Giant cell arteritis and thyroid dysfunction: multicentre case-control study. The Groupe de Recherche sur l'Artériteá Cellules Géantes.
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In small-cell lung cancer, the optimal combination of chemotherapy and radiotherapy is not clearly established. To assess the value of delayed thoracic radiotherapy, we performed a randomized clinical trial in 53 complete responder patients after eight courses of chemotherapy. Twenty-seven patients received a mean of 46.5 Gy-equivalent of radiotherapy and 26 patients received no treatment until relapse. No patient dropped out of the study. Median survival time from radiotherapy randomization was 316 days in the radiotherapy group and 496 days in the no radiotherapy group. No difference was observed in survival between the two groups (p = 0.66, log-rank test) perhaps because of the small sample size. In fact, this delayed thoracic radiotherapy seemed to worsen the outcome of complete responders with small-cell lung cancer and should be avoided.
STUDY OBJECTIVE: To determine the prognostic significance of supraclavicular lymph node (SCLN) involvement in small cell lung cancer. MATERIALS AND METHODS: Patients (1,370) with small cell lung cancer were included in four consecutive clinical trials and classified as having either limited or extensive forms of disease using the Veterans Administration staging system. RESULTS: SCLN was present in 17% of patients (n = 234). Median survival was 258 days for patients with SCLN (n = 234) and 297 days for patients without SCLN (n = 1136) (p = 0.002). SCLN involvement was correlated with the presence of distant metastases at baseline (169 vs 65, p = < 0.001). Median survival was 375 days for patients with limited forms without SCLN (n = 529), 332 days for those with limited forms with SCLN (n = 65) (p = 0.12), 244 days for those with extensive forms without SCLN (n = 604), and 228 days for those with extensive forms with SCLN (n = 169) (p = 0.94). The 2-year survival rates were 17%, 12%, 2%, and 4%, respectively. Cox models confirmed that SCLN did not provide any significant additional prognostic information. CONCLUSION: SCLN is highly correlated with extensive forms explaining its overall prognostic value. In limited disease, SCLN is only a minor poor prognostic factor, not justifying any amendment to the staging system currently used.
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BACKGROUND: Although thoracic radiotherapy is considered to be useful for the treatment of patients with small cell lung carcinoma (SCLC), its optimal administration schedule is still controversial. METHODS: In a multicenter clinical trial, 164 patients with limited SCLC (of whom 156 were eligible for the study) were randomized to receive either concurrent thoracic irradiation, initiated immediately after the second cycle of chemotherapy (Days 30-64) at a dose of 50 grays in 20 fractions, or alternating thoracic irradiation, scheduled in 3 courses between the second, third, fourth, and fifth cycles of chemotherapy with a 7-day rest period after and before chemotherapy at a dose of 20 grays in 8 fractions (Days 36-47 and Days 64-75) and then 15 grays in 6 fractions (Days 92-101). The same chemotherapy regimen (cyclophosphamide-doxorubicin or vindesine-etoposide) was administered every 4 weeks in both groups. RESULTS: Concurrent radiotherapy-induced lung toxicity led to early termination of this trial when a significant difference was observed (6 cases vs. 1, P = 0.05, 2-sided log rank test). Objective response rates were 89% in the 82 patients of the concurrent radiotherapy group and 95% in the 74 patients of the alternating radiotherapy group. Median survival periods were 13.5 and 14.0 months, respectively, with no significant difference between the two survival distributions (P = 0.15, 2-sided log rank test). Toxic deaths due to bone marrow hypoplasia were similar in both groups (3 vs. 2), but mortality due to lung toxicity (pulmonary fibrosis) was more frequent with concurrent radiotherapy (6 patients) than with alternating radiotherapy (1 patient) in long term analysis (P = 0.05, 2-sided log rank test). CONCLUSIONS: Although no statistically significant overall survival difference was observed between the two radiation therapy schedules, the better tolerance of the alternating schedule justifies the choice of this schedule with this chemotherapy regimen, although it may not be applicable to other chemotherapy regimens.
