Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection. Before the shortage, lorazepam was used an average of 95 times per month on the palliative care unit. The overall use of benzodiazepines decreased substantially following the recommendation for the therapeutic alternative, midazolam, during the shortage. Once the shortage ended, use roughly returned to pre-shortage baselines. During this time, there were no patient safety events documented on the palliative care unit. Moreover, no changes to the care experience were reported by patients, family/caregivers, providers, or staff. The collaborative effort between pharmacy and palliative care specialists resulted in alternative treatments for palliative care patients during the drug shortage. This preserved the hospital's supply of lorazepam injection for a patient population with no suitable alternatives while still allowing for management of palliative patients.
Lorazepam , Palliative Care , Humans , Lorazepam/therapeutic use , Benzodiazepines , Midazolam
Immune checkpoint inhibitors have revolutionized the treatment paradigm of several cancers. However, not all patients respond to treatment. Tumor cells reprogram metabolic pathways to facilitate growth and proliferation. This shift in metabolic pathways creates fierce competition with immune cells for nutrients in the tumor microenvironment and generates by-products harmful for immune cell differentiation and growth. In this review, we discuss these metabolic alterations and the current therapeutic strategies to mitigate these alterations to metabolic pathways that can be used in combination with checkpoint blockade to offer a new path forward in cancer management.
Background Ensuring blood safety is the primary goal of transfusion medicine. Despite extensive serological tests and strict safety measures, the risk of transfusion-transmitted infections (TTIs) still exists. As applied to blood screening, Nucleic Acid Amplification Test (NAT) offers much higher sensitivity for detecting viral infections. It is, however, currently available to a handful of centers due to the high cost. This study aims to establish the Effectiveness of NAT by assessing the NAT yield and residual risk of transmission of Hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV with and without NAT testing. Material and method This prospective cross-sectional study recruited blood donors from January 2020 to November 2022. All donors underwent routine serologic screening. Only serologically negative donors were tested for HBV, HCV, and HIV by NAT. The NAT yield and residual risk (RR) per million donors were computed for viral infections in seronegative blood donors and calculated using the incidence/window period model. Result A total of 59708 donors were included during the study period. The overall prevalence of TTI's were: For HCV 1.7% (n = 1018), HBV 1.5% (n = 918), HIV 0.07% (n = 47), Syphilis 1.2% (n = 758) and malaria 0.3% (n = 218). Out of 57759 seronegative donors, thirty-four NAT-reactive samples were identified, with 3 cases of HCV, 31 cases of HBV, and Nil HIV cases. NAT yield of HBV was 1 in 1863 with an RR of 8.6 per million, followed by HCV with a NAT yield of 1 in 19253 and RR of 0.8 per million donations. NAT testing reduced RR for HBV by 48.9% and HCV by 94.5%. Conclusion Our study showed that NAT detected 34 out of 57759 cases initially missed by serological tests. The study suggests that the parallel use of serology and NAT screening of donated blood would be beneficial.
The stage at diagnosis is the single most important predictor of lung cancer outcome. Therefore, detecting lung cancer early is of utmost importance. Low-dose computed tomography (LDCT) has proven beneficial in the early detection and mortality reduction of lung cancer. Despite this, very few of the high-risk population get annual LDCT done. Patients' attitudes towards tobacco usage and preventive care can be a factor in getting LDCT. We analyzed the relationship between the willingness to undergo LDCT and a person's readiness to try tobacco cessation medication or get the pneumococcal vaccine. We also analyzed the relationship between patients who had tobacco cessation counseling and their willingness to get LDCT and pneumococcal vaccine. Medical records of high-risk patients seen in the East Tennessee State University (ETSU) clinics between January 1, 2016, and November 30, 2020, were analyzed retrospectively. In the data obtained, a total of 2,834 patients were current smokers and were included in the research. The study subjects were assessed in two ways, which from here on will be referred to as method one and method two. In the first method, patients who underwent LDCT were assessed, and the outcome investigated was tobacco cessation counseling, tobacco cessation medication prescription, and pneumococcal vaccination. In the second method, patients who had tobacco cessation counseling were assessed, and the outcome evaluated was LDCT, tobacco cessation medication prescription, and pneumococcal vaccination. In the first method, out of 2,834 total population, 570 had undergone at least one LDCT screening during the study period. Of the 570 patients who underwent LDCT, 22.8% tried one of the tobacco cessation medications at least once during the study period (vs. 9.8% in patients who did not get the LDCT). Also, 71.5% of patients who had LDCT received at least one dose of pneumonia vaccine (vs. 35.5% in patients who did not get the LDCT). In the second method, 1,673 out of 2,834 patients received at least one tobacco cessation counseling, and out of those, 27.5% had LDCT screening (vs. 9.5% among those who never received counseling). Also, 54.9% received a pneumococcal vaccine (vs. 45.1% among those who did not receive counseling). The study demonstrates a relationship between getting LDCT and getting a pneumococcal vaccine or tobacco cessation medications. It also reveals that tobacco cessation counseling increases the odds of getting LDCT, tobacco cessation medications, and pneumococcal vaccine.
Discussion of the hematologic complications of vaccination for severe acute respiratory syndrome coronavirus-2 (COVID-19) has primarily focused on the development of vaccine-associated immune thrombosis with thrombocytopenia (VITT). Other hematologic complications are uncommon. We report the case of a patient who developed immunoglobulin G (IgG)-mediated autoimmune hemolytic anemia (AIHA) after the Moderna COVID-19 messenger ribonucleic acid (mRNA) vaccine.
Anemia, Hemolytic, Autoimmune , COVID-19 , Vaccines , Anemia, Hemolytic, Autoimmune/chemically induced , COVID-19 Vaccines , Humans , RNA, Messenger/genetics , SARS-CoV-2
Background Gastric cancer is one of the most prevalent cancers in the world and the third most common cause of death from cancer. The diagnosis and treatment are often complex and require a multifaceted approach. Hence, appropriate and timely management is essential for better patient outcomes. Our aim was to determine if rural inhabitation affects the mortality of patients with gastric adenocarcinoma. If such an association exists, we propose to ascertain whether this is related to delayed diagnosis, differing tumor characteristics, or treatment inequalities. Methods The Cox model was applied to gastric adenocarcinoma cases diagnosed during 2004-2011 in American residents aged 20+ years in the Surveillance, Epidemiology, and End Results (SEER) program to determine the impact of rurality on mortality. Binary logistic regression was used to compare the odds of not receiving surgical treatment for localized tumors between rural and urban areas. It was also used to measure the association of rurality with stage at diagnosis (non-metastatic vs. metastatic). Results There was a significant association of rurality on 5-year mortality [HR 1.14 (1.09-1.20), p < 0.01]. No significant association was observed between rural-urban residency and stage at diagnosis, with an odds ratio (OR) of 0.95 (0.87-1.03), p = 0.21. The median time from diagnosis to any first-course treatment was one month for both rural and urban counties. Rural residents were far more likely not to receive surgical treatment for localized tumors than their urban counterparts [OR 1.70 (1.41-2.05), p < 0.01]. A greater percentage of rural inhabitants had cardia tumors as compared to urban ones, 39.8% vs. 33.8% respectively. Non-cardia tumors were far less likely not to receive surgical treatment (i.e., more likely to receive surgical treatment) than cardia tumors [OR 0.35 (0.30-0.41), p < 0.01]. Conclusions Rurality is associated with worse gastric adenocarcinoma mortality. This may be due to a lesser probability of receiving surgical treatment for early-stage disease and differences in the primary site of the tumor between rural and urban counties, but not due to differences in stage at presentation. Future research should focus on improving health care access in rural communities.
Thrombotic microangiopathies (TMA) are disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microthrombi leading to organ dysfunction. Atypical hemolytic uremic syndrome (aHUS) is a rare subtype of TMA mediated by complement dysregulation. We present a case of a 59-year-old female who presented with acute kidney injury and mild thrombocytopenia but with normal hemoglobin. We highlight the importance of prompt diagnosis of aHUS and initiating appropriate treatment with eculizumab.
Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer. It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge.
Anti-glomerular basement membrane disease is a rare but classic example of an antibody-mediated disease. The scale of injury that it entails depends on the site where the antibodies are deposited, with some patients presenting with a composite of pulmonary and renal damage. In other scenarios, the renal system is the main site of affliction with patients deteriorating to a status of acute renal failure within days of diagnosis. Due to the paucity of its incidence, we present our findings of anti-glomerular basement disease with pulmonary sparing. Herein, we also review the array of different physical findings, different forms of perpetrating antibodies, the diagnostic tools at our disposal, and the treatment modalities utilized to prevent catastrophic tissue injuries.
