Computational pathology identifies immune-mediated collagen disruption to predict clinical outcomes in gynecologic malignancies.

BACKGROUND: The role of immune cells in collagen degradation within the tumor microenvironment (TME) is unclear. Immune cells, particularly tumor-infiltrating lymphocytes (TILs), are known to alter the extracellular matrix, affecting cancer progression and patient survival. However, the quantitative evaluation of the immune modulatory impact on collagen architecture within the TME remains limited. METHODS: We introduce CollaTIL, a computational pathology method that quantitatively characterizes the immune-collagen relationship within the TME of gynecologic cancers, including high-grade serous ovarian (HGSOC), cervical squamous cell carcinoma (CSCC), and endometrial carcinomas. CollaTIL aims to investigate immune modulatory impact on collagen architecture within the TME, aiming to uncover the interplay between the immune system and tumor progression. RESULTS: We observe that an increased immune infiltrate is associated with chaotic collagen architecture and higher entropy, while immune sparse TME exhibits ordered collagen and lower entropy. Importantly, CollaTIL-associated features that stratify disease risk are linked with gene signatures corresponding to TCA-Cycle in CSCC, and amino acid metabolism, and macrophages in HGSOC. CONCLUSIONS: CollaTIL uncovers a relationship between immune infiltration and collagen structure in the TME of gynecologic cancers. Integrating CollaTIL with genomic analysis offers promising opportunities for future therapeutic strategies and enhanced prognostic assessments in gynecologic oncology.

The role of cells that are part of our immune system in altering the structure of the protein collagen within cancers is not fully understood, particularly within cancers that affect women such as ovarian, cervical and uterine cancers. Here, we developed a computer-based method called CollaTIL to explore how immune cells influence collagen in these tumors and affect their growth. We found that a higher presence of immune cells leads to less organized collagen in the tumor. Conversely, when there are fewer immune cells, the collagen tends to be more structured. Additionally, CollaTIL identifies patterns that predict patient outcomes in these cancers. These findings not only enhance our understanding of tumor biology but also may be useful in helping clinicians to predict which patients are at risk of their disease progressing.

Computational Image and Molecular Analysis Reveal Unique Prognostic Features of Immune Architecture in African Versus European American Women with Endometrial Cancer.

Endometrial cancer (EC) disproportionately affects African American (AA) women in terms of progression and death. In our study, we sought to employ computerized image and bioinformatic analysis to tease out morphologic and molecular differences in EC between AA and European-American (EA) populations. We identified the differences in immune cell spatial patterns between AA and EA populations with markers of tumor biology, including histologic and molecular subtypes. The models performed best when they were trained and validated using data from the same population. Unsupervised clustering revealed a distinct association between immune cell features and known molecular subtypes of endometrial cancer that varied between AA and EA populations. Our genomic analysis revealed two distinct and novel gene sets with mutations associated with improved prognosis in AA and EA patients. Our study findings suggest the need for population-specific risk prediction models for women with endometrial cancer.

Siddha fasting in obese acute decompensated heart failure may improve hospital outcomes through empowerment and natural ketosis.

BACKGROUND: Morbid obesity (BMI > 35 kg/m2 with comorbid conditions) is present in 25 - 35% of acute decompensated heart failure (AHF) patients. Prevalence of HF increases with duration of morbid obesity from 30% at 15 years to over 90% at 30 years. There is a need to develop pragmatic therapies that address the unique physical and mental challenges faced by obese AHF patients. Siddha is 5,000 year old Tamil Medicine using yoga and mind-body methods towards higher consciousness. Hunger gratitude Experience (HUGE) is intuitive Siddha fasting method which may improve in-hospital AHF outcomes independent of weight reduction. CASE SUMMARY: We present 5 cases of morbidly obese patients with cardiorenal syndrome (CRS) that began intermittent fasting either during their AHF hospitalization or in the outpatient setting for refractory symptoms despite hospitalization. Initiation of fasting correlated with reduction of respiratory distress and edema as well as improvements in psychological wellbeing and functional capacity. DISCUSSION: Siddha fasting mediates hemodynamic and anti-inflammatory effects through natural ketosis and psychological benefits through empowerment in AHF. Potential role of fasting in reducing myocardial workload, coronary steal, angina, volume overload, and CRS needs further study in cardiac patients.

The Use of Prazosin in Treatment of Drug Dreams in Adolescents with Substance Use Disorder: Two Case Reports.

~ Nightmares are psychologically distressing events that may cause significant effects on mental health, physical well-being and overall quality of life, in addition to their negative impact on quality and duration of sleep. Drug dreams are a variant of nightmares and a known phenomenon in addiction medicine, and have been studied as a potential causative factor in relapse of substance use. Recent studies have noted that addictive behaviors and drug dreams share a similar neurobiological pathway, and that certain neurotransmitters, most notably those of the noradrenergic system, may underlie these complex processes. This has led to the theory that alleviation of drug dreams and suppression of involved neurocircuits may potentially reduce subsequent craving and relapse in the treatment of substance use disorders, with an important potential agent being the alpha-1 antagonist, prazosin.

