Rejected

Palmitoylethanolamide (PEA, -hexadecanoylethanolamide) is an endogenous compound belonging to the family of -acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.

A six-year-old, male-neutered, domestic short-haired cat was referred for further management of a three-month history of uncontrolled diabetes mellitus. The cat visited the hospital on three occasions during a three-week time period. Hyperglycemia was documented at all visits. The cat initially presented with evidence of hypovolemia, cranial abdominal pain and dehydration. Moderate hyperglycemia, mild ketonemia and severe hypokalemia were documented. A 3 × 2 cm skin lesion with associated alopecia and erythema was first noticed at a routine follow-up examination (visit two) one week later. A diagnosis of diabetic ketoacidosis was made six days later. The previously identified skin lesion now measured 6 × 2.5 cm. Two episodes of respiratory distress were identified at this visit, with no evidence of cardiac or pulmonary pathology. The cat developed a moderate anemia (packed cell volume 16 %, total solids 7.9 g/dL) on the fifth day of hospitalization. Fluid therapy, electrolyte supplementation, regular insulin, anti-emetic and analgesia medications were administered during visits one and three. Due to development of anemia, suspected pulmonary thromboembolism events and progression of skin lesions, euthanasia was elected. A diagnosis of cutaneous vasculopathy with secondary ischemic necrosis was made post-mortem and pulmonary thromboembolism was confirmed. To the authors' knowledge, this is the first report of cutaneous vasculopathy and pulmonary thromboembolism in a cat with confirmed diabetes mellitus, warranting further research to assess if hypercoagulability is common in this patient population, as routine thromboprophylaxis and anti-coagulation may be potentially indicated.

Postburn pruritus is a common complication of scars in burn patients. In our previous study, we discovered increased expression of TRPV3, TRPV4, and TRPA1. Among them, TRPV3, in particular, is predominantly expressed in the epidermis of the tissue of pruritic burn scars. We sought to evaluate the correlation between the expression of TRPV3 activators and itching after application of TRPV3 activator carvacrol over burn scars. Design: This was a double-blind clinical trial with non-randomized distribution.

Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ-tetrahydrocannabinol (Δ-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ-THC appear more effective in treating animal models of multiple sclerosis. While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals. Drugs which deliver a combination of Δ-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist). The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments. It is important to note that treatment with cannabinoid compounds may cause significant cognitive dysfunction. Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.

To study the correlation between the duration of labor and postpartum hemorrhage. The delivery data of singleton first-term pregnant women who delivered vaginally at Beijing Obstetrics and Gynecology Hospital from January 1, 2017 to December 31, 2017 were collected, 3 104 cases met inclusion criteria. According to the duration of the first labor (t), they were divided into two groups: t≥8 hours was the observation group, t<8 hours was the control group. In order to ensure the baseline characteristics of the subjects in the two groups were balanced, propensity score matching (PSM) was adopted, with matching ratio 1∶1. Then the observation group was divided into four subgroups: group 8-12 h, group 12-16 h, group 16-20 h, group ≥20 h. According to the presence or absence of labor intervention (oxytocin use, artificial rupture of membranes, labor analgesia), the observation group and control group were divided into non-labor intervention observation group, non-labor intervention control group, labor intervention observation group, and labor intervention control group. The case data of 3 104 subjects were analyzed and the duration of labor and atonic postpartum hemorrhage rate of each subgroup were compared with the control group. The duration of the second stage of labor and the first+second stages of labor in the observation group (median:0.8, 13.3 hours) and its subgroups were both longer than those in the control group (median:0.6, 5.1 hours), with statistically significant differences (all <0.01). The rate of atonic postpartum hemorrhage in the observation group, group 16-20 h and group ≥20 h were higher than that in the control group [8.0%(124/1 552), 14.3%(41/287), 14.1%(12/85), 4.6%(72/1 552)], with significant statistical differences (all <0.01). The duration of the second stage of labor and the first+second stages of labor in the observation group were both longer than those in the control group, regardless of the presence or absence of labor intervention, with statistically significant differences (all <0.01). In both the observation group and the control group, the duration of the first stage of labor, the second stage of labor, and the first+second stages of labor with labor intervention were longer than those of the non-labor intervention, with significant statistical differences (all <0.01). The rate of atonic postpartum hemorrhage in the observation group with labor intervention [8.7%(110/1 263)] was higher than that in the observation group without labor intervention [4.8%(14/289)], with a statistical difference (<0.05). With the increase of the duration of the first stage of labor, the rate of atonic postpartum hemorrhage increases. The first stage of labor is closely related to the second stage of labor, and to a certain extent the duration of the second stage of labor increases with the length of the first stage of labor. With the increase of the duration of the first stage of labor, the rate of labor intervention and atonic postpartum hemorrhage also increase, which could serve as a clinical warning that excessive labor intervention may indicate a higher incidence of atonic postpartum hemorrhage.

