Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.

BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Relations between obstructive sleep apnea syndrome and specific cephalometric measurements, body mass index, and apnea-hypopnea index.

PURPOSE: To evaluate the relation of specific cephalometric landmarks, body mass index, and the apnea-hypopnea index in patients diagnosed with obstructive sleep apnea syndrome (OSAS) and treated with functional upper airway surgery. MATERIALS AND METHODS: This was a retrospective cohort analysis of 89 consecutive patients over a 3-year period diagnosed with overnight-attended polysomnogram-confirmed OSAS who underwent functional upper airway surgery. Five predetermined specific cephalometric parameters were analyzed: posterior airway space, soft palate length, hyoid to mandibular plane angle, sella-nasion to mandibular plane angle, and gonion to gnathion length. Simple and multiple linear regression analyses were used to establish a relation between independent and dependent variables. RESULTS: There were no statistically significant associations between the 5 specific cephalometric craniofacial structures in combination with other potential confounders, body mass index and apnea-hypopnea index, and the presence of OSAS. CONCLUSIONS: No one skeletal or soft tissue parameter can be directly linked to OSAS.

Clinical foundation for efficient treatment of obstructive sleep apnea.

Only a few decades ago, the entity known as obstructive sleep apnea (OSA) was unknown and untreated. Now, there is a rush to put literally millions of Americans on continuous positive airway pressure devices. Community practice standards are changing yearly under pressure from strong forces based on economic incentives for industry, government, and physicians, independent of the actual medical evidence supporting treatment and efficacy. Medicare has lowered the diagnostic threshold for diagnosis and reimbursement; the International Classification of Sleep Disorders, Revision 2 (2005) has allowed OSA to be diagnosed exclusively by a laboratory test without the patient having clinical symptoms of excessive daytime sleepiness; and industry is poised to have the public buy computer-assisted continuous positive airway pressure machines without need of a physician prescription. Because of this paradigm shift away from physician-directed diagnosis and treatment, this article will critically evaluate the present state of medical evidence regarding the clinical foundation for treatment of OSA.

Combined open rhinoplasty with spreader grafts and laser-assisted uvuloplasty for sleep-disordered breathing: long-term subjective outcomes.

PURPOSE: To subjectively assess the long-term outcomes of combined functional open rhinoplasty with spreader grafts and laser-assisted uvuloplasty (LAUP) for polysomnogram (PSG)-confirmed sleep-disordered breathing (SDB). METHODS: Postoperative Epworth Sleepiness Scale (ESS) questionnaires were given to 30 patients and compared with preoperative ESS. Patients were also asked questions concerning postoperative improvement in upper airway breathing, nasal appearance, and snoring. Statistical analysis used 2-tailed parametric and nonparametric tests. RESULTS: Thirty patients (average age 55 years) with an average (+/- standard deviation) preoperative apnea-hypopnea index (AHI) of 37 +/- 27 and mean follow-up times of 21 months were evaluated. A statistically significant 50% (P < .001) postoperative decrease in average ESS was observed. Patients with severe (AHI > 30) and very severe obstructive sleep apnea (OSA) (AHI > 60) also had statistically significant (61% and 66%, respectively, P < .001) postoperative decreases in average ESS. In all patients, subjective upper airway breathing was statistically improved (P < .008), graded as significantly in 47% and moderately in 33% of patients. According to the patient's bed partner, snoring was improved and/or decreased in 76% of patients (P = .008). All patients were satisfied with the postoperative cosmetic appearance of their nose (P < .0001). Finally, 90% of patients stated that they would have the procedure again (P = .009) and 90% stated that they would recommend the procedure to a friend or relative with the same condition (P = .009). CONCLUSION: Subjective assessment at long-term follow-up for combined open rhinoplasty with spreader grafts and LAUP for PSG-confirmed SDB produced a statistically significant decrease in excessive daytime sleepiness, even in patients with very high AHI, with high patient satisfaction.

Primarily generalized seizures are more effective than partial seizures in arousing patients from sleep.

The purpose of this study was to determine the characteristics of generalized and partial seizures which awaken patients from sleep, using a retrospective review of intracranial EEG recordings in 8017 electrographic and 7571 clinical seizures in 172 patients undergoing evaluation for epilepsy brain surgery. Seizure onset during sleep followed by awakening occurred in 99% of 308 seizures in 22 patients during daytime naps. Four events consisted of spontaneous awakening followed by the seizure. In contrast electrographic seizures almost never awakened the patient if they were partial in onset (0.02% temporal, 0% frontal), but did so 26% of the time if they were generalized (p < 0.001). Conversely, generalized clinical seizures awakened the patient only 0.3% of the time (p < 0.001) versus 3% for temporal and 6% for frontal lobe. Partial and generalized seizures differ during sleep. Partial seizures do not awaken until they propagate outside the lobe and evolve into a clinical seizure. Generalized seizures when only electrographic, include wake-regulating structures at their onset (presumably thalamus, hypothalamus, brainstem). Our results suggest that rather than sleep transitions being a facilitatory cause of seizures, seizures awaken us from sleep via endogenous stimulation of the brain's sleep/wake structures. This pathway information may be relevant to planning epilepsy brain surgery.

Photonegative response in brown planaria (Dugesia tigrina) following regeneration.

The photonegative response was investigated in regenerated brown planaria (Dugesia tigrina). Old, middle, and young animals were tested, bisected into heads and tails, and allowed to regenerate. Different regeneration times affected function, with generally older planaria achieving full functionality of the photonegative response before younger planaria. Counterintuitively, the heads of the middle and young lost this function initially (despite only needing to regenerate their tails) and regained it over time. The size of the animal was not a factor in the photonegativity response. The biological basis for the photonegative response is complex, requiring nervous and locomotive system function and integration. Using the heads from young planaria may serve as a model in aging, degenerative diseases, or environmental toxins.