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Korean Journal of Radiology Aug 2023Radiologists and trauma surgeons should monitor for early killers among patients with thoracic trauma, such as tension pneumothorax, tracheobronchial injuries, flail... (Review)
Review
Radiologists and trauma surgeons should monitor for early killers among patients with thoracic trauma, such as tension pneumothorax, tracheobronchial injuries, flail chest, aortic injury, mediastinal hematomas, and severe pulmonary parenchymal injury. With the advent of cutting-edge technology, rapid volumetric computed tomography of the chest has become the most definitive diagnostic tool for establishing or excluding thoracic trauma. With the notion of "time is life" at emergency settings, radiologists must find ways to shorten the turnaround time of reports. One way to interpret chest findings is to use a systemic approach, as advocated in this study. Our interpretation of chest findings for thoracic trauma follows the acronym "ABC-Please" in which "A" stands for abnormal air, "B" stands for abnormal bones, "C" stands for abnormal cardiovascular system, and "P" in "Please" stands for abnormal pulmonary parenchyma and vessels. In the future, utilizing an artificial intelligence software can be an alternative, which can highlight significant findings as "warm zones" on the heatmap and can re-prioritize important examinations at the top of the reading list for radiologists to expedite the final reports.
Topics: Humans; Artificial Intelligence; Thoracic Injuries; Flail Chest; Lung Injury; Cone-Beam Computed Tomography; Wounds, Nonpenetrating
PubMed: 37500576
DOI: 10.3348/kjr.2022.1021 -
Blood Advances Sep 2023Patients with relapsed/refractory primary mediastinal large B-cell lymphoma (R/R PMBL) have poor responses to salvage therapy. Nivolumab and brentuximab vedotin (BV)...
Patients with relapsed/refractory primary mediastinal large B-cell lymphoma (R/R PMBL) have poor responses to salvage therapy. Nivolumab and brentuximab vedotin (BV) showed promising early efficacy in patients with R/R PMBL in the phase 1/2 open-label, multicenter CheckMate 436 study; we report safety and efficacy findings from the 3-year follow-up. Patients who were eligible were aged ≥15 years with R/R PMBL previously treated with either high-dose chemotherapy plus autologous hematopoietic cell transplantation (HCT) or ≥2 prior multiagent chemotherapies, and had Eastern Cooperative Oncology Group performance status scores of 0 to 1 and CD30 expression of ≥1%. Patients were treated with nivolumab 240 mg and BV 1.8 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR); secondary end points included complete response rate, duration of response, progression-free survival (PFS), and overall survival (OS). Safety was monitored throughout. At final database lock (30 March 2022), 29 patients had received nivolumab plus BV; median follow-up was 39.6 months. Investigator-assessed ORR was 73.3%; median time to response was 1.3 months (range, 1.1-4.8). Median PFS was 26.0 months; median OS was not reached. PFS and OS rates at 24 months were 55.5% (95% confidence interval [CI], 32.0-73.8) and 75.5% (95% CI, 55.4-87.5), respectively. The most frequently occurring grade 3/4 treatment-related adverse event was neutropenia. Consolidative HCT was received by 12 patients, with a 100-day complete response rate of 100.0%. This 3-year follow-up showed long-term efficacy for nivolumab plus BV in R/R PMBL, with no new safety signals. This trial was registered at www.clinicaltrials.gov as #NCT02581631.
Topics: Adult; Humans; Brentuximab Vedotin; Nivolumab; Follow-Up Studies; Hodgkin Disease; Neoplasm Recurrence, Local; Lymphoma, B-Cell
PubMed: 37352266
DOI: 10.1182/bloodadvances.2023010254 -
Cancers Nov 2023Surgical resection remains the gold standard of treatment for early-stage lung cancer. Several risk models exist to predict postoperative morbidity and mortality. Psoas...
Surgical resection remains the gold standard of treatment for early-stage lung cancer. Several risk models exist to predict postoperative morbidity and mortality. Psoas muscle sarcopenia has already successfully been used for morbidity prediction in lung transplantation and is not yet included in the available risk scores for pulmonary resections. We hypothesized that the skeletal muscle index and mediastinal adipose tissue might also have an impact on postoperative outcomes after primary surgery for primary lung cancer. The institutional database was queried for patients with primary lung cancer who were treated with primary lobectomy or segmentectomy between February 2009 and November 2018. In total, 311 patients were included for analysis. Patients receiving neo-/adjuvant chemotherapy or with a positive nodal status were excluded to rule out any morbidity or mortality due to (neo-)adjuvant treatment. Sarcopenia was defined as a skeletal muscle index of <34.4 cm/m for women and <45.4 cm/m for men. Mediastinal adipose tissue was defined with a radiodensity of -150 to -30 Hounsfield units. Sarcopenia was diagnosed in 78 (25.1%) of the 311 patients. Male patients were significantly more likely to suffer from sarcopenia (31.5% vs. 18.1%, = 0.009). Comorbidities, lung function, tumour histology, pathologic tumour staging, mediastinal adipose tissue and age did not differ between groups with or without sarcopenia. Sarcopenic patients had a significantly longer length of stay, with 13.0 days vs. 9.5 ( = 0.003), and a higher rate of any postoperative complications (59.0% vs. 44.6%, = 0.036). There was no difference in recurrence rate. Five-year overall survival was significantly better in the patient cohort without sarcopenia (75.6% vs. 64.5%, = 0.044). Mediastinal adipose tissue showed no significant impact on length of stay, postoperative complications, recurrence rate, morbidity or survival. Sarcopenia, quantified with the skeletal muscle index, is shown to be a risk factor for postoperative morbidity and reduced survival in primary lung cancer. Efforts should be taken to pre-emptively screen for sarcopenia and start countermeasures (e.g., physical prehabilitation, protein-rich nutrition, etc.) during the preoperative workup phase.
