scholarly journals An analysis of early morning acth levels in the first case of pembrolizumab-induced adrenalitis as a delayed immune-related event (dire) – case study

2020 ◽  
Vol 73 (2) ◽  
pp. 396-400
Author(s):  
Igor Alexander Harsch ◽  
Anastasiia Gritsaenko ◽  
Peter Christopher Konturek

The aim: The levels of adrenocorticotrophic hormone (ACTH) are elevated in primary adrenal failure (Addison’s disease) with a peak in the early morning hours. This also occurs under hydrocortisone replacement therapy due to the unphysiological substitution regime. The aim was to study ACTH levels under two different replacement regimens. This is exemplified in a patient with adrenalitis after immunotherapy for malignant melanoma (MM), since (elevated) levels of ACTH and its cleavage product alpha-melanocyte stimulating hormone (α-MSH) raise concerns since receptors for both hormones can be expressed in melanoma cells. Material and methods: A female with MM had immunotherapy with pembrolizumab and developed adrenalitis with Addison crisis about one year after discontinuation of this therapy (delayed immune-related event = DIRE). ACTH levels were measured hourly (4-8 a.m.) during a “conventional” hydrocortisone replacement therapy and during a therapy with dual-release hydrocortisone. Results: Salient differences between the morning ACTH profiles under the “conventional” hydrocortisone replacement regimen with 10-5-5 mg/die compared to the single-dose regimen with 20 mg dual-release hydrocortisone were not discernible. Conclusion: DIRE could be an underestimated problem in immunotherapy and could put the patients at hazard. Especially in case of an endocrinological DIRE concerning the adrenocorticotrophic axis, life-threatening situations can arise for the patients. As for the special situation with M. Addison and MM, where hormonal feedback mechanisms may cause further problems beyond the normal hormonal replacement therapy, we observed no salient differences in the early morning ACTH profiles under different hydrocortisone replacement regimens.

2021 ◽  
Vol 9 (9) ◽  
pp. 2262-2266
Author(s):  
Shridharaiah M.H ◽  
Venkatesh P

Shwasa is a chronic condition that developed as a result of Pranavaha sroto dushti, here the shwasa roga is developed due to two types of srodo dushti i.e. sangha (Due to kapha avarodha) and vimarga gamana (of the udana vata). Asthma is a condition that affects the quality of life of an individual. Especially this condition aggravates and worsens in the cold season. Depending on the sign and symptoms Shwasa roga can be compared with Asthma. Asthma is a chronic inflammatory disease that affects the airway of lungs and leads to narrowing of air passage, it is an episodic disease manifested clinically by paroxysms of dyspnoea, tightness of chest along with wheezing sound and coughing usually more at night or early morning. Asthma rapidly increasing in India due to pollution, Among India’s 1.31 billion people, about 6% of children and 2% of adults are suffering from asthma.[1] Tamaka shwasa is one among the Shwasaroga and it is predominantly Vatakaphajavyadhi. This disease is maintainable by giving proper medication like shodhana (Vmana, Virechana, etc...) and shamana chikitsa (Swasa kutara rasa, swasamrita etc...), if the proper treatment is not given to the patient is proper time, then this condition gets worse and become life-threatening. So, the following case study is explaining about the management of Swasa roga of 8 years history with Ayurvedic medications. Keywords: Tamaka Shwasa, Deppana, Paachana, Shodhana, Shamana.


2020 ◽  
Vol 106 (6) ◽  
pp. NP23-NP28
Author(s):  
Alessandro Guidi ◽  
Martina Violati ◽  
Miriam Blasi ◽  
Elettra Ferrari ◽  
Andrea Luciani ◽  
...  

