Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

Evaluation of an educational module on dengue and Aedes aegypti for schoolchildren in Honduras]

OBJECTIVE: To evaluate the effectiveness of a special course on environmental health and dengue, given to primary school students and intended to promote behavioral changes in the mothers of those students that would lead to the safe handling of water, adequate disposal of trash, and control of household breeding sites of Aedes aegypti, the mosquito vector for dengue. METHODS: In the period from April to November 2002 a community field trial was carried out that included four public schools in the city of Comayaguela, Honduras. Two of the schools formed the intervention group, and the two others made up the comparison or control group. The data collection activities before and after the intervention included knowledge tests for the schoolchildren and the teachers; surveys of the knowledge, attitudes, and practices of the students' mothers; entomological surveys (systematic checking in order to find water containers, to search for mosquito larvae) in the homes of the schoolchildren; in-depth interviews with the students' mothers; observation in the classrooms; and postintervention focus group with the teachers. RESULTS: During the intervention period the largest epidemic of classical dengue ever in the history of Tegucigalpa, the capital of Honduras, occurred. That event prompted the Secretariat of Health to undertake large-scale control activities. In the two intervention schools there was a significant increase in the students' knowledge of the following three variables: dengue caused by a virus, life cycle of the vector, and reduction of breeding sites, which is the most effective measure for controlling the vector (P < 0.0001 for all those increases in knowledge). There were also significant increases in the knowledge of the same variables among the teachers in the intervention schools: dengue caused by a virus (P = 0.03), life cycle of the vector (P = 0.01), and reduction of breeding sites (P = 0.004). Reducing the number of breeding sites as being the best measure for controlling Aedes aegypti was the knowledge variable that showed the greatest change among the mothers in the intervention group (P = 0.02). The values for two of the entomological indices (the House index and the Breteau index) were better in the intervention group than in the control group, but the difference was not statistically significant. However, there was a statistically significant difference in the Breteau index values between the two control group schools and the one intervention school where the education course was implemented more adequately than in the other intervention school. CONCLUSIONS: The application of educational interventions directed to schoolchildren, as a part of a comprehensive plan for controlling Aedes aegypti, is an effective way to raise the awareness of teachers and parents with respect to the problem of dengue, and it also helps in encouraging family members to be involved in reducing breeding sites in the home. In moving to control the dengue vector, this strategy should take into consideration the involvement not only of families but also of civic and public institutions in the community. Given our results, it appears that this approach of using a special course for schoolchildren can constitute a fundamental pillar in the strategy for integrated dengue control.     

The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis.

PURPOSE: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease commonly associated with epilepsy refractory to anticonvulsants. Individual reports indicate that seizures in children with tuberous sclerosis might benefit from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years of age in three boys with tuberous sclerosis and refractory partial seizures. METHODS: On admission a classical LCT ketogenic diet was initiated and patients were followed for 12 months. Antiepileptic drugs were maintained unless adverse effects required reduction. RESULTS: Two patients became seizure-free within 2 months on the diet. In the third patient drop attacks decreased significantly. On follow-up the diet was well accepted and without adverse effects. CONCLUSION: The ketogenic diet should be considered as a treatment option for children with tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data support the need for further studies in larger cohorts to confirm the effectiveness of the ketogenic diet in this entity.     

Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors study.

PURPOSE: Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients. PATIENTS AND METHODS: Patients > or = 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion. RESULTS: By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival. CONCLUSION: Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.     

Epididymal metastases as the first sign of a colon cancer recurrence

Metastastic tumours involving the epididymis are rare and most often found in patients with disseminated disease. It is even more unusual when the metastasis of the epididymis is the first sign of tumour recurrence. We report a case of an asymptomatic recurrent colon carcinoma presenting as metastasis in the epididymis. Although metastatic cancer presenting as an intra-scrotal mass is extremely rare, it should be considered as a possibility in patients who present with a mass involving the testicle or epididymis.     

