Dual immunological blockade in the treatment of metastatic non-small cell lung cancer: reality and perspectives

Nowadays immunotherapy is a crucial option in the treatment of non-small cell lung cancer. There are a lot of actual options of the first-line therapy for the patients with metastatic lung cancer, including dual immunological blockade of PD-1/PD-L1 and CTLA-4 pathways. This review is an attempt to clarify the place of dual immunological blockade now and in the future. The scientific rationale for dual immunotherapy is a possible synergy and overcome resistance to single-drug therapy. The review collected information from open sources, both current studies with dual immunological blockade, and already obtained results of the trials for nivolumab and ipilimumab, tremelimumab and durvalumab, and other combinations for the treatment of patients with metastatic non-small cell lung cancer. This approach is promising for the possible overcoming of resistance to monoimmunotherapy with anti-PD1/PD-L1 antibodies, especially in the population with low and negative PD-L1 status.

A REVIEW ON AMALTAAS (CASSIA FISTULA LINN.) AS AN EKAL DRAVYA CHIKITSA IN BRIHATRAYEE

Cassia fistula, also known as golden shower, is a plant with many medicinal uses being used for various therapeutic purposes. It is also known by name Aaragvadha, which means “disease killer”. Its leaves, fruits and flowers are known to have medicinal relevance in Ayurveda. The fruit pulp is known to have laxative properties. It has many health benefits due to its constituents of variety of biologically active compounds those have various medicinal properties in its different part. Amaltaas is a potential medicine when used in Ekal form as well as in compound formulations. Since ancient times, it has been used in different traditional system of medicines for various ailments. This article aims to provide a comprehensive review on the use of Amaltaas as an Ekal Dravya for treating many ailments like diabetes, hematemesis, leucoderma, pruritis, intestinal disorders, as an antipyretic, analgesic and laxative. Amaltaas is being used as a one of the best prescribed remedy for many of the common ailments in day today’s life by large number of physicians. Using Amaltaas as a single dravya with various anupaan may results in optimum health benefit. Ekal dravya concept of using single substances has been mentioned in our ancient Ayurvedic literature. Use of amaltaas as a single drug therapy has been evidenced at various instances in Brihatrayee which is being reviewed in this article. Using Amaltaas as an ekal dravya and with other medicinal substances as an anupaan is also been considered and taken for the review.

A STUDY ON DRUG-DRUG INTERACTION BETWEEN GLIPIZIDE AND CIMETIDINE IN RABBITS

Objective: To study the effect of Cimetidine (H2 receptor antagonist) in combination with Glipizide (Sulfonylurea) on the blood sugar level in rabbits. Methods: Six albino rabbits were taken for the study. Glipizide was administrated to each rabbit as a single drug therapy on day 1 and it was co-administrated with Cimetidine to each rabbit as a combinational drug therapy on day 7. Cimetidine was administrated to each rabbit from day 2 to day 6 as single drug therapy. Blood sugar levels were estimated on day 1 and on day 7 at 0, 1, 2, 4, and 6 h. Results: The mean blood sugar level readings at 0, 1, 2, 4 and 6 h on day 1 were 90.4, 69.4, 62.9 and 65.7 mg% and on day 7 were 89.4, 74.8, 65.5, 56.4 and 61.2 mg % respectively. When mean blood sugar level on day 1 and day 7 was considered, there was a significant reduction in blood sugar level at 1, 2, 4 and 6 h and there was no significant fall in blood sugar level at 0 hour after co-administration of Glipizide and Cimetidine. Conclusion: Cimetidine, when co-administered with Glipizide, significantly increases the hypoglycaemic action of Glipizide.

Concept of Ekal Dravya Chikitsa (Single Drug Therapy) in Sushrut Samhita

Ayurveda is a holistic health care system which, aims to offer the user an optimum health by alleviating diseases and helps in maintaining, promoting health by advising proper daily and seasonal regimen along with rationalized therapeutics when indicated. A good physician is one who uses minimum substances for desired effect or maximum results. From ancient past, it has been revealed that Ayurveda had a vast knowledge in the field of application of medicinal plants. Medicinal plants have significant importance in human life as it helps in maintaining human health and in improving the quality of life. Also this application in the form of single dravya has also been evidenced in many of Ayurveda texts. Sushrut Samhita is one of the classical text of Ayurveda, basically a part of Brihatrayee, have been surviving from ancient time and considered to be an important treatise on medicine and surgery. It is one of the two foundational Hindi texts alongside the Charak Samhita, which includes knowledge about medicine as well as surgical training, instruments and procedures. Likewise in charak samita, use of EDC has been also mentioned in Sushrut Samhita for both inervention as well as surgical management of disease. Using Ekal Dravya for curing many disease has been mentioned in past by many of Aacharyas, considering Sushrut Samhita as the first Samhita of Ayurveda to use therapeutic interventions as well as surgical procedure for the management of clinical condition, It has been reviewed to assess the extent of use of EDC. Using single herb for managing diseased condition has been evidenced at various instances in Sushrut Samhita in conceptual as well as in applied form. This provides an evidenced based proof that EDC was mentioned in our ancient Ayurvea texts which now need to be explored, so as to minimize the load on biodiversity for using minium herbs in a disease where it is sufficed.

Ivabradine versus carvedilol in the management of palpitation with sinus tachycardia among recovered COVID-19 patients

Introduction: One of the major complications among COVID-19 patients include cardiac arrhythmias. Commonest arrhythmia is sinus tachycardia which is usually associated with palpitation causing discomfort to patients. In this study, we present a comparative study of use of Ivabradine vs. Carvedilol for sinus tachycardia in post-COVID-19 infected patients. Method: 50 consecutive recovered COVID-19 patients with sinus tachycardia were included in this open labelled RCT. 25 patients received Ivabradine and remaining 25 received Carvedilol. Single therapy non-responders were treated with Ivabradine with Atorvastatin. Results: The mean age of all patients is 48.8±7.66 years (Males 49.5 ± 7.21 years; Females 47.68 ± 8.23 years). The mean heart rate (MHR) of all patients is 125.52 ± 9.07/min (Males 125.67 ± 8.78/min; Females 125.26 ± 9.5/min). After five days of single drug therapy the mean drop in the heart rate was 35.04 ± 10.55/min (Males 34.41 ± 9.71/min; Females 36.05 ± 11.72/min), resulting in 27.88 ± 8.11% (Males 27.38 ± 7.56%; Females 28.69 ± 8.89%) reduction in MHR. Among the two groups, the Carvedilol group showed improvement of MHR in 14(56%) patients; whereas in Ivabradine group 18(72%) patients improved out of 25 patients each (p: 0.2385). In the Carvedilol group the MHR reduced from 128.6 ± 8.44 to 95.68 ± 10.63 (p < 0.001), which is statistically significant; similarly, the Ivabradine group showed a MHR from 122.44 ± 8.62 to 85.28 ± 10.52 (p < 0.001). The monotherapy therapy non-responders were treated with dual-therapy of (Ivabradine + Atorvastatin). Discussion: Ivabradine is more effective in controlling heart rate compared to Carvedilol. Also, Ivabradine group scores very well in ‘patient-satisfaction’ with regards to symptom (palpitation) relief. Conclusion: The COVID-19 sequelae of sinus tachycardia can be better controlled with Ivabradine when compared to Carvedilol.

Olopatidine and Ketorolac Vs Olopatidine Alone in Treatment of Seasonal Allergic Conjunctivitis [Combination Vs Single Drug Therapy Study]

Purpose: To compare the therapeutic effects of combination of Olopatidine and Ketorolac vs Olopatidine alone (0.1% Olopatidine hydrochloride and 0.5% Ketorolac tromethamine) in seasonal allergic conjunctivitis (SAC).Methods: 200 patients with the signs and symptoms of SAC (i.e. hyperaemia, itching, mucus discharge, tearing) were included in this study. In group 1 (100 patients) each patient was treated with “olopatadine and Ketorolac” and group 2 patients were treated with Olopatidine alone. The principle signs and symptoms of SAC (hyperaemia, itching, watering and photophobia) were evaluated at day 0, day 7, day 15 and day 21 by using a 4 point scale. Mean scores of each of the parameters were calculated using paired t test.Results: When the mean scores of Group 1 (Olopatidine plus Ketorolac) were compared to the scores of Group 2 (Olopatidine only) the mean scores of hyperaemia, itching and watering were found to be lower in Group 1, indicating better therapeutic effectiveness with a significant difference statistically (p<0.05%) on day 7,day 15 and on day 21.Conclusions: Olopatadine and Ketorolac combination therapy is an effective treatment for seasonal allergic conjunctivitis when compared to Olopatidine alone.

Comparison of oral nifedipine and oral labetalol as a single drug therapy for control of blood pressure in preeclampsia

Background: Worldwide hypertension during pregnancy is a common cause of maternal and fetal morbidity and mortality. Effective control of blood pressure is one of the important steps in management of preeclampsia. Few drugs like nifedipine, labetalol, methyldopa, and hydralazine have acceptable high safety profile during pregnancy.Methods: In this study 120 antenatal women with non-severe preeclampsia were compared by giving either nifedipine or labetalol as a single drug therapy for control of blood pressure. Various parameters like control of blood pressure, side effects of drugs, gestational age at the time of delivery, mode of delivery, any complication and perinatal outcome were assessed.Results: In this study authors found that in both group, adequate control of blood pressure was achieved. This study shows slightly higher rate of pre term delivery and LSCS with labetalol and minimal side effects with nifedipine but difference in each group is insignificant.Conclusions: Labetalol and nifedipine both the drugs are equally effective in reducing blood pressure and any of it can safely be used as a first choice of drug for management of hypertension in preeclampsia and it can be decided as per clinician’s experience and familiarity with drug.

GestaTIonal TrophoblAstic NeoplasIa Ultrasound assessMent: TITANIUM study

BackgroundThere are limited data on ultrasound morphologic features of gestational trophoblastic neoplasia. A predictive model to determine predictors of response to therapy would be ideal in the management of patients with this rare disease.Primary Objectives and Study HypothesisTITANIUM is a prospective, multicenter, observational study aiming to describe ultrasound features of gestational trophoblastic neoplasia and to investigate the role of ultrasound in identifying patients at high risk of resistance to single-drug therapy. The study hypothesis is that ultrasound could improve the International Federation of Gynecology and Obstetrics (FIGO) scoring system for early identification of patients predisposed to single-drug resistance.Trial Design and Major Inclusion/Exclusion CriteriaPatients eligible have a diagnosis of gestational trophoblastic neoplasia according to FIGO or the criteria set by Charing Cross Hospital, London, UK. At diagnosis, patients are classified as low-risk (score 0–6) or high-risk (score >6) according to the FIGO risk scoring system, and a baseline ultrasound scan is performed. Patients receive treatment according to local protocol at each institution. Follow-up ultrasound examinations are performed at 1, 4, 10, 16, and 22 months after start of chemotherapy, and at each scan, serum human chorionic gonadotropin (hCG) level, and chemotherapy treatment, if any, are recorded.Primary EndpointsOur aims are to define ultrasound features of gestational trophoblastic neoplasia and to develop a predictive model of resistance to single-drug therapy in low-risk patients.Sample SizeThe sample size was calculated assuming that 70% of patients with gestational trophoblastic neoplasia are at low risk, and estimating the rate of resistance to single-drug therapy in this group to be 40%. Assuming a dropout rate of 10%, we should recruit at least 120 patients. With this sample size, we can attempt to create a mathematical model with three variables (either two ultrasound parameters in addition to the risk score or three ultrasound variables statistically significant at univariate analysis) to predict resistance to single-drug therapy in low-risk patients.Estimated Dates for Completing Accrual and Presenting ResultsThe accrual started in February 2019. Additional referral centers for gestational trophoblastic disease, with similar ultrasound expertise, are welcome to participate in the study. Enrollment should be completed by December 2021, and analysis will be conducted in December 2023.Trial RegistrationThe study received the Ethical Committee approval of the Coordinator Center (Rome) in January 2019 (Protocol No. 0004668/19).