L-glutamine for sickle cell disease: more than reducing redox.

Oxidative stress is a major contributor to the pathophysiology of sickle cell disease (SCD) including hemolysis and vaso-occlusive crisis (VOC). L-glutamine is a conditionally essential amino acid with important roles, including the synthesis of antioxidants, such as reduced glutathione and the cofactors NAD(H) and NADP(H), as well as nitric oxide. Given the increased levels of oxidative stress and lower (NADH):(NAD + + NADH) ratio in sickle erythrocytes that adversely affects the blood rheology compared to normal red blood cells, L-glutamine was investigated for its therapeutic potential to reduce VOC. While L-glutamine was approved by the United States (US) Food and Drug Administration to treat SCD, its impact on the redox environment in sickle erythrocytes is not fully understood. The mechanism through which L-glutamine reduces VOC in SCD is also not clear. In this paper, we will summarize the results of the Phase 3 study that led to the approval of L-glutamine for treating SCD and discuss its assumed mechanisms of action. We will examine the role of L-glutamine in health and propose how the extra-erythrocytic functions of L-glutamine might contribute to its beneficial effects in SCD. Further research into the role of L-glutamine on extra-erythrocyte functions might help the development of an improved formulation with more efficacy.

Perforated Gastric Cancer: A Case Report and Literature Review.

Gastric cancer perforation is a rare but life-threatening complication of gastric cancer. We present the case of a 53-year-old male with acquired immune deficiency syndrome (AIDS) who presented to the emergency department with severe abdominal pain, was found to have an acute abdomen, and was eventually diagnosed with gastric perforation due to metastatic gastric cancer. This case highlights the challenges in diagnosing and managing perforated gastric cancer and discusses the surgical management options, including the use of laparoscopic techniques and the role of chemotherapy, particularly hyperthermic intraperitoneal chemotherapy (HIPEC).

Synchronous Pelvic Schwannoma With Metastatic Prostate Cancer: A Rare Case and Pathology Review.

Schwannomas are benign tumors arising from well-differentiated Schwann cells of peripheral nerves. They are usually found on the limbs, head, and neck. It is uncommon for schwannoma to occur in the pelvis and when it does, it is often diagnosed late. Pelvic schwannoma when diagnosed are often bigger in size (>5 cm) and may present with local symptoms such as constipation and bladder outlet obstruction. We hereby present a patient with concurrent metastatic prostate carcinoma and pelvic schwannoma. The patient is a 57-year-old man initially diagnosed with prostate cancer and was lost to follow-up. One year later, he presented with metastatic prostate disease and bladder outlet obstruction. Further evaluation revealed a concurrent pelvic mass that was increasing in size. The biopsy of this mass was suggestive of schwannoma. It was decided at the multidisciplinary tumor board conference to offer treatment for his metastatic prostate disease and observe the schwannoma. His obstructive symptoms worsened in the face of clinical evidence of regression of his prostatic disease, and it was decided to resect the pelvic mass. The surgery revealed a huge soft tissue mass within the pelvis that was adherent to the bladder, prostate, and rectum. Morphology and immunohistochemistry studies of the pelvic mass confirmed the diagnosis of ancient schwannoma. We hereby highlight the clinical importance of this presentation and the diagnostic and therapeutic dilemma involved in the management of this patient who presented with two pathologic conditions causing similar symptoms but of different prognostic and therapeutic significance.

Native Valve Infective Endocarditis Secondary to Acute Cholecystitis in the Setting of Escherichia coli Bacteremia: A Case Report.

Infective endocarditis is an infection of the endocardium that affects the heart valves. It is usually caused by bacteremia secondary to distant infections such as urinary tract infections, surgical procedures, or other sources of pathogenic entry into the blood. It often affects damaged native valves, as well as prosthetic valves, and is primarily caused by Gram-positive bacteria, such as Staphylococcus aureus. Infective endocarditis secondary to Escherichia coli is rare, despite E. coli being one of the most common pathogens causing Gram-negative bacteremia. Between 1909 and 2002, 36 cases of native valve infective endocarditis were reported that met Duke criteria. The majority were secondary to urinary tract infections due to E. coli. Infective endocarditis secondary to E. coli bacteremia in the setting of acute cholecystitis is highly uncommon, and this case report aims to highlight this unusual presentation of infective endocarditis.

New therapeutics for soft tissue sarcomas: Overview of current immunotherapy and future directions of soft tissue sarcomas.

Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a 'cold', non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.

Metastatic Adrenocortical Carcinoma With Chromothripsis: A Case Report and Literature Review.

Metastatic adrenocortical carcinoma (ACC) often has a poor outcome, with a five-year survival of less than 25%. We report a rare case of metastatic ACC with a myxoid variant with chromothripsis. We review the histologic variants of ACC, including myxoid type, molecular drivers, and current and investigational therapies for adrenocortical carcinoma. We also discuss the mechanism of chromothripsis, chromothripsis in ACC tumorigenesis, and propose potential therapies targeting chromothripsis.

A Rare Case of Benign Metastasizing Leiomyoma Causing T11 Spinal Cord Compression: A Report and Literature Review.

Diagnosis of uterine smooth muscle tumors depends upon histologic characteristics as both benign and malignant share clinical features such as metastases. A benign metastasizing leiomyoma is a rare benign smooth muscle tumor that metastasizes to extrauterine sites with simultaneous uterine leiomyoma or previously biopsy-proven leiomyoma during myomectomy or hysterectomy. Benign metastasizing leiomyoma metastasizes outside the uterus, predominantly to the lungs and lymph nodes. However, the involvement of other organs, such as the heart, liver, spine, and soft tissue, is also reported. Here, we present a case of a 42-year-old woman with a history of uterine leiomyoma with prior myomectomy and hysterectomy, who presented with worsening back pain and lower extremity weakness and was found to have an acute cord compression, a serious complication caused by mass effect and a medical emergency that requires prompt attention to prevent permanent spinal cord damage. Sacral soft tissue biopsy and T11 spinal bone biopsy both demonstrated leiomyoma with immunostains positive for desmin, smooth muscle actin, and positive estrogen and progesterone receptors. No atypia, necrosis, and mitosis were identified. The patient had hepatic and pulmonary metastasis on imaging. The final diagnosis was benign metastasizing leiomyoma. There is no standard treatment for benign metastasizing leiomyoma. Both surgical and pharmacological approaches are employed. Although most cases are benign, there is a possibility for life-threatening complications. Benign metastasizing leiomyomas can be considered when multiple soft tissue tumors are found in premenopausal women with a history of uterine leiomyomas. Multidisciplinary discussion between oncologists, gynecologists, and relevant specialists is crucial in the optimal evaluation and treatment of benign metastasizing leiomyoma.