Rejected

Antidepressant discontinuation syndrome (ADDS) is reported to occur in almost 30-50% of the patients who take antidepressants for a duration of at least four to six weeks and then suddenly discontinue the drug. Since there is an increase in the use of antidepressants for various reasons by general practitioners, patient education about when and how to discontinue a drug is not acknowledged enough. It is reported to occur with the use of different classes of antidepressants – selective serotonin reuptake inhibitor (SSRI), monoamineoxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), and atypical antipsychotics like risperidone, trazodone, clozapine, and venlafaxine. Slow tapering off the drugs has also caused ADDS. Symptoms start within two to four days of quitting the drug and are usually mild lasting for two to four weeks (can persist for six to 12 months) but could be severe enough leaving the patient nonambulatory. Here, we represent a case of a 55-year-old female who presented to the outpatient clinic with complaints of headache, vomiting, and diarrhea. The patient had 10 to 12 episodes of watery diarrhea every day and bilateral, continuous, pressing headache associated with multiple episodes of non-projectile vomiting. She was investigated for ultrasound sonography (USG) abdomen, CT head, and lab investigations which turned around to be normal. A follow-up visit with detailed history revealed she suddenly stopped taking escitalopram after six months by herself without tapering off the dose, two days before the onset of symptoms. Escitalopram was reinstated and the symptoms started to resolve in two to three days. All the unnecessary investigations and treatment could have been prevented if the proper history was taken and revealed at the initial visit.

Background – Yellow fever (YF) is a viral hemorrhagic fever that is transmitted by arthropods. It can occur with little symptomatic manifestations to the most fulminant forms. The most effective way to avoid YF is through vaccination. There is a lack of information about the immune response of the vaccine in childhood. Methods – We described children and adolescents with YF who had been previously immunized in Minas Gerais State from July 2017 to June 2018. Results – 527 cases of YF were observed representing an incidence of 7.6/100,000 inhabitants. Only 26 patients (4.9%) were ≤ 20 years and 501 (95.1%) were > 20 years. Only 9 vaccinated patients were ≤ 20 years and 15 were > 20 years. 34.6% (9/26) of YF patients ≤ 20 years were previously vaccinated and 3% (15/501) of those > 20 years (p < 0.001). The median age at vaccination was 1 year between those ≤ 20 years and 31 years between those > 20 years (p = 0.002). Among 9 vaccinated children and adolescents ≤ 20 years, age ranged from 7 to 18 years, the most described symptoms were fever (88%), headache (77%), myalgia (77%), and abdominal pain (66%). All patients recovered from the disease and none died. Conclusion – Prior YF vaccination may be associated with mild forms of the disease in children and adolescents. YF vaccination in the first years of life may be associated with poor vaccine response and high infection rates in this group as it fail to seroconvert a significant proportion of infants.

To investigate the effects of patient-controlled intravenous analgesia with butorphanol versus sufentanil on early postoperative rehabilitation following radical laparoscopic nephrectomy. One hundred patients undergoing radical laparoscopic nephrectomy in Affiliated Cancer Hospital of Zhengzhou University from September 2018 to February 2020 were divided into two groups (=50) using a random number table: butorphanol patient-controlled intravenous analgesia group (group A) and sufentanil patient-controlled intravenous analgesia group (group B). Patient-controlled intravenous analgesia (PCIA) was performed at the end of surgery. The formulation of group A was butorphanol (0.15 mg/kg) and ketorolac tromethamine (180 mg) using the physiological saline at a dilution of 100 ml. The formulation of group B was sufentanil (1.5 μg/kg) and ketorolac tromethamine (180 mg) using the physiological saline at a dilution of 100 ml. At the time points of 4, 8, 24, 48 h after operation (T(1), T(2), T(3), T(4)), VAS scores at rest and cough were recorded. The incidence of remedial analgesia, the number of pressings during 48 h after the operation, the postoperative anal exhaust recovery time of the patients were recorded. Quality of recovery-40(QoR-40) scores were recorded at T(3) and T(4). Adverse reactions were recorded. There was no significant difference in VAS scores at rest and cough at T(1), T(2), T(3) and T(4) between two groups (all >0.05). There was no significant difference in the incidence of remedial analgesia and the number of pressings during 48 h after the operation between two groups (all >0.05). The postoperative anal exhaust recovery time of the patients in group A was (32±6) h, which was lower than that in group B with statistically significant difference [(40±5) h, =7.937, <0.01]. The QoR-40 total scores in group A were higher than those in group B at T(3) and T(4), which were (185.8±2.5) vs (170.7±2.7), (194.8±1.9) vs (183.6±2.6), and the differences were statistically significant (=28.878, 25.025, all <0.01). The incidence of nausea, retching/vomiting, respiratory depression and itch during 48 h after the operation in group A were 10%, 6%, 2%, 2%, which were lower than that in group B (32%, 20%, 14%, 18%), with statistically significant difference (χ(2)=7.294, 4.322, 4.891, 5.983, all <0.05). PCIA with butorphanol or sufentanil can provide satisfactory analgesia for patients undergoing radical laparoscopic nephrectomy, but butorphanol can promote postoperative rehabilitation with fewer adverse reactions.

Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases.

To explore pain complaints and health-related conditions, verifying if permanent or temporary usage of forearm crutches could be associated with them. We designed a cross-sectional study from a sample who answered a five-month public call. We organized data into five domains: (1) diseases, signs and symptoms; (2) personal factors related to age, sex, marital status, and paid occupation; (3) body structure and functional components defined by body mass index, arterial pressure, mental state, and pain; (4) activities and participation assessed by satisfaction with Assistive Technology; (5) and environmental factors focused on medicines and forearm crutch usage. The sample was geo-referenced by address, and the frequency of the codified health conditions was distributed according to ICD-10's chapters. We recruited three times more permanent than temporary users dealing with chronic and external causes of diseases. Pain mapping suggested different pattern of complaints between permanent and temporary users. Women who were temporary users seemed more likely to be injured because of external causes. Moreover, both users reported intense (31%) and moderate (53%) levels of pain. In contrast, mild pains were only reported by permanent users (16%), suggesting a distinction between acute and chronic pain according to the kind of forearm crutch usage.

Reunion Island was struck by a massive Chikungunya outbreak in 2005-2006. Chikungunya infection is characterized by inflammatory joint symptoms, which may evolve into chronic arthritis.

Non-radiographic axial spondyloarthritis (nr-axSpA) is a subgroup of axial spondyloarthritis (axSpA) without fulfilling the modified New York criteria of sacroiliac joint radiographs for ankylosing spondylitis (AS). AS and nr-axSpA share various demographic and clinical features and disease burden, although sex and objective inflammatory findings such as elevated serum C-reactive protein level are slightly different between AS and nr-axSpA. Recently, diagnostic guidance for nr-axSpA in Japan was proposed for epidemiological studies of a population with a low prevalence of HLA-B27 positivity and the use of molecular targeted agents suitable for the unique medical care system in Japan. A biological agent targeting interleukin-17 was approved for nr-axSpA by the Pharmaceutical and Medical Devices Agency (PMDA) in August 2020. Some other biological agents will be also available for Japanese patients with nr-axSpA in the near future.

BACKGROUNDWhile mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure (HF) is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level.METHODSWe compared the PBMC mitochondrial respiration of 19 hospitalized patients with stage D HF with that of 19 healthy participants. We then created an in vitro model of sterile inflammation by treating healthy PBMCs with mitochondrial damage-associated molecular patterns (MitoDAMPs) isolated from human heart tissue. Last, we enrolled patients with stage D HF and sampled their blood before and after taking 5 to 9 days of oral nicotinamide riboside (NR), a NAD precursor.RESULTSWe demonstrated that HF is associated with both reduced respiratory capacity and elevated proinflammatory cytokine gene expressions. In our in vitro model, MitoDAMP-treated PBMCs secreted IL-6 that impaired mitochondrial respiration by reducing complex I activity. Last, oral NR administration enhanced PBMC respiration and reduced proinflammatory cytokine gene expression in 4 subjects with HF.CONCLUSIONThese findings suggest that systemic inflammation in patients with HF is causally linked to mitochondrial function of the PBMCs. Increasing NAD levels may have the potential to improve mitochondrial respiration and attenuate proinflammatory activation of PBMCs in HF.TRIAL REGISTRATIONClinicalTrials.gov NCT03727646.FUNDINGThis study was funded by the NIH, the University of Washington, and the American Heart Association.

To compare the dye distribution following either two lateral abdominal or one lateral abdominal and one subcostal ultrasound-guided transversus abdominis plane (TAP) injections of a clinically relevant volume of dye solution in dogs.

Laparoscopic surgery is the cornerstone of modern gynaecological surgery, with shorter hospital stays and a quicker return to normal activities. However postoperative pain remains problematic. No strategy to reduce phrenic nerve irritation, including heating or humidifying the insufflating gas, alternatives to CO, and intraperitoneal analgesics, has shown superiority.