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Background: Having failed at least two pharmacotherapies, treatment-resistant depression (TRD) constitutes a major burden to healthcare in the US and globally, affecting close to a third of people diagnosed with depression in the US. Several studies have demonstrated the higher economic burden associated with TRD. This study sought to investigate changes in the availability of TRD somatic treatment options (Electroconvulsive therapy [ECT], Ketamine infusion therapy (KIT), and Transcranial Magnetic Stimulation [TMS]) in the US between 2014 and 2020 and the geographic variations in availability of TRD treatment options in the US as of 2020. Method: This study is a cross-sectional study of US mental health facilities providing TRD treatment options between 2014 and 2020. We used the 2014 to 2020 National Mental Health Services Survey (N-MHSS) data from the Substance Abuse and Mental Health Service Administration (SAMHSA). We estimated service availability per 100,000 US adults, both nationally and regionally, and computed a random-effect logistic regression to calculate the changes in the availability of the services over the study period. Result: Overall, availability of any one of ECT, KIT, or TMS in US mental health facilities declined between 2014 and 2019 (0.23 vs. 0.18 per 100,000 US adults) but increased to 0.24 in 2020. While availability of ECT consistently declined between 2014 and 2020, ketamine and TMS reportedly became available only in 2020. North Dakota, Wyoming, and Utah had the highest availability per 100,000 US adults (0.86, 0.67, and 0.65) while Nevada, Oregon and Georgia had the lowest availability (0.04, 0.06, and 0.06) regionally. Conclusion: The US had less than one mental health facility offering somatic treatment options for TRD per 100,000 US adults as of 2020. Also, the observed increase in the availability of somatic treatment options for TRD across the US between 2014 and 2020 did not reflect the increasing need for more treatment options for the treatment of TRD.

Pegvaliase, an injectable form of phenylalanine ammonia lyase, is an enzyme substitution therapy for adults with phenylketonuria (PKU). Experience with pegvaliase during lactation is scarce. Limited evidence suggests that pegvaliase does not pass into breast milk. The case presented here describes the pregnancy and lactation experience of a woman with PKU who was treated with pegvaliase prior to pregnancy, discontinued pegvaliase and was treated with a phenylalanine-restricted diet in preparation for and during pregnancy, and then reinstituted pegvaliase two weeks after giving birth and throughout lactation. No pegvaliase activity was detected in pumped breast milk samples prior to reinstituting pegvaliase, and at doses of 80, 110 and 140 mg/week during lactation. The phenylalanine content of breast milk samples collected during pegvaliase therapy were not significantly different than controls, and the infant has grown and developed normally, indicating that pegvaliase therapy during lactation is safe.

We present Boston Children's Hospital's clinic model for pegvaliase therapy in adults with phenylketonuria (PKU) and clinical outcomes in 46 patients over the first 1.5 years of commercial therapy. Approximately 70% (18/26) of patients starting pegvaliase achieved blood phenylalanine (Phe)

Fabry disease is an X-linked lysosomal storage disorder which often presents with renal, cardiac, gastrointestinal, and nervous system abnormalities. Available enzyme replacement therapies have demonstrated efficacy at significantly reducing elevated biomarkers associated with increased disease activity, while improving the clinical symptoms associated with Fabry disease. In two cases with classical Fabry disease, we demonstrate that the initiation of enzyme replacement therapy prior to the onset of overt clinical disease is well tolerated and effectively reduces elevated biomarkers, mitigating unnecessary organ damage that may occur prior to the onset of clinical manifestations of disease. This proactive approach should be considered as a best-practice management strategy which has the potential to significantly improve health outcomes in patients with classical Fabry patients, particularly in the context of newborn screening for Fabry disease. Keywords: Fabry disease, Enzyme replacement, Globotriaosylceramide, Pediatric

Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs) after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-α (mAKAPα) is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPα early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPα in the adult increased RGC death after optic nerve crush. Importantly, mAKAPα was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP) after injury. These results identify mAKAPα as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury.

This report describes a case in which bedside manipulation of an Impella CP led to device entanglement in the aorta. Using a snare and counter-traction, we were able to untangle and re-deliver it into the left ventricle to restore normal device support. (Level of Difficulty: Advanced.)