Search

Abstract In China, tuberculosis (TB) is endemic and the Bacillus Callmette–Güerin (BCG) vaccine is administered to all the newborns, which may lead to BCG infection in patients with chronic granulomatous disease (CGD). Infection of BCG/TB in CGD patients can be fatal and pulmonary is the most affected organ. Our objective was to assess the imaging of pulmonary BCG/TB infection in CGD. We screened 169 CGD patients and identified the patients with pulmonary BCG/TB infection. BCG infection was diagnosis according to the vaccination history, local infection manifestation, acid-fast bacilli staining, specific polymerase chain reaction, and/or spoligotyping. PPD, T-SPOT and acid-fast bacilli staining were used for diagnosis of TB. Totally 58 patients were identified, including TB (n = 7), solely BCG (n = 18), BCG + bacterial (n = 20), and BCG + fungi (n = 13). The onset of BCG disease was much earlier than TB. For those patients only with BCG, lymphadenopathy was the first and most prevalent feature. The most found location was the left axilla, followed by the ipsilateral cervical areas and mediastinal or hilar area. On chest CT, ground-glass opacities, multiple nodules and pulmonary scarring were the most common findings. For TB patients, the pulmonary infections were more serious, including large masses, severe lymphadenopathy, and extensive pulmonary fibrosis. Pulmonary infection of BCG were more common than TB in CGD patients, but much less severe.

Abstract Background Pulmonary hypertension in left heart disease (PH-LHD), which includes combined post- and precapillary PH (Cpc-PH) and isolated postcapillary PH (Ipc-PH), differs significantly in prognosis. We aimed to assess whether cardiopulmonary exercise testing (CPET) predicts the long-term survival of patients with PH-LHD. Methods A single-center observational cohort enrolled 89 patients with PH-LHD who had undergone right heart catherization and CPET (mean pulmonary arterial pressure > 20 mm Hg and pulmonary artery wedge pressure ≥ 15 mm Hg) between 2013 and 2021. A receiver operating characteristic curve was plotted to determine the cutoff value of all-cause death. Survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test. The Cox proportional hazards model was performed to determine the association between CPET and all-cause death. Results Seventeen patients died within a mean of 2.2 ± 1.3 years. Compared with survivors, nonsurvivors displayed a significantly worse 6-min walk distance, workload, exercise time and peak oxygen consumption (VO2)/kg with a trend of a lower oxygen uptake efficiency slope (OUES) adjusted by Bonferroni’s correction. Multivariate Cox regression revealed that the peak VO2/kg was significantly associated with all-cause death after adjusting for Cpc-PH/Ipc-PH. Compared with Cpc-PH patients with a peak VO2/kg ≥ 10.7 ml kg−1 min−1, Ipc-PH patients with a peak VO2/kg

A synthetic strategy involving salicylaldehyde, 2-chloroprop-2-ene-1-sulfonyl fluoride (CESF), and pyrrole has been developed to construct novel pyrrole-4H-chromene-embedded vinyl sulfonyl fluoride derivatives with exclusive regioselectivity. This method exhibits moderate to excellent yields (45–93%) and showcases a wide substrate scope with excellent functional group compatibility. Additionally, the resulting sulfonyl fluorides were further diversified via sulfur fluoride exchange (SuFEx) reactions to produce sulfonates and sulfonamides, which are valuable structural motifs in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Background and Aims: Sleep‐disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. Methods: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. Results: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty‐two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single‐breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). Conclusion: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH. [ABSTRACT FROM AUTHOR]

Abstract Background Management of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remains a clinical challenge. Currently, riociguat, a soluble guanylate-cyclase stimulator is recommended by international guidelines. More recently, balloon pulmonary angioplasty (BPA) develops as an alternative treatment for inoperable CTEPH. Method This study is a single-center randomized controlled trial. Subjects with inoperable CTEPH are randomized into either a BPA combined with riociguat or riociguat monotherapy group (2:1) and observed for 12 months after initiation of treatment. The primary endpoint is the change in pulmonary vascular resistance from baseline to 12 months after initiation of treatment. The secondary endpoints include 6-min walk distance (6MWD), WHO-FC, NT-proBNP, SF-36, and other hemodynamic parameters. Safety endpoints are analyzed too. Discussion This study aims to compare the efficacy and safety of BPA combined with riociguat and riociguat monotherapy for inoperable CTEPH. Trial registration Chinese Clinical Trial Registry ChiCTR2000032403 . Registered on 27 April 2020.

