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OBJECTIVES One of the major contributing factors to the opioid crisis, marked by a surge in opioid prescriptions, includes inadequate adherence to guideline-based pain management practices, highlighting the need for a comprehensive curriculum during residency training. In this study, we aim to assess opioid exposure prevalence among hospitalized patients and examine potential associations between disease conditions, patient demographics, and opioid prescriptions during their hospital stay. METHODS In this retrospective cohort study at a southern California county teaching hospital, we analyzed the medical records of 2272 patients admitted to the IM resident inpatient teaching service for 1 year, from September 2017 through September 2018. RESULTS The study found that 44% of patients received opioid prescriptions during their hospital admission, with 23% receiving prescriptions at discharge and 45% having prior opioid exposure. Patients with prehospital opioid exposure had a 2-fold increased risk at discharge (Relative Risk: 2.51; P

Hemophagocytic lymphohistiocytosis (HLH) is a rare but often fatal condition characterized by a hyperinflammatory immune response leading to multiorgan failure. It is predominantly observed in the pediatric population and can be classified as familial or acquired HLH. The latter is more common in adults, often associated with malignancy, infection, or autoimmune diseases. Among acquired HLH cases, hematologic neoplasms account for the majority, with only a few isolated reports documenting solid neoplasms as the cause. Herein, we present a case of adult HLH associated with colorectal adenocarcinoma, which, to the best of our knowledge, is only the second reported case of HLH associated with this type of cancer.

Acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS) is an angioproliferative neoplasia caused by infection with human herpesvirus 8 (HHV-8). It typically presents with mucocutaneous involvement, but it can be disseminated. Initial presentation with primarily pulmonary KS is rare. We present a case of a 32-year-old male with untreated human immunodeficiency virus (HIV) diagnosed 1 year before presentation who developed progressively worsening cough and shortness of breath for 6 months. He was hospitalized twice and treated for unresolved pneumonia in an outside hospital. The patient concomitantly developed purplish nodules on his face, then the upper trunk, back, chest, and thighs bilaterally that gradually increased in size and number. Histopathology findings from skin lesions were consistent for KS. Bronchoscopy found multiple erythematous plaques throughout the tracheobronchial tree with telangiectasias and inflammation suggestive of pulmonary KS. His imaging findings and positive serum HHV-8 polymerase chain reaction (PCR) were consistent with disseminated KS. He started antiretroviral therapy (ART) to treat his HIV infection, followed by liposomal doxorubicin chemotherapy. But both ART and chemotherapy were interrupted due to adherence and insurance issues. The patient was readmitted with acute respiratory failure requiring mechanical ventilation with multiple vasopressors that led to the patient’s demise. The late recognition of KS diagnosis and delayed treatment can lead to worse outcomes.

We present the case of a 30-year-old man with no prior medical history who presented to the hospital with a myriad of symptoms such as shortness of breath, generalized weakness, lower limb weakness, and urinary retention. He was recently diagnosed with “disseminated coccidioidomycosis” by an outside provider on an outpatient basis and started on fluconazole orally. However, due to a lack of improvement and significant symptoms, he was sent to the hospital to initiate liposomal amphotericin B treatment. After a comprehensive workup, an alternative diagnosis was suspected and eventually confirmed as metastatic germ cell carcinoma. Due to the vast dissemination and his poor functional status despite chemotherapy initiation, the patient elected for palliative care and expired shortly after at hospice. This case demonstrates the similarity of clinical findings between disseminated infections and malignancies.

Histoplasma capsulatum is a geographically specific dimorphic fungus that can cause a spectrum of diseases. While most cases are asymptomatic pulmonary infections, in severe cases, particularly in immunocompromised patients, disseminated disease can occur. Histoplasmosis in California is limited to only a few case reports. In this article, we describe a rare case of disseminated histoplasmosis in a non-endemic region presenting with diagnostically challenging symptomatology, including altered mental status, status epilepticus, septic shock, and bilateral adrenal masses.

