Immune Checkpoint Inhibitors (ICPIs), while revolutionizing cancer therapy through potentiation of anti-tumour responses via targeted blockade of T-lymphocyte inhibitory receptors, are associated with immune-related adverse events (irAEs), including diverse renal manifestations. This report presents a case of a 69-year-old male with urothelial carcinoma who developed Acute Kidney Injury (AKI) and nephrotic-range proteinuria following initiation of nivolumab, an anti-PD1 antibody, necessitating renal biopsy to clarify the aetiology. The biopsy revealed Focal Segmental Glomerulosclerosis (FSGS) with endotheliopathy, suggesting a direct ICPI-induced glomerular injury. This case underscores the need for heightened awareness of ICPI-associated glomerular disease, alongside more common renal adverse events such as Acute Interstitial Nephritis (AIN), and for the need for renal biopsy in such cases. While the incidence of ICPI-associated AKI is approximately 17%, and AIN is a more frequent finding, FSGS and other glomerular pathologies should also be considered. Current treatment for such renal events involves discontinuation of the ICPI agent and initiation of immunosuppression with glucocorticoids. The management of these cases requires prompt detection, timely diagnosis, and often interdisciplinary collaboration, thus highlighting the need for more case reports, research, and better treatment strategies.
Pulmonary Embolism (PE) can present with symptoms resembling pneumonia, creating a diagnostic challenge, particularly in patients with comorbidities. We report the case of a 67-year-old male who presented with cough, hemoptysis, shortness of breath, fever, and pedal edema. Initially diagnosed with consolidation based on chest X-ray findings, he was treated with antibiotics. However, persistent symptoms prompted further evaluation, leading to the diagnosis of PE with pulmonary infarction and deep vein thrombosis on computed tomography pulmonary angiography and Doppler ultrasound. This case highlights the need to consider PE in the differential diagnosis of consolidation, particularly in high-risk individuals, to avoid delays in appropriate management.
Globally, evidence-based healthcare practices are the most dependable framework for effective healthcare decisions and practices. In all nations, financial resources, people, and time are always insufficient. Healthcare professionals should recommend healthcare interventions that have been proven to be safe, effective, and affordable. All healthcare professionals must be creative to be involved in the creation and compilation of trustworthy evidence to support the decrease in morbidity and mortality of communicable and non-communicable diseases, particularly in developing nations. Regretfully, most developing nations still exhibit weaknesses and barriers to promoting health research and evidence-based healthcare. Evidence indicates that developing countries contribute 1% - 2% of health research activities to address global health problems and challenges. As a result, many individuals in these nations continue to have below-average health conditions. The lack of creativity, innovation, and motivation to gain health research competencies for healthcare professionals causes all these issues. Creativity and innovation are the foundations for the effective implementation of evidence-based healthcare. Surprisingly, no researchers have explored how creativity and innovation heighten evidence-based healthcare practices. The primary objective of this project will be to foster pathways and explore the creativity that advances health research abilities among healthcare professionals to improve evidence-based healthcare practices in resource-limited healthcare settings.
Quantum fluctuations, usually arising from the inherent uncertainty in the quantum fields, are pivotal in understanding the universe at both the small and large scales. Even though fluctuations are usually unobservable and rather small, they give significant observable effects during specific epochs under specific conditions. During the early epochs of the universe, the fluctuations were scaled, resulting in the primordial density perturbations that gave rise to the large-scale structure of the universe and the observed inhomogenities. In this paper, we study the basic origin, structure, evolution, and imprints of fluctuations during the inflationary period resulting in large-scale structure formation. We use the Mukhanov-sasaki formalism to model scalar perturbations, embedding the theoretical results into observations. Theoretical predictions show an almost scale-invariant power spectrum with stringent constraints on the inflationary parameters. It further states that in the very early universe, the inflatons that are quanta of the primordial field were highly filled in the degenerate quantum state. This carries large potential energy that results in an exponential expansion of the universe. During post post-inflationary period the inflaton dominated the Universe’s energy density; they interact among themselves and due to non-linear effects, these inhomogeneities grow which amalgamate into spatially distinguishable patches in our observable universe. Our understanding projects us towards the fact that fluctuations play a pivotal role in understanding the structure formation at micro, macro, and far-macro scales. This study also addresses the significance of quantum fluctuations in cosmic evolution and manifests the enduring relevance in addressing some of the profound mysteries of our universe.
Pulak Azad*, Yasir Sultan Rizvi, Lakshmi Kant Jha, Pranav Tyagi, Sachin Jain and Twinkle Malik
Published on: 5th February, 2025
The prevalence of gallbladder stones is higher in Chronic Kidney Disease (CKD) patients and it has been shown to increase with the advancement of the disease stage, from 7.7% in stage 1% to 21.3% in stage 5. Gallstone ileus is a rare complication which presents in just 0.3% - 0.5% of patients with cholelithiasis. A 61-year-old female patient, with a known case of CKD on maintenance hemodialysis, (thrice a week) with primary disease of hypertensive and diabetic nephropathy; presented with multiple episodes of loose stool, vomiting, and diffuse abdominal pain for 2 days. Abdomen Ultrasonography (USG) was suggestive of intestinal obstruction. CT abdomen with oral contrast revealed grossly dilated jejuna loops with air-fluid levels and transition zone in the pelvis, in distal jejunal loops/proximal ileum with ovoid intraluminal filling defect cystic polyp and collapsed bowel loops. The patient underwent exploratory laparotomy in view of persistent small bowel obstruction. Resection and anastomosis of the mass-bearing small bowel segment were performed. On cutting and opening the specimen, a large stone was revealed. This gallstone was causing bowel obstruction-gall stone ileus. A gallstone 2.6 cm x 2.1 cm has traversed through a cholecysto-duodenal fistula and got stuck in the proximal ileum, causing small bowel obstruction. The lesson learned is uraemia can cause gastrointestinal symptoms like anorexia, abdominal pain, vomiting, and ileus and hence mimic serious differentials of the acute abdomen like gallstone ileus. Thus no stone should be left unturned especially when the prevalance of gallstones is high in chronic kidney disease patients.
