Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Asthma mortality in Danish children and young adults, 1973-1994: epidemiology and validity of death certificates.

Several reports indicate that asthma mortality has increased during the last few decades. International comparisons reveal some striking differences in the pattern of asthma mortality. The authors investigated the asthma mortality rate in the Danish child and youth population 1973-1994 and studied the validity of death certificates. The authors reviewed all death certificates coded as asthma death in the International Classification of Diseases (ICD 8-ICD 10 (1994)) and adjacent respiratory code numbers for the age group 1-19 yrs. Hospital records and autopsy reports were assessed to validate the cause of death. Age-standardized and age-specific mortality rates were calculated. From 1973 to 1987 there was a significant upward trend in the mortality. On subdivision, this trend was limited to the age group 15-19 yrs. Generally the mortality rate decreased from 1988 to 1994. Four per cent coded as asthma were false positive. Twelve per cent were false negative asthma deaths, wrongly coded as due to other causes. Only 62% of all true positive death caused by asthma were appropriately coded. The number of false negative certifications increased with increasing autopsy frequency. Asthma mortality rates in Denmark increased in adolescents during 1973-1987 and decreased from 1988 to 1994. A possible explanation may be an increased awareness of asthma symptoms combined with a steadily improved treatment of asthma. Even in children and young adults under the age of 20 yrs, validity problems still make comparisons between countries difficult; even interpretation of national trends requires caution.

[Occurrence of tuberculosis among children in the area of Copenhagen 1984-1993]. / Tuberkuloseforekomst blandt børn i Københavnsområdet 1984-1993.

This study was undertaken to describe the epidemiology, clinical manifestations and prognosis of childhood tuberculosis in Copenhagen, with special attention to differences between Danish children and children of foreign origin. Medical records for all children with tuberculosis cared for in the hospitals of the Copenhagen area 1984-1993 were reviewed. Sixty-six patients were identified. Sixteen of 20 Danish patients (80%) and 67% of foreign children had respiratory tuberculosis. Tuberculosis located in cervical lymph nodes was found only in children of foreign origin. Five patients had meningitis. The high incidence among foreign children reflects the incidence in their home countries, but poorer living conditions among ethnic minorities in Denmark may facilitate transmission of tuberculosis. Severe manifestations of tuberculosis still occur, even in a low incidence country.

Interactions of the invasive pathogens Salmonella typhimurium, Listeria monocytogenes, and Shigella flexneri with M cells and murine Peyer's patches.

Invasive enteric bacteria must pass through the intestinal epithelium in order to establish infection. It is becoming clear that a common target for intestinal mucosa penetration is the specialized epithelial cell of Peyer's patches, the M cell. In order to gain a better understanding of how bacteria interact with M cells, we have compared the interactions of Salmonella typhimurium, Listeria monocytogenes, and Shigella flexneri with M cells by using a murine ligated-loop model. Our results indicate that S. typhimurium possesses a highly efficient mechanism for M cell entry that targets and destroys these cells, while L. monocytogenes and S. flexneri appear to be internalized into M cells in a less disruptive fashion. Early uptake of Listeria or Shigella into M cells appeared to lead to the death of some cells, as evidenced by the appearance of holes in the intestinal epithelium. At later time points, the follicle-associated epithelium of animals infected with these bacteria displayed extensive destruction. These data indicate that enteric pathogens use different strategies to interact with M cells and initiate infection of a host.

[Latex allergy]. / Latexallergi.

Latex allergy has been described with increasing frequency throughout the last years. The prevalence in Denmark is not yet known. The growing frequency is partly explained by the extensive use of latex-containing products (especially gloves), which has followed the appearance of the HIV-epidemic. The symptoms of latex allergy are usually those produced by type-I hypersensitivity. Type-IV allergy (contact dermatitis) to rubber chemicals is well described but is not directly associated with the latex proteins. The allergens in latex have nearly been identified; diagnostic tools are known but are not yet satisfactory. Cross-reacting antigens are found in banana, kiwi, avocado, chestnut and other plants. It is concluded, that attention to latex allergy has to be intensified and the risk factors reduced, especially concerning the health care units.

[Latex allergy in children]. / Latexallergi hos børn.

More than a thousand cases of type-1 latex allergy have been presented. In children the condition is most often described in patients with spina bifida. Six cases of latex allergy in atopic children are presented. Five of these had food allergies, especially to banana. The allergy was verified with prick-test, LHR-test and measurement of specific IgE. It is concluded that attention to latex allergy in atopic children has to be intensified. Prick-test with standardised latex extracts is the preferred method for diagnosis of the allergy. Latex dummies, latex toys, balloons etc, have to be avoided.

Management of the non-descended testis: doubtful value of luteinizing-hormone-releasing-hormone (LHRH). A double-blind, placebo-controlled multicentre study.

In a double-blind, placebo-controlled multicentre study, the effect of luteinizing-hormone-releasing-hormone (LHRH) in 141 boys was analysed after 4-week treatment period with 0.4 mg LHRH nasal spray or placebo nasal spray three times daily. Data from 123 boys was analysed, with 62 boys in the treatment group and 61 in the placebo group. Full response i.e. the testis at the bottom of the scrotum on both sides in boys with bilaterally undescended testes, was found in six patients, one of them in the placebo group [Therapeutic gain of LHRH with 95% CI: 8.1% (0.1-16.6%, P = 0.12)]. Only in these boys could surgery be avoided. Considering the number of testes (and not the number of boys) a significant effect was found on at least one testis in 25% of boys with bilaterally undescended testes [Therapeutic gain with 95% CI: 24.0% (13.2-34.8%, P = 0.001)]. In unilateral undescended testes, the LHRH treatment showed no effect (P = 1.00). The inclusion of retractile testes did not affect our results. In our opinion LHRH has a limited place in treatment of the non-descended testis.