Rejected

Headache is the most frequent neurological symptom in childhood and the main reason for admission to pediatric emergency departments. The aim of this consensus document is to define a shared clinical pathway between primary care pediatricians (PCP) and hospitals for the management of children presenting with headache. For the purposes of the study, a group of hospital pediatricians and a group of PCP from the Emilia Romagna's health districts were selected to achieve consensus using the RAND/UCLA appropriateness method. Thirty-nine clinical scenarios were developed: for each scenario, participants were asked to rank the appropriateness of each option from 1 to 9. Agreement was reached if ≥75% of participants ranked within the same range of appropriateness. The answers, results, and discussion helped to define the appropriateness of procedures with a low level of evidence regarding different steps of the diagnostic-therapeutic process: primary care evaluation, emergency department evaluation, hospital admission, acute therapy, prophylaxis, and follow-up. The RAND proved to be a valid method to value appropriateness of procedures and define a diagnostic-therapeutic pathway suitable to the local reality in the management of pediatric headache. From our results, some useful recommendations were developed for optimizing the healthcare professionals' network among primary care services and hospitals.

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or postexertional symptom exacerbation. In a two-day model of PEM, submaximal exercise induced significant changes in activation of the dorsal midbrain during a high cognitive load working memory task (Washington 2020) (Baraniuk this issue). Controls had no net change. However, ME/CFS had increased activity after exercise, while GWI had significantly reduced activity indicating differential responses to exercise and pathological mechanisms. These data plus findings of the midbrain and brainstem atrophy in GWI inspired a review of the anatomy and physiology of the dorsal midbrain and isthmus nuclei in order to infer dysfunctional mechanisms that may contribute to disease pathogenesis and postexertional malaise. The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI.

Managing neurological emergencies is an essential element of emergency physicians' armamentarium, irrelevant of the specific nature of their practice. The combination of evolving literature and advances in imaging fuel the rapidly changing standards of care, especially in high-stakes diagnoses such as stroke. Navigating the emergency neurology literature to stay abreast of the current updates is becoming more challenging with the sheer volume of publications, combined with the recent dominance of COVID-19 on the literature and media attention. This review article summarizes emergency neurology literature updates that can help you improve your care of these high-risk presentations; articles covering stroke, dizziness, intracerebral hemorrhage, head trauma imaging, headache, seizures, and COVID-19 are reviewed.

Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX.

Vulvovaginal candidiasis (VVC) is one of the most frequent diseases induced by () during pregnancy, which results in enormous pain to women and their partners in daily life. Perillaldehyde (PAE), a natural monoterpenoid, has significant anti-microbial, anti-inflammatory and anti-oxidation effects. Reactive oxygen species (ROS) are key factors for the host to resist the invasion of fungi. However, excess ROS can cause additional damage independent of the pathogen itself, and the mechanism of ROS in VVC has not been investigated. In this murine study, we revealed that infection increased the expression of NADPH oxidase 2 (NOX2) and the content of malonaldehyde (MDA). inhibited the activity of antioxidant enzymes in the vagina, including superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase (HO-1), which were returned to normal levels after treatment with PAE. Furthermore, PAE inhibited the activities of Keap1 and promoted Nrf2 transfer from cytoplasm to nucleus, which were mediated by excessive accumulation of ROS in the VVC mice. In this study, we also indicated that PAE inhibited the apoptosis of vagina cells via Caspase 9- Caspase 7-PARP pathway and prevented the release of IL-1ꞵ in VVC mice. In summary, this study revealed that the treatment of VVC in mice with PAE might be mediated by inhibition of ROS, and established the therapeutic potential of PAE as an antifungal agent for the treatment of VVC.

Meta-analysis suggests that migraine patients are no more sensitive to experimentally evoked pain than healthy control subjects. At the same time, studies have linked some migraine symptoms to quantitative sensory testing (QST) profiles. Unfortunately, previous studies associating migraine symptoms and QST have important methodological shortcomings, stemming from small sample sizes, and frequent use of univariate statistics for multivariate research questions. In the current study, we seek to address these limitations by using a large sample of episodic migraine patients (n = 103) and a multivariate analysis that associates pain ratings from many thermal intensities simultaneously with 12 clinical measures ranging from headache frequency to sleep abnormalities. We identified a single dimension of association between thermal QST and migraine symptoms that relates to pain ratings for all stimulus intensities and a subset of migraine symptoms relating to disability (Headache Impact Test 6 and Brief Pain Inventory interference), catastrophizing (Pain Catastrophizing Scale), and pain severity (average headache pain, Brief Pain Inventory severity, and Short-Form McGill Pain Questionnaire 2). Headache frequency, allodynia, affect, and sleep disturbances were unrelated to this dimension. Consistent with previous research, we did not observe any difference in QST ratings between migraine patients and healthy control subjects. Additionally, we found that the linear combination of symptoms related to QST was modified by the mind-body therapy enhanced mindfulness-based stress reduction (MBSR+). These results suggest that QST has a selective relationship with pain symptoms even in the absence of between-subjects differences between chronic pain patients and healthy control subjects.

Laparoscopic surgery has many advantages over open surgery. At the same time, it is not without its risks. In this review, we discuss steps that could enhance the safety of laparoscopic surgery. Some of the important safety considerations are ruling out pregnancy in women of the childbearing age group; advanced discussion with the patient regarding unexpected intraoperative situations, and ensuring appropriate equipment is available. Important perioperative safety considerations include thromboprophylaxis; antibiotic prophylaxis; patient allergies; proper positioning of the patient, stack, and monitor(s); patient appropriate pneumoperitoneum; ergonomic port placement; use of lowest possible intra-abdominal pressure; use of additional five-millimetre (mm) ports as needed; safe use of energy devices and laparoscopic staplers; low threshold for a second opinion; backing out if unsafe to proceed; avoiding hand-over in the middle of the procedure; ensuring all planned procedures have been performed; inclusion of laparoscopic retrieval bags and specimens in the operating count; avoiding 10-15 mm ports for placement of drains; appropriate port closures; and use of long-acting local anaesthetic agents for analgesia. Important postoperative considerations include adequate analgesia; early ambulation; careful attention to early warning scores; and appropriate discharge advice.

Fenestration of the cervical segment of the internal carotid artery is a very rare finding, and its origin is still not fully understood. Explanations of its genesis range from dissections leading to the fenestration to the more common interpretation as a developmental vascular variant. However, most reported cases were symptomatic and presented with dissections, where even endovascular treatment of the fenestration of the cervical segment of the internal carotid artery became necessary. Here we report a case of a fenestration of the cervical segment of the internal carotid artery suffering a transitory ischemic attack and local pain in absence of any sign of dissection.