PubMed: 38067372
DOI: 10.3390/cancers15235666 -
JCI Insight Nov 2023Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and...
Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Furthermore, we document that: (a) CD8 T cell memory persists in multiple tissues for > 200 days; (b) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; and (c) adoptively transferred splenic memory CD8 T cells traffic to the airways and promote lung SARS-CoV-2 clearance. These findings provide insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants.
Topics: Humans; Animals; Mice; COVID-19 Vaccines; Memory T Cells; COVID-19; SARS-CoV-2; Lung
PubMed: 37796612
DOI: 10.1172/jci.insight.172510 -
Mediastinum (Hong Kong, China) 2024Lung cancers and mediastinal masses can invade the veins in the upper mediastinum and neck. It can be challenging to determine management options and the feasibility of... (Review)
Review
Lung cancers and mediastinal masses can invade the veins in the upper mediastinum and neck. It can be challenging to determine management options and the feasibility of resection particularly when tumors involve the major venous junctions. Furthermore, impaired flow in these veins can have devastating complications such as Paget-Schroetter syndrome, which describes a constellation of symptoms (arm swelling, cyanosis, pain) due to stenosis of the subclavian vein. This section will provide an overview of venous drainage of the brain, which can be divided into two major systems-superficial medullary venous system and deep medullary venous system. The anatomy and function of the great veins of the neck and upper mediastinum, including the internal jugular vein, subclavian vein, and brachiocephalic (i.e., innominate) vein will be described. Also discussed will be principles of ligation of the venous structures and the importance of keeping the venous junctions intact to facilitate and maximize the development of collateral flow. This section will also discuss ensuing complications when blood flow is impaired, such as development of upper extremity deep venous thrombosis and cerebral venous thrombosis (CVT). CVT can result in a stroke and is an umbrella term that refers to problems in cerebral venous outflow due to numerous etiologies.
PubMed: 38322186
DOI: 10.21037/med-23-15 -
HemaSphere Jul 2023UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal...
UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans. Primary end point was event-free survival (EFS). A subgroup of 131 patients with PMBCLs was included (median age, 34 y; 54% female, 79% elevated lactate dehydrogenase (LDH), 20% LDH >2× upper limit of normal [ULN], and 24% extralymphatic involvement). Eighty-two (R-CHOP-21: 43 and R-CHOP-14: 39) patients were assigned to radiotherapy and 49 (R-CHOP-21: 27, R-CHOP-14: 22) to observation. The 3-year EFS was superior in radiotherapy arm (94% [95% confidence interval (CI), 89-99] versus 78% [95% CI, 66-89]; = 0.0069), due to a lower rate of partial responses (PRs) (2% versus 10%). PR triggered additional treatment, mostly radiotherapy (n = 5; PR: 4; complete response/unconfirmed complete response: 1). No significant differences were observed in progression-free survival (PFS) (95% [95% CI, 90-100] versus 90% [95% CI, 81-98]; = 0.25) nor in overall survival (OS) (98% [95% CI, 94-100] versus 96% [95% CI, 90-100]; = 0.64). Comparing R-CHOP-14 and R-CHOP-21, EFS, PFS, and OS were not different. A prognostic marker for adverse outcome was elevated LDH >2× ULN (EFS: = 0.016; PFS: = 0.0049; OS: = 0.0014). With the limitation of a pre-PET-era trial, the results suggest a benefit of radiotherapy only for patients responding to R-CHOP with PR. PMBCL treated with R-CHOP have a favorable prognosis with a 3-year OS of 97%.
PubMed: 37427145
DOI: 10.1097/HS9.0000000000000917 -
Journal of Thoracic Disease Jul 2023Resuscitative therapies for respiratory and cardiac failure are lifesaving and extended by using extracorporeal life support (ECLS) as mechanical circulatory support... (Review)
Review
BACKGROUND AND OBJECTIVE
Resuscitative therapies for respiratory and cardiac failure are lifesaving and extended by using extracorporeal life support (ECLS) as mechanical circulatory support (MSC). This review informs the debate to identify the life-threatening thoracic emergencies in which patients may be cannulated for ECLS support.
METHODS
An advanced search was performed in PubMed, Embase, Google Scholar, and references query, assessed in June 2022, identified 761 records. Among them, 74 publications in English were included in the current narrative review.
