Key PointsQuestionIs the anti–interleukin-1β antibody canakinumab effective to treat patients hospitalized with COVID-19 and hyperinflammation?FindingThis randomized clinical trial included 454 patients hospitalized with severe COVID-19 not requiring invasive mechanical ventilation (IMV) and with elevated C-reactive protein or ferritin levels. Treatment with intravenous canakinumab vs placebo resulted in survival without IMV at 29 days of 88.8% vs 85.7%, a difference that was not statistically significant.MeaningAmong patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV.
Streptococcus equi subsp. zooepidemicus infections are infrequent in humans. A clinical and epidemiological study of a milk-borne outbreak caused by this organism is described. Fifteen patients (5 females, 10 males) with a median age of 70 years (range 47-86) were infected. Twelve (80%) had underlying diseases. Infection with S. equi subsp. zooepidemicus presented as primary bacteremia in six cases, as bacteremia associated with aortic aneurism in four cases, as septic arthritis in two cases, as pneumonia in two cases, and as meningitis in one case. Five (33.3%) patients died. A case-control study proved that consumption of inadequately pasteurized cheese of a specific brand was associated with S. equi subsp. zooepidemicus disease (OR=4.5; 95% CI 1.57-19.27; p<0.001). This outbreak serves as a reminder that S. equi subsp. zooepidemicus causes serious infections that are usually zoonoses. Identification of beta-hemolytic streptococci to the species level to detect contaminated foods of animal origin is important for preventing new food-borne outbreaks. For a precise characterization of the isolates, the application of molecular markers is recommended.
In this paper, we study noise-like pulse generation in a km-long fibre ring laser including a doubleclad erbium-ytterbium fibre and passively mode-locked through nonlinear polarization evolution. Although single noise-like pulsing is only observed at moderate pump power, pulse energies as high as 120 nJ are reached in this regime. For higher pump power, the pulse splits into several noise-like pulses, which then rearrange into a stable and periodic pulse train. Harmonic mode locking from the 2nd to the 48th orders is readily obtained. At pump powers close to the damage threshold of the setup, much denser noise-like pulse trains are demonstrated, reaching harmonic orders beyond 1200 and repetition frequencies in excess of a quarter of a GHz. The mechanisms leading to noise-like pulse breaking and stable high-order harmonic mode locking are discussed.
To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.
In this work we study multiple noise-like pulse generation in a 320 m long passively mode-locked erbium-doped figure-eight fibre laser in the normal net dispersion regime. The nonlinear optical loop mirror (NOLM) that is used as a mode locker operates through polarization asymmetry, which allows us to control its switching power by birefringence adjustments at the NOLM input, using a half-wave retarder (HWR). Over some range of the HWR orientation, a single noise-like pulse is observed in the cavity. Its peak power is adjustable as it remains clamped to the variable switching power, and its duration varies inversely between ∼5 and ∼22 ps. Beyond the HWR position, corresponding to the longest duration, the pulse splits into several noise-like pulses. These multiple pulses usually present a walkoff, however they can be synchronized through slight birefringence adjustments, although they are not evenly spaced in time. Up to 12 simultaneous noise-like pulses were observed experimentally, with a duration of ∼2 ns. Multiple pulsing and synchronization of the pulses are interpreted in terms of mechanisms of interaction between pulses. Multiple pulsing appears to be indirectly related to the peak power limiting effect of the NOLM.
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