Erratum to "Bilateral cerebellar hemorrhagic infarcts as an early presentation following opioid-induced toxic encephalopathy in an adult patient" [Radiology Case Reports 16 (2021) 1207-1210].

[This corrects the article DOI: 10.1016/j.radcr.2021.02.073.].

Tissue engineered cancer metastases as cancer vaccine to improve cancer immunotherapy.

Radiotherapy is often used to improve cancer immunotherapy outcomes. While there are both pre-clinical and clinical data supporting this approach, there are also significant challenges. One key challenge is that not all patients have tumors that can be easily treated with radiotherapy due to potential normal tissue toxicity and prior treatment. In addition, it is difficult to control the tumor microenvironment to promote the immune response after radiosurgery. To overcome these challenges, we hypothesize that we can engineer cancer metastasis and utilize irradiated engineered tumor cells as a personalized cancer vaccine to improve cancer immunotherapy. Herein, we report the development of engineered lung metastasis using decellularized rat lung tissue. Using the B16F10 melanoma tumor model, we showed that radiotherapy-treated engineered metastases are highly effective in improving cancer immunotherapy responses and more effective than in vivo metastasis. Our work has demonstrated the potential of applying tissue engineering to cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Combination of radiation and immunotherapy are an effective way to treat metastasis. Despite their success, long term response still remains low. Tumor microenvironment evading the immune response, normal tissue toxicity to radiation and inaccessibility to radiosurgery are some of the limitations. To overcome these challenges, in this paper we present with data supporting the use of high dose radiation treated ex vivo engineered B16F10 metastasis model using decellularized lung scaffolds. These engineered metastases closely mimic the in vivo tumors and when given into tumor bearing mice along with check point inhibitors are highly effective in improving the cancer immunotherapy response.

Mucinous carcinoma in a male patient: Diagnosis and management of breast cancer in male patients.

Male breast cancer is a rare but serious condition that impacts an increasing number of men each year. Due to low incidence rate, there is a current lack of established diagnostic and management practices. Here, we provide a review of the current epidemiology, classification, diagnosis, and treatment of male breast cancer. We present a rare case of mucinous breast cancer in a 74-year-old male patient detected after he presented with a retroareolar mass. The patient underwent mammography, targeted ultrasound, and ultrasound-guided core needle biopsy, which established the diagnosis. He was treated surgically with left mastectomy and sentinel lymph node biopsy with axillary lymph node dissection, followed by post-adjuvant tamoxifen and has remained free of recurrence and metastasis since.

Bilateral cerebellar hemorrhagic infarcts as an early presentation following opioid-induced toxic encephalopathy in an adult patient.

In the midst of the national opioid crisis, it is necessary for emergency physicians and radiologists to be familiar with presentations of opioid-related complications. We describe a case report of a 51-year-old female who developed bilateral cerebellar hemorrhages following opioid and benzodiazepine overdose. Malignant cerebellar edema is a rare but recognized complication following opiate overdose in children or chronic heroin toxicity. However, acute cerebellar involvement is rarely reported in adults. We feel that clinicians and radiologists should keep in mind the possibility of opioid toxic encephalopathy in their differential for adults with acute bilateral cerebellar infarcts and/or hemorrhages.

Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging.

G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains. High field MRM of actively-stained mouse brains from GIT1-KO and wild type (WT) controls (n = 6 per group) allowed segmenting 37 regions, based on co-registration to the Waxholm Space atlas. Overall brain size in GIT1-KO mice was ~32% smaller compared to WT controls. After correcting for brain size, several regions were significantly different in GIT1-KO mice relative to WT, including the gray matter of the ventral thalamic nuclei and the rest of the thalamus, the inferior colliculus, and pontine nuclei. GIT1-KO mice had reduced volume of white matter tracts, most notably in the anterior commissure (~26% smaller), but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, the basal ganglia appeared enlarged in GIT1-KO mice, including the globus pallidus, caudate putamen, and particularly the accumbens - supporting a possible vulnerability to addiction. Volume based morphometry based on high-resolution MRM (21.5 µm isotropic voxels) was effective in detecting overall, and local differences in brain volumes in GIT1-KO mice, including in white matter tracts. The reduced relative volume of specific brain regions suggests a critical, but not uniform, role for GIT1 in brain development, conducive to brain microcephaly, and aberrant connectivity.

Discovering metabolic disease gene interactions by correlated effects on cellular morphology.

OBJECTIVE: Impaired expansion of peripheral fat contributes to the pathogenesis of insulin resistance and Type 2 Diabetes (T2D). We aimed to identify novel disease-gene interactions during adipocyte differentiation. METHODS: Genes in disease-associated loci for T2D, adiposity and insulin resistance were ranked according to expression in human adipocytes. The top 125 genes were ablated in human pre-adipocytes via CRISPR/CAS9 and the resulting cellular phenotypes quantified during adipocyte differentiation with high-content microscopy and automated image analysis. Morphometric measurements were extracted from all images and used to construct morphologic profiles for each gene. RESULTS: Over 107 morphometric measurements were obtained. Clustering of the morphologic profiles accross all genes revealed a group of 14 genes characterized by decreased lipid accumulation, and enriched for known lipodystrophy genes. For two lipodystrophy genes, BSCL2 and AGPAT2, sub-clusters with PLIN1 and CEBPA identifed by morphological similarity were validated by independent experiments as novel protein-protein and gene regulatory interactions. CONCLUSIONS: A morphometric approach in adipocytes can resolve multiple cellular mechanisms for metabolic disease loci; this approach enables mechanistic interrogation of the hundreds of metabolic disease loci whose function still remains unknown.

Metformin-Induced Lactic Acidosis: A Case Study.

Metformin is the first line management for patients with Type 2 diabetes mellitus. Metformin-induced lactic acidosis (MALA) is a severe side effect of metformin in high doses. However, there have not been many reported cases of MALA. The threshold metformin concentration needed to induce lactic acidosis is still not fully understood. It is important for physicians to measure metformin levels upon admission in Type 2 diabetes patients who take metformin and present with suspected lactic acidosis. We present a case of a 40-year-old Caucasian male who presented with severe lactic acidosis shortly after overdosing on metformin.

Frequency of generalised anxiety disorder and associated factors in an urban settlement of Karachi.

OBJECTIVE: The study was undertaken to find the frequency of Generalised Anxiety Disorder (GAD) along with associated factors in an urban settlement of Karachi. METHOD: A cross-sectional study was conducted at Defence Housing Authority (DHA), a posh area of Karachi. The sample population consisted of residents of ages between 18 and 65. The sample of 420 was completed by randomly going to residences in the DHA area. Self-administered questionnaires were handed out after taking informed consent. General Anxiety Disorder (GAD) 7 scale was used to estimate the anxiety level. The data was entered and analysed using SPSS version 16.0. Pearson's chi-square was used as the primary statistical test. RESULTS: The mean anxiety score of the total individuals selected was 5.1 +/- 3.79. Males reported a mean score of 4.99 +/- 4.01 while females reported a mean score of 5.25 +/- 3.42. A score of 5 is considered as the threshold for anxiety and anything below 5 is considered as normal. Based on this benchmark, out of the total sample size of 420, 211 (50.2%) individuals reported some degree of anxiety. Employment and education status were found to be significantly associated (p = 0.01) with anxiety among the participants. CONCLUSION: Based on the results, the high prevalence of anxiety in one of the most developed areas of Karachi is alarming. For 50.2% of the respondents to have anxiety is high considering the sample chosen represented individuals that were educated and had a high standard of living. The major factors responsible for anxiety cited by respondents were chronic diseases and emotional harm.