Cocaine-Induced Toxic Leukoencephalopathy: A Case Report.

Cocaine is a widely abused controlled substance. Cocaine use is associated with a myriad of side effects and a sequelae of consequences secondary to its harmful nature and potential adulterants, the most recently described and less known sequelae being leukoencephalopathy. In our case, we describe a 58-year-old male who presented to the ED with agitation and acute stroke-like symptoms with reported rapid onset. Cocaine induced toxic leukoencephalopathy is a diagnosis of exclusion, thus other etiologies of disease were ruled out in a full neurological and infectious workup; most importantly consisting of extensive brain imaging, alluding to the diagnosis of acute cocaine induced toxic leukoencephalopathy in an individual with a confirmed history of cocaine and cannabinoid abuse. Although there is no targeted therapy for the condition to our knowledge, we utilized a supportive approach to treatment in contrast to other reported treatment modalities which included the use of steroids, plasma exchange, and intravenous immunoglobulin. Furthermore, we describe the clinical evaluation and treatment throughout the patient's hospital course with his eventual marked improvement from initial presentation.

Small-molecule inhibitor HI-TOPK-032 improves NK-92MI cell infiltration into ovarian tumours.

The effectiveness of natural killer (NK) cells transferred adoptively in combating solid tumours is limited by challenges such as their difficulty in penetrating tumours from the bloodstream and maintaining viability without the support of interleukin-2 (IL-2). Genetically modified NK-92MI cells, which can release IL-2 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL-2 administration. The role of PSD-95/discs large/ZO-1 (PDZ)-binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK-92MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small-molecule inhibitor HI-TOPK-032, which inhibits PBK, enhances the cytotoxicity of NK-92MI cells toward OV cells. It increases the production of interferon-γ and tumour necrosis factor-α, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI-TOPK-032 upregulates CD107a on NK-92 cells. In vivo studies demonstrated that HI-TOPK-032 improves the antitumour effects of NK-92MI cells in OVCAR3Luc xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI-TOPK-032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK-92MI cells with HI-TOPK-032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation.

The Optimal Initial Dose and Route of Naloxone Administration for Successful Opioid Reversal: A Systematic Literature Review.

This systematic literature review aims to determine the optimal initial dose of naloxone for successful opioid overdose reversal across different administration routes. Types of participants included adults who have opioid overdoses and adults who are suspected to have opioid overdoses. Pregnant women, children, animals, and populations outside the US were excluded. The interventions included were intranasal (IN), intramuscular (IM), and intravenous (IV) naloxone administration. The data collected for this systematic review were studies from PubMed, CINAHL, PsyINFO, and Cochrane Central Register of Controlled Trials registers between January 2015 and July 2021. The risk of bias was assessed via the Review Manager application. Six studies met the inclusion criteria. A meaningful statistical analysis was unable to be conducted with such few studies. The studies reveal 2 mg IN as the most popular dosing for initial naloxone for successful opioid reversal. The most common route of naloxone administration for successful reversal could not be studied but most studies revealed successful initial naloxone dosing in IN equivalents. With minimal studies emerging from our review, further research is warranted in naloxone dosing for optimal opioid reversal in order to fully treat patients. Healthcare workers must be vigilant of potential withdrawal from high naloxone dosing as well as the inefficiency of lower naloxone dosing for adequate opioid overdose reversal in order to treat patients with opioid overdoses properly.

Emergency Hysterectomy Following Placental Abruption in a Patient With a History of Substance Abuse: A Case Report.

Placental abruption is a serious medical condition that can occur during pregnancy, involving the premature separation of the placenta from the inner uterine wall before childbirth. This detachment often leads to severe bleeding, and if conventional methods prove ineffective in managing the bleeding, a hysterectomy may be deemed necessary to ensure the mother's safety. This case report details the management of a 22-year-old female, gravida IV, para III, who experienced placental abruption during her fourth pregnancy. An emergent cesarean section resulted in severe postpartum hemorrhage and disseminated intravascular coagulation (DIC). Positive drug tests for cocaine and methamphetamines added further complexity, leading to an unplanned hysterectomy for life-saving measures. This case underscores the critical importance of early recognition, multidisciplinary collaboration, and timely intervention in managing obstetric emergencies within the context of substance abuse.

How bad could it be? Alcohol dampens stress responses to threat of uncertain intensity.

Stress response dampening is an important motive for alcohol use. However, stress reduction via alcohol (alcohol SRD) is observed inconsistently in the laboratory, and this has raised questions about the precise mechanisms and boundary conditions for these effects. Emerging evidence indicates that alcohol SRD may be observed selectively during uncertain but not certain threats. In a final sample of 89 participants, we measured stress response via potentiation of defensive startle reflex in response to threat of shock in blocks with certain (low and high) and uncertain shock intensity. Our alcohol-administration procedure produced blood alcohol concentrations (BACs) across a broad range (0.00%-0.12%) across participants. Increasing BACs were associated with linearly decreasing startle potentiation and self-reported anxiety. This SRD effect was greater during uncertain than certain threat. More broadly, these results suggest that distinct mechanisms are involved in response to threats of uncertain intensity and threats of certain intensity.