Both tinnitus and headache are very prevalent conditions in the general population, with bidirectional co-occurrence of them. A number of studies revealed a high prevalence of headache in tinnitus patients; however, most of them used self-reported symptoms, questionnaires, or health databases and were retrospective. The aim of this study was to evaluate the prevalence of different types of headache in a cohort of tinnitus patients and to assess the influence of headache on tinnitus parameters, focusing on appropriate headache and tinnitus diagnosis verified by clinical examination. This prospective study involved 286 patients diagnosed with subjective non-pulsating tinnitus. Patients' clinical information was thoroughly assessed by the multidisciplinary team, including tinnitus characteristics and severity according to the Tinnitus Handicap Inventory (THI), loudness assessed by the Visual Analogue Scale (VAS), audiometry, type of headache diagnosed according to the third edition of the International Classification of Headache Disorders, severity of headache assessed by the Numeric Rating Scale (NRS), and impact of headache using the Headache Impact Test (HIT). In total, 141 (49.3%) tinnitus patients were diagnosed with headache, most of them with tension-type headache or migraine. They were significantly younger; mostly women; had bilateral tinnitus, vertigo, and depression more frequently; and had hearing loss less frequently as compared with the non-headache group. In total, 82 (58.16%) patients had the same localization of tinnitus and headache. Younger age, female gender, higher tinnitus burden measured by THI, and coexistence of hearing loss were independent variables connected with the occurrence of headache in the tinnitus group. According to our study, headaches impact tinnitus on many different levels and may be an important co-factor for tinnitus subtyping. We recommend screening for headache coexistence in all tinnitus patients.

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl injection. In order to confirm that the action of PDRN occurs through the adenosine A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A receptor antagonist, was treated with PDRN. Administration of CCl impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl. Administration of CCl activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

There has been increased interest in the use of low dose ketamine (LDK) as an alternative analgesic for the management of acute pain in the emergency department (ED). The objective of this systematic review was to compare the analgesic effectiveness and safety profile of LDK and morphine for acute pain management in the ED.

BACKGROUND COVID-19 is a newly emerging disease that is not yet fully understood. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that is easily transmitted from human to human through the respiratory route. Usually, it presents with fever, headache, fatigue accompanied by respiratory symptoms like cough and dyspnea, and other systemic involvements. Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative neoplasm characterized by absolute lymphocytosis and demonstration of clonality unlike other causes of lymphocytosis. Patients with CLL are considered immunocompromised because of impaired humoral immunity (mainly) and cellular immunity. Therefore, they are vulnerable to various infections including COVID-19. Little is known about the COVID-19 infection when it unmasks CLL. CASE REPORT A 49-year-old man with no significant previous illnesses, and an unremarkable family history, presented with a moderate COVID-19 infection. He initially presented to the emergency department with fever and mild shortness of breath. A complete blood count showed a high white blood cell count with absolute lymphocytosis. Flow cytometry revealed the clonality of the lymphocytes confirming the diagnosis of CLL. Despite having CLL, he developed a moderate COVID-19 infection and recovered in a few days. To the best of our knowledge, this is the first report of CLL, which presented with a COVID-19 infection as the initial presentation. CONCLUSIONS Lymphocytosis is an unexpected finding in patients diagnosed with COVID-19 infection and the elevated lymphocytes may be indicative of other conditions. Secondary causes of lymphocytosis like malignancy or other infections should be considered in these cases.

BACKGROUND The objective of the present study was to test the hypothesis that intravenous dexmedetomidine is safe and effective when administered to women before and during cesarean section. MATERIAL AND METHODS The analysis included 392 women who received spinal anesthesia and no analgesia prior to undergoing elective cesarean delivery. Of them, 115 women received dexmedetomidine before anesthesia and during delivery (DX cohort), 109 received normal saline before anesthesia and during delivery and dexmedetomidine after delivery (SC cohort), and 168 received normal saline only before anesthesia and during delivery (CN cohort). Data about the women's consumption of sufentanil and ondansetron during hospitalization, onset of lactation, and hospital stays were retrospectively collected and analyzed. RESULTS Most of the women in the study were primiparous (362/392). The women in the DX cohort received less sufentanil during their hospital stays than those in either of the other 2 cohorts (SC comparison: 151.45±11.15 μg vs. 175.12±25.15 μg, P<0.0001, q=8.776; CN comparison: 151.45±11.15 μg vs. 185.42±37.45 μg, P<0.0001, q=13.911). Also, the women in the DX cohort received less ondansetron before discharge and had shorter times to first lactation and hospital stays than those in the SC and CN cohorts. CONCLUSIONS Administering dexmedetomidine before spinal anesthesia appears to be safe and effective for women undergoing elective cesarean delivery.