Bernth Jensen JM, Dinh KM, Hindhede L, Erikstrup LT, Hansen AG, et al.
Medical microbiology and immunology •
IgG antibodies against terminal galactose-α-1,3-galactose (anti-αGal antibodies) are naturally occurring in humans, but their origins remain poorly understood. These antibodies target various microorganisms including Staphylococcus aureus, a common nasal commensal and the major cause of skin abscesses. This study investigates the impact of S. aureus colonization and abscess events on plasma anti-αGal antibody levels. We measured plasma anti-αGal antibody levels using a quantitative immunoassay in: (i) 101 pairs of healthy individuals with and without nasal S. aureus colonization, (ii) 106 healthy individuals before and after abscess formation, and (iii) 43 patients with recurrent skin abscesses compared with 75 patient controls and 60 healthy controls. We observed a 35% reduction (95%CI: 7-54%) in anti-αGal antibody levels in nasal S. aureus carriers. Conversely, we found a 30% increase (95%CI: 4-66%) in individuals within 187 days post-skin abscess, and patients with recurrent skin abscesses exhibited 81% higher (95%CI: 14-190%) levels than patient controls, and 110% higher (95%CI: 39-230%) than healthy controls. This study suggests that skin abscesses lead to elevated plasma anti-αGal antibody levels and that these antibodies might convey or correlate with mucosal immunity to S. aureus.
von Döbeln GA, Wagenius G, Holtved E, Jacobsen AB, Nilsson M, et al.
Cancer treatment and research communications •
Chemoradiotherapy is standard treatment for localized oesophageal cancer unsuitable for surgery. We aimed to evaluate the efficacy of cetuximab in combination with chemoradiotherapy. This non-randomised multicentre phase II trial recruited patients aged 18-75 with WHO performance status 0-2 having squamous cell carcinoma or adenocarcinoma in the oesophagus or gastro-oesophageal junction, T2-4, N0-3, M0 not suitable for surgery. Chemotherapy was three 21-day cycles of fluorouracil 750 mg/m2 D1-5 and oxaliplatin D1 (cycle 1:130mg/m 2, cycle 2-3:85 mg/m 2). Radiotherapy was 50Gy in 2Gy/fraction, 5 days a week, concurrent with cycle 2 and 3 and weekly cetuximab. The primary objective was loco-regional control at one year. 52 patients were included. 51 were eligible for toxicity and survival analysis and 46 for recurrence analysis. Full radiotherapy dose was delivered to 80%, 75% received all three cycles of chemotherapy and 75% received four or more doses of cetuximab. The most common related grade III-IV adverse events were gastro-intestinal(16), hypersensitivity(6) and infection(5). There were two drug-related deaths. Within six months from the end of treatment, six patients died from complications from fistulas. The loco-regional control rate at one year was 47.3%(95%CI 30.9%-62.1%). Overall survival at three years was 29.1%(95% CI 17.4-41.9%). Oxaliplatin and fluorouracil given concurrent with radiotherapy and cetuximab had an acceptable safety profile and showed a clinical response in patients with locoregionally advanced oesophageal cancer unsuitable for surgery. However, the primary end-point was not met, and the addition of cetuximab to definitive chemoradiotherapy cannot be recommended.
Jensen MK, Havndrup O, Christiansen M, Andersen PS, Axelsson A, et al.
The international journal of cardiovascular imaging •
Identification of the first echocardiographic manifestations of hypertrophic cardiomyopathy may be important for clinical management and our understanding of the pathogenesis. We studied the development of pre-diagnostic echocardiographic changes in young relatives to HCM patients during long-term years follow-up. HCM-relatives not fulfilling the diagnostic criteria for HCM and age of <18 years were included in this study. We performed echocardiographic evaluations at inclusion and after 12 ± 1 years follow-up. Based on family screening of 11 sarcomere genes, CRYAB, α-GAL, and titin, we evaluated: (1) non-carriers (known family mutation ruled out-controls), (2) carriers (phenotype negative gene mutation carriers) and (3) phenotype negative relatives with unknown genetic status (relatives from families without identified mutations). At inclusion (age 11 ± 5 years), there were no differences in echocardiographic chamber dimensions, systolic or diastolic function between the three groups. During follow-up (age 23 ± 5 years), carriers (n = 8) developed lower left ventricular end-diastolic dimension (LVEDd) compared to non-carriers (n = 23) (41 ± 4 vs. 46 ± 4 mm; p = 0.04) and a higher ratio of early left ventricular filling velocity and early diastolic velocity of lateral mitral annulus (E/e' 6 ± 1 vs. 5 ± 1; p = 0.003). No significant differences in LVEDd or E/e' were found between relatives with unknown genetic status (n = 24) and non-carriers though Z-scores for these parameters were >2 in a subset of relatives with unknown genetic status. Children carrying pathogenic sarcomere gene mutations develop reduced LVEDd and increased E/e' as first pre-diagnostic echocardiographic manifestations during follow-up into adulthood.
Holländer C, Baeksgaard L, Sorensen M, Albertsson P, Damstrup L, et al.
Anticancer research •
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of concurrent chemoradiotherapy and cetuximab in patients with non-resectable locally advanced esophageal cancer. Escalating doses of oxaliplatin every second week and daily tegafur/uracil were given concurrently with radiotherapy, 59.4 Gy in 33 fractions. Cetuximab was given on day 15 (400 mg/m(2)) and weekly (250 mg/m(2)) during radiotherapy. Fixed doses of oxaliplatin (130 mg/m(2)) and tegafur/uracil (300 mg/m(2)) were administered before, and after radiotherapy. Eleven patients were included in the study; two were excluded due to allergic reactions to cetuximab. In DL2 (tegafur/uracil 300 mg/m(2), oxaliplatin 30 mg/m(2)) two grade 3/4 fistula and one grade 3 neuropathy were observed. Six patients were enrolled in DL1 (tegafur/uracil 150 mg/m(2)/, oxaliplatin 30 mg/m(2)) with no DLTs. Four out of 9 patients had complete response. Concomitant chemoradiotherapy and cetuximab had significant activity. DL1 was established as the MTD.