Primary diffuse large B-cell lymphoma presenting as an extranodal site in the pelvis is rare and can mimic a gynecological malignancy. Although management for diffuse large B-cell lymphoma is standardized and curative, prognosis depends on timely diagnosis and therapy. Diagnosis can be challenging as patients lack classical symptoms of fever, night sweats, weight loss, and lymphadenopathy associated with lymphoma. A multidisciplinary approach is recommended to diagnose and treat judiciously. In this article, we present cases of 2 females who presented with pelvic masses with initial suspicion of a gynecological malignancy but were ultimately diagnosed as diffuse large B-cell lymphoma of the pelvis and managed accordingly.

Several vaccines have been developed and are being administered against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Common side effects include fever, chills, headache, myalgia, and soreness at the injection site. However, some rare adverse effects have also been reported. We present a case of induced thrombocytopenia presenting with petechiae and mucosal bleeding which developed as an adverse response after first-dose administration of the Moderna COVID-19 vaccine.

In this article, we describe a case of neutrophilic dermatosis of the dorsal hands (NDDH) complicated with myelodysplastic syndrome and chronic active hepatitis C infection. NDDH was first suggested by Galaria et al in 2000. After comparing features of NDDH with Sweet syndrome in terms of encompassing clinical, laboratory, and histological characteristics, it can be concluded that “distributional or localized variant” of Sweet syndrome is classified as NDDH. Early diagnosis and treatment can improve prognosis. Systemic glucocorticoids are the mainstay of treatment.

Plasmablastic lymphoma (PBL) is a subtype of non-Hodgkin’s lymphoma that manifests in patients with the diagnosis of human immunodeficiency virus (HIV), more prominently in the head, neck, and oral mucosal region. The diagnosis of this rare lymphoma serves as a concomitant diagnosis of acquired immunodeficiency syndrome. The case is of a 33-year-old previously healthy male, with an unknown diagnosis of HIV with a painful right mandibular mass. He was subsequently diagnosed with PBL and HIV. This case of PBL illustrates the importance of linking a rare and potentially life-threatening diagnosis as a possible first manifestation of HIV.

Locus minoris resistentiae refers to a region of decreased resistance within the body. This occurs from changes to the microenvironment secondary to previous trauma and results in increased vulnerability. As a result, infection, inflammatory processes, and malignancy may localize to this area. In this article, we describe 2 unique cases of malignancy, primary prostate carcinoma and serous carcinoma of the ovary, both of which disseminated to sites of prior trauma. We review the available literature, discuss proposed pathophysiology, and highlight the need for further investigations along with increased clinician awareness.

Vasculitis is an inflammatory process involving blood vessels of various sizes, including the small vessels in the kidneys to the large vessels, such as the aorta. This inflammatory condition is usually autoimmune in nature and is associated with involvement of many locations, such as the sinuses, lungs, kidneys, and even the heart. Specifically, eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis that may initially hide as asthma, allergic rhinitis, and/or sinusitis. However, it is known to become a lethal disease once progressed to include cardiovascular manifestations. It is important to remember EGPA as a differential for any patient with a history of asthma, allergic rhinitis, and/or sinusitis who also presents with cardiovascular complaints and eosinophilia. Treatment recommendations focus on immunosuppression in such cases. In this article, we discuss the case of a 62-year-old male, with a known history of asthma, who presented to the emergency department with concern for his chest pain and right-sided weakness. He was later diagnosed with EGPA with eosinophilic myocarditis. Diagnosis and treatment are described.

Acquired isolated factor VII deficiency is a rare bleeding disorder and has been reported in 31 cases. This is in contrast to congenital factor VII deficiency, which while also infrequent is the most common rare congenital bleeding disorder. Acquired isolated factor VII deficiency has been described primarily in patients with solid malignancies, sepsis, and in the presence of anti-factor VII autoantibodies. We report a case of acute myelogenous leukemia with an associated trisomy 8 cytogenetic abnormality presenting with factor VII deficiency. The factor VII deficiency cleared after induction chemotherapy and with the disappearance of the cytogenetic and molecular abnormalities. We discuss a possible link between trisomy 8 and vitamin K metabolism, which might result in acquired factor VII deficiency in acute myelogenous leukemia.

