Rejected

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiologic diagnosis that affects children and adolescents, but it is much more frequently reported in adults. Clinically, patients present with severe and commonly recurrent thunderclap headaches. Typical precipitating triggers include vasoactive substances, serotonergic agents, and the postpartum period. There may be associated neurologic complications at presentation or in the weeks following, such as convexity subarachnoid hemorrhage, stroke, cerebral edema, cervical artery dissection (CeAD), and seizures. Angiographically, the cerebral arteries demonstrate segmental vasoconstriction and dilation, although imaging early in the clinical course may be normal. Work-up is performed to exclude intracranial disorders such as vasculitis, subarachnoid hemorrhage due to ruptured aneurysm, meningitis, and intracranial venous sinus thrombosis. Within 1 month of initial symptom onset, clinical symptoms such as severe headache have ceased, and within 3 months, the cerebral vasoconstriction is much improved or resolved. Management involves avoidance of precipitating triggers and potentially short-term pharmacotherapy with calcium channel blockers for patients with associated neurologic complications. Steroids are not recommended and may worsen the clinical outcome. Prognosis is excellent in the large majority of patients, and only 5% of patients experience a recurrence of RCVS.

Background Gabapentinoids are known to reduce neuropathic pain. The aim of this experimental study was to investigate whether gabapentinoids exert anti-inflammatory and/or anti-nociceptive effects at the cellular level using primary cultures of rat dorsal root ganglia (DRG). Methods Cells from rat DRG were cultured in the presence of gabapentin or pregabalin, and we tested the effects of subsequent stimulation with lipopolysaccharide (LPS) on the expression of genes (real-time polymerase chain reaction) and production of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) by specific bioassays. Using Ca2+ imaging, we further investigated in neurons the effects of gabapentinoids upon stimulation with the TRPV-1 agonist capsaicin. Results There is a small influence of gabapentinoids on the inflammatory response to LPS stimulation, namely, a significantly reduced expression of IL-6. Pregabalin and gabapentin further seem to exert a moderate inhibitory influence on capsaicin-induced Ca2+ signals in DRG neurons. Conclusions Although the single inhibitory effects of gabapentinoids on inflammatory and nociceptive responses are moderate, a combination of both effects might provide an explanation for the proposed function of these substances as an adjuvant for the reduction of neuropathic pain.

Quality of life (QoL) is one of the most important health outcome concepts expressed subjectively. Chronic pain (CP) is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Taking into account the poor QoL and the CP already described in metabolic syndrome (MSy) individuals, this study aimed to evaluate the effects of WBVE on these parameters in this population. Thirty-three MSy patients were divided in subgroup A (WBVeG, n=17, 15 females/02 males, 61.1±8.4 yrs) and B (control group, CG, n=16, 14 females/02 males, 58.2±9.1 yrs). The subgroup A performed 10 sessions (twice per week) of WBVE (18 minutes/each session, with a frequency from 5 up to 14 Hz and a peak to peak displacement (PPD) of 2.5, 5.0 and 7.5 mm) on the side alternating vibrating platform (VP) (Novaplate, Fitness Evolution ®, São Paulo, Brazil). The subgroup B did the same protocol, but the VP was turned off. The individuals answered the World Health Organization Quality of Life bref (WHOQoL-bref) questionnaire, before the first and after the 10 session. The CPL was measured by a numeric rating scale (NRS) (0-10), before and at the end of each session. Significant improvements were found in physical health (=0.05) and psychological health (=0.04) domains of WHOQoL-bref in WBVeG. A significant acute reduction of the CPL was found in the WBVeG after the protocol, considering the first session (FS) and at the last session (LS). WBVE marginally improved physical health and psychological health and decrease the CPL in acute interventions.

Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences, but leading to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about ten-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high resolution crystal structures of the 5-HT1B receptor with both ligands have been solved, the high similarity between these two complex structures does not sufficiently explain their activity differences and the activation mechanism of the receptor. Hence, an examination of the dynamic motion of both drugs with the receptor is required. In this study, we ran a total of 6.0 µs molecular dynamics simulations on each system. Our simulation data show the subtle variations between the two systems in terms of the ligand-receptor interactions and receptor secondary structures. More importantly, the ligand and protein root-mean-square fluctuations (RMSF) for the two systems were distinct, with ERG having a trend of lower RMSF values, indicating it to be bound tighter to 5-HT1B with less fluctuations. The Molecular Mechanism-General Born Surface Area (MM-GBSA) binding energies further illustrate this, as ERG has an overall stronger MM-GBSA binding energy. Analysis of several different micro-switches has shown that the 5-HT1B-ERG complex is in a more active conformation state than 5-HT1B-DHE, which is further supported by the dynamic network model, reference to mutagenesis data with the critical nodes and the first three low energy modes from the normal mode analysis. We also identify Trp3276.48 and Phe3316.52 as key residues involved in the active state 5-HT1B for both ligands. Using the detailed dynamic information from our analysis we made predictions for possible modifications to DHE and ERG that yielded 5 derivatives that might have more favorable binding energies and reduced structural fluctuations.

Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behavior and the presence of pruriginous nodules. A comprehensive understanding of this condition, especially regarding its clinical characteristics and impact on quality of life is still lacking.

Cutaneous adverse events (AE) are the most prevalent toxicity under checkpoint-inhibitors in clinical trials. In "real-life" conditions of use, skin toxicities under anti-PD-1 have not been described to date in a large cohort. The objective of this study was to determine the clinical features of skin toxicities in patients with advanced melanoma receiving anti-PD-1 therapy under "real-life"-conditions of use. Secondary objectives were to evaluate the characteristics of patients with skin toxicities and to analyze associated extra-cutaneous toxicities, progression-free-survival (PFS) and overall-survival (OS).

Hidradenitis suppurativa (HS) is a chronic skin disease with point prevalence between 1% and 4%, characterized by recurrent inflammation and painful formation of nodules in the intertriginous areas of the skin. In some patients, these lesions progress into the formation of abscesses and/or tunnels, ultimately causing restrictive scaring, and health-related quality of life impairment. Growing evidence suggests that the primary event is infundibular hyperkeratosis at the terminal follicles causing follicle dilatation and perifollicular inflammation followed by cyst formation. However, the exact aetiology of HS is still unknown, but likely multifactorial with involvement of genetic and immunological factors.

Pelvic inflammatory diseases (PID) must be suspected when spontaneous pelvic pain is associated with induced adnexal or uterine pain (grade B). Pelvic ultrasonography is necessary to rule out tubo-ovarian abscess (TOA) (grade C). Microbiological diagnosis requires endocervical and TOA sampling for molecular and bacteriological analysis (grade B). First-line treatment for uncomplicated PID combines ceftriaxone 1 g, once, IM or IV, doxycycline 100 mg ×2/day, and metronidazole 500 mg ×2/day PO for 10 days (grade A). First-line treatment for complicated PID combines IV ceftriaxone 1 to 2 g/day until clinical improvement, doxycycline 100 mg ×2/day, IV or PO, and metronidazole 500 mg ×3/day, IV or PO for 14 days (grade B). Drainage of TOA is indicated if the pelvic fluid collection measures more than 3 cm (grade B). Follow-up is required in women with sexually transmitted infections (STIs) (grade C). The use of condoms is recommended (grade B). Vaginal sampling for microbiological diagnosis is recommended 3 to 6 months after PID (grade C), before the insertion of an intrauterine device (grade B), and before elective termination of pregnancy or hysterosalpingography. When specific bacteria are identified, antibiotics targeted at them are preferable to systematic antibiotic prophylaxis.

Improved patient outcomes and satisfaction associated with enhanced recovery after surgery protocols have increasingly replaced traditional peri-operative anesthesia care. Fast-track surgery pathways have been extensively validated in patients undergoing hysterectomies, yet impact on fertility-sparing laparoscopic gynecologic operations, particularly those addressing chronic pain conditions, has not been examined.