Mesiodistal crown diameters were measured from dental casts of the permanent teeth of 198 Jordanians (86 males and 112 females), aged 13.4-19.1 years. The differences in the crown diameters between the right- and left-hand sides of the dental arch were not significant, suggesting that either right- or left-side measurements could be taken to represent the tooth size of the study population. Males had significantly larger teeth than females, ranging from p < 0.05 for the incisors to p < 0.001 for the first molars. In both sexes, the maxillary lateral incisors showed the greatest variability [coefficient of variation (CV) 8.8%] and the first molar the least (CV 5.8%) in mesiodistal diameter. Canines displayed greater sexual dimorphism in crown size than any other tooth class. The cumulative tooth widths of males exceeded those of females by a sum of 3.1 mm in the maxilla and 3.6 mm in the mandible. These differences were statistically significant (p < 0.01). Comparisons of the mesiodistal crown diameters between population groups showed that Jordanians have tooth sizes close to those of Iraqis, but significantly larger than those of Yemenite-Jews, Caucasians and Chinese.

Studies of sheep experimentally poisoned with Hypericum perforatum.

Sheep given different dosages and frequencies of Hypericum perforatum had decreased hemoglobin, red blood cell count, packed cell volumes, total protein, glucose, cholesterol, triglycerides, and serum alkaline phosphotase activities. Blood urea nitrogen, sodium, potassium, bilrubin (total and direct), and the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma glutamyltransferase increased. Hemato-biochemical assays were useful diagnostic aids to determine the severity of this plant's toxic effects.

Heart preservation: analysis of cardioprotective infusate characteristics. Membrane stabilization, calcium antagonism, and protease inhibition on myocardial viability: a biochemical, ultrastructural, functional study.

Thirty-three canine hearts were isolated after initial cardioplegia and preserved for 6 hours in 4 degrees C saline solution with intermittent infusion of cardioprotective solution every hour. Reperfusion was observed for 2 hours under normothermic cross-circulation. Hearts were divided into five groups depending on the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP) infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group II (n = 7) received betamethasone (250 mg/L) added to the formula for group I; group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of group III. Coronary sinus MB fraction of creatine kinase level was significantly decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme release decreased in group IV. Myocardial adenosine triphosphate levels and total adenine nucleotides showed no significant difference among the groups at the end of reperfusion; however, myocardial adenosine diphosphate and adenosine monophosphate levels during reperfusion increased significantly in group I, and myocardial adenosine diphosphate and adenosine monophosphate levels at the end of reperfusion in groups I and IV were significantly higher than those of the control. Calcium overload, which was lowest in group II, was not completely prevented during reperfusion in any group. Left ventricular end-systolic pressure volume relationship in group II showed the "best" functional recovery. In addition, the ultrastructure of the left ventricular myocardium was well preserved in all groups. These results suggest that membrane stabilization with lidocaine and betamethasone affords beneficial effects on myocardial biochemical and functional viability. Diltiazem appears to be less effective in preventing calcium overload during ischemia-reperfusion, and protease inhibition with aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal enzyme activation-release and maintaining myocardial adenosine diphosphate and adenosine monophosphate levels.

The significant role of membrane stabilization in hypothermic cardioplegic cardiac preservation in a canine experimental model.

Isolated mongrel hearts were preserved for 6 h at 5 degrees C followed by normothermic reperfusion for 2 h. The dogs were divided into three groups; K+-cardioplegic solution alone, group C, n = 7; K+-cardioplegic solution with lidocaine 200 mg/l, group L, n = 7; and K+-cardioplegic solution with betamethasone 250 mg/l and lidocaine 200 mg/l, group B + L, n = 7. Ventricular fibrillation occurred early during reperfusion in all dogs in group C, in one of seven in group L, and in two of seven dogs in group B + L. The serum MB fraction of creatinine kinase (MB-CK), mitochondrial aspartate aminotransferase (m-AAT) and calcium overload were suppressed to a greater extent in both groups L and B + L during reperfusion compared to group C. Myocardial ATP, total adenine nucleotide, and creatine phosphate did not differ between the three groups at the end of reperfusion. Myocardial ADP and AMP declined significantly during reperfusion in group C, however, they remained unchanged in group B + L and increased in group L which showed significantly higher levels compared to group C. Left ventricular functional recovery during reperfusion was consistently better in both group L and B + L compared to group C. These results suggested that membrane stabilization prevents myocardial damage from hypothermia and cardioplegia and provides better myocardial viability and functional recovery in donor heart preservation.