Introduction: Head and neck cancer represents a variety of tumors involving different organs in the cervical district, burdened by poor prognosis when diagnosed in an advanced stage. Immunotherapy with both anti-PD-1 nivolumab and pembrolizumab has the aim of increasing overall survival for patients with this malignancy. We report the first case of immune-related encephalitis caused by nivolumab in this setting of disease and present a brief review of the literature. Case description: A 60-year-old woman had been treated with concomitant chemoradiotherapy for a locally advanced human papillomavirus–negative squamous cell carcinoma of the tonsil. After local recurrence, she was treated with platinum-based first-line chemotherapy, followed by nivolumab at further progression within 6 months. Nivolumab was administered for 19 weeks, then discontinued due to the occurrence of immune-related hypothyroidism and grade 2 diarrhea. A month after the onset of the endocrinopathy, the patient also developed steroid-responsive encephalitis, considered as a consequence of anti-PD-1 therapy. One year after discontinuation of immunotherapy, toxicities have resolved and the patient is maintaining a complete radiologic response. Conclusions: Immunotherapy is a relatively new and promising therapy in the field of oncology. Its mechanism of action, which aims to stimulate the immune system against cancer cells, is not comparable to systemic and cytotoxic chemotherapy, which directly attacks and destroys malignant cells. Despite these differences, immunotherapy is not to be considered free from side effects, sometimes life-threatening.


2021 ◽  
Vol 2 (3) ◽  
pp. 27-30
Author(s):  
Anupam Bhambhani ◽  
Sahithi Sharma ◽  
Aditi Nadamani

We report here a rare case of dabigatran-related spontaneous cardiac tamponade, which appeared in absence of the known risk factors that predispose the patient to bleed related to anticoagulant drugs. A 65-year-old lady presented to the emergency room with sudden onset dyspnea which woke her up in the early morning hours. Four days earlier, she had been started on dabigatran therapy for DVT. On examination, she was in shock. Transthoracic echocardiography confirmed cardiac tamponade. Emergent pericardiocentesis was done, draining 480 ml of haemorrhagic fluid, which tested negative for microbes and malignant cells. The patient recovered rapidly and fluid did not re-accumulate after withdrawal of dabigatran therapy. Spontaneous cardiac tamponade is rare with the use of direct anticoagulants, especially dabigatran, in the absence of predisposing risk factors. This case study highlights the need for clinicians to be cognizant of this potentially life-threatening adverse drug reaction of dabigatran so that appropriate timely action can be taken toward diagnosis and management of this complication.


Author(s):  
Tewogbade Adeoye Adedeji ◽  
Simeon Adelani. Adebisi ◽  
Nife Olamide Adedeji ◽  
Olusola Akanni Jeje ◽  
Rotimi Samuel Owolabi

Background: Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. Objectives: We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). Methods: A cross-sectional analysis was performed on 170 consecutive newly diagnosed ART-naïve, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). Results: eGFR showed significant difference between patients’ and controls’ medians (47.89ml/min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 – 2.2) versus 1.1 mmol/L (IQR: 0.3 – 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 – 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96 % (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). Conclusion: HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naïve HIV patients.


Author(s):  
Kathryn M. de Luna

This chapter uses two case studies to explore how historians study language movement and change through comparative historical linguistics. The first case study stands as a short chapter in the larger history of the expansion of Bantu languages across eastern, central, and southern Africa. It focuses on the expansion of proto-Kafue, ca. 950–1250, from a linguistic homeland in the middle Kafue River region to lands beyond the Lukanga swamps to the north and the Zambezi River to the south. This expansion was made possible by a dramatic reconfiguration of ties of kinship. The second case study explores linguistic evidence for ridicule along the Lozi-Botatwe frontier in the mid- to late 19th century. Significantly, the units and scales of language movement and change in precolonial periods rendered visible through comparative historical linguistics bring to our attention alternative approaches to language change and movement in contemporary Africa.


Author(s):  
A.C.C. Coolen ◽  
A. Annibale ◽  
E.S. Roberts

This chapter reviews graph generation techniques in the context of applications. The first case study is power grids, where proposed strategies to prevent blackouts have been tested on tailored random graphs. The second case study is in social networks. Applications of random graphs to social networks are extremely wide ranging – the particular aspect looked at here is modelling the spread of disease on a social network – and how a particular construction based on projecting from a bipartite graph successfully captures some of the clustering observed in real social networks. The third case study is on null models of food webs, discussing the specific constraints relevant to this application, and the topological features which may contribute to the stability of an ecosystem. The final case study is taken from molecular biology, discussing the importance of unbiased graph sampling when considering if motifs are over-represented in a protein–protein interaction network.


