Tetanus and Occam's Razor: Almost Forgotten but Not Gone: A Case Report.

Tetanus is a rare disease in industrialized countries, largely due to the highly protective effect of immunization. We present a case of tetanus in a formerly preterm infant with myelomeningocele repaired in utero, who presented at 44 days of age with poor feeding, lethargy, and increased tone. His symptoms progressed despite a course of antibiotics for presumed meningitis. At 73 days of age (on 29th day of hospitalization), a clinical diagnosis of tetanus was made based on the presence of risus sardonicus, trismus, and generalized hypertonicity. Consequently, tetanus immune globulin, muscle relaxants, and metronidazole were administered. Five months later, the infant has had complete resolution of the hypertonicity, has regained normal jaw movement and swallowing, and is regaining oral feeding skills. This case involved a delay in diagnosis despite clinical symptoms and signs classic, in retrospect, for tetanus, highlighting the importance of recognizing the constellation of symptoms that should lead us to consider this rare diagnosis.

Omega-3 fatty acids modulate neonatal cytokine response to endotoxin.

Neonatal immune response is characterized by an uncompensated pro-inflammatory response that can lead to inflammation-related morbidity and increased susceptibility to infection. We investigated the effects of long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) pre-treatment on cytokine secretion to low-concentration endotoxin (lipopolysaccharide, LPS) in THP-1 monocytes and neonatal cord blood (CB) from healthy full-term infants. Pre-treatment of THP-1 cells, with either n-3 PUFA at 25 or 100 µM significantly reduced IL-6, IL-10, and IL-12 secretion while DHA, but not EPA, reduced TNF-α response to LPS. DHA inhibition was stronger compared to EPA and effective at the low concentration. The same concentrations of n-3 PUFAs inhibited IL-12 but not IL-10 cytokine response in whole CB from 9 infants pre-treated for 24 h. To assess clinical relevance for acute response to LPS, the effects of low-concentration DHA at 25 µM or 12.5 µM were assessed before and after LPS exposure of isolated CB mononuclear cells from 20 infants for 1 h. When added before or after LPS, physiologic DHA treatment produced significant concentration-dependent inhibition of TNF-α, IL-6, IL-1ß, and IL-8 secretion. The results demonstrate prophylactic and therapeutic modulation of neonatal cytokine response to LPS and provide proof-of-concept that low-concentration administration of n-3 PUFA could attenuate or resolve neonatal inflammatory response.

Phase I trial and pharmacokinetic study of lexatumumab in pediatric patients with solid tumors.

PURPOSE: Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor-related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. PATIENTS AND METHODS: This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age≤21 years with recurrent or progressive solid tumors. RESULTS: Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response. CONCLUSION: Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.

A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas.

PURPOSE: Patients with metastatic or recurrent Ewing's sarcoma family of tumors and alveolar rhabdomyosarcoma have <25% 5-year survival in most studies. This study administered a novel immunotherapy regimen aimed at consolidating remission in these patients. EXPERIMENTAL DESIGN: Fifty-two patients with translocation positive, recurrent, or metastatic Ewing's sarcoma family of tumors or alveolar rhabdomyosarcoma underwent prechemotherapy cell harvest via apheresis for potential receipt of immunotherapy. Following completion of standard multimodal therapy, 30 patients ultimately initiated immunotherapy and were sequentially assigned to three cohorts. All cohorts received autologous T cells, influenza vaccinations, and dendritic cells pulsed with peptides derived from tumor-specific translocation breakpoints and E7, a peptide known to bind HLA-A2. Cohort 1 received moderate-dose recombinant human interleukin-2 (rhIL-2), cohort 2 received low-dose rhIL-2, and cohort 3 did not receive rhIL-2. RESULTS: All immunotherapy recipients generated influenza-specific immune responses, whereas immune responses to the translocation breakpoint peptides occurred in 39%, and only 25% of HLA-A2(+) patients developed E7-specific responses. Toxicity was minimal. Intention-to-treat analysis revealed a 31% 5-year overall survival for all patients apheresed (median potential follow-up 7.3 years) with a 43% 5-year overall survival for patients initiating immunotherapy. CONCLUSIONS: Consolidative immunotherapy is a scientifically based and clinically practical approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer. Patients receiving immunotherapy experienced minimal toxicity and favorable survival. The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach. Future studies will seek to increase efficacy by using more immunogenic antigens and more potent dendritic cells.

The safety and efficacy of laparoscopic surgical staging of apparent stage I ovarian and fallopian tube cancers.

OBJECTIVE: To compare the safety and efficacy of laparoscopic staging of ovarian or fallopian tube cancers to staging via laparotomy for epithelial ovarian carcinoma. STUDY DESIGN: We performed a case-control study of all patients with apparent stage I adnexal cancers who had laparoscopic staging from October 2000 to March 2003. The control group consisted of all patients with apparent stage I epithelial ovarian carcinoma who had staging via laparotomy during the same time period. RESULTS: Staging was laparoscopic in 20 patients and via laparotomy in 30. There were no differences in mean age and body mass index. There were also no differences in omental specimen size and number of lymph nodes removed. Estimated blood loss and hospital stay were lower for laparoscopy, but operating time was longer. There were no conversions to laparotomy or complications in the laparoscopic group, compared with 3 minor complications in the laparotomy group. CONCLUSION: In this preliminary analysis, it appears that patients with apparent stage I ovarian or fallopian tube cancer can safely and adequately undergo laparoscopic surgical staging.

Subcutaneous tumor implantation after laparoscopic procedures in women with malignant disease.

OBJECTIVE: To describe the incidence of clinically detected laparoscopy-related subcutaneous tumor implantation in women with malignant disease who were treated by a gynecologic oncology service. METHODS: We reviewed all cases of primary or metastatic malignancy who underwent a transperitoneal laparoscopy. Open laparoscopy technique was used in all cases with the Hasson trocar, usually placed near the umbilicus. A carbon dioxide pneumoperitoneum was used in all cases, with maximum intraabdominal pressure set at 15 mm Hg. All trocar sites more than 5 mm were closed at the fascia level. Identifying subcutaneous implantation was performed by a detailed review of all available medical records and by review of a prospectively maintained comprehensive complications database. RESULTS: In a 12-year period (July 1991 to July 2003), 2,593 laparoscopic procedures were performed, including 1,335 transperitoneal laparoscopies in 1,288 women with malignant disease. Malignant disease sites included adnexa/peritoneum (584), uterine corpus (355), uterine cervix (100), and other (249). There were no "isolated" trocar-related subcutaneous tumor implantations during the study period. Subcutaneous tumor implantations (n = 13, 0.97%) usually occurred with carcinomatosis, with synchronous metastases to other sites, and in the setting where the preceding laparoscopy was performed in the presence of advanced or recurrent abdominopelvic disease. CONCLUSION: Laparoscopy-related subcutaneous tumor implantation is rare (0.97%) in women undergoing transperitoneal laparoscopy with malignant disease. Subcutaneous implantation appears to occur in patients with known metastatic disease and is detected in the setting of synchronous advanced intraabdominal or pelvic metastasis and progression of carcinomatosis. The risk of subcutaneous tumor implantation should not be used as an argument against laparoscopy in the majority of women with gynecologic malignancies managed by gynecologic oncologists. LEVEL OF EVIDENCE: II-2