Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure.

Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.

Engineering CRISPR/Cas9 therapeutics for cancer precision medicine.

The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) technology has revolutionized field of cancer treatment. This review explores usage of CRISPR/Cas9 for editing and investigating genes involved in human carcinogenesis. It provides insights into the development of CRISPR as a genetic tool. Also, it explores recent developments and tools available in designing CRISPR/Cas9 systems for targeting oncogenic genes for cancer treatment. Further, we delve into an overview of cancer biology, highlighting key genetic alterations and signaling pathways whose deletion prevents malignancies. This fundamental knowledge enables a deeper understanding of how CRISPR/Cas9 can be tailored to address specific genetic aberrations and offer personalized therapeutic approaches. In this review, we showcase studies and preclinical trials that show the utility of CRISPR/Cas9 in disrupting oncogenic targets, modulating tumor microenvironment and increasing the efficiency of available anti treatments. It also provides insight into the use of CRISPR high throughput screens for cancer biomarker identifications and CRISPR based screening for drug discovery. In conclusion, this review offers an overview of exciting developments in engineering CRISPR/Cas9 therapeutics for cancer treatment and highlights the transformative potential of CRISPR for innovation and effective cancer treatments.

Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Retrospective analysis of veno-occlusive disease/sinusoidal obstruction syndrome in paediatric patients undergoing hematopoietic cell transplantation -a multicentre study.

Background: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear. Methods: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients. Findings: The incidence of sinusoidal obstruction syndrome in this cohort (n = 488) was higher by pEBMT (21.5%) vs historic modified Seattle (15.6%) and Baltimore (7.0%) criteria (p < 0.001). Application of pEBMT criteria identified 44 patients who were not previously diagnosed with sinusoidal obstruction syndrome. Overall, 70.5% of all patients diagnosed with sinusoidal obstruction syndrome ultimately developed very severe disease and almost half of diagnosed patients required critical care support. Overall survival was significantly lower in patients who were diagnosed with sinusoidal obstruction syndrome vs those who were not. Interpretation: Taken together, pEBMT criteria may be a sensitive method for prompter diagnosis of patients who subsequently develop severe/very severe sinusoidal obstruction syndrome. To our knowledge, this is the first multi-centre study in the United States (US) to demonstrate that pEBMT guidelines are associated with earlier detection of sinusoidal obstruction syndrome. Since early initiation of definitive treatment for sinusoidal obstruction syndrome has been associated with improved survival in paediatric patients and implementation of pEBMT criteria appears feasible in the US, universal adoption should facilitate prompter diagnosis and lead to improved outcomes of children with sinusoidal obstruction syndrome. Funding: None.

Burden of Chronic Nonhealing Wounds: An Overview of the Worldwide Humanistic and Economic Burden to the Healthcare System.

Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.

Cardiovascular manifestations of Erdheim-Chester disease: A narrative review with two cases.

Erdheim-Chester disease (ECD) is a rare 'L' (Langerhans) group histiocytic neoplasm that affects a multitude of organ systems, causing osteosclerotic bone lesions, periaortic encasement ('coated' aorta), retroperitoneal fibrosis involving kidneys and ureters ('hairy kidney'), and infiltration of the central nervous system. Cardiovascular involvement can occur in up to 70% of patients and is usually found during computed tomography/magnetic resonance imaging evaluation. When present, cardiovascular symptoms can have wide variability in presentation from asymptomatic to pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication. Cardiac involvement found on imaging includes right atrial pseudotumor, right atrioventricular groove infiltration, and pericardial effusions. ECD can involve the large- and medium-sized arteries, often seen as periarterial thickening (commonly coating the aorta) with stenosis/occlusion. Although more cardiovascular ECD cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of ECD.

Aplastic anaemia following antibiotic use for urinary tract infection.

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.

Venoarterial Extracorporeal Life Support Use in Acute Pulmonary Embolism Shows Favorable Outcomes.

