Pipecolic Acid, a Putative Mediator of the Encephalopathy of Cerebral Malaria and the Experimental Model of Cerebral Malaria.

BACKGROUND: We explored a metabolic etiology of cerebral malaria (CM) coma. METHODS: Plasma metabolites were compared between Malawian children with CM and mild Plasmodium falciparum malaria. A candidate molecule was further studied in animal models of malaria. RESULTS: Clinically abnormal concentrations of pipecolic acid (PA) were present in CM plasma, and nearly normal in mild malaria samples. PA is renally cleared and the elevated PA blood levels were associated with renal insufficiency, which was present only in CM subjects. Prior studies demonstrate that PA has neuromodulatory effects and is generated by malaria parasites. PA brain levels in Plasmodium berghei ANKA-infected animals in the experimental cerebral malaria (ECM) model inversely correlated with normal behavior and correlated with blood-brain barrier (BBB) permeability. Mice infected with malaria species that do not induce neurological abnormalities or manifest BBB permeability had elevated plasma PA levels similar to ECM plasma at 7 days postinfection; however, they had low PA levels in the brain compared to ECM mice brains at 7 days postinfection. CONCLUSIONS: Our model suggests that malaria-generated PA induces coma in CM and in ECM. The role of BBB permeability and the mechanisms of PA neuromodulation in CM will require additional investigation.

Antibodies to PfsEGXP, an Early Gametocyte-Enriched Phosphoprotein, Predict Decreased Plasmodium falciparum Gametocyte Density in Humans.

Background: Antigametocyte-specific immune responses may regulate Plasmodium falciparum gametocyte density, providing the rationale for pursuing transmission-blocking vaccines (TBVs) that target gametocytes in the human host. Methods: To identify novel antigametocyte TBV antigens, we interrogated the gametocyte proteome with our whole proteome differential screening method using plasma from a treatment-reinfection study conducted in western Kenya. At the start of the high-transmission season, 144 males (12-35 years) were enrolled and treated with quinine and doxycycline, peripheral venous blood samples were obtained, volunteers were observed, and weekly blood films were obtained for 18 weeks to quantify gametocytemia. Using plasma pooled from individuals with low versus high gametocyte carriage, we differentially screened a P falciparum gametocyte stage complementary deoxyribonucleic acid expression library. Results: We identified 8 parasite genes uniquely recognized by gametocyte-resistant but not by gametocyte-susceptible individuals. Antibodies to one of these antigens, PfsEGXP, predicted lower gametocytemia measured over the 18-week transmission season (P = .021). When analyzed dichotomously, anti-PfsEGXP responders had 31% lower gametocyte density over 18 weeks of follow-up, compared with nonresponders (P = .04). Conclusions: PfsEGXP is one of the first reported gametocyte-specific target of antibodies that predict decreased gametocyte density in humans and supports our novel TBV antigen discovery platform.

Short-Term Reported Urologic Adverse Events Following COVID-19 Immunization: A Vaccine Adverse Event Reporting System Analysis.

INTRODUCTION: Medical misinformation regarding COVID-19 immunization remains rampant and a public concern, and as such, there is a need for national studies evaluating the immunization's safety profile. We sought to quantify and analyze urologic adverse events and symptoms after COVID-19 immunization, compare these events reported between COVID-19 vaccine types, and compare these events reported following COVID-19 immunization relative to those reported following other immunizations. METHODS: We conducted a retrospective case-control disproportionality analysis by querying the Food and Drug Administration Vaccine Adverse Event Reporting System for all reported symptoms following COVID-19 immunization through December 23, 2022, as well as for all non-COVID immunizations. RESULTS: Using a total of 704,231 event reports containing 2,982,187 symptoms related to COVID vaccination and a total of 770,975 event reports containing 2,198,993 symptoms related to all vaccinations other than COVID-19 for disproportionality analysis, no urologic symptom produced a positive signal when grouping all vaccinations. When stratifying by manufacturer, some symptoms related to Janssen vaccination were positive, but this may be in part due to overreporting secondary to media attention rather than a strong association between Janssen vaccination and urologic adverse events. CONCLUSIONS: Although there have been anecdotal reports of adverse events associated with the COVID-19 vaccine, our review of the Vaccine Adverse Event Reporting System database did not produce positive signals across all 4 measures for any potential adverse event. Our findings do not suggest increased scrutiny is required regarding these adverse events potentially related to the COVID-19 immunization. Further evaluation and analysis of the COVID-19 immunization is ongoing.

Cochlear Implants: What the Neurosurgeon Needs to Know.