Author(s):  
Ashish Singla ◽  
Jyotindra Narayan ◽  
Himanshu Arora

In this paper, an attempt has been made to investigate the potential of redundant manipulators, while tracking trajectories in narrow channels. The behavior of redundant manipulators is important in many challenging applications like under-water welding in narrow tanks, checking the blockage in sewerage pipes, performing a laparoscopy operation etc. To demonstrate this snake-like behavior, redundancy resolution scheme is utilized using two different approaches. The first approach is based on the concept of task priority, where a given task is split and prioritize into several subtasks like singularity avoidance, obstacle avoidance, torque minimization, and position preference over orientation etc. The second approach is based on Adaptive Neuro Fuzzy Inference System (ANFIS), where the training is provided through given datasets and the results are back-propagated using augmentation of neural networks with fuzzy logics. Three case studies are considered in this work to demonstrate the redundancy resolution of serial manipulators. The first case study of 3-link manipulator is attempted with both the approaches, where the objective is to track the desired trajectory while avoiding multiple obstacles. The second case study of 7-link manipulator, tracking trajectory in a narrow channel, is investigated using the concept of task priority. The realistic application of minimum-invasive surgery (MIS) based trajectory tracking is considered as the third case study, which is attempted using ANFIS approach. The 5-link spatial redundant manipulator, also known as a patient-side manipulator being developed at CSIR-CSIO, Chandigarh is used to track the desired surgical cuts. Through the three case studies, it is well demonstrated that both the approaches are giving satisfactory results.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Markus J. Ankenbrand ◽  
Liliia Shainberg ◽  
Michael Hock ◽  
David Lohr ◽  
Laura M. Schreiber

Abstract Background Image segmentation is a common task in medical imaging e.g., for volumetry analysis in cardiac MRI. Artificial neural networks are used to automate this task with performance similar to manual operators. However, this performance is only achieved in the narrow tasks networks are trained on. Performance drops dramatically when data characteristics differ from the training set properties. Moreover, neural networks are commonly considered black boxes, because it is hard to understand how they make decisions and why they fail. Therefore, it is also hard to predict whether they will generalize and work well with new data. Here we present a generic method for segmentation model interpretation. Sensitivity analysis is an approach where model input is modified in a controlled manner and the effect of these modifications on the model output is evaluated. This method yields insights into the sensitivity of the model to these alterations and therefore to the importance of certain features on segmentation performance. Results We present an open-source Python library (misas), that facilitates the use of sensitivity analysis with arbitrary data and models. We show that this method is a suitable approach to answer practical questions regarding use and functionality of segmentation models. We demonstrate this in two case studies on cardiac magnetic resonance imaging. The first case study explores the suitability of a published network for use on a public dataset the network has not been trained on. The second case study demonstrates how sensitivity analysis can be used to evaluate the robustness of a newly trained model. Conclusions Sensitivity analysis is a useful tool for deep learning developers as well as users such as clinicians. It extends their toolbox, enabling and improving interpretability of segmentation models. Enhancing our understanding of neural networks through sensitivity analysis also assists in decision making. Although demonstrated only on cardiac magnetic resonance images this approach and software are much more broadly applicable.


2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Li-Fen Yang ◽  
Jia-Chang Ding ◽  
Ling-Ping Zhu ◽  
Li-Xia Li ◽  
Meng-Qi Duan ◽  
...  

Abstract Background Capillary leak syndrome (CLS) is a rare disease characterized by profound vascular leakage and presents as a classic triad of hypotension, hypoalbuminemia and hemoconcentration. Severe CLS is mostly induced by sepsis and generally life-threatening in newborns, especially in premature infants. Continuous renal replacement therapy (CRRT) plays an important role of supportive treatment for severe CLS. Unfortunately, CRRT in preterm infants has rarely been well defined. Case presentation We report the case of a 11-day-old girl with CLS caused by sepsis, who was delivered by spontaneous vaginal delivery (SVD) at gestational age of 25 weeks and 4 days, and a birth weight of 0.89 Kilograms(kg). The infant received powerful management consisting of united antibiotics, mechanical ventilation, intravenous albumin and hydroxyethyl starch infusion, vasoactive agents, small doses of glucocorticoids and other supportive treatments. However, the condition rapidly worsened with systemic edema, hypotension, pulmonary exudation, hypoxemia and anuria in about 40 h. Finally, we made great efforts to perform CRRT for her. Fortunately, the condition improved after 82 h’ CRRT, and the newborn was rescued and gradually recovered. Conclusion CRRT is an effective rescue therapeutic option for severe CLS and can be successfully applied even in extremely-low-birth-weight premature.


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