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Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that SRRT may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRTs potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and, very often, ineffective medical and surgical therapeutic options. The treatment of patients with advanced unresectable PDAC is restricted to systemic chemotherapy, a therapeutic intervention to which most eventually develop resistance. Recently, nab-paclitaxel (n-PTX) has been added to the arsenal of first-line therapies, and the combination of gemcitabine and n-PTX has modestly prolonged median overall survival. However, patients almost invariably succumb to the disease, and little is known about the mechanisms underlying n-PTX resistance. Using the conditionally reprogrammed (CR) cell approach, we established and verified continuously growing cell cultures from treatment-naïve patients with PDAC. To study the mechanisms of primary drug resistance, nab-paclitaxel-resistant (n-PTX-R) cells were generated from primary cultures and drug resistance was verified in vivo, both in zebrafish and in athymic nude mouse xenograft models. Molecular analyses identified the sustained induction of c-MYC in the n-PTX-R cells. Depletion of c-MYC restored n-PTX sensitivity, as did treatment with either the MEK inhibitor, trametinib, or a small-molecule activator of protein phosphatase 2a. IMPLICATIONS: The strategies we have devised, including the patient-derived primary cells and the unique, drug-resistant isogenic cells, are rapid and easily applied in vitro and in vivo platforms to better understand the mechanisms of drug resistance and for defining effective therapeutic options on a patient by patient basis.

Background: The presenting symptoms of patients with Hirschsprung's disease (HD) are a failure to pass meconium, abdominal distension, and bilious vomiting. The gold standard diagnosis is a rectal biopsy to confirm aganglionosis. The aim of our study was to describe the diagnostic pathway of Hirschsprung's disease at our institution and document the indication for a rectal biopsy. Methods: We have performed a prospective collection of all patients who underwent a rectal biopsy to exclude HD from December 2022 until September 2023 including. The following data were collected: patient's age, presenting symptoms, type of biopsy, failure rate, complications, and histopathological results. Results: We identified 33 patients who underwent 34 rectal biopsies at 0.6 years of age. A total of 17 patients had a rectal suction biopsy (RSB), and 17 patients underwent a partial thickness under general anaesthesia (GA). 1/17 (6%) patients had an inconclusive RSB and subsequently underwent a biopsy under GA. Constipation and chronic abdominal distension plus vomiting were the most common presenting symptoms throughout all ages. Five patients (15%) had a rectal biopsy that was positive for HD. Conclusion: A protocolised approach to the assessment of infants and children with suspected HD ensures the appropriate utilisation of invasive procedures such as biopsy. [ABSTRACT FROM AUTHOR]

We report a 39-year-old male who presented with severe chest pain and diaphoresis who suffered from pulseless polymorphic ventricular tachycardia en route to the hospital. His initial electrocardiogram showed De Winter's Pattern (dWP). Coronary angiography revealed 100% thrombotic ostial occlusion of the left anterior descending artery. In young males presenting with chest pain and diaphoresis, dWP should be part of a clinician's differential diagnosis when analyzing the initial electrocardiogram. The medical community needs increased awareness to prevent delay of revascularization because dWP is an ST-segment elevation myocardial infarction (STEMI) equivalent and does not present like a typical STEMI on electrocardiogram. [ABSTRACT FROM AUTHOR]

Background Pump thrombosis is a serious complication of continuous-flow left ventricular assist device (CF-LVAD) therapy. In this study, we aim to report a novel protocol of an intermittent, low-dose, and slow infusion of tissue plasminogen activator (alteplase). Case summary We treated seven LVAD pump thrombosis events (HeartMate® II and HeartWare) in four patients with a median age of 52 years (31–63), and all were female. The protocol was applied from January 2015 to December 2018, and it consisted of an intermittent, low-dose, and slow infusion of systemic thrombolytic therapy in the intensive care unit. This therapy resulted in successful resolution of pump thrombosis in six out of seven events. Bleeding complication occurred in one patient, which included a ruptured haemorrhagic ovarian cyst and a small cerebellar intra-parenchymal haemorrhage. All patients were discharged home in a stable condition, except one patient who died during hospitalization because of severe sepsis, pump thrombosis with subsequent pump exchange, and multi-organ failure. Discussion A low-dose, prolonged, and systemic thrombolytic infusion protocol is an effective and relatively safe treatment that can lead to a sustained resolution of pump thrombosis with low bleeding complications and failure rates. [ABSTRACT FROM AUTHOR]