Blood Culture-Negative Endocarditis Secondary to Skin Popping.

Infectious endocarditis (IE) is a diagnosis in which thorough evaluation must be performed and certain diagnostic criteria must be met. Thorough history and detailed physical examination can affect and guide the management of a patient from the very beginning. One of the main causes of endocarditis that physicians deal with in the hospital is intravenous drug abuse. This case report is of a 29-year-old male presenting to a rural emergency department with a two-week history of altered mental status after being struck on the head with a metal pipe. The patient also endorsed using intravenous drugs along with subcutaneous injections (skin popping). The patient was initially treated as a traumatic intracranial hemorrhage, but it was later found to be secondary to septic emboli from blood culture-negative endocarditis. Throughout this case report, we will approach the difficulties of diagnosing IE in a patient who represented many of the less common findings including dermatologic manifestations of diseases such as Osler nodes and Janeway lesions.

Posterior Reversible Encephalopathy Syndrome in a Male With Polysubstance Abuse: A Case Report.

Posterior reversible encephalopathy syndrome (PRES) is a neurologic disorder with multiple etiologies. The signs and symptoms of PRES are non-specific, making the differential diagnosis broad. Although PRES is suspected clinically, a diagnosis requires characteristic findings on imaging. In patients with undiagnosed PRES, the coexistence of substance abuse can divert the care provider from pursuing imaging studies, leading to a missed diagnosis. We describe the case of a 51-year-old male who presented with altered mental status and was diagnosed with PRES despite having a positive urine drug screen.

Management of New Onset Amphetamine-Induced Acute Decompensated Heart Failure in a Young Adult: Case Report.

Amphetamine-induced heart failure is a well-recognized complication of chronic amphetamine abuse. Although the exact mechanisms underlying the development of this condition are not fully understood, it is believed to be due to a combination of direct toxicity to the myocardium, increased sympathetic activity, and oxidative stress. Amphetamine-induced heart failure typically presents with symptoms such as dyspnea, fatigue, and peripheral edema and can lead to significant morbidity and mortality. Diagnosis is based on a combination of clinical and laboratory findings, including echocardiography and cardiac biomarkers. Treatment typically involves cessation of amphetamine use, management of heart failure symptoms, and aggressive medical therapy with agents such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. However, the long-term prognosis for patients with amphetamine-induced heart failure remains poor, highlighting the need for increased awareness and prevention efforts surrounding this growing public health concern. In this case, a 21-year-old male presented to the emergency department (ED) with acute-onset decompensated heart failure due to amphetamine abuse.

A Rare and Complex Case of Non-suicidal Self-Mutilation in a Patient With Schizophrenia.

The literature describing acts of non-suicidal self-mutilation (NSSM) in the adult population is limited. Of the cases that document NSSM, a disproportionate number of these individuals have a history of psychiatric illnesses. Although the motivation to perform NSSM varies across patients, the literature suggests that past self-injurious behaviors, extreme religious delusions, and command hallucinations are the most significant risk factors. The primary forms of NSSM include ocular, genital, and limb mutilation. Limb mutilation is the least common of the three and typically occurs proximal to the wrist or hand. Here, we present a rare case involving a 42-year-old man with schizophrenia who was hospitalized due to osteomyelitis of his autoamputated digits. This case is unique in involving multiple digits of the hand and using a rare amputation method. We aim to compare this case with the existing body of work on NSSM and identify factors that may predispose patients to act on these extreme impulses. We also highlight a novel interventional program that reduces psychiatric and medical comorbidities.

Substance Abuse Amongst Adolescents: An Issue of Public Health Significance.

Adolescence is a crucial time for biological, psychological, and social development. It is also a time when substance addiction and its adverse effects are more likely to occur. Adolescents are particularly susceptible to the negative long-term effects of substance use, including mental health illnesses, sub-par academic performance, substance use disorders, and higher chances of getting addicted to alcohol and marijuana. Over the past few decades, there have been substantial changes in the types of illegal narcotics people consume. The present article deals with the review of substance abuse as a public health problem, its determinants, and implications seen among adolescents. A systematic literature search using databases such as PubMed and Google Scholar was undertaken to search all relevant literature on teenage stimulant use. The findings have been organized into categories to cover essential aspects like epidemiology, neurobiology, prevention, and treatment. The review showed that substance addiction among adolescents between 12 to 19 years is widespread, though national initiatives exist to support young employment and their development. Research on psychological risk factors for teenage substance abuse is vast, wherein conduct disorders, including aggression, impulsivity, and attention deficit hyperactivity disorder, have been mentioned as risk factors for substance use. Parents' attitudes toward drugs, alcohol, academic and peer pressure, stress, and physical outlook are key determinants. Teenage drug usage has a significant negative impact on users, families, and society as a whole. It was found that a lot has been done to provide correct intervention to those in need with the constant development of programs and rehabilitative centers to safeguard the delicate minds of youths and prevent them from using intoxicants. Still, there is much need for stringent policy and program guidelines to curb this societal menace.