Unveiling the potential of ursolic acid modified hyaluronate nanoparticles for combination drug therapy in triple negative breast cancer.

Triple negative breast cancer (TNBC) represents the most aggressive and heterogenous disease, and combination therapy holds promising potential. Here, an enzyme-responsive polymeric prodrug with self-assembly properties was synthesized for targeted co-delivery of paclitaxel (PTX) and ursolic acid (UA). Hyaluronic acid (HA) was conjugated with UA, yielding an amphiphilic prodrug with 13.85 mol% UA and a CMC of 32.3 µg/mL. The HA-UA conjugate exhibited ∼14 % and 47 % hydrolysis at pH 7.4 and in tumor cell lysate. HA-UA/PTX NPs exhibited a spherical structure with 173 nm particle size, and 0.15 PDI. The nanoparticles showed high drug loading (11.58 %) and entrapment efficiency (76.87 %) of PTX. Release experiments revealed accelerated drug release (∼78 %) in the presence of hyaluronidase enzyme. Cellular uptake in MDA-MB-231 cells showed enhanced uptake of HA-UA/PTX NPs through CD44 receptor-mediated endocytosis. In vitro, HA-UA/PTX NPs exhibited higher cytotoxicity, apoptosis, and mitochondrial depolarization compared to PTX alone. In vivo, HA-UA/PTX NPs demonstrated improved pharmacokinetic properties, with 2.18, 2.40, and 2.35-fold higher AUC, t1/2, and MRT compared to free PTX. Notably, HA-UA/PTX NPs exhibited superior antitumor efficacy with a 90 % tumor inhibition rate in 4T1 tumor model and low systemic toxicity, showcasing their significant potential as carriers for TNBC combination therapy.

Patient Perspectives After Surgery-Related Complications Among Breast Cancer Patients from a LMIC.

Long-term quality of life in breast cancer patients has been studied and published regularly. However, the lived experiences of patients who develop complications after surgery are not well understood. Determining this experience of patients is challenging in most low- and middle-income countries where the majority of patients belong to poor strata of society and are uneducated. We aimed to explore the thoughts, feelings, and experiences of patients with surgery-related complications after breast cancer surgery. Purposive sampling was used to identify patients who developed any postoperative complication, and semi-structured interviews were conducted. Common patterns of patient experiences were identified and analyzed using descriptive thematic analysis. Twenty-eight patients out of 210 developing complications postoperatively were identified. The median age was 48 years (range 32-65 years). The majority (n = 26) were housewives, educated below the primary level (n = 11) and below the poverty line (n = 13). Complications included seroma (n = 17), flap necrosis and infection (n = 5), and hematoma (n = 1). Seven domains emerged from the interviews-knowledge of complications, psychological impact, burden, disruptiveness, social impact, relationship with the surgical team, and suggestions to improve the experience. The themes identified in the present study provide insights into the lived experiences and can inform the future development of patient-reported outcome measures and quality improvement programs, including more effective pre-operative counseling and consent. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01721-z.

Hepatocellular carcinoma: Preclinical and clinical applications of nanotechnology with the potential role of carbohydrate receptors.

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer; accounts for 75-85% of cases. The treatment and management of HCC involve different sanative options like surgery, chemotherapy, immunotherapy, etc. Recently, various advancements have been introduced for the diagnosis and targeting of hepatic tumor cells. Among these, biomarkers are considered the primary source for the diagnosis and differentiation of tumor cells. With the advancement in the field of nanotechnology, different types of nanocarriers have been witnessed in tumor targeting. Nanocarriers such as nanoparticles, liposomes, polymeric micelles, nanofibers, etc. are readily prepared for effective tumor targeting with minimal side-effects. The emergence of various approaches tends to improve the effectiveness of these nanocarriers as demonstrated in ample clinical trials. This review focuses on the significant role of carbohydrates such as mannose, galactose, fructose, etc. in the development, diagnosis, and therapy of HCC. Hence, the current focus of this review is to acknowledge various perspectives regarding the occurrence, diagnosis, treatment, and management of HCC.

Overcoming skin barriers through advanced transdermal drug delivery approaches.

