Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome.

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Value of adding an IGRA to the TST to screen for latent tuberculous infection in Greek health care workers.

SETTING: Ioannina University Hospital, Ioannina, Greece. OBJECTIVE: To evaluate the value of adding an interferon-gamma release assay (IGRA) to the tuberculin skin test (TST) for detecting latent tuberculous infection (LTBI) in a Greek university hospital among health care workers (HCWs) predominantly vaccinated with bacille Calmette-Guérin (BCG). DESIGN: Of 788 HCWs enrolled, 68.1% were BCG-vaccinated. A TST ⩾ 10 mm was considered positive and was followed by the QuantiFERON-TB(®) Gold In-Tube assay (QFT-GIT) in a two-step strategy. RESULTS: Of the enrolled HCWs, 36.4% were TST-positive, of whom only 14.4% were IGRA-positive. Agreement between the tests was poor (κ = 0.019; 95%CI -0.014-0.05, P = 0.355). Both TST and IGRA positivity increased with TST diameter, from 5.7% in TST 10-14 mm to 48.8% in TST ⩾20 mm. TST-positive, IGRA-negative results were most likely in younger, recently BCG-vaccinated HCWs (84.6% in those aged 20-29 years) and less likely in older HCWs (45% in those aged 50-59 years). The two-step strategy would have been more cost saving compared to the TST-only approach if adherence to LTBI treatment in our cohort had been ⩾24%. CONCLUSIONS: Poor overall agreement between TST and QFT-GIT was found. Use of IGRA as a second step in TST-positive cases offers an appropriate tool for LTBI detection among BCG-vaccinated HCWs in low-TB-incidence settings.

Tuberculin skin test overestimates tuberculosis hypersensitivity in adult patients with psoriasis.

BACKGROUND: Tuberculin skin testing (TST) is still the reference method for the diagnosis of latent tuberculosis infection (LTBI). OBJECTIVE: To evaluate the effect of psoriasis on TST. METHODS: Comparison of TST results of consecutive dermatology (n = 91) and internal medicine (n = 615) inpatients. TST was uniformly ordered, performed and evaluated according to the Mantoux method using purified protein derivative. RESULTS: (a) Significantly larger TST indurations were measured in dermatology (median: 7 mm) compared to internal medicine inpatients (median: <1 mm; p < 0.0001). More dermatology inpatients showed 'positive' (>5 mm) and 'strongly positive' (>or=15 mm) TST results (53 vs. 29% and 22 vs. 13%, respectively). (b) Among dermatology inpatients, the TST reactions were significantly larger (p < 0.01) in psoriatics (n = 28) compared to the remaining patients (n = 63). (c) In psoriatics, the TST correlated positively with the psoriasis area and severity index score (p = 0.015). CONCLUSION: Overt psoriasis is associated with increased TST measurements. This observation is suggestive of a possible overtreatment of these patients for LTBI.

Bioglass-derived glass-ceramic scaffolds: study of cell proliferation and scaffold degradation in vitro.

Cell support function as well as cell proliferation on highly porous Bioglass(R)-derived glass-ceramic scaffolds (designed for bone tissue engineering) have been assessed in vitro using osteoblast-like cells (MG 63) cultured for up to 6 days. The biodegradation and mechanical stability of the scaffolds in the cell-culture medium have also been investigated. It was found that the scaffolds had excellent cell supporting ability, with cells effectively infiltrating into and surviving at the center of the scaffolds. A quantitative study using the AlamarBlue assay revealed that the proliferation of cells on the glass-ceramic materials was comparable to that on the noncrystallized Bioglass. While the crystalline phase in the glass-ceramic scaffolds transformed into a biodegradable amorphous calcium phosphate phase during cell culture, the mechanical strength of the scaffolds was maintained when compared with that of scaffolds incubated in simulated body fluid or immersed in cell-free culture medium. It is believed that the attached cells and collagen secreted by cells could fill the micropores and microcracks on the surface of the foam struts, thus contributing to the mechanical stability of the degrading scaffolds. In summary, the developed glass-ceramic scaffolds possess the most essential features of a scaffold for bone tissue engineering: they are capable to support and foster relevant cells, able to provide temporary mechanical function, and biodegradable.

Candida colitis in a middle-aged male receiving permanent haemodialysis.

Candida infections of the gastrointestinal tract are not rare, especially in immunocompromised patients. We present a case of candida colitis in a patient receiving permanent haemodialysis. Candida colitis can be a life-threatening condition and should be treated promptly, especially in immunocompromised patients.