Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined. Methods: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality. Results: This study included 156 patients (median age = 72 years (range = 22–97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0–37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03–1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03–1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84–0.96) were independent prognostic factors. Conclusions: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.
Lung cancer is the leading cause of cancer death worldwide. Age and smoking are the primary risk factors for lung cancer. Treatment based on surgical removal in the early stages of the disease results in better survival. Screening programmes for early detection that used chest radiography and sputum cytology failed to attain reduction of lung cancer mortality. Screening by low-dose computed tomography (CT) demonstrated high rates of early-stage lung cancer detection in a high-risk population. Nevertheless, no mortality advantage was manifested in small randomised control trials. A large randomised control trial in the USA, the National Lung Screening Trial (NLST), showed a significant relative reduction of 20% in lung cancer mortality and 6.7% reduction in total mortality, yet no reduction was evidenced in the late-stage prevalence. Screening for lung cancer by low-dose CT reveals a high level of false-positive lesions, which necessitates further noninvasive and invasive evaluations. Based primarily on the NLST eligible criteria, new guidelines have recently been developed by major relevant organisations. The overall recommendation coming out of this collective work calls for lung cancer screening by low-dose CT to be performed in medical centres manned by specialised multidisciplinary teams, as well as for a mandatory, pre-screening, comprehensive discussion with the patient about the risks and advantages involved in the process. Lung cancer screening is on the threshold of a new era, with ever more questions still left open to challenge future studies. @ERSpublications Lung cancer screening is on the threshold of a new era, with wider application of CT screening now recommended
Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.
(1) Lung-sparing resection and HPCP is feasible and safe. (2) In thymoma with pleural spread it offers excellent survival despite moderate pleural control. (3) Preliminary results with stage IVa TC are disappointing.
Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.
Background: The life expectancy of hemophiliacs is similar to that of the general population. As a result, the prevalence of age-related cardiovascular diseases has increased. We present our experience with hemophilia patients who underwent cardiac surgery in our Medical Center between 2004 and 2019. Methods: All hemophilia patients who underwent cardiac surgery were identified, and their peri-operative data evaluated retrospectively. Results: Ten patients were identified: six with hemophilia-A, one with hemophilia-B, and three with hemophilia-C (factor XI deficiency). Cardiac procedures included ten coronary artery bypass grafts and one aortic valve replacement. Hemophilia-A and B patients were treated with factor substitution, whereas patients with factor XI deficiency were treated with fresh frozen plasma. One patient died, and one patient suffered from non-active gastrointestinal bleeding. Conclusions: While major cardiac surgery can be performed safely on patients with hemophilia, a multidisciplinary team approach and strict postoperative monitoring are essential in order to achieve optimal results.
OBJECTIVES: To investigate short-and long-term outcomes of a conservative decalcification approach in mitral valve replacement (MVR) surgery in the presence of mitral annulus calcification (MAC). METHODS:Of the 1038 patients who underwent MVR, 133 (13%) had significant MAC with at least 30% of the annular circumference heavily calcified. In most patients, the surgical approach to MAC included conservative decalcification, supra-annular prosthesis implantation and insertion of a pericardial patch between the MV annulus and the prosthesis. These patients were matched by a propensity score to a group of patients who underwent MVR without MAC (n = 118 in each group) and served as a control group.RESULTS: There were 6 early deaths in each group with an overall mortality of 5% (P = 0.90). Early complications included one major stroke in the non-MAC group and acute renal failure needing dialysis in 2 and 3 patients in the MAC and non-MAC groups, respectively. Mean follow-up was 55 ± 37 months and 99.1% complete. There were 38 (33%) and 33 (29%) late deaths with an estimated survival of 61% and 69% at 6 years in the MAC and non-MAC groups, respectively (P = 0.55). At follow-up, functional class did not differ between groups (P = 0.096). Mean echo follow-up time was 40 ± 35 months and was 83% complete. Freedom from moderate or severe mitral regurgitation was 95% and 98%, with an estimated freedom of 95% and 96% at 6 years (P = 0.20), and mean gradient was 4.9 ± 2.3 mmHg and 5.2 ± 2.0 mmHg for MAC and non-MAC groups, respectively (P = 0.58). CONCLUSIONS:A conservative approach for dealing with MAC is suitable for the majority of patients. Early and late clinical and echocardiographic outcomes did not differ between the MAC and non-MAC patients, including freedom from early and late occurrence of MV prosthesis paravalvular leak.
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