Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.

BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.

Combined use of risperidone and olanzapine in the treatment of patients with resistant schizophrenia: a preliminary case series report.

Polypharmacy, or the use of multiple drugs in the therapy of psychiatric disorders, is not recommended. However, appropriate combinations of pharmacologic mechanisms may enhance the efficacy of antipsychotic drugs and alter the course of schizophrenia. In recent years, some articles have been published about the successful use of clozapine and risperidone in combination for the treatment of patients with resistant schizophrenic and schizoaffective disorders. However, safety of this drug combination is open to discussion. This report presents the results of a preliminary study of five patients with resistant schizophrenia successfully treated with risperidone-olanzapine combination. The results suggest that this combination may be useful. In the future, the efficacy of risperidone-olanzapine combination should be confirmed in larger study populations before its clinical application is considered.

[Carbapenems (thienam and Meronem). Their clinical and economic efficacy]. / Karbapenamy (tienam i meronem). K voprosu o klinicheskoi i ékonomicheskoi éffektivnosti.

The authors describe 229 cases of carbapenem use in intensive care wards. Tienam was used in 205 cases since 1993, meronem in 24 cases since 1996. There were 149 men and 80 women aged 15-76 years (mean age 46.4 +/- 0.7 years). Carbapenemes were administered by 5-7-day courses in a daily dose of 2-6 g (2-4 g for tienam and 2-6 g for meronem). Carbapenemes were administered as monotherapy; in 196 cases nisoral was added to antibiotic therapy starting from day 3 as an antimycotic agent. Bacteriological studies were carried out in 367 patients (413 inoculations). Sensitivity of cultured microflora to disks with tienam (329 tests) and meronem (97 tests) showed their high activity towards gram-positive and gram-negative flora. The results were less demonstrative in cerebral abscesses, which is explained by specific pharmacokinetics of tienam. Analysis of the cost/efficacy ratio confirmed the economic efficacy of this group of drugs.

[Treatment of purulent and necrotic lesions of the lower extremities in patients with diabetes mellitus]. / Likuvannia hniino-nekrotychnykh urazhen nyzhnikh kintsivok u khvorykh na tsukrovyi diabet.

The results of complex treatment of 172 diabetic patients with purulent-inflammatory lesions of the lower extremities, using intensive purposeful antibacterial and desintoxicative therapy, timely and sufficient opening of purulent foci as well as administration of desagregants, stimulators of reparative processes, anabolic hormones, vitamins etc., are presented. Correction of carbohydrate metabolism was performed by means of insulin therapy according to the optimized scheme. Use of UV irradiation of the blood of the patients and local antiinflammatory roentgenotherapy contributed to increase in effectiveness of treatment. Incidence of amputation of an extremity at a level of a thigh was 20.2%, lethality-8.1%.

[The morphological characteristics of the cardiac lymphatic bed in chronic coronary failure]. / Morfologicheskie osobennosti limfaticheskogo rusla serdtsa pri khronicheskoi koronarnoi nedostatochnosti.

A study is presented of the morphological changes of the lymphatic circulation in chronic ischemic heart disease (IHD). Examinations were carried out on clinical material: intraoperative cardiac biopsies and on hearts of patients who died of this disease at the age of 36-59 years. Transmission electron microscopy was used. A clinical comparison was realized of changes of intramyocardial and subepicardial regions of the heart lymph circulation and morphological equivalents of disorders of outflow of lymph from the heart in chronic IHD were evaluated. The obtained data indicate the lymph stasis possessing cardiotoxic and sclerogenous properties is an essential pathogenetic factor of myocardial fibrotization in chronic coronary insufficiency.

[The basic patterns in the development of lymph circulatory failure in the heart]. / Osnovnye zakonomernosti razvitiia nedostatochnosti limfoobrashcheniia v serdtse.

63 adult rabbits were used to stimulate single physical exercise, acute and relapsing coronary insufficiency, alimentary atherosclerosis and to study adaptive and pathologic changes in the lymphatic channel (LC) of the heart. LC of the heart in animals with alimentary atherosclerosis after cholesterol exclusion from their diet was studied to determine reversibility of these changes. LC of the heart was injected by differently coloured masses and was investigated by the stereoangioscopic method on clarified preparations, on semithin sections and by the electron-microscopic method. Changes in different elements of a lymphatic net were of the stereotype character, as a whole. Morphofunctional reactions determining the development of the chronic insufficiency of the lymph flow in the heart form as successively following phases which change both due to exposition of the pathological process-initiated effect and due to certain endogenic factors arising during arrangement of LC of the heart.

[Activities of a day hospital of the city polyclinic]. / Deiatel'nost' dnevnogo statsionara gorodskoi polikliniki.

Highlighted is the experience gained in the organization of a day hospital created for general and neurologic patients at Polyclinic N 166 of the Krasnogvardeisk region of Moscow. The preliminary outcomes of the treatment of 167 patients are briefly analyzed. The results of the study on the population's opinion on the exapediency of day hospitals are provided. It is pointed out that treatment in a day hospital is regarded as an advanced form of medical care.