Youth Suicide: A Population Crying for Help? A System Overloaded? Who Can Help?

Suicide is the second leading cause of death in young adults (15-24 years old). There continues to be limited access to mental health services for many patients who are in mental health crisis because of shortage of trained psychiatrist and mental health providers. Patients identified with high risk factors should get a full comprehensive psychiatric evaluation. Management should focus on preventative strategies, early identification as well as treatment with appropriate psychopharmacology and psychotherapy.

Metalophagia: Splenic artery pseudoaneurysm after foreign body ingestion and retrieval.

Persistent eating of non-nutritive, nonfood substances (Pica) is seen in children and adult patients with psychiatric problems. Ingestion of multiple metallic FBs with resultant bezoar formation is rare. While many FBs are passed without complication, mucosal injury, bleeding, obstruction or perforation can occur in some cases. Endoscopic FB removal is performed in 20% of patients following FB ingestion. Generally, these are safe procedures, and very effective in extracting ingested FBs. We report, a 25-year-old male patient with a metal ingestion predominant Pica, requiring multiple prior extraction procedures (including open gastrostomy). He developed a splenic artery pseudoaneurysm following his latest endoscopic FB removal, that was successfully treated with transarterial coil embolization. The unique circumstances leading to this rare complication and its successful endovascular management make this case worthy of report.

Psychosis.

PURPOSE OF REVIEW: Psychosis is a psychiatric condition that has significant overlap with neurologic disease. This article is intended to educate the neurologist on the psychiatric manifestations of psychosis and its evaluation, diagnosis, and treatment. How to differentiate a primary psychiatric cause of psychosis from psychosis secondary to a medical or neurologic condition is also reviewed. RECENT FINDINGS: Current research in psychotic disorders has focused increasingly on negative symptoms and cognitive impairment in psychotic illness, as it is now recognized that these cause the greatest impact on functional deficits for patients. A number of new medications have also been introduced to target negative symptoms and cognitive deficits in psychotic illness. These have new implications in terms of treatment overlap with medications being prescribed by providers in psychiatry, neurology, and general practice. SUMMARY: This article discusses the current methods for evaluating, diagnosing, and treating psychosis. Psychosis as a primary mental health disorder is a diagnosis of exclusion, as psychosis can be a direct symptom of underlying medical or neurologic disease. Delirium and dementia are the two most important disorders to rule out. This article will help readers be more prepared to assess and treat the patient with psychosis.

Aripiprazole Long-Acting Injectable for Maintenance Treatment of Bipolar I Disorder in Adults.

Bipolar I disorder is a serious and disabling psychiatric illness. It is associated with a significant reduction in quality of life and an increased risk for suicide. Pharmacotherapy is essential for both the acute and maintenance treatment of bi-polar I disorder. While multiple oral medications are recommended for the maintenance treatment, there are not many long-acting injectable medications approved for this indication. New treatments that would improve patient adherence have the potential for decreasing relapses and improving patients' ability to remain functional members of society. In this paper we discuss the available data for safety and efficacy of aripiprazole long-acting injectable in bipolar disorder.

Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation.

Long-acting injectable aripiprazole: how might it fit in our tool box?

Schizophrenia is a severe mental illness with a lifetime prevalence of approximately one percent worldwide. Maintenance antipsychotic treatment has been effective in preventing relapses in long-term follow-up studies. Logically it can be proposed that long-acting injectable antipsychotics (LAI) might reduce both unintentional and intentional nonadherence. Long-acting injectable aripiprazole was approved for the treatment of schizophrenia by the U.S. FDA on 28th February 2013 and will be marketed under the name Abilify Maintena. Aripiprazole LAI (ALAI) is a lyophilized powder that needs to be reconstituted with sterile water to form an injectable suspension without affecting the original molecule. The monthly injection interval is very attractive since patients prefer fewer injections. From a tolerability perspective, ALAI appears to be both weight neutral and lacking metabolic side effects. This can confer an advantage over the other currently available second-generation antipsychotic LAIs. Simple constitution with sterile water and no requirement to refrigerate make storage and administration easier. Like all medications, there are always potential disadvantages to ALAI. There is a period of oral coverage, while not as long as for long-acting risperidone microspheres (RLAI), that is required. Care must be taken to review concomitant medications for the presence of metabolic inducers and inhibitors. One would also expect some patients to be sensitive to extrapyramidal symptoms, especially akathisia which is well documented in the oral preparation. All things considered, we welcome our new tool, ALAI, to our work-place and predict both clinical practice and post marketing analysis and studies will discover its true value.