Patients with cochlear implants (CIs) commonly undergo neurosurgical interventions for concurrent pathologies. The neurosurgeon must be aware of the limitations these devices place on treating these patients and all pertinent interactions CIs have with common neurosurgical instruments and procedures. A literature search was performed utilizing the terms "cochlear implant" and "neurosurgery" or "neurosurgical" and all associated iterations. We reviewed the abstracts of 146 generated reports and eight published papers discussing the interaction and limitations of CI use in different neurosurgical procedures. Five realms were identified in which a CI may potentially interfere with standard neurosurgical care: Magnetic resonance imaging (MRI), radiotherapy, deep brain stimulation (DBS), intraventricular shunt placement, and intraoperative neuromonitoring (IONM). First, MRI use with CIs is limited due to thermal injury risk, imaging disruption, and implant damage. Secondly, high-dose >50 Gy single-fraction linear accelerator-based radiosurgery has been demonstrated to result in a loss of radio frequency link range in CIs, interfering with their function. Next, during surgery for DBS, the need for MRI and microelectrode recording requires CI magnet removal by neurotology and the surgeon must communicate with a non-hearing patient. Tunneling of shunts must accommodate CI position retroauricularly, if ipsilateral, and programmable valves must be placed >2 cm from the CI to prevent interference. Intraoperative neuromonitoring may produce voltages that interfere with CIs, and while monopolar cautery may pose the same risk, no study has proven this to date. Generally, bipolar cautery is safe and favored >1 cm from CIs. MRI use is limited in CI patients, although MRI-safer devices are in production. DBS electrodes may be successfully placed after CI magnet removal. Programmable shunt valves may be placed >2 cm away from CIs and radiosurgery <50 Gy has not demonstrated harm to these devices. IONM and monopolar cautery have not been demonstrated to directly affect CIs; however, more research is needed.

Cement Augmentation of Two-Level Lumbar Corpectomy Cage After Malposition: A Novel Salvage Procedure Technical Note.

Intervertebral cage mispositioning is an uncommon complication of a posterior lumbar corpectomy. Most frequently, cages are placed obliquely, laterally, or protruding. However, there are few reports of implanted cages that fail to contact the adjacent vertebral endplate and thus no descriptions of successful revisions. The objective of this case report is to report a unique case of minimally invasive rescue vertebroplasty with cement augmentation following a lumbar corpectomy that resulted in graft-endplate noncontact in a medically complicated patient A 60-year-old male with a history of active intravenous (IV) drug use, untreated hepatitis C virus (HCV) infection, and chronic malnourishment presented with low back pain. He had a history of vertebral osteomyelitis managed with intravenous antibiotics, although he was noncompliant with infusions. The diagnosis of L2-L3 discitis-osteomyelitis with intradiscal abscess causing cord compression was made using inpatient lumbar imaging. The initial intervention was accomplished with L2 and L3 vertebral corpectomy with decompression and expandable cage placement as well as a T10-pelvis posterior fixation. Despite the resolution of presenting symptoms, routine postoperative radiographs identified noncontact between the inferior surface of the cage and the superior endplate of the L4 vertebral body. Salvage therapy was pursued via fluoroscopy-guided vertebroplasty with cement augmentation to correct cage malposition. Secondary surgical intervention was successful in bringing the intervertebral cage into contact with the adjacent vertebral body. Lower extremity strength improved, and back pain was resolved. The postoperative motor examination remained unchanged after the rescue procedure. Accurate intraoperative cage placement can be difficult in patients with poor bone quality, especially in the setting of ongoing infection and cachexia. For this reason, routine postoperative imaging is crucial to assessing graft complications. In patients who are poor candidates for revision surgery, we demonstrate that an interventional radiology-based approach may be successful in correcting cage mispositioning and preventing further changes during healing and fusion.

Shoulder arthroplasty in dwarfism: A case report of pseudoachondroplasia with 17-year follow-up.

The purpose of this case report is to report the long-term outcome following shoulder hemiarthroplasty in a patient with dwarfism. A 60-year old female with pseudoachondroplasia dwarfism presented 17 years post-operative with a Subjective Shoulder Value of 90% and minimal pain. Custom designed implants were critical for surgical success. Preoperative planning with a CT scan was important in assessing glenoid dysplasia and determining the feasibility of glenoid resurfacing. The emergence of 3D CT virtual preoperative planning tools can further assist in the recognition of deformity to determine if custom designed implants are needed. Shoulder arthroplasty in dwarfism can lead to excellent long-term outcomes.