BACKGROUND: Differences in outcomes by indication for venoarterial extracorporeal life support (VA-ECLS) are poorly described. We hypothesized that patients on VA-ECLS for acute pulmonary embolism (PE) have fewer complications and better survival than patients on VA-ECLS for other indications. METHODS: All patients ≥18 years on VA-ECLS from the Extracorporeal Life Support Organization global registry (2010-2019) were evaluated (n = 29,842). After excluding patients aged >79 years (n = 729) and those with incomplete indication data (n = 2530), patients were stratified by VA-ECLS indication for PE vs all other indications. The association between being discharged alive and each type of complication with VA-ECLS indication was assessed. RESULTS: Of 26,583 patients included in the analysis, 978 (3.7%) were on VA-ECLS for a primary diagnosis of acute PE. Acute PE patients were younger (53.1 vs 56.7 years, P < .001) and were more likely to be women (52.1% vs 32.3%, P < .001). Patients who underwent VA-ECLS for acute PE were 78% more likely to be discharged alive vs patients supported with VA-ECLS for other reasons (P < .001). Acute PE patients had fewer cardiovascular and renal complications (26.6% vs 38.0% and 31.1% vs 39.4%, respectively; adjusted P < .001). Acute PE patients had higher odds of having clots and mechanical complications (8.7% vs 7.9% and 16.7% vs 14.6%, respectively; adjusted P < .001). CONCLUSIONS: Patients undergoing VA-ECLS for acute PE have higher odds of survival to hospital discharge compared with those supported for other indications. Additionally, VA-ECLS in this population is associated with fewer cardiovascular and renal complications but higher mechanical complications.

Segmental Abdominal Paresis Attributed to Herpes Zoster Infection Mimicking an Abdominal Hernia: An Interesting Case From a Surgical Unit of a Tertiary Healthcare Center.

The varicella-zoster virus reactivates to cause herpes zoster, commonly referred to as shingles. Shingles traditionally manifest as itchy vesicles in a dermatomal distribution, accompanied by related constitutional symptoms in immunocompetent patients. Usually, the rash resolves completely in seven to ten days. Herpetic neuralgia is the most typical herpes zoster consequence. Around 1% to 5% of individuals have motor impairments, with Ramsay-Hunt syndrome being the most prevalent ailment. Additional problems encompass abdominal pseudohernia, paralytic ileus/colonic pseudo-obstruction, hemidiaphragm paralysis, bladder dysfunction, localized paresis, constipation, and visceral neuropathy. Herpes zoster infection typically involves the posterior root ganglia, and most of the symptoms are sensory. Motor involvement can occur in the same distribution but is relatively uncommon. Segmental zoster paresis is a rare motor complication of herpes zoster, mimicking an abdominal hernia, which has an incidence of approximately 0.7%, but it needs no surgery different from the real abdominal wall hernia. In this case report, we describe a patient who, three weeks after developing a herpes zoster rash, acquired an abdominal protrusion, i.e., herpes-induced pseudohernia.

A Case Series on Acute Mesenteric Ischemia (AMI) Leading to Intestinal Gangrene Following Blunt Trauma to the Abdomen.

The term "acute mesenteric ischemia" (AMI) refers to a set of conditions where the blood supply to various segments of the small intestine is cut off, causing ischemia and subsequent inflammatory changes that might result in bowel gangrene. Estimates place the incidence between 0.09% and 0.2% of all acute surgical hospitalizations. Early diagnosis is essential, despite the entity being a rare cause of abdominal discomfort, because if left untreated, mortality is 50%. Herein, we present a case series of three patients with bowel ischemia following blunt abdominal trauma.

Case Report: Serum methotrexate monitoring by immunoassay: confusion by by-product, confusion by antidote.

