Ratios of cumulants of net proton-number fluctuations measured by the STAR Collaboration show strong deviations from a skellam distribution, which should describe thermal properties of cumulant ratios, if proton-number fluctuations are generated in equilibrium and a hadron resonance gas (HRG) model would provide a suitable description of thermodynamics at the freeze-out temperature. We present some results on sixth order cumulants entering the calculation of the QCD equation of state at non-zero values of the baryon chemical potential (mu_B) and discuss limitations on the applicability of HRG thermodynamics deduced from a comparison between QCD and HRG model calculations of cumulants of conserved charge fluctuations. We show that basic features of the $mu_B$-dependence of skewness and kurtosis ratios of net proton-number fluctuations measured by the STAR Collaboration resemble those expected from a O(mu_B^2) QCD calculation of the corresponding net baryon-number cumulant ratios.