Effect of aprotinin to improve myocardial viability in myocardial preservation followed by reperfusion.

Isolated canine hearts were preserved at 4 degrees C with multi-dose cardioplegic solution every hour for 6 hours. Reperfusion was observed for 2 hours under cross-circulation without cardiotonic drugs. The aprotinin group (n = 8), which received cardioplegic solution with added aprotinin (150 KIU/mL), was compared with the control group (n = 6). The increase in tissue adenosine triphosphate and total adenine nucleotide content during reperfusion was significant in the aprotinin group; there was no change in the control group, and the levels at the end of reperfusion tended to be higher in the aprotinin group than in the control group. Tissue adenosine diphosphate levels remained unchanged in both groups. Tissue adenosine monophosphate levels declined during reperfusion in both groups and were slightly lower in the control group. Tissue levels of cyclic adenosine monophosphate remained unchanged in the aprotinin group whereas they increased during ischemia and declined significantly during reperfusion in the control group. Tissue levels of cyclic guanosine monophosphate declined during reperfusion in both groups without difference. Creatine phosphate levels recovered in both groups without difference. Serum cyclic guanosine monophosphate concentration tended to be lower in the aprotinin group than in the control group. Serum creatine kinase-MB level increased slightly during reperfusion in both groups without difference. N-acetyl-beta-D-glucosaminidase levels were significantly suppressed during reperfusion in the aprotinin group as compared with the control group. These results suggest that aprotinin is effective in preserving adenine nucleotide and adenosine triphosphate levels and in stabilizing tissue cyclic adenosine monophosphate levels in prolonged hypothermic cardioplegic preservation followed by reperfusion.

Clinical experience of coenzyme Q10 to enhance intraoperative myocardial protection in coronary artery revascularization.

Seventy-eight patients undergoing coronary artery bypass grafting (CABG) were compared retrospectively to evaluate whether pretreatment with coenzyme Q10 (CoQ) is effective in preventing left ventricular depression in early reperfusion following CABG. CoQ (5 mg/kg, intravenously) was given to 60 patients, 2 hours prior to the onset of cardiopulmonary bypass (CPB). CABG was performed using saphenous vein under CPB associated with cold cardioplegia in the standard fashion. Heart rate, mean arterial pressure, and cardiac index showed no significant difference between the CoQ and control groups. However, left ventricular stroke work index was significantly elevated at 6 and 10 hours of reperfusion following CABG in the CoQ-treated group compared with the controls. Serum MB-CK was lower at 0 and 6 hours of reperfusion in the CoQ group compared with the controls. These results suggest that pretreatment with intravenous CoQ is effective in preventing left ventricular depression in early reperfusion and in minimizing myocardial cellular injury during CABG followed by reperfusion.

The tonsillar carriage of Pasteurella haemolytica in lambs.

To study colonization of the tonsils by Pasteurella haemolytica, attempts were made to isolate the organism from the tonsils of lambs which died or were killed in the course of unrelated experiments. In addition, repeated tonsillar swabs were taken from 37 lambs and their 28 dams over a 3-month period. From lambs under 3 days old, only A serotypes and untypable strains of P. haemolytica were recovered, while T serotypes were first detected in 3-week-old lambs. As the age of the lambs increased, the fall in the isolation rate of A serotypes and of untypable strains was accompanied by an increase in T serotype isolation. In lambs 9 to 12 weeks old, over 80 per cent of isolates were T serotypes. Of the 222 swabs from live lambs, 88 (40 per cent) yielded P. haemolytica, with more than one serotype being recovered from 24 of the 88 positive swabs. Multiple isolations, mostly of 2 serotypes, were made from lambs of all ages but were commonest at 12 weeks of age. Of the 117 isolates, 70 (60 per cent) were of biotype T, 31 (26 per cent) were of biotype A and 16 (14 per cent) were untypable. P. haemolytica was isolated from 25 of the 28 ewes on 1 to 5 of the 6 sampling occasions. The 65 positive swabs yielded 81 T serotypes (78 per cent), 21 A serotypes (20 per cent) and one untypable strain as 32 single and 33 multiple isolations. The typed isolates comprised 7 A serotypes and 3 T serotypes. Only one serotype (A6) isolated from lambs was not recovered from ewes.(ABSTRACT TRUNCATED AT 250 WORDS)