Pembrolizumab-Induced Pancreatitis: Take It With a Grain of Salt.

Keytruda (pembrolizumab) is an immunomodulator that prevents the interaction between programmed cell death protein (PD-1) and programmed death ligand (PD-L1/2) on immune cells and tumour cells, thereby preventing T cell dysfunction. At times, mounting a strong immune response against tumour cells may not spare normal cells, leading to a variety of multisystemic adverse effects. With this, we present a case of a 64-year-old male who developed acute pancreatitis after completing eight cycles of Keytruda for castrate-resistant metastatic prostate cancer for six months, after all other causes of pancreatitis were excluded.

Trolox aids coenzyme Q10 in neuroprotection against NMDA induced damage via upregulation of VEGF in rat model of glutamate excitotoxicity.

Glutamate induced damage to retinal ganglion cells (RGCs) requires tight physiological regulation of the N-methyl-D-aspartate (NMDA) receptors. Previously, studies have demonstrated the neuroprotective abilities of antioxidants like coenzyme Q10 (CoQ10) and vitamin E analogs like α-tocopherol against neuropathies resulting from NMDA insult, but have failed to shed light on the effect of CoQ10 and trolox, a hydrophilic analog of vitamin E, on glaucomatous neurodegeneration. In the current study, we wanted to investigate whether the combined effect of trolox with CoQ10 could alleviate NMDA-induced death of retinal cells while also trying to elucidate the underlying mechanism in relation to the yet unexplained role of vascular endothelial growth factor (VEGF) in NMDA-mediated excitotoxicity. After successful NMDA-induced degeneration, we followed it up with the treatment of combination of Trolox and CoQ10. The structural damage by NMDA was repaired significantly and retina retained structural integrity comparable to levels of control in the treatment group of Trolox and CoQ10. Detection of ROS generation after NMDA insult showed that together, Trolox and CoQ10 could significantly bring down the high levels of free radicals while also rescuing mitochondrial membrane potential (MMP). A significant increase in NMDA receptor Grin2A by CoQ10 alone as well as by CoQ10 and trolox was accompanied by a lowered Grin2B receptor expression, suggesting neuroprotective action of Trolox and CoQ10. Subsequently, lowered VEGFR1 and VEGFR2 receptor expression by NMDA treatment also recovered when subjected to combined treatment of Trolox and CoQ10. Western blot analyses also indicated the same whereby Trolox and CoQ10 could increase the diminished levels of phosphorylated VEGFR2. Immunofluorescence studies also indicated a positive correlation between recovered VEGFR2 and NMDAR2A levels and diminished levels of NMDAR2D, confirming the results obtained by RT-PCR analysis. This is the first report in our knowledge that demonstrates the efficacy of trolox in combination with CoQ10 highlighting the importance of maintaining VEGF levels that are lowered in ocular diseases due to NMDA-related toxicities.

Navigating the Storm: Managing Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) in a High-Risk Pregnancy.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare, life-threatening condition causing significant thrombocytopenia and bleeding with the risk of developing intracerebral hemorrhage (ICH). It results from maternal immunizations against fetal platelet antigens. Here, we report a case of a pregnant patient at 30 weeks gestation who presented to the hospital with a low platelet count of 90 th/mm3 and was found to have anti-human platelet antigen (HPA) 1a, 2b antibodies. She was treated with a weekly infusion of IV immunoglobulins. However, her condition was complicated by the development of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which was treated promptly with a platelet transfusion and intravenous magnesium. Even though the child had severe thrombocytopenia and its associated complications, there were no signs of post-delivery thrombocytopenia or any other adverse effects. This case report highlights the importance of the antenatal management of the FNAIT to prevent severe fetal complications, such as ICH.

Insulin like growth factor-1 works synergistically with dopamine to attenuate diabetic retinopathy by downregulating vascular endothelial growth factor.

AIM: Levels of Insulin-like growth factor-1 (IGF-1), a proangiogenic growth factor is elevated and dopamine downregulated in proliferative diabetic retinopathy (PDR). This study aims to investigate whether IGF-1 with dopamine can together modulate vascular endothelial growth factor (VEGF) to prevent proliferative diabetic retinopathy while also attenuating angiogenic effects of IGF-1. METHODS: Effect of combination of levodopa L-Dopa with IGF-1 was tested on normal retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cells (HUVEC), followed by tube formation. Invivo analysis of anti-angiogenic potential assessed by chick chorioallantoic membrane (CAM) assay. Diabetes induction in wistar rats at two time points, 12 and 16 weeks, treated with L-Dopa+IGF-1 and analysed for morphological variations, serum and tissue dopamine levels, gene expression by real-time PCR and western blot assay. RESULTS: L-Dopa+IGF-1 on ARPE-19 cells caused no toxicity and worked synergistically. Reduced number of vessels observed. Significant improvement in inner retina thickness (*p < 0.05) was observed when L-Dopa was given alone and/or with IGF-1. Dopamine levels improved significantly in both serum and tissue (*p < 0.05). Levels of VEGF and IGF-1 receptors reduced significantly in 12 weeks. Western studies suggest that L-Dopa+IGF-1 modulates its effects via Akt/ERK dependent pathway. CONCLUSION: First ever report on synergistic effect of L-Dopa+IGF-1 in a rat model of diabetic retinopathy. Even though the effect of L-Dopa in combination with IGF-1 is comparable to levels of L-Dopa alone, this study presents an interesting finding of neuroprotective function of IGF-1, which has been studied in disease models of Parkinson's but not diabetes.