Upon exhaustive research, the transdermal drug delivery system (TDDS) has appeared as a potential, well-accepted, and popular approach to a novel drug delivery system. Ease of administration, easy handling, minimum systemic exposure, least discomfort, broad flexibility and tunability, controlled release, prolonged therapeutic effect, and many more perks make it a promising approach for effective drug delivery. Although, the primary challenge associated is poor skin permeability. Skin is an intact barrier that serves as a primary defense mechanism to preclude any foreign particle's entry into the body. Owing to the unique anatomical framework, i.e., compact packing of stratum corneum with tight junction and fast anti-inflammatory responses, etc., emerged as a critical physiological barrier for TDDS. Fusion with other novel approaches like nanocarriers, specially designed transdermal delivery devices, permeation enhancers, etc., can overcome the limitations. Utilizing such strategies, some of the products are under clinical trials, and many are under investigation. This review explores all dimensions that overcome poor permeability and allows the drug to attain maximum potential. The article initially compiles fundamental features, components, and design of TDDS, followed by critical aspects and various methods, including in vitro, ex vivo, and in vivo methods of assessing skin permeability. The work primarily aimed to highlight the recent advancement in novel strategies for effective transdermal drug delivery utilizing active methods like iontophoresis, electroporation, sonophoresis, microneedle, needleless jet injection, etc., and passive methods such as the use of liposomes, SLN, NLC, micro/nanoemulsions, dendrimers, transferosomes, and many more nanocarriers. In all, this compilation will provide a recent insight on the novel updates along with basic concepts, the current status of clinical development, and challenges for the clinical translation of TDDS.

Chronicle of Hypoxemia: Transfusion-Associated Circulatory Overload Versus Transfusion-Related Acute Lung Injury.

The preeminent causes of blood transfusion-related morbidity and mortality are transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). These occur within hours of blood transfusion and lead to acute respiratory distress. The differentiation between TACO and TRALI has always been a great challenge in the context of underlying etiology, whether it is volume overload or lung injury, or both. This is a case report of a 64-year-old female with multiple comorbidities, who was brought to the emergency department with generalized weakness. She was hemodynamically unstable and encephalopathic. Her hemoglobin was 6.5 gm/dl with no active evidence of bleeding. She was started on a norepinephrine drip and one unit of packed red blood cells was transfused. A few hours post-transfusion, she became extremely tachypneic and hypoxic. A chest x-ray post-transfusion showed diffuse bilateral fluffy alveolar infiltrates and the N-terminal (NT)-pro hormone Brain Natriuretic Peptide (NT-proBNP) was significantly elevated. The transfusion reaction workup was negative. Due to worsening hypoxia, she required a rapid transition from non-invasive to invasive mechanical ventilation. The chronology of this case report depicts a unique presentation of acute respiratory distress and the course of hypoxemia.

Decision-Making Dilemma in Preoperative Cardiac Evaluation: Should We Turn the Page or Close the Book?

Coronary artery disease is one of the most dreadful and life-threatening diseases out of all cardiac diseases. The diagnosis and management of coronary artery disease comprise stepwise approaches. All these approaches are mostly guideline-driven. While the majority of the time, guidelines help us take the most appropriate care, exceptions do exist. For example, patients may have unusual risk factors and abnormal test results; however, they do not fit into the guideline algorithm to proceed further.  This case report of a 68-year-old male patient depicts a true example of such a situation. He presented to the cardiologist's office for pre-operative cardiac evaluation for urological surgery. In view of associated risk factors, an exercise stress test was done, which showed critical abnormalities. As per the pre-operative cardiac assessment guidelines, the patient did not meet the criteria for further testing. However, a clinician's strong judgment and persistent negotiation superseded those barriers. Given critical abnormalities of the exercise stress test, the patient underwent cardiac catheterization. He was found to have triple vessel disease on cardiac catheterization. The scheduled surgery was withheld, and the patient underwent a coronary artery bypass graft. This life-threatening condition could have been easily missed if only the guidelines were to be followed. While guidelines cover a significant portion of the bell curve, this case report represents the importance of not missing the tail ends of the curve. It enhances the importance of thinking out of the box based on clinical training and expertise.

A Case Report on QTc Prolongation: Understanding the Medication Risks and Electrolyte Imbalance.

Prolonged QTc interval is one of the critical risk factors for sudden cardiac death. We all know that sudden cardiac death is often caused by acute onset ventricular arrhythmia, and QTc prolongation is one of the potential risk factors. It can be congenital or acquired. The acquired ones are commonly witnessed in day-to-day clinical practice. Several classes of mediations are well known to cause these conditions. Among many antiarrhythmic agents, especially amiodarone, is a critical drug to be monitored, as it strongly potentiates QTc prolongation. Especially in combination with metabolic abnormalities, this abnormality can occur rapidly with notable clinical presentation. This case report elicits an interesting clinical scenario in which a 79-year-old pleasant lady with multiple comorbidities presents with a syncopal episode. Missing the cardiologist's appointment for dose adjustments of her medication, amiodarone was noteworthy. Also, an acute electrolyte imbalance from the possibly recent use of diuretics aggravated the clinical situation. On presentation, the electrocardiogram showed a remarkably prolonged QTc, which was way more compared to the prior ones available. Discontinuation of amiodarone and repletion of the electrolytes brought down the QTc interval to almost a normal range and no syncopal episode within two days. Hence, understanding the medications' potential risks and having a close watch on the possible side effects is key to avoiding dreadful complications of arrhythmia and sudden cardiac death from the same. This case report cumulatively covers this essential medical knowledge and practical, vital points.