Prognostic impact of the preoperatory neutrophil/lymphocyte index on early surgical complications of patients with colorectal cancer

Colorectal cancer (CRC) is found among those with greatest frequency and exponential increase worldwide, with high mortality rates, which are observed as increasing due to the postsurgical complications that come to present. Systemic inflammation participates in the development and progression of cancer; therefore, inflammatory and/or immunological response markers such as the neutrophil/lymphocyte index (NLI) can aid us in predicting the poor results of our interventions. The purpose of our study was to determine the impact of an NLI of ≥2.6 as a predictor of early postsurgical complications. By means of a prospective cohort, we analyzed 158 patients with CRC who were submitted to elective surgery with a later 30-day follow-up. We found that the preoperatory NLI of ≥2.6 obtained an odds ratio (OR) = 2.24 (95% confidence interval [CI], 1.15-4.36) as a prognostic factor of early postsurgical complications according to the Clavien-Dindo classification scale, which represents a low prognostic impact due to its predictive yield with low accuracy, which is the opposite of what other reports have previously published. The use of chemotherapy before the surgical procedure was also determined to be a risk factor for post-surgical complications.     

Dental anomalies in cleft lip and palate: A case–control comparison of total and outside the cleft prevalence

This study’s objective was to compare the total and outside the cleft prevalence of dental anomalies (DA) between patients with cleft lip and palate (CLP) and a control group. This retrospective cross-sectional study was done under a case–control design. The case group consisted of 192 non-syndromic patients with complete CLP, while the control group included 411 patients. All subjects had orthopantomography, intra, and extraoral photographs. The prevalence of dental agenesis, supernumerary teeth, impacted teeth, dental transposition, and microdontia were compared using a chi-squared test (P < .05). Next, a second test was made, but only the anomalies outside the cleft were considered for this study. Total prevalence was 89.1% for cases, and 20.9% for controls (P < .01). The prevalence of each DA was significantly higher for the case group. In the analysis of DAs outside the cleft, the total prevalence was still significantly associated (P < .01); however, only dental agenesis was statistically significant (P < .01). Further analysis found that a high rate of upper premolar absence (P < .01) could explain this event. Patients with CLP have a higher prevalence of DAs compared to controls. After considering only the DAs outside the cleft, the total prevalence remains significantly higher. However, this phenomenon is explained mainly by the elevated prevalence of upper premolars’ agenesis. This study’s results suggest that environmental factors are behind the high prevalence of DAs in subjects with CLP.     

Anti‐SARS‐CoV‐2 IgG antibody levels among Thai healthcare providers receiving homologous and heterologous COVID‐19 vaccination regimens

BackgroundWe examined SARS‐CoV‐2 anti‐spike 1 IgG antibody levels following COVID‐19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer‐BioNTech [PZ]) among Thai healthcare providers.MethodsBlood specimens were tested using enzyme‐linked immunosorbent assay. We analyzed seven vaccination regimens: (1) one dose of AZ or SV, (2) two doses of homologous (2AZ, 2SV) or heterologous (1AZ + 1PZ) vaccines, and (3) three doses of heterologous vaccines (2SV + 1AZ, 2SV + 1PZ). Differences in antibody levels were assessed using Kruskal–Wallis statistic, Mann–Whitney test, or Wilcoxon matched‐pairs signed‐rank test. Antibody kinetics were predicted using fractional polynomial regression.ResultsThe 563 participants had median age of 39 years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22–23 days in both 1AZ and 2SV vaccinees and dropped below assay''s cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55 days among 1AZ vaccinees compared with 117 days among 2SV vaccinees. 1AZ + 1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1–4 weeks post vaccination. 2SV + 1PZ vaccinees had significantly higher antibody levels than 2SV + 1AZ vaccinees 4 weeks post vaccination (3423 vs. 2105 BAU/ml; p‐value < 0.01), and during weeks 5–8 (3656 vs. 1072 BAU/ml; p‐value < 0.01). Antibodies peaked at 12–15 days in both 2SV + 1PZ and 2SV + 1AZ vaccinees, but those of 2SV + 1AZ declined more rapidly and dropped below assay''s cutoff in 228 days while those of 2SV + 1PZ remained detectable.Conclusions1AZ + 1PZ, 2SV + 1AZ, and 2SV + 1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti‐S1 IgG antibodies for possible protection against SARS‐CoV‐2 infection.