Rejected

To assess the relationship between memory performance defined by the Stages of Objective Memory Impairment (SOMI) system and the Alzheimer's disease (AD) ATN (amyloid beta [A], pathologic tau [T], and neurodegeneration [N]) biomarker system.

The coronavirus disease 2019 (COVID-19) has been shown to affect several systems, notably the respiratory system. However, there has been considerable evidence implicating the nervous system in COVID-19 infection. This study aims to investigate the clinical characteristics of patients whose cerebrospinal fluid (CSF) tested positive for SARS-CoV-2.

Migraine is a disease whose aetiology and mechanism are not yet clear. Chuanxiong Rhizoma (CR) is employed in traditional Chinese medicine (TCM) to treat various disorders. CR is effective for migraine, but its active compounds, drug targets, and exact molecular mechanism remain unclear. In this study, we used the method of systems pharmacology to address the above issues. We first established the drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network related to the treatment of migraine with CR and then established gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results suggest that the treatment process may be related to the regulation of inflammation and neural activity. The docking results also revealed that PTGS2 and TRPV1 could directly bind to the active compounds that could regulate them. In addition, we found that CR affected 11 targets that were more highly expressed in the liver or heart but were the lowest in the whole brain. It also expounds the description of CR channel tropism in TCM theory from these angles. These findings not only indicate that CR can be developed as a potential effective drug for the treatment of migraine but also demonstrate the application of systems pharmacology in the discovery of herbal-based disease therapies.

Among all coloproctological diseases, hemorrhoids rank first among the reasons for visiting a proctologist. Its prevalence is 130-145 per 1.000 adults, and its proportion in the structure of colorectal diseases ranges from 34 to 41%. After hemorrhoidectomy, a long period of rehabilitation is necessary. There are long periods of incapacity for work (at least two weeks) and quite high complications rate, which generally leads to economic burden. Therefore, an urgent problem of current coloproctology and physiotherapy is the development of new approaches to medical rehabilitation of the patients after surgery for their fast recovery and prevention of complications.

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) ( = 80) to chronic migraine (CM) ( = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) ( = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment ( < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) ( < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) ( < 0.05). There was no significant efficacy difference between low (4-7 migraine days/month, = 22) and high frequency (8-14 days, = 59) EM nor between patients with CM with ( = 50) or without ( = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

Sepsis development in patients with trauma is associated with bad prognosis. This study investigated the effect of immunomodulatory interventions in major trauma patients at high risk for sepsis. In a randomized, double-blinded, controlled design, severe trauma patients were stratified by leukocyte anti-sedimentation rate (LAR) test into high risk (HR) and low risk (LR) for sepsis. The HR patients were randomly allocated into intravenous vitamin C plus vitamin B1 (HR-CB), intramuscular vitamin D plus oral probiotics (HR-DP), or control (HR-C) groups. The clinical trial was registered at clinicaltrials.gov (https://clinicaltrials.gov/show/NCT04216459). The primary outcome was Acute Physiologic Assessment and Chronic Health Evaluation score II (APACHE II) score. Secondary outcomes included sepsis incidence, changes in Sequential Organ Failure Assessment (SOFA) score, and serum monocyte chemoattractant protein-1 (MCP-1) on day 6 from baseline, 28-day mortality, intensive care unit (ICU), and hospital discharge. The HR-DP, HR-CB, and LR groups showed a significantly lower incidence of sepsis development (20%, 20%, and 16%, respectively, versus 60% in the HR-C group, -value = 0.004). The three groups also showed a significant improvement in APACHE II and SOFA scores. Besides, MCP-1 levels were significantly decreased in HR-DP and HR-CB groups compared to the HR-C group (-value ≤ 0.05). Significantly decreased mortality (10% and 16% versus 60% in the HR-C group) and increased ICU discharge (95% and 84% versus 45% in the HR-C group) were observed in HR-CB and LR groups (-value = 0.001). Both combinations of interventions improved APACHE II scores and reduced sepsis incidence in trauma patients. The LAR combined with injury severity score were good sepsis predictors.

