Rejected

Barrett's Esophagus is a common condition associated with chronic gastroesophageal reflux disease. It is well known that it has an association with a higher incidence of esophageal adenocarcinoma, but this neoplastic transformation is first preceded by the onset of low and high-grade dysplasia. The evaluation of low grade dysplastic esophageal mucosa is still controversial; although endoscopic surveillance is preferred, several minimally invasive endoscopic therapeutic approaches are available. Endoscopic mucosal resection and radiofrequency ablation are the most used endoscopic treatments for the eradication of low-grade dysplasia, respectively, for nodular and flat dysplasia. Novel endoscopic treatments are cryotherapy ablation and argon plasma coagulation, that have good rates of eradication with less complications and post-procedural pain.

Extratubal secondary trophoblastic implants following laparoscopic salpingectomy is an extremely rare form of persistent ectopic pregnancy. These cases usually result in a small amount of vaginal bleeding and sudden lower abdominal pain thereby presenting with hemoperitoneum in emergencies. Owing to the urgency of hemoperitoneum and the uncertainty of the location of persistent ectopic pregnancy after laparoscopic salpingectomy, the risk of reoperation is increased. It is necessary to prevent in first surgery and diagnose these cases in the early following up phase. We report a case of 26-year-old woman, gravida 3, para 0, presenting a little vaginal bleeding and slight lower abdominal pain after laparoscopic bilateral salpingectomy for more than 1 month. The patient's serum β-HCG was still high (3981 mIU/ml), and no abnormalities were found through auxiliary examination (ultrasound, abdominal CT, and pelvic MRI). Finally, emergency laparoscopy revealed many blue purple nodules on the surface of ovaries, small intestine, omentum, and periumbilical peritoneum, with a diameter of 3-20 mm. The lesions were completely removed as far as possible. Pathology showed trophoblastic proliferation and β-HCG soon decreased to negative after this operation. Therefore, it is important to follow up serum β-HCG even after salpingectomy and avoid iatrogenic dissemination of trophoblast tissue through careful operation.

Homocysteine is a sulfur-containing endogenous amino acid leading to neurotoxic effects at high concentrations. Population studies suggest an association between plasma homocysteine levels and the risk of migraine headaches. The aim of this study was to analyze the sensitivity of rats with prenatal hyperhomocysteinemia (hHCY) in respect of the development of behavioral correlates of headache and spreading cortical depolarization (CSD) in a migraine model induced by the administration of the nitric oxide (NO) donor nitroglycerin. Animals with hHCY were characterized by migraine-related symptoms such as mechanical hyperalgesia, high-level anxiety, photophobia, as well as an enhanced level of neuronal activity in the somatosensory cortex along with a lower threshold of CSD generation. Likewise, acute or chronic intermittent administration of nitroglycerin also induced the development of mechanical allodynia, photophobia and anxiety in control groups. However, these symptoms were more pronounced in rats with hHCY. Unlike hHCY, nitroglycerin administration did not affect the threshold of CSD generation, but like hHCY, increased the background neuronal activity in layers 2/3 and 4 of the cerebral cortex. The latter was more pronounced in animals with hHCY. Thus, the migraine profile associated with hHCY can be further exaggerated in conditions with enhanced levels of migraine triggering the gaseous transmitter NO. Our data are consistent with the view that high levels of plasma homocysteine can act as a risk factor for the development of migraine.

Inflammatory bowel disease (IBD) is characterized as chronic inflammation in the gastrointestinal tract, which includes two main subtypes, Crohn's disease and ulcerative colitis. Endoscopy combined with biopsy is the most effective way to establish IBD diagnosis and disease management. Imaging techniques have also been developed to monitor IBD. Although effective, the methods are expensive and invasive, which leads to pain and discomfort. Alternative noninvasive biomarkers are being explored as tools for IBD prognosis and disease management. This review focuses on novel biomarkers that have emerged in recent years. These serological biomarkers and microRNAs could potentially be used for disease management in IBD, thereby decreasing patient discomfort and morbidity.

A 30-year-old male diagnosed three years previously with reversible cerebral vasoconstriction syndrome (RCVS) presented to the department of neurology with an accumulation of attacks mimicking previous RCVS attacks and fulfilling the diagnostic criteria for RCVS after receiving the first Pfizer COVID-19 vaccine. The neurologic exam, blood samples, electrocardiogram (ECG), and computer tomography of the head (CTC) were normal. The patient was treated with the angiotensin 2 receptor antagonist, losartan, with a good response and was discharged with a prescription for losartan lasting until three days after the second Pfizer COVID-19 vaccine. No further RCVS attacks were reported. These findings indicate that the COVID-19 vaccine might induce RCVS attacks in susceptible individuals, and targeting the angiotensin 2 receptor could be a preventive option.