Primary spinal cord giant cell glioblastoma multiforme of the thoracic spinal cord is a rarely-diagnosed primary spinal cord tumor in comparison to neoplasms in intracranial locations. In this article, we highlight a young adult who was diagnosed with intramedullary giant cell glioblastoma, IDH wild-type, World Health Organization grade IV/IV of the thoracic spinal cord. This case report describes the treatment approach with a postsurgical combination of radiation therapy and temozolomide, which resulted in the patient to return to her baseline of health only to later develop neurological symptoms significant for a recurrence of malignancy. In a review of the literature of described cases of primary spinal cord glioblastoma multiforme, prognosis continues to be unfavorable as current treatment options of the aggressive malignancy remain absent of a cure.

Leptomeningeal carcinomatosis, leptomeningeal meningitis, or, as referred here, leptomeningeal metastasis (LM), is a rare but frequently fatal complication seen in advanced stage of cancer either locally advanced or after a metastasis of a known primary cancer. We present a rare and uncommon case of leptomeningeal metastases from carcinoma of unknown primary. A 32-year-old female was diagnosed with LM; however, no known primary carcinoma was identified after 2 separate biopsies. The first biopsy of the right pre-tracheal lymph node showed poorly differentiated pan-keratin (AE1 and AE3) and placental alkaline phosphatase with the possibility of germ cell origin. Second cytology of cervical lymphadenopathy was remarkable for cytokeratin 7 and 20, placental alkaline phosphatase, and CDX2 suggestive of germ line tumor with both mucinous ovarian and gastrointestinal carcinomas. Unfortunately, the LM progressed rapidly despite multiple cycles of germ cell origin directed systemic and intrathecal chemotherapy, and the patient opted for hospice care without getting a chance to identify the primary source.

In this article, we present a patient diagnosed synchronously with metastatic male breast cancer and prostate cancer. This is a 63-year-old male and recent immigrant from Nigeria, who sought medical attention for progressively worsening of shortness of breath and acute progression of a chronic right breast mass. An invasive breast carcinoma was diagnosed by the core biopsy of the right breast mass. Within 2 months of his breast cancer diagnosis, the patient also was diagnosed with prostate adenocarcinoma after being worked up for urinary retention. By presenting this patient with a synchronous diagnosis with metastatic male breast cancer and prostate cancer, history of chronic right breast mass, and gynecomastia, we speculate on possible cancer etiologies and risk factors.

The risk of thromboembolism is increased when associated with the human immunodeficiency viral (HIV) infection. Various factors are involved in promoting thrombosis, and the presence of a patent foramen ovale augments the potential for a paradoxical embolism. We describe the case of a 56-year-old man receiving antiretroviral therapy with features of right heart failure and pulmonary embolism. Due to the high incidence of life-threatening thromboembolism in the HIV-infected group, the need for long-term anticoagulation has to be evaluated.

Reactive cutaneous coccidioidal skin manifestations are commonly noticed during the early stage of coccidioidomycosis. These skin lesions are devoid of any active coccidioidal organism, and the immune trigger mechanisms are not elucidated. We describe 6 cases of unusual reactive cutaneous coccidioidal manifestation, characterized by painful vesiculobullous lesions known as erythema sweetobullosum. The biopsy of the lesions revealed neutrophilic dermatosis with inflammatory cells resulting in a cleft and elevation of the most superficial layer of the skin forming a bulla. The reactive cutaneous lesion is self-limited and requires no specific therapy.

Invasive fungal infections are commonly associated with some form of immunosuppression. On the nasal epithelial surface, Aspergillus flavus , under favorable conditions, can aggressively breach multiple cell lines invading the local tissues. We present the case of a 35-year-old woman with granulomatous invasive Aspergillus flavus infection involving the nasal sinuses and the brain. Antifungal agents administered in the previous episodes contained the infection; however, the infected site evolved over time surrounded with calcified tissues in the left maxillary sinus. The current infection involved the other side of the maxillary sinus and extended to the orbital cavity eroding the parts of the skull and retro-orbital structures and was treated with a long course of isavuconazole therapy.