Takayasu arteritis is a rare chronic granulomatous inflammation involving the aorta and its main branches. In this report, we describe an extremely rare elderly male patient with Takayasu arteritis (TA) after coronary artery bypass grafting (CABG). A 61-year-old male patient with persistent precordial pain underwent angiography. Vascular murmurs could be heard in carotid artery and bilateral renal artery by auscultation. Laboratory parameters showed high Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP). CT coronary angiography showed multiple stenoses of aorta and its main branches, such as carotid and renal artery involvement. Coronary angiography showed that the coronary artery had multiple branch stenoses, the left anterior descending artery (LAD) had severe stenosis, the distal end of which was reversed to the right coronary artery (RCA), and the RCA was completely occluded. Because of the high level of markers of inflammatory activity, the patient began to take glucocorticoid. Although the patient still had multibranch stenosis of coronary artery, considering the previous CABG operation history, surgery, and interventional therapy of the patient were not feasible, the patient was given conservative drug for further treatment. After treatment, the inflammatory index was significantly descended, and N terminal-pro Brain natriuretic peptide (NT-pro BNP) was decreased. A rare case of an elderly male patient with Takayasu arteritis after coronary artery bypass grafting was reported. In addition to hypertension, hyperlipidemia, and other risk factors, coronary artery involvement caused by TA may be a major cause of aggravation of symptoms in patients with acute myocardial infarction (AMI), especially after CABG.

Pancreatitis is known to be painful in humans and companion animals. However, the extent of pain in experimental mouse models of acute pancreatitis is unknown. Consequently, the severity classification of acute pancreatitis in mice is controversially discussed and standardized pain management is missing. In this study, we investigated acute Cerulein-induced pancreatitis with pain-specific and well-being orientated parameters to detect its impact on mice. Male C57BL/6J male mice were injected with Cerulein; animals that received saline injections served as control group. The animals were observed for weight change and water intake. To assess pain, behaviors like stretch-and-press and reduced rearing, the Mouse Grimace Scale, and von Frey hypersensitivity were assessed. Fecal corticosterone metabolites and burrowing behavior were assessed to detect changes in the animal's well-being. Pancreatitis severity was evaluated with amylase and lipase in the blood and pancreas histology. To investigate whether different analgesics can alleviate signs of pain, and if they influence pancreas inflammation, animals received Buprenorphine, Paracetamol in combination with Tramadol, or Metamizole in the drinking water. The calculated intake of these analgesics drinking reached values stated to be efficient for pain alleviation. While pancreatitis did not seem to be painful, we detected acute pain from Cerulein injections that could not be alleviated by analgesics. The number of inflammatory cells in the pancreas did not differ with the analgesic administered. In conclusion: (1) Cerulein injections appear to be acutely painful but pain could not be alleviated by the tested analgesics, (2) acute pancreatitis induced by our protocol did not induce obvious signs of pain, (3) analgesic substances had no detectable influence on inflammation. Nevertheless, protocols inducing more severe or even chronic pancreatitis might evoke more pain and analgesic treatment might become imperative. Considering our results, we recommend the use of Buprenorphine drinking water in these protocols. Further studies to search for efficient analgesics that can alleviate the acute pain induced by Cerulein injections are needed.

Pituitary adenoma (PA) is a frequent intracranial lesion, that needs surgical evacuation. In this study, we evaluated the surgical outcome of PA treated via endoscopic and microscopic trans-sphenoidal approach. In this retrospective cross-sectional study, we evaluate ten years of PA surgery experience in the northwest of Iran. 721 patients underwent trans sphenoidal surgery of PA. Complication of the surgery, extension of tumors resection, demographic and clinical findings (gender, age, tumor type,..) were reviewed in this study. SPSS version 25 and statistical tests including chi square and T-test were used. P-value ˂0.5 was considered as statistically significant. 483 males (58.9%) and 336 females (41.02%) were included in this study. Mean age of patients was 47.3±1.96 years.The most common initial complaints were deterioration of vision (n=528, 64.4%) and headache (n=343, 41.88%), followed by accelerated development (n=254, 31.01%), amenorrhea and galactorrhea (n=253, 30.8%). 57 (6.95%) patients had symptoms of Cushing's disease. 105 (12.8%) patients had acromegaly. TR was achieved in 87.5% of cases and sub-TR in 103 (12.5%) cases and no patient had a partial or insufficient resection. After surgery, the endocrine function was normalized in 76 (31.7%) patients who had preoperative hyper hormonal levels. 36 (4.3%) patients developed postoperative CSF leakage; of which, 4 (0.48 %) patients did not improve by lumbar drainage and other conservative treatments and needed reoperation for reconstruction of the skull base. The combination of microscopic and endoscopic trans-sphenoidal approach in PA surgery can be lead to total resection of tumors.

People with HIV (PWH) are at a disproportionate risk for experiencing both chronic pain and opioid use disorder (OUD). Prescription opioid tapering is typically addressed within the "silo model" of medical care, whereby attention is focused solely on opioid addiction rather than also addressing chronic pain management, and limited communication occurs between patient and providers.