The opioid agonist hydromorphone is indicated for the management of severe acute and chronic pain given that alternate treatments are insufficient. While the genotoxicity profile of hydromorphone is well investigated, little is known about the genotoxic potential of its impurities. In this study, 2,2-bishydromorphone was tested and for both its mutagenic potential in an Ames test performed with and tester strains up to a maximum concentration of 5 mg per plate in the absence and presence of metabolic activation. Furthermore, it was tested for its ability to induce micronuclei in TK6 cells in a micronucleus test up to a maximum concentration of 500 µg/mL with or without an exogenous metabolic activation system. 2,2-Bishydromorphone did not reveal any potential for inducing mutagenicity or clastogenicity under the conditions of the respective tests and is therefore considered non-mutagenic and non-clastogenic/aneugenic . These results are in line with negative  quantitative structure-activity relationship (QSAR) prediction for 2,2-bishydromorphone mutagenicity and clastogenicity and provide evidence of good correlation of and in data. Conclusively, these studies add important new clinically relevant information on the safety of hydromorphone as the impurity of 2,2-bishydromorphone is proven to be non-mutagenic and non-clastogenic.

Saffron is the most expensive spice in the world. In addition to its culinary utilization, this spice is used for medicinal purposes such as in pain management. In this study, the analgesic activity of stigma extract (CSSE) was evaluated in rodents and its possible physiological mechanism was elucidated. The anti-nociceptive effect of CSSE was evaluated using three animal models (hot plate, writhing, and formalin tests). The analgesic pathways involved were assessed using various analgesia-mediating receptors antagonists. The oral administration of CSSE, up to 2000 mg/kg, caused no death or changes in the behavior or in the hematological and biochemical blood parameters of treated animals nor in the histological architecture of the animals' livers and kidneys. CSSE showed a central, dose-dependent, anti-nociceptive effect in response to thermal stimuli; and a peripheral analgesic effect in the test of contortions induced by acetic acid. The dual (central and peripheral) analgesic effect was confirmed by the formalin test. The anti-nociceptive activity of CSSE was totally or partially reversed by the co-administration of receptor antagonists, naloxone, atropine, haloperidol, yohimbine, and glibenclamide. CSSE influenced signal processing, by the modulation of the opioidergic, adrenergic, and muscarinic systems at the peripheral and central levels; and by regulation of the dopaminergic system and control of the opening of the ATP-sensitive K channels at the spinal level. The obtained data point to a multimodal mechanism of action for CSSE: An anti-inflammatory effect and a modulation, through different physiological pathways, of the electrical signal generated by the nociceptors. Further clinical trials are required to endorse the potential utilization of Moroccan saffron as a natural painkiller.

The aim of the present paper was to assess neuropathic pain and its predictors among patients with sciatica. In addition, we sought to investigate the predictors of functional disability in sciatica patients with neuropathic pain. A cross-sectional study was carried out on a sample of 100 sciatica patients aged 18 years and older with a radiating pain from the lower back down to the leg below the knee. Information about socio-demographic characteristics, duration of symptoms, being treated or not, type of treatment, side of sciatica, presence of back pain, leg pain occurrence, leg pain intensity, functional disability, and pain catastrophizing were collected. Of the total patients, 57% had neuropathic pain. Multivariable analysis showed that leg pain intensity was higher in the neuropathic pain group as compared to the non-neuropathic pain group. Also, patients with left sciatica were less likely to have neuropathic pain than patients with right sciatica. Patients with neuropathic pain having high levels of pain catastrophizing and being on bed rest for at least one week were at a higher risk of developing functional disability as compared to their counterparts. Low levels of pain catastrophizing and less bed rest should be considered in interventions aimed at improving the functional ability for sciatica patients with neuropathic pain.

Guidelines are increasingly being used for clinical decision-making. Such guidelines are usually based on meta-analyses, which are generally derived from RCTs. However, their interpretations are often hindered as they do not always consider current clinical relevance. Analyses of RCTs assessing analgesic efficacy of advanced regional analgesic techniques in knee arthroplasty show that the majority of trials do not include a package of basic analgesics such as paracetamol, NSAIDs or cyclooxygenase-2 specific inhibitors, dexamethasone, and local infiltration analgesia in the comparator group. Consequently, the current approach to analyse meta-analyses of pain interventions is not optimal, and may lead to inadequate or inappropriate conclusions and clinical guidance.

Background and ImportanceCOVID-19 is a viral infection that mainly affects the respiratory tract, but can also cause multiple inflammatory reactions, including neurological and cerebrovascular manifestations. We report the case of a COVID-19 patient who developed 'de novo' multiple cerebral aneurysms with no risk factors for aneurysm formation.Clinical PresentationA 55-year-old man with SARS-CoV-2 infection came to our attention for left eye blindness accompanied by ptosis, palpebral chemosis and retro-orbital pain. Brain CT and CT-angiography were negative for hemorrhages and for vascular malformations. Repeated intracerebral hemorrhages and neurological deterioration then occurred, and a new CT-angiography showed multiple intracranial aneurysms that were not present before.ConclusionIntracranial aneurysm formation as a complication of COVID-19 has not been previously reported. As other viral infections do, COVID-19 may be able to determine a vascular damage that can ultimately lead to development of an aneurysm. It is reasonable to hypothesize an involvement of the renin-angiotensin system as a pathogenic mechanism.A conservative therapy aiming at inflammatory modulation and vascular damage prevention may be warranted in these patients.