Situs Inversus Totalis in the Critical Care Unit: A Case Report and Literature Review.

Situs inversus is a rare congenital disorder where the reversal of some of the major thoracic or abdominal organs is present. In this disorder, alterations in the fetus's organ lateralization lead to a complete reversal in the arrangement of the internal organs. Most of the time, they are found incidentally when having a procedure or imaging modality. Little has been written regarding the challenges encountered while providing critical care to these patients. Here we present the case of a 68-year-old male patient admitted to the intensive care unit (ICU) with hypoxemic respiratory failure secondary to pneumonia who underwent diagnostic bronchoscopy for organism identification and was confirmed to have situs inversus totalis. Situs inversus totalis represents a challenge at different levels of care to these patients, including in the ICU. Limitations in critical care can be seen upon imaging identification, and during routine procedures performed at the ICU. Confusion might appear while performing bedside point of care ultrasound, obtaining vascular access, performing electrocardiogram, and sample identification, among others. The case brings the relevance of being able to recognize this rare disorder, which can be diagnosed even in advanced age since it might present the clinician with challenges at the time of providing care to patients.

Leukemia Cutis As the Initial Manifestation of Chronic Lymphocytic Leukemia Progression.

Chronic lymphocytic leukemia (CLL) is a malignant proliferation of monoclonal mature B-cells in peripheral blood. Leukemia cells can commonly spread from the blood to other sites such as the lymph nodes, liver, and spleen. However, contrary to T-cell lymphomas that can involve the skin, CLL metastasis to the skin is unusual and is rarely the first manifestation of systemic disease. When leukemia cells invade the skin, it is termed leukemia cutis. Furthermore, multiple skin morphologies can be present in leukemia cutis making diagnosis challenging. Likewise, it can be mistaken for other common etiologies such as drug or substance allergy, infection, and scabies, among others. We herein present a case of CLL with leukemia cutis as the initial manifestation of systemic disease. The initial punch biopsy results were non-specific for inflammatory changes, but a subsequent biopsy revealed findings confirming leukemia cutis. This case not only demonstrates that identifying malignant skin manifestations in a timely manner and treating them is essential, as it improves the quality of life and survival, but also demonstrates that leukemia cutis can be a dynamic disease where multiple biopsies may be needed to confirm the diagnosis, as histopathology can change over time.

Immunoblot Validation of Phospho-Specific Antibodies Using Lung Cancer Cell Lines.

The cancer phenotype is usually characterized by deregulated activity of a variety of cellular kinases, with consequent abnormal hyper-phosphorylation of their target proteins. Therefore, antibodies that allow the detection of phosphorylated versions of proteins have become important tools both preclinically in molecular cancer research, and at the clinical level by serving as tools in pathological analyses of tumors. In order to ensure reliable results, validation of the phospho-specificity of these antibodies is extremely important, since this ensures that they are indeed able to discriminate between the phosphorylated and unphosphorylated versions of the protein of interest, specifically recognizing the phosphorylated variant. A recommended validation approach consists in dephosphorylating the target protein and assessing if such dephosphorylation abrogates antigen immunoreactivity when using the phospho-specific antibody. In this chapter, we describe a protocol to validate the specificity of a phospho-specific antibody that recognizes a phosphorylated variant of the Retinoblastoma (Rb) protein in lung cancer cell lines. The protocol consists in the dephosphorylation of the Rb-containing protein lysates by treating them with bovine intestinal phosphatase, followed by assessment of the dephosphorylation by immunoblot.

Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.

Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs.