BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

BACKGROUND AND PURPOSE: Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive sensorimotor and autonomic polyneuropathy. This systematic literature review and meta-analysis evaluated the efficacy and safety of tafamidis in TTR-FAP patients, with the aim of improving the evidence-based medical evidence of this treatment option for TTP-FAP. METHODS: A systematic search of the English-language literature in five databases was performed through to May 31, 2018 by two reviewers who independently extracted data and assessed the risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: The meta-analysis identified six relevant studies. The tafamidis group showed smaller changes from baseline in the Neuropathy Impairment Score–Lower Limbs [mean difference (MD)=−3.01, 95% confidence interval (CI)=−3.26 to −2.75, p < 0.001] and the Norfolk Quality of Life-Diabetic Neuropathy total quality of life score (MD=−6.67, 95% CI=−9.70 to −3.64, p < 0.001), and a higher modified body mass index (MD=72.45, 95% CI=69.41 to 75.49, p < 0.001), with no significant difference in total adverse events [odds ratio (OR)=0.69, 95% CI=0.35 to 1.35, p=0.27]. The incidence of adverse events did not differ between tafamidis and placebo treatment except for fatigue (OR=0.13, 95% CI=0.02 to 0.72, p=0.02) and hypesthesia (OR=0.16, 95% CI=0.03 to 0.92, p=0.04). CONCLUSIONS: This systematic review and meta-analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life. The rates of adverse events did not differ between the patients in the tafamidis and placebo groups. Tafamidis might be a safer noninvasive option for patients with TTR-FAP.
Amyloid Neuropathies ; Amyloid Neuropathies, Familial* ; Amyloidosis ; Bias (Epidemiology) ; Body Mass Index ; Extremities ; Fatigue ; Humans ; Hypesthesia ; Incidence ; Nutritional Status ; Polyneuropathies ; Population Characteristics ; Prealbumin* ; Publication Bias ; Quality of Life

Dual antiplatelet therapy is the standard treatment for patients with acute coronary syndrome (ACS) and coronary heart disease interventional treatment. Clopidogrel, a traditional antiplatelet agent, has some disadvantages, such as slow onset time, individual differences and dissatisfy the antithrombosis requirement in ischemia of high-risk patients. In addition, for ACS patients with indications of anticoagulation, antiplatelet therapy cannot prevent venous thromboembolic events. However, dual antiplatelet combined with anticoagulant therapy may decrease the risk of ischemic events at the price of increasing bleeding. With the development of new antithrombotic agents, the antithrombotic strategy for ACS has made some progress, such as antiplatelet strategy for ACS, antithrombotic strategy for ACS with indication of anticoagulation and new antithrombotic drugs. With the development of clinical antithrombotic drug research, the patients with ACS will benefit from the optimized strategy of combined with antithrombotic therapy.

OBJECTIVETo study the changes of partial pressure of oxygen in brain tissue (P(bt)O(2)) and brain temperature (BT) in patient s in acute phase of severe head injury, and to study the effect of mild hypothermia on P(bt)O(2) and BT.

METHODSThe P(bt)O(2) and the BT of 18 patients with severe head injury were monitored, and the patients were treated with mild hypothermia within 20 hours after injury. The rectal temperature (RT) of the patients was kept on 31.5-34.9 degrees C for 1-7 days (57.7 hours+/-28.4 hours averagely), simultaneously, the indexes of P(bt)O(2) and BT were monitored for 1-5 days (with an average of 54.8 hours+/-27.0 hours). According to Glasgow Outcome Scale (GOS), the prognosis of the patients was evaluated at 6 months after injury.

RESULTSWithin 24 hours after severe head injury, the P(bt)O(2) was significantly lower (9.6 mm Hg+/-6.8 mm Hg, 1 mm Hg=0.133 kPa) than the normal value (16-40 mm Hg). After treatment of mild hypothermia, the mean P(bt)O(2) increased to 28.7 mm Hg+/-8.8 mm Hg during the first 24 hours, and the P(bt)O(2) was still maintained within the range of normal value at 3 days after injury. The BT was higher than the RT in the patients in acute phase of severe head injury, and the difference between the BT and the RT significantly increased after treatment of mild hypothermia. Hyperventilation (the partial pressure of carbon dioxide in artery (P(a)CO(2)) approximately 25 mm Hg) decreased the high intracranial pressure (ICP) and significantly decreased the P(bt)O(2).

CONCLUSIONSThis study demonstrates that P(pt)O(2) and BT monitoring is a safe, reliable and sensitive diagnostic method to follow cerebral oxygenation. It might become an important tool in our treatment regime for patients in the acute phase of severe head injury requiring hypothermia and hyperventilation.

Adult ; Aged ; Blood Gas Monitoring, Transcutaneous ; Body Temperature ; Brain ; metabolism ; Craniocerebral Trauma ; metabolism ; therapy ; Female ; Glasgow Coma Scale ; Humans ; Hypothermia, Induced ; Male ; Middle Aged ; Oxygen ; metabolism ; Treatment Outcome