Methotrexate is a commonly used agent in the treatment of many malignancies and rheumatologic/inflammatory diseases. Working by inhibiting dihydrofolate reductase and thereby preventing eventual formation of tetrahydrofolate, methotrexate inhibits synthesis of purines and thymidylate, therefore disabling a malignant cell's ability to replicate. While it is able to effectively do this, methotrexate also holds potential for significant toxicity. Therefore, serum methotrexate monitoring is of utmost importance when administering the drug, particularly when high doses are used. Although there are several different measurement systems, the immunoassay is a commonly used monitoring system that may be prone to interference when using agents with similar carbon backbone as methotrexate, including folinic acid (leucovorin) at high doses, as well as in the setting of glucarpidase use and consequent methotrexate breakdown. However, adjusting leucovorin dosing policy and being aware of the potential of the immunoassay to be "confused" by similar molecules have allowed for the efficient and effective use of the immunoassay while preventing prolonged hospital stays at our institution.

Accuracy of combined multi-parametric MRI and PSMA PET-CT in diagnosing localized prostate cancer: newer horizons for a biopsy-free pathway.

INTRODUCTION: Prostate-specific antigen (PSA) is a reliable biomarker for identification of prostate cancer, although a biopsy is still the gold standard for detecting prostate cancer. Similar to higher PIRADS lesions on MRI, the maximal standard uptake value (SUV max) on PSMA PET is linked to a higher likelihood of prostate cancer. Can an mpMRI in conjunction with PSMA PET Scan accurately predict prostate cancer and further trigger omission of biopsy similar to other solid organ urological malignancies? METHODS: Ga-68 PSMA PET and mpMRI were performed for each patient who was a part of this retrospective study. The PET-positive lesion's maximum standardized uptake value (SUVmax) was recorded. Prostate biopsies were performed on patients who had PSMA PET avid lesions and a PIRADS score of 4 or 5. Robot-assisted radical prostatectomy (RARP) was afterward performed on patients who had cancer on their prostate biopsy. The prostatectomy specimen's histopathological information was recorded. Cutoff values and correlations between the variables were determined using the ROC curves and Pearson's correlation test. RESULT: On the basis of suspicious DRE findings or elevated PSA, 70 men underwent mpMRI and PET scans. PIRADS 4 patients had a median (IQR) SUVmax of 8.75 (11.95); whereas, PIRADS 5 patients had an SUVmax of 24.5 (22). The mean SUVmax for patients whose biopsies revealed no cancer was 6.25 ± 1.41. With an AUC of 0.876 on the ROC curve, it was found that there was a significant positive correlation between the results of the mpMRI and PET scans and those of the histopathological investigation. A SUVmax ≥ 8.25 on PSMA PET for a PIRADS 4/5 lesion on mpMRI will aid in correctly predicting malignancy, with a sensitivity of 82.8% and specificity of 100%. CONCLUSION: The findings of this study were positive and indicated that patients with a high suspicion of prostate cancer on mpMRI and PSMA PET (PIRADS ≥ 4 and SUVmax ≥ 8.25). This study substantiates the fact that a combination of mpMRI and PSMA PET can accurately predict localized prostate cancer.

An Unexpected Finding of Isolated Hydatidosis of the Spleen With Concomitant Visceromegaly in an Elderly Female.

Hydatidosis of the spleen is a rare zoonotic clinical entity. The occurrence of isolated splenic hydatid cysts in the absence of these cysts in any other portion of the body is referred to as primary splenic hydatidosis. It is a rare disorder that accounts for only 2% of the burden of hydatid disease worldwide. After the liver and the lungs, the spleen is the organ that is most frequently affected by this condition.

An Interesting Case of Isolated Cysticercosis of Breast Masquerading as a Breast Lump in a Young Female.

Human cysticercosis can affect any tissue or organ in the body and may be asymptomatic or manifest clinical signs and symptoms depending on the area of the body where cysticerci are found. However, at the same time, the involvement of the breast by cysticercosis is an extremely rare phenomenon, with very few case reports published before. In this report, we present the case of a 26-year-old married woman who came with a history of painless swelling in the left breast.

Giant Lipoma of the Arm Masquerading as an Accessory Breast: A Report of a Rare Case.