Charcot-Marie-Tooth (CMT) disease is a hereditary demyelinating disease of the peripheral nervous system that results in sensory and motor dysfunction. CMT includes a spectrum of diseases with different types of mutations in the genes encoding myelin protein, resulting in a variety of dysfunctions in its life cycle. In CMT subtype 1A there is duplication mutation of peripheral myelin protein 22 gene on chromosome 17. Incomplete penetrance, gene-dosage effect, and variable expressivity can attribute to the asymptomatic nature of the disease in some subset of patients. Vincristine administration is contraindicated in patients who are alrea\dy diagnosed with CMT disease. We report a case of asymptomatic CMT disease unmasked only by the neurotoxic effects of vincristine. Genetic testing for a patient with a preexisting family background of inherited diseases before starting vincristine therapy can potentially prevent a disability.

Low-risk human papillomavirus types 6 and 11 can manifest as giant condylomata acuminata (GCA) of Buschke-Lowenstein. Up to 50% of GCA can slowly progress over years to fungating, invasive tumors. The malignant potential is attributed to unique immune evading abilities of the human papillomavirus. A 42-year-old male presented with pain and foul-smelling discharge from his genital warts. The histopathological examination of the mass showed invasive squamous cell carcinoma, and it was associated with paraneoplastic hypercalcemia. The timely removal of long-standing GCA in order to prevent a carcinomatous transition is a priority.

Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, occurring in 1 to 2 per 100,000, with chemotherapy options not well defined. Our case involved a 49-year-old female who had hepatic masses and metastasis to the lungs with a liver biopsy revealing HEH. After developing a rash from sorafenib, thalidomide was started with the progression of disease stabilized. Resection is only an option in 10% of the cases; therefore, chemotherapy is the only line of treatment. Newer chemotherapy alternatives are targeting angiogenesis via the vascular endothelial growth factor. Thalidomide was first used as an antiemetic, but, sadly, soon linked to phocomelia birth defects. Given the mechanism of action against angiogenesis, thalidomide has a valid role in vascular tumors. In conclusion, the use of thalidomide as chemotherapy is novel and promising, especially in the setting of a rare vascular liver tumor such as HEH.

The development of gene therapy vectors for treating diseases of the cardiovascular system continues at a steady pace. Moreover, in the field of gene therapy the utility of "disease-specific promoters" has strong appeal. Many therapeutic genes, including transforming growth factor beta 1 or interleukin 10, are associated to adverse effects. The use of a disease-specific promoter might minimize toxicity. The lectin-like oxidized low density lipoprotein receptor 1 is a marker of cardiovascular disease and a potential therapeutic target. The lectin-like oxidized low density lipoprotein receptor 1 is known to be up-regulated early during disease onset in a number of cell types at the sites where the disease will be clinically evident. In this study an adeno-associated virus-2 DNA vector (AAV2) using the AAV8 capsid, and containing the full length The lectin-like oxidized low density lipoprotein receptor 1 promoter, was generated and assayed for its ability to express human interleukin 10 in low density lipoprotein receptor knockout mice on high cholesterol diet. The cytomegalovirus early promoter was used for comparison in a similarly structured vector. The two promoters were found to have equal efficacy in reducing atherogenesis as measured by aortic systolic blood velocity, aortic cross sectional area, and aortic wall thickness. This is the first head-to-head comparison of a constitutive with a disease-specific promoter in a therapeutic context. These data strongly suggest that the use of a disease-specific promoter is appropriate for therapeutic gene delivery.

The development of novel targeted therapies has become an important research focus for lung cancer treatment. Our previous study has shown leptomycin B (LMB) significantly inhibited proliferation of lung cancer cells; however, p53 wild type lung cancer cells were resistant to LMB. Therefore, the objective of this study was to develop and evaluate a novel therapeutic strategy to sensitize LMB-resistant lung cancer cells by combining LMB and doxorubicin (DOX). Among the different treatment regimens, pretreatment with DOX (pre-DOX) and subsequent treatment with LMB to A549 cells significantly decreased the 50% inhibitory concentration (IC50) as compared to that of LMB alone (4.4 nM vs. 10.6 nM, P

Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM). Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF)-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM.