KEY CONTENT AND FINDINGS
ECLS is an additional tool for organ support in life-threatening thoracic emergencies. It provides bridging to recovery or to decision about destination as definitive therapy, intervention, or surgery. Non-traumatic emergencies include mediastinal mass, acute lung injury (ALI), aspiration, embolisms, acute and chronic heart failure. However, based on the current evidence, trauma, and especially blunt thoracic trauma, is one of the main indications for ECLS use in thoracic emergencies, among others in chest wall fractures, blunt and penetrating lung injuries. ECLS use is always individualized to patient's needs, injury pattern and kind of organ failure, circulatory arrest inclusive, depending on if respiratory or cardiac and circulatory support is needed. Further, ECLS offers the possibility for fast volume resuscitation and rewarming, thus preventing the lethal of trauma: hypothermia, hypoperfusion and acidosis. Anticoagulation may be omitted for some hours or days. Interdisciplinary cooperation between the intensivists, surgeons, anesthesiologists, emergency medical services, an appropriately organized and trained staff, equipment resources and logistical planning are essential for successful outcomes.
CONCLUSIONS
ECLS use in selected life-threatening thoracic emergencies is increasing. The summarized findings appeal to policymakers, and we hope that our summary of recommendations may impact clinical practice and research.
PubMed: 37559625
DOI: 10.21037/jtd-22-1307 -
Haematologica Feb 2024Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors exhibit favorable...
Outcomes after programmed death-1 (PD-1) blockade in B-cell lymphomas are disappointing with few durable responses. Histone deacetylase inhibitors exhibit favorable immunomodulatory effects and demonstrate synergistic anti-tumor immune responses with anti-PD-1 therapy in preclinical models. We, therefore, developed a phase I study to evaluate the safety and preliminary efficacy of pembrolizumab with vorinostat in relapsed/refractory B-cell lymphomas. Patients were treated in a dose-escalation cohort using a Rolling 6 design followed by an expansion cohort at the recommended phase II dose (R2PD). Fifty-two patients were enrolled (32 Hodgkin and 20 non-Hodgkin lymphoma [NHL]). Here, we report safety data from the dose escalation cohort, and the toxicity and efficacy within NHL patients. Vorinostat was administered twice daily on days 1-5 and 8-12 (dose-level [DL]1: 100 mg; DL2: 200 mg) and pembrolizumab (200 mg) was administered on day 1 of each 3-week cycle. Of six patients treated at DL1, one had a dose-limiting toxicity (DLT) (Stevens-Johnson syndrome [SJS]), and one of six had a DLT at DL2 (thromboembolism); therefore, DL2 was the RP2D. The patient developing SJS was treated with corticosteroids, infliximab, and cyclosporine but ultimately died of invasive fungal infection from the extensive immunosuppression used to treat the SJS. The most common adverse events were hypertension, diarrhea, and cytopenias. Of 20 NHL patients, nine had follicular lymphoma (FL) and 11 had diffuse large B-cell lymphoma (DLBCL). Five DLBCL patients had primary mediastinal B-cell lymphoma (PMBL). The complete and overall response rates (CR and ORR) were 11% and 22% for FL and 45% and 55% for all DLBCL. Amongst DLBCL, the CR and ORR was 80% and 80% for PMBL and 17% and 33% for non-PMBL. In conclusion, pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL (clinicaltrials gov. Identifier: NCT03150329).
Topics: Humans; Vorinostat; Neoplasm Recurrence, Local; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Antibodies, Monoclonal, Humanized
PubMed: 37470137
DOI: 10.3324/haematol.2023.283002 -
Journal of Autoimmunity Oct 2023Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper...
RATIONALE
Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper (Th)17.1 signature, which correlates with non-resolving sarcoidosis. We hypothesize that the peripheral blood (PB) T cell phenotype may correlate with outcome.
OBJECTIVES
To compare frequencies, phenotypes and function of circulating T cell populations in sarcoidosis patients with healthy controls (HCs) and correlate these parameters with outcome.
METHODS
We used multi-color flow cytometry to quantify activation marker expression on PB T cell subsets in treatment-naïve patients and HCs. The disease course was determined after 2-year follow-up. Cytokine production was measured after T cell stimulation in vitro.
MEASUREMENTS AND MAIN RESULTS
We observed significant differences between patients and HCs in several T cell populations, including CD8 and CD4 T cells, Th1/Th17 subsets, CD4 T memory stem cells, regulatory T cells (Tregs) and γδ T cells. Decreased frequencies of CD4 T cells and increased frequencies of Tregs and CD8 γδ T cells correlated with worse outcome. Naïve CD4 T cells displayed an activated phenotype with increased CD25 expression in patients with active chronic disease at 2-year follow-up. A distinctive Treg phenotype with increased expression of CD25, CTLA4, CD69, PD-1 and CD95 correlated with chronic sarcoidosis. Upon stimulation, both naïve and memory T cells displayed a different cytokine profile in sarcoidosis compared to HCs.
CONCLUSIONS
Circulating T cell subpopulations of sarcoidosis patients display phenotypic abnormalities that correlate with disease outcome, supporting a critical role of aberrant T cell activation in sarcoidosis pathogenesis.
PubMed: 37863732
DOI: 10.1016/j.jaut.2023.103120