Mequindox (MEQ) is a synthetic antibacterial agent. Recent studies showed that MEQ and its primary metabolites exhibit strong genotoxicity to mammalian cells, and MEQ induced carcinogenicity in mice. These findings suggest that chronic exposure to MEQ could lead to an increased risk of cancer later in life. In the present study, four groups of Wistar rats (55 rats/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110â¯mg/kg) for 2 years. The results showed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive systems, were the main targets for MEQ. Liver toxicity mediated by MEQ was associated with apoptosis and the nuclear factor κB (NF-κB) signaling pathway. In addition, MEQ increased the incidence of tumors in rats. Phosphorylated histone H2AX (γ-H2AX) is identified as a biomarker of cellular response to DNA double-strand breaks (DSB). Our data demonstrated that γ-H2AX expression was significantly increased in tumors. Thus, high levels of DSB might be responsible for carcinogenesis in rats, and further investigation is absolutely required to clarify the exact molecular mechanisms for carcinogenicity caused by MEQ in vivo.
Apoptosis/drug effects , Carcinogens/toxicity , DNA Damage , Quinoxalines/toxicity , Animals , Body Weight/drug effects , Dietary Exposure , Female , Histones/biosynthesis , Immunohistochemistry , Liver/drug effects , Liver/metabolism , Male , NF-kappa B/metabolism , Neoplasms, Experimental/metabolism , Organ Size/drug effects , Phosphoproteins/biosynthesis , Rats, Wistar , Survival Analysis
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder, characterized by impairments in social communication and restricted, repetitive behaviors. Neuroimaging studies have shown complex patterns and functional connectivity (FC) in ASD, with no clear consensus on brain-behavior relationships or shared patterns of FC with typically developing controls. Here, we used a dimensional approach to characterize two distinct clusters of FC patterns across both ASD participants and controls using k-means clustering. Using multivariate statistical analyses, a categorical approach was taken to characterize differences in FC between subtypes and between diagnostic groups. One subtype was defined by increased FC within resting-state networks and decreased FC across networks compared with the other subtype. A separate FC pattern distinguished ASD from controls, particularly within default mode, cingulo-opercular, sensorimotor, and occipital networks. There was no significant interaction between subtypes and diagnostic groups. Finally, a dimensional analysis of FC patterns with behavioral measures of IQ, social responsiveness, and ASD severity showed unique brain-behavior relations in each subtype and a continuum of brain-behavior relations from ASD to controls within one subtype. These results demonstrate that distinct clusters of FC patterns exist across ASD and controls, and that FC subtypes can reveal unique information about brain-behavior relationships.
Antidepressants are extensively used during pregnancy and associated with severe outcomes, including innate malformations, prematurity, and low birth weight, etc. A recent study suggested that prenatal exposure to antidepressants may impair child neurodevelopment process. Thus, the aim of this review is to investigate the potential association between prenatal use of selective 5-HT reuptake inhibitors (SSRIs) and the risk of autism spectrum disorders (ASDs). Twelve studies related to the linkage between SSRI exposure during pregnancy and ASD in children were explored and compiled. However, there is a knowledge gap concerning the potential link between gestational exposure to antidepressants and the risk of ASDs. Despite such limitations, the available data show that some signal exists and signifies that antenatal exposure to SSRIs may increase the risk of ASDs. Thus, there is a vital need for further, large and well-designed research to definitively evaluate the existence and the magnitude of this severe risk.
Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system (CNS) with no distinct etiology but implications include infections and commonly administered vaccinations. In this case report, we present the case of ADEM in a young female who was subsequently diagnosed with acute intermittent porphyria (AIP) that was the instigator of the initial CNS assault. Our case highlights the peculiar presentation of ADEM which can present as a diagnostic challenge and brings forth AIP as a new and previously unknown affiliate of this rare CNS disease. We also discuss the pathophysiology, diagnostic criteria, and subsequent treatment options for this rare clinical entity.
Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), has been extensively used as a synthetic antibacterial agent. To evaluate the reproductive toxicity of MEQ, different concentrations of MEQ were administered to Wistar rats by feeding diets containing 0, 25, 55, 110, and 275 mg/kg, respectively. Each group consisting of 25 males and 25 females (F0) was treated with different concentrations of MEQ for 12-week period time, prior to mating and during mating, gestation, parturition and lactation. At weaning, 25 males and 25 females of F1 generation weanlings per group were randomly selected as parents for the F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. The number of live litter and indexes of mating and fertility were significantly decreased in the F1 and F2 generation at 110 and 275 mg/kg groups. Significant decrease in pup vitality during lactation was observed in F1 litter at 275 mg/kg group, in F2 litter at 55, 110, and 275 mg/kg groups. A downward trend in the body weights was observed in F1 pups at 55, 110, and 275 mg/kg MEQ groups, and in F2 pups at 110 and 275 mg/kg MEQ groups. The changed levels of ALT, AST, CREA, BUN, UA, Na, and K were noted in the serum of rats. The histopathologic examination showed that MEQ induced toxicity in the liver, kidney, adrenal, uterus and testis. The no-observed-adverse-effect level (NOAEL) for reproduction toxicity of MEQ was 25 mg/kg diet. The malformations and severe maternal toxicity of MEQ caused adverse effects on the conceptus and embryo, which result in fetal malformations and fetal deaths. In summary, the present study showed that MEQ induced maternal, embryo and reproductive toxicities as well as teratogenicity in rats.
The lungs are a common site of metastatic spread of an osteosarcoma. An affiliated simultaneous bilateral spontaneous pneumothorax (SBSP) is a rare clinical sequela of this malignancy. In this case report, we present the clinical circumstances of a young teenager who presented to our clinical setting following a diagnosis of osteosarcoma. We also illustrate the postulated pathophysiology, the tools for diagnosis and a subsequent management for this rare clinical entity.
Amyand's hernia is characterized by the presence of an inflamed, non-inflamed or perforated appendix within the sac of an inguinal hernia. This is an exceedingly rare presentation and most of the cases are diagnosed incidentally during surgery. Here we describe a case of an Amyand's hernia in a patient who presented in our outpatient clinic with an irreducible right-sided inguinal hernia. There were no signs of ischemic complications. During the surgery, an appendix was found within the hernial sac. An uneventful appendectomy along with a tension-free darn repair was performed. The current case report emphasizes that this pathology must be kept in mind while treating a patient with a right-sided inguinal hernia.
Bilateral adrenal hemorrhage (BAH) is a rare but potentially fatal entity that carries a mortality rate of 15%. Most cases are associated with sepsis, antiphospholipid syndrome, the use of anticoagulants, as well as trauma and surgery. In this case report, we present a case of BAH in a previously healthy man with a recent history of corticosteroid use. Our case emphasizes the ambiguous clinical presentation of BAH, which poses a challenge in the establishment of a correct diagnosis. We also illustrate the pathophysiology, diagnosis, and subsequent therapeutic approach to this rare clinical entity.
Hemophagocytic lymphohistiocytosis (HLH) has been recognized as an inflammatory endpoint for a variety of conditions including autoimmune diseases, malignancies and infections. It can be further classified as primary and secondary HLH. Primary HLH is also known as familial HLH. It usually presents in childhood and can be associated with gene mutations. Secondary HLH is also known as acquired HLH and usually presents in adulthood. In comparison to children, it is difficult to diagnose adults with HLH since it occurs with a variety of different diseases and most of the literature on HLH is derived from a pediatric population. In this case series, we report two cases of HLH that illustrate the difficulty of making this diagnosis and a brief review of the literature on its pathophysiology, clinical presentation, diagnosis, and a subsequent therapeutic approach.
Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo.
T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40â¯nM) for 12, 24, 36 and 48â¯h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (â³Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells.
Cell Cycle/drug effects , Genes, p16/drug effects , Pituitary Gland/drug effects , Retinoblastoma Protein/biosynthesis , Signal Transduction/drug effects , T-2 Toxin/toxicity , Animals , Cell Cycle/physiology , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Genes, p16/physiology , Pituitary Gland/metabolism , Pituitary Gland/ultrastructure , Rats , Signal Transduction/physiology