BACKGROUND: To assess whether the addition of cisplatin (100 mg/m(2) administered intravenously on Day 1) to CDE (cyclophosphamide [1000 mg/m(2) on Day 1], doxorubicin [45 mg/m(2) on Day 1], and etoposide [150 mg/m(2) on Days 1 and 2] combination is useful in the treatment of patients with small cell lung carcinoma (SCLC). METHODS: In a multicenter clinical trial, 457 patients were randomized from May 1988 to March 1993 to receive either CDE (n = 228) or cisplatin-CDE (PCDE, n = 229) chemotherapy every 4 weeks for 6 cycles. As patients with limited SCLC were included in a concomitant trial assessing thoracic radiotherapy, the current study mainly included patients with extensive stage (79%) or limited stage disease and a contraindication for thoracic radiotherapy. RESULTS: The objective response rate was higher in the cisplatin-CDE group (72%) than in the CDE group (53%) (P = 0.0001). The median overall survival was similar for the groups that received CDE (266 days) and PCDE (271 days) (P = 0.93, log rank test). A higher fatal neutropenia rate was observed in the PCDE group (n = 23) than in the CDE group (n = 4) (P < 0.001, log rank test), mainly for patients with extensive disease (n = 26; P = 0.015, log rank test). CONCLUSIONS: The addition of cisplatin to a CDE regimen is toxic to patients with extensive SCLC and does not improve overall survival. The PCDE combination must be avoided for patients with extensive SCLC; CDE or cisplatin-etoposide combinations remain standard chemotherapy for these patients. The PCDE combination associated with granulocyte-colony stimulating factors could only be assessed in patients with good prognoses.
Streptococcus pyogenes is a common cause of necrotizing cutaneous infections in otherwise healthy children and adults. Several surface components are involved in the processes of adherence and invasiveness, such as protein M and capsulae. Streptolysin O and other bacterial products, such as pyrogenic exotoxins, are involved in tissue injury and necrosis. Toxins A and C act as superantigens and are expressed by strains associated with the toxic shock syndrome. Staphylococcus aureus, alone or in association with streptococci, is also commonly isolated form all body sites, but bacteremia is inconstant. Capsule, protein A, and the staphylococcal toxic shock syndrome toxin are the major pathogenicity factors. In infections of the face and the neck, the predominant anaerobes recovered in association with group A streptococci are Peptostreptococcus magnus, oral Prevotella, Porphyromonas spp., and Fusobacterium spp. Bacteroides fragilis, Clostridium, enterobacteria, and enterococci are recovered in infections located next to the perineal area. Penicillin is the drug of choice for the treatment of streptococcal infections. However benzylpenicillin may be not sufficient for severe infections and large inoculum, therefore the administration of clindamycin or another inhibitor of protein synthesis is recommended. Since the infection may be polymicrobial, the initial therapy should include treatment for staphylococci and anaerobes. In some cases broad- spectrum antibiotics also, effective on enterobacteria, are needed. The efficacy of appropriate parenteral antibiotics, however, depends on the prompt and aggressive exploration and debridement of suspected deep-seated infection, and supportive care of shock and multiple organ failure.
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The global mortality for Fournier's gangrene is one in five. In half the cases, the infection is polymicrobial with either anaerobes or gram negative bacilli. Factors which worsen prognosis include renal insufficiency, streptococcal infection, or need for hospital admission. Diagnosis must be prompt and treatment multidisciplinary involving the surgeon, intensivist, and infectious disease specialist; early and adequate surgical debridement must be accompanied by well-chosen antibiotics and hyperbaric oxygen therapy. Post-debridement therapy requires a long period of dressing changes and skin grafting to achieve final wound closure. This is an aggressive disease with a high mortality, but the depth and extent of invasive infection does not determine prognosis; the first priority is prompt and wide surgical excision/debridement of infected tissues to pre-empt the development of systemic sepsis; this should not be deferred while arranging transfer to a facility with a hyperbaric chamber.
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