Accessory breast is an extremely rare condition that develops in 0.4%-6% of females. It is primarily found in the axilla and is frequently misdiagnosed. It is usually bilateral and manifests during pregnancy or lactation as an asymptomatic tumor. The diagnosis of ectopic breast tissue is crucial because it is capable of undergoing the same pathological changes as normal breast tissue, including mastitis, fibrocystic changes of the breast tissue, and, in extreme cases, even malignancy. We present the case of a 40-year-old female who presented with swelling in the left upper arm for the past eight years, which was associated with pain. Initially, accessory breast was kept as the clinical diagnosis. However, further imaging and histological analysis revealed it to be a giant lipoma of the upper arm.

Successful Surgical Management of Post-traumatic Superficial Femoral Artery Pseudoaneurysm With Delayed Presentation.

Pseudoaneurysms of the superficial femoral artery are uncommon and typically iatrogenic. The majority of publications on this topic that have been published in English literature are case reports. It is unclear how often arterial pseudoaneurysms (APAs) caused by limb trauma occur, and their treatment is not standardised. A review of the literature usually follows the presentation of a case report, but no recent update with reliable data has been published. In this case study, a 24-year-old patient who had a piece of iron lodged in the middle third of his thigh and a pulsatile mass that revealed a pseudoaneurysm of the superficial femoral artery is described. The patient underwent an emergency operation without employing a venous graft. We directly sutured the arterial lesion, with positive outcomes.

Oligometastatic carcinoma prostate - An overview of the last decade.

Introduction: Oligometastatic prostate cancer (OMPC) has gained profound interest lately due to its different tumor biology and our ability to use multimodality therapy for cure or prolonged survival. Selecting the appropriate patient for treatment has become the aim of treating urologists, medical oncologists, and radiation oncologists. Through this review, we try to highlight the management of OMPC in light of recent literature. Methods: Literature search was performed on Pubmed, Scopus and Embase using keywords "Oligometastatic", " Prostate Cancer" using operators such as "And" & "Or". Relevant articles were screened and all the latest articles on this emerging entity were included in this review. Results: All trials relevant to oligometastatic prostate cancer defining the role of surgery, radiotherapy and systemic therapy were included and appropriate inferences were drawn. Relevant studies were compiled in tabular form for this article. Conclusion: The current standard of care of management for OMPC remains systemic therapy on the lines of hormone-sensitive metastatic prostate cancer. The evolving role of surgery, and radiotherapy along with systemic therapy is highlighted in this article.

Antibody-Drug Conjugates in Solid Tumor Oncology: An Effectiveness Payday with a Targeted Payload.

Antibody-drug conjugates (ADCs) are at the forefront of the drug development revolution occurring in oncology. Formed from three main components-an antibody, a linker molecule, and a cytotoxic agent ("payload"), ADCs have the unique ability to deliver cytotoxic agents to cells expressing a specific antigen, a great leap forward from traditional chemotherapeutic approaches that cause widespread effects without specificity. A variety of payloads can be used, including most frequently microtubular inhibitors (auristatins and maytansinoids), as well as topoisomerase inhibitors and alkylating agents. Finally, linkers play a critical role in the ADCs' effect, as cleavable moieties that serve as linkers impact site-specific activation as well as bystander killing effects, an upshot that is especially important in solid tumors that often express a variety of antigens. While ADCs were initially used in hematologic malignancies, their utility has been demonstrated in multiple solid tumor malignancies, including breast, gastrointestinal, lung, cervical, ovarian, and urothelial cancers. Currently, six ADCs are FDA-approved for the treatment of solid tumors: ado-trastuzumab emtansine and trastuzumab deruxtecan, both anti-HER2; enfortumab-vedotin, targeting nectin-4; sacituzuzmab govitecan, targeting Trop2; tisotumab vedotin, targeting tissue factor; and mirvetuximab soravtansine, targeting folate receptor-alpha. Although they demonstrate utility and tolerable safety profiles, ADCs may become ineffective as tumor cells undergo evolution to avoid expressing the specific antigen being targeted. Furthermore, the current cost of ADCs can be limiting their reach. Here, we review the structure and functions of ADCs, as well as ongoing clinical investigations into novel ADCs and their potential as treatments of solid malignancies.