Manikya Bhasma is a nanomedicine to affect cancer cell viability through induction of apoptosis.

BACKGROUND: Ayurveda is an ancient medicine system practiced in the Indian sub-continent. Ayurvedic Bhasma is incinerated herbo-metallic/mineral preparations that consist of the particles in the range of nano/micrometers with therapeutic effects against different diseases. Manikya Bhasma (MB) is composed of purified ruby, orpiment, and purified arsenic sulfide. OBJECTIVE: This study was conducted to identify the potential of MB as a nanomedicine that can be used for the treatment of cancer. MATERIALS AND METHODS: Biophysical characterization to determine the morphology and composition of bhasma particles was done using several techniques such as DLS, FTIR, FETEM, FESEM, EDX, and XRD. Cell viability assays were conducted to identify the cytotoxic effect of MB against different cancer cell lines and also to determine the mode of death caused by MB. RESULTS: The biophysical characterization of MB indicates that it is crystalline with a particle size of 70 nm. MB exhibits anticancer activity against MDAMB-231, HeLa, HCT-116, DLD-1, MG-63 cancer cells with an IC50 in the range of 105-155 µg/mL. MB induces oxidative stress in cancer cells, which in turn affects their cell-cycle with an accumulation of cells in the G1-phase. Also, apoptosis induced by MB involves loss of mitochondrial membrane potential, the release of Cyt c, activation of caspases, and DNA degradation. CONCLUSION: Our study highlights the dual potential of MB as a nano-carrier to deliver the drugs and exerting cytotoxic effects against cancer cells.

Upper Back Pain: A Rare Clinical Presentation in Pericardial Effusion.

Pericardial effusion is an important cardiac condition seen in clinical practice with several known underlying etiologies. We are aware of the challenge that exists in diagnosing the effusion. An interesting challenge that has caught our attention is the highest chance of missing the diagnosis if there is an atypical clinical presentation of the patient. In this case report, our objective is to discuss a case that enhances the importance of careful and meticulous investigation of a patient with an atypical clinical picture. This is a case report of a 92-year-old woman who presented to the emergency department with a chief complaint of upper back pain for a few days. She was found to have cardiomegaly on further imaging. An echocardiogram showed a moderate size pericardial effusion. Pericardiocentesis was done and a drain was left in place. Of note, the patient reported remarkable resolution of the back pain after the fluid was taken out. The serial echocardiogram post pericardiocentesis showed minimal drainage, hence the drain was taken out, and the patient was observed for clinical monitoring 24 hours post drain removal. A timely diagnosis and treatment saved our patient from the most dreadful life-threatening condition along with a secure discharge from the hospital.

Cardiac Syndrome X: The Sensitive Heart of a Young Adult Man.

Cardiac syndrome X (CSX), now well known as microvascular angina, is a mysterious cardiac condition in medical science. While the symptoms suggest obstructive coronary disease, the actual angiography turns out to be negative or nonsignificantly obstructive. Despite being a benign condition, its presence increases the risk of adverse cardiovascular events and leads to poor quality of life in the patients. The prevalence of cardiac syndrome X is higher in women, mostly in postmenopausal states. This case report sets a different clinical picture of cardiac syndrome X, where a young male patient is found to have this syndrome. A 38-year-old male went to the hospital with a chief complaint of substernal chest pain for one hour. An electrocardiogram (EKG) showed nonspecific ST-T wave changes, and the cardiac troponin results were nonsignificant. On the contrary, the myocardial perfusion scan came back positive for significant ischemia in various parts of the heart. The patient underwent a coronary angiogram, which showed normal coronary arteries. In view of similar chest pain episodes in the past and the presence of risk factors, he was discharged with extensive counseling on lifestyle modification and medical management. This case report raises awareness about this syndrome's classic clinical scenario and chronology of events in a rare class of the population. Through this case report, clinicians can learn the art of diagnosing this syndrome and provide appropriate patient care in near-miss situations.