Sperm protein (Sp17) is an attractive target for ovarian cancer (OC) vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17) was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

Curcumin, a polyphenolic compound, is the active component of Curcuma longa and has been extensively investigated as an anticancer drug that modulates multiple pathways. Eukaryotic initiation factors (eIFs) have been known to play important roles in translation initiation, which controls cell growth and proliferation. Little is known about the effects of curcumin on eIFs in lung cancer. The objective of this study was to exam the curcumin cytotoxic effect and modulation of two major rate-limiting translation initiation factors, including eIF2α and eIF4E protein expression levels in lung adenocarcinoma epithelial cell line A549. Cytotoxicity was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and protein changes were determined by Western blot. A549 cells were treated with 0-240 μM curcumin for 4-96 h. The inhibitory effects of curcumin on cytotoxicity were dose- and time-dependent ( P < 0.001). The 50% inhibitory curcumin concentrations (IC50s) at 24, 48, 72, and 96 h were 93, 65, 40, and 24 μM, respectively. Protein expressions of eIF2α, eIF4E, Phospho-4E-BP1 were down-regulated, while Phospho-eIF2α and Phospho-eIF4E were up-regulated after A549 cells were treated with 20 and 40 μM curcumin for 24 h. In addition, the effects of curcumin on these protein expression changes followed a significant dose-response ( P < 0.05, trend test). These findings suggest that curcumin could reduce cell viability through prohibiting the initiation of protein synthesis by modulating eIF2α and eIF4E. [ABSTRACT FROM AUTHOR]

Abl interactor 1 (Abi1) is a key regulator of actin polymerization/depolymerization. The involvement of Abi1 in the development of abnormal cytoskeletal functions of cancer cells has recently been reported. It remains unclear, however, how Abi1 exerts its effects in tumor cells and whether it contributes to tumor progression in vivo. We report here a novel function for Abi1 in the regulation of invadopodia formation and Src-inhibitor of differentiation protein 1 (Id1)-matrix metalloproteinase (MMP)-9 pathway in MDA-MB-231 human breast cancer cells. Abi1 is found in the invadopodia of MDA-MB-231 cells. Epigenetic silencing of the Abi1 gene by short hairpin RNA in MDA-MB-231 cells impaired the formation of invadopodia and resulted in downregulation of the Src activation and Id1/MMP-9 expression. The decreased invadopodia formation and MMP-9 expression correlate with a reduction in the ability of these cells to degrade extracellular matrix. Remarkably, the knockdown of Abi1 expression inhibited tumor cell proliferation and migration in vitro and slowed tumor growth in vivo. Taken together, these results indicate that the Abi1 signaling plays a critical role in breast cancer progression and suggest that this pathway may serve as a therapeutic target for the treatment of human breast cancer. [ABSTRACT FROM PUBLISHER]

Abl interactor (Abi) 1 was first identified as the downstream target of Abl tyrosine kinases and was found to be dysregulated in leukemic cells expressing oncogenic Bcr-Abl and v-Abl. Although the accumulating evidence supports a role of Abi1 in actin cytoskeleton remodeling and growth factor/receptor signaling, it is not clear how it contributes to Bcr-Abl-induced leukemogenesis. We show here that Abi1 gene silencing by short hairpin RNA attenuated the Bcr-Abl-induced abnormal actin remodeling, membrane-type 1 metalloproteinase clustering and inhibited cell adhesion and migration on fibronectin-coated surfaces. Although the knock down of Abi1 expression did not affect growth factor-independent growth of Bcr-Abl-transformed Ba/F3 cells in vitro, it impeded competitive expansion of these cells in non obese diabetic (NOD)/ severe combined immuno-deficiency (SCID) mice. Remarkably, the knock down of Abi1 expression in Bcr-Abl-transformed Ba/F3 cells impaired the leukemogenic potential of these cells in NOD/SCID mice. Abi1 contributes to Bcr-Abl-induced leukemogenesis in part through Src family kinases, as the knock down of Abi1 expression attenuates Bcr-Abl-stimulated activation of Lyn. Together, these data provide for the first time the direct evidence that supports a critical role of Abi1 pathway in the pathogenesis of Bcr-Abl-induced leukemia. [ABSTRACT FROM AUTHOR]