Pulak Azad*, Lakshmi Kant Jha, Yasir Sultan Rizvi and Pranav Tyagi
Published on: 4th February, 2025
Amyloidosis-associated kidney disease commonly manifests with chronic glomerular symptoms including heavy proteinuria predominantly albuminuria. Clinical presentation ranges from full-blown nephrotic syndrome, hematuria, and hypertension to renal failure. In India patients with chronic kidney disease are mainly attributed to hypertension and diabetes but an underlying etiology such as amyloidosis needs to be unearthed and shouldn’t be ignored as an etiology. We report a case of a 60-year-old man with hypertension and hypothyroidism who presented with frothy urine for several years, b/l pedal edema for 15 days. Over the past 3 months, there was a serial increase in creatinine. As per CKD-EPI equation, the patient was CKD-4. As the patient was suspected to be rapidly progressive renal failure; a renal biopsy was planned. Biopsy reports were suggestive of Amyloidosis. Glomerular, vascular, and tubulointerstitial deposition of amyloid was seen. Based on renal biopsy and IHC staining; the patient’s diagnosis was AA-associated secondary renal amyloidosis. Thus in this case renal amyloidosis was an unearthed etiology.
Bifurcation analysis and Multiobjective Nonlinear Model Predictive Control (MNLMPC) calculations were performed on a model of circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The MATLAB program MATCONT was used to perform the bifurcation analysis. The optimization language PYOMO was used along with the state-of-the-art global optimization solvers IPOPT and BARON for the MNLMPC calculations. The bifurcation analysis revealed oscillation causing Hopf bifurcations while the MNLMPC calculations revealed the existence of spikes in the control profiles. Both Hopf bifurcation points and the control profile spikes were eliminated using an activation factor involving the hyperbolic tangent function.
Public-Private Partnership (PPP) road projects are being promoted worldwide to encourage road investments; however, research on the appropriate rate of return for these projects is insufficient. This is likely because the return on investment for PPP road projects is determined through negotiations between the government and the private sector, a process that remains confidential. The rate of return for PPP road projects is not only a key indicator for evaluating project performance but also a potential driver for future government financial subsidies. Therefore, research on the appropriate rate of return for PPP road projects is necessary for the sustainability of these projects.This study, based on the concept that both the government and the private sector share the anticipated risks of the project, quantifies six types of risks and proposes a model for predicting the appropriate rate of return. The model is able to explain approximately 68% of the cases in South Korea’s PPP road projects. The risk with the greatest influence on the rate of return was found to be an economic risk, while the least influential was regulation change risk.Due to the confidentiality of data related to PPP road projects, this study only utilized 54 cases from South Korea. It is hoped that a wider range of data will be collected and further research on the appropriate rate of return will continue to enhance the sustainability of PPP road projects.
The article conducted a study of computer acoustic analysis of Jitter and Shimmer voice parameters in children with dysphonia after laryngeal surgery. The study found that children with dysphonia had significantly lower preoperative Jitter and Shimmer scores (574359, 587, and 2.3) compared to healthy children (1316743.376 and 4.84). At 1 month after surgery, affected children showed a decrease in Jitter and Shimmer indices compared with these acoustic indices before surgery. However, at 2 months, there was a significant increase in Jitter and Shimmer scores, and at 3 months, Jitter and Shimmer scores were comparable to Jitter and Shimmer scores in healthy children without dysphonia. The results of the study show that the method of analyzing the acoustic parameters of the voice Jitter and Shimmer allows a phoniatrist to objectively assess the occurrence of a voice disease in patients with dysphonia, and this method is the most accurate criterion for determining the pathologies of dysphonia and determining the treatment program for the disease.
Blood cell production through hematopoiesis within the bone marrow serves both to maintain blood equilibrium and to respond to tissue injury and infectious demands. Hematopoietic stem cell (HSC) therapy developments have revolutionized medical treatment approaches for anemia leukemia and bone marrow failure caused by chemotherapy or radiation exposure. The therapeutic compounds present in medicinal plants have traditionally supported blood health and researchers now understand these plants could help regenerate bone marrow tissue. The analysis investigates how phytochemicals affect HSC proliferation and differentiation while supporting HSC survival. The medicinal plants Panax ginseng, Astragalus membranaceus, and Curcuma longa receive special attention for their documented ability to enhance hematopoiesis in preclinical and clinical settings. This review examines the challenges that include standardization issues, toxicity concerns, and regulatory barriers alongside future perspectives about combining plant-based therapies with traditional treatments to improve bone marrow recovery and health results.
The Journal Clinical Nephrology provides a good opportunity for readers to stay updated in the field of clinical nephrology. Additionally - it provides a good opportunity for authors to publish their...
Assaf Harofeh Medical Center, Israel
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