Outcomes of a Standardized Pain Pathway for Transgender Patients Undergoing Vaginoplasty and Vulvoplasty.

OBJECTIVE: To establish and evaluate a multimodal, opioid-minimizing pathway for gender-affirming vaginoplasty (GAVa) and vulvoplasty (GAVu) in treating postoperative pain. METHODS: A standardized pain pathway including opioids, non-opioid analgesics, and patient counseling was implemented at a single academic institution with a center for transgender care. Postoperative pain levels, analgesia methods, and opioid use for 84 GAVa and 64 GAVu patients were prospectively gathered during inpatient postoperative days 2-4 and outpatient follow-up at 2 weeks. Pertinent patient, operative, and medication administration data were extracted from patient charts and outpatient pain was measured with the Brief Pain Inventory short form (BPI-sf). RESULTS: On average, GAVa patients used 89.3 MME and GAVu patients used 41.8 MME during inpatient stay. MME decreased daily for both groups. There was no difference in MME between open and robotic GAVa. Forty-nine percent of GAVa patients and 54% of GAVu patients used ketorolac with decreasing daily inpatient use. Postoperative pain levels were similar between GAVa and GAVu patients. Fifty percent of respondents denied postoperative pain in the 24 hours preceding the survey. Forty-four percent of GAVa and of GAVu patients did not use any opioid medications in the outpatient setting, while 81% of GAVa and 83% of GAVu patients used fewer than 20 of 30 prescribed opioid tablets. Ibuprofen and acetaminophen were rated the most effective outpatient analgesics among GAVa and GAVu patients, respectively. CONCLUSION: The multimodal pathway demonstrated effective postoperative pain control for GAVa and GAVu patients while minimizing opioid use and has changed institutional prescribing practice.

Does oxidative DNA damage trigger histotoxic hypoxia via PARP1/AMP-driven mitochondrial ADP depletion-induced ATP synthase inhibition in Alzheimer's disease?

The low cerebral metabolic rate of oxygen despite the relatively preserved perfusion in Alzheimer's disease (AD) patients' medial temporal lobes suggest histotoxic hypoxia due to mitochondrial dysfunction that is independent of, but could precede, insulin resistance. Neuropathological, metabolomic, and preclinical evidence are consistent with the notion that this mitochondrial dysfunction may be contributed to by oxidative stress and DNA damage, leading to poly-(ADP-ribose)-polymerase-1 (PARP1) activation and consequent AMP accumulation, clogging of mitochondrial adenine nucleotide transporters (ANTs), matrix ADP deprivation, and ATP synthase inhibition. Complementary mechanisms may include mitochondrial-protein poly-ADP-ribosylation and mitochondrial-biogenesis suppression via PARPs outcompeting Sirtuin-1 (SIRT1) for nicotinamide-adenine-dinucleotide (NAD+).

Tibial artery duplex ultrasound-derived peak systolic velocities may be an objective performance measure after above-knee endovascular therapy for arterial stenosis.

OBJECTIVE: The ankle-brachial index (ABI) is a well-established measure of distal perfusion in lower extremity ischemia; however, the ABI is of limited value in patients with noncompressible lower extremity arteries. We sought to demonstrate whether duplex ultrasound-determined tibial artery velocities can be used as an alternative to ABI as an objective performance measure after endovascular treatment of above-knee arterial stenosis. METHODS: Thirty-six patients undergoing above-knee endovascular intervention had preprocedure and postprocedure duplex ultrasound examination within 6 months of intervention. Preprocedure vs postprocedure changes in tibial artery mean peak systolic velocity (PSV; mean of proximal, mid, and distal velocities) were compared with changes in ABI and a reference (control) cohort of 68 patients without peripheral vascular disease. RESULTS: Thirty-six patients (41 limbs) had an above-knee endovascular intervention and had preprocedure and postprocedure duplex ultrasound examinations of the ipsilateral extremity including the tibial arteries. Before the procedure, mean tibial artery PSVs in the 36 patients undergoing intervention were outside (below) the 95% confidence intervals for the control patients. In comparing preprocedure and postprocedure PSVs, the mean anterior tibial (P < .01), mean peroneal (P < .01), and mean posterior tibial (P < .01) PSVs all increased and correlated with an increase in ABI (P < .01). After endovascular intervention, duplex ultrasound-derived mean PSVs fell within or near established reference ranges for patients without peripheral arterial disease. Mean tibial artery PSV increases were similar in patients with and without noncompressible vessels. CONCLUSIONS: Tibial artery PSVs increase, correlate with an increase in ABI, and fall within or near confidence intervals for normal controls after above-knee endovascular interventions. After endovascular intervention, tibial artery PSVs can supplement ABI as an objective performance measure in patients with and in particular without compressible tibial arteries.