Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Characterization of laser cooling in microgravity via long-term operations in TianGong-2 space lab.

The invention of laser cooling has fundamentally influenced the research frontier of atomic physics and quantum physics, and recently an intense focus has been on the studies of cold atom physics in microgravity environments. Herein, we report the results of our laser cooling experiment in TianGong-2 space lab, which operated for 34 consecutive months in orbit. Over such an extended operation time, the quality of laser cooling did not experience any significant decline, while the properties of laser cooling in orbital microgravity were systematically studied. In particular, we demonstrate magneto-optical trapping and polarization-gradient cooling in orbit and carefully examine their performances. A comparison of the in-orbit and on-ground results indicates that a higher cooling efficiency exists in microgravity, including a smaller loss rate during the trapping and cooling process and lower ultimate temperature of laser-cooled atoms. Our progress has laid the technical foundations for future applications of cold atoms in space missions with operation times of the order of years.

Design and operation of a transportable 87Rb atomic fountain clock.

A transportable fountain clock with high reliability is important for high-precision time-frequency measurements. Because of its relatively small cold atoms' collision frequency shift and ease of attaining high quantum state preparation efficiency, the rubidium atomic fountain clock has an indicated higher stability and reliability. This paper reports the design and operation of a transportable rubidium atomic fountain clock developed by the Shanghai Institute of Optical and Fine Mechanics, Chinese Academy of Science. After being transported more than 1000 km from Shanghai to the Changping Campus of the National Institute of Metrology, China, the optical platform and other hardware of the fountain clock did not need to be adjusted. The rubidium fountain clock maintained a stability of 4.0 × 10-13τ1/2, reaching 5.0 × 10-16 at 300 000 s. After transportation, the rubidium fountain clock and a cesium fountain clock (NIM5) were operated together against the reference frequency of a hydrogen maser. In three separate operating periods, over a total of nearly three months, the average frequency repeatability of the rubidium fountain was less than 3.8 × 10-15.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BACKGROUND: This retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB. METHODS: We retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS). RESULTS: A total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence. CONCLUSIONS: Concurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Space qualified microwave source for cold atom clock operating in orbit.

The space cold atom clock (CAC) suffers more degradation of frequency stability from the local oscillator noise compared with fountain clocks operating on the ground because of the larger dead time of the clock cycle. Therefore, low phase noise is required for the microwave source of the space CAC in addition to robustness, compactness, and adaptability to the space environment. This paper presents the design and measurements of a low-phase-noise space qualified microwave source for the cold atom clock experiment in space CAC operating in the Tiangong-2 Chinese space laboratory. At frequencies near the carrier, a phase noise level of 10-6.7 × f -1.5 rad2/Hz (f is the Fourier frequency) is achieved. This guarantees a frequency stability of 1.4 × 10-13 τ -1/2 (τ is the average time in seconds) for the typical space CAC operation cycle.

In-orbit operation of an atomic clock based on laser-cooled 87Rb atoms.

Atomic clocks based on laser-cooled atoms are widely used as primary frequency standards. Deploying such cold atom clocks (CACs) in space is foreseen to have many applications. Here we present tests of a CAC operating in space. In orbital microgravity, the atoms are cooled, trapped, launched, and finally detected after being interrogated by a microwave field using the Ramsey method. Perturbing influences from the orbital environment on the atoms such as varying magnetic fields and the passage of the spacecraft through Earth's radiation belt are also controlled and mitigated. With appropriate parameters settings, closed-loop locking of the CAC is realized in orbit and an estimated short-term frequency stability close to 3.0 × 10-13τ-1/2 has been attained. The demonstration of the long-term operation of cold atom clock in orbit opens possibility on the applications of space-based cold atom sensors.