ObjectiveWhether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS.MethodsWe conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients.ResultsExercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O2 and lower VO2/VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO2/VE, and TAPSE and higher VE/VCO2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO2/VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO2/VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO2/VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival.ConclusionExercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O2, VO2/VE, and TAPSE than those without EIS. VO2/VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO2/VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored.

BackgroundThere is little evidence of the effectiveness of switching from the endothelin receptor antagonists (ERAs) bosentan and ambrisentan to a novel ERA, macitentan, in patients with pulmonary arterial hypertension (PAH). Therefore, a systematic review and meta-analysis was performed to evaluate the efficacy and safety of patients with PAH switching from other ERAs to macitentan.MethodsWe retrieved the relevant literature published before January 2022 for the meta-analysis from the PubMed, EMBASE, and Cochrane Library databases. Efficacy included changes in the 6-min walk distance (6MWD), World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, hemodynamics, echocardiography and survival.ResultsNine studies, consisting of 408 PAH patients, that met the inclusion criteria were included. The switch from bosentan or ambrisentan to macitentan effectively increased the 6MWD by 20.71 m (95% CI: 10.35-31.07, P < 0.00001, I2 = 0%). Six months after conversion, the tricuspid annular plane systolic excursion was found to improve from 19.0 ± 4.0 to 21.0 ± 5.0 mm in adults and from 16.00 ± 5.0 to 18.25 ± 4.8 mm in children. Ordinal logistic regression showed that the WHO-FC significantly improved by 0.412 (95% CI: 0.187-0.908, P = 0.028). The switch did not show significant improvement in NT-proBNP levels. In addition, the switch was well tolerated.ConclusionThe switch from bosentan or ambrisentan to macitentan significantly increased the 6MWD in PAH patients, improved the WHO-FC, and exerted safety benefits. The effects of the switch on NT-proBNP levels, hemodynamics, and echocardiography still need to be further confirmed.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021292554].

Various predictive biomarkers are needed to select candidates for optimal and individualized treatments. Tumor‐infiltrating immune cells have gained increasing interest in cancer research for the prediction of therapeutic response and survival. However, the role of dendritic cells (DCs) in PD-1 blockade immunotherapy remains unclear. In this study, we identified a population of PD-1+ DCs in the tumor microenvironment (TME) of cervical cancer (CC). The accumulation of PD-1+ DCs in cervical tumors was correlated with advanced stages, elevated preoperative squamous cell carcinoma antigen levels and lymph-vascular space invasion. PD-1 expression was induced on activated tumor-associated DCs (TADCs) in vitro compared with their resting counterparts. This PD-1+ DC population was characterized by reduced secretion of cytokines (IL-12, TNF-α, and IL-1β) and dysfunctional induction of T cell proliferation and cytotoxic reaction. PD-1 blockade significantly reinvigorated PD-1+ DCs to release IL-12, TNF-α, and IL-1β compared with PD-1- DCs. TILs from samples with higher PD-1+ DC infiltration could be induced to achieve a greater killing effect of PD-1 blockade treatment. Our findings suggested a role for PD-1+ DCs in immune surveillance dysfunction and CC progression. PD-1+ DC density in the TME may serve as a diagnostic factor for predicting the optimal beneficiaries of PD-1/PD-L1 blockade immunotherapy in CC.

BackgroundSignificantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes.MethodsA total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups.ResultsPatients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up.ConclusionPatients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management.