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Involvement of the cerebellum in migraine.

Migraine is a disabling neurological disease characterized by moderate or severe headaches and accompanied by sensory abnormalities, e.g., photophobia, allodynia, and vertigo. It affects approximately 15% of people worldwide. Despite advancements in current migraine therapeutics, mechanisms underlying migraine remain elusive. Within the central nervous system, studies have hinted that the cerebellum may play an important sensory integrative role in migraine. More specifically, the cerebellum has been proposed to modulate pain processing, and imaging studies have revealed cerebellar alterations in migraine patients. This review aims to summarize the clinical and preclinical studies that link the cerebellum to migraine. We will first discuss cerebellar roles in pain modulation, including cerebellar neuronal connections with pain-related brain regions. Next, we will review cerebellar symptoms and cerebellar imaging data in migraine patients. Lastly, we will highlight the possible roles of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine symptoms, including preclinical cerebellar studies in animal models of migraine.

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Increased prevalence of clonal hematopoiesis of indeterminate potential in hospitalized patients with COVID-19.

Clonal hematopoiesis of indeterminate potential (CHIP) leads to higher mortality, carries a cardiovascular risk and alters inflammation. All three aspects harbor overlaps with the clinical manifestation of COVID-19. This study aimed to identify the impact of CHIP on COVID-19 pathophysiology. 90 hospitalized patients were analyzed for CHIP. In addition, their disease course and outcome were evaluated. With a prevalence of 37.8%, the frequency of a CHIP-driver mutation was significantly higher than the prevalence expected based on median age (17%). CHIP increases the risk of hospitalization in the course of the disease but has no age-independent impact on the outcome within the group of hospitalized patients. Especially in younger patients (45 – 65 years), CHIP was associated with persistent lymphopenia. In older patients (> 65 years), on the other hand, CHIP-positive patients developed neutrophilia in the long run. To what extent increased values of cardiac biomarkers are caused by CHIP independent of age could not be elaborated solely based on this study. In conclusion, our results indicate an increased susceptibility to a severe course of COVID-19 requiring hospitalization associated with CHIP. Secondly, they link it to a differentially regulated cellular immune response under the pressure of SARS-CoV-2 infection. Hence, a patient's CHIP-status bears the potential to serve as biomarker for risk stratification and to early guide treatment of COVID-19 patients.

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Dysphagia lusoria in a young woman with chest pain.

Patients with dysphagia often have an esophageal disorder. This case report describes a patient with persistent dysphagia and chest pain who had a normal esophagogastroduodenoscopy. Computed tomography of the chest with contrast revealed an aberrant right subclavian artery compressing the esophagus. A vascular procedure was performed and corrected the dysphagia. This case demonstrates that aberrant vessels can occasionally cause dysphagia.

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New insight into the analgesic recipe: A cohort study based on smart patient-controlled analgesia pumps records.

Intravenous patient-controlled analgesia (IV-PCA) has been widely used; however, regimen criteria have not yet been established. In China, the most often used opioid is sufentanil, for which repeated doses are a concern, and empirical flurbiprofen axetil (FBP) as an adjuvant. We hypothesized that hydromorphone would be a better choice and also evaluated the effectiveness of FBP as an adjuvant. This historical cohort study was conducted in two tertiary hospitals in China and included 12,674 patients using hydromorphone or sufentanil for IV-PCA between April 1, 2017, and January 30, 2021. The primary outcome was analgesic insufficiency at static (AIS). The secondary outcomes included analgesic insufficiency with movement (AIM) and common opioid-related adverse effects such as postoperative nausea and vomiting (PONV) and dizziness. Sufentanil, but not the sufentanil-FBP combination, was associated with higher risks of AIS and AIM compared to those for hydromorphone (OR 1.64 [1.23, 2.19], < 0.001 and OR 1.42 [1.16, 1.73], < 0.001). Hydromorphone combined with FBP also decreased the risk of both AIS and AIM compared to those for pure hydromorphone (OR 0.74 [0.61, 0.90], = 0.003 and OR 0.80 [0.71, 0.91], < 0.001). However, the risk of PONV was higher in patients aged ≤35 years using FBP (hydromorphone-FBP vs. hydromorphone and sufentanil-FBP vs. hydromorphone, OR 1.69 [1.22, 2.33], = 0.001 and 1.79 [1.12, 2.86], = 0.015). Hydromorphone was superior to sufentanil for IV-PCA in postoperative analgesia. Adding FBP may improve the analgesic effects of both hydromorphone and sufentanil but was associated with an increased risk of PONV in patients <35 years of age.

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Safety, Tolerability and Pharmacokinetics of Icapamespib, a Selective Epichaperome Inhibitor, in Healthy Adults.

Neurodegenerative diseases are devastating conditions that most commonly affect individuals 65 years and older. Currently there are no effective treatments or cures for neurodegenerative diseases, and therapeutics that selectively target the underlying causes of these diseases are needed. Epichaperomes play a major role in the maintenance and progression of neuronal pathology. Inhibiting epichaperomes induces degradation of disease associated proteins and is a promising therapeutic approach to treat neurodegenerative diseases, in particular Alzheimer's Disease and amyotrophic lateral sclerosis.

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Effects of Combined Spinal Epidural Anesthesia in Orthopaedic Surgery of Elderly Patients.

Combined spinal epidural anesthesia (CSEA) is applied to lower limb orthopaedic surgery in the elderly. This study is aimed at exploring the effect of CSEA in orthopaedic surgery of elderly patients.

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Butorphanol as an Adjuvant to Ropivacaine for Adductor Canal Blocks in Total Knee Arthroplasty Patients: A Randomized, Double, Blind Study.

The objective of this study was to observe the effects of butorphanol as an adjuvant to ropivacaine for the adductor canal block (ACB) on postoperative analgesia in patients undergoing total knee arthroplasty (TKA).

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The Clinical Efficacy and Safety of Extracorporeal Shock Wave Lithotripsy in the Treatment of Patients with Urinary Calculi.

To evaluate the clinical efficacy of extracorporeal shock wave lithotripsy (ESWL) for urinary calculi and precautions of postoperative complications.

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A Diagnosis Not to Miss: A Case of Fitz-Hugh-Curtis Syndrome.

Fitz-Hugh-Curtis syndrome is a rare disease attributed to complications of pelvic inflammatory disease secondary to chlamydia or gonorrhea infections. Patients generally complain of vague abdominal pain that is often acute in onset, with or without genitourinary complaints. We present a case of Fitz-Hugh-Curtis syndrome with a young female who presents with a complaint of right upper quadrant abdominal pain for 2 months' duration. She initially had no genitourinary complaints. She underwent a diagnostic laparoscopy and cholecystectomy during which adhesions from the lateral liver to the abdominal wall were visualized. The cholecystectomy did not relieve her pain. She later complained of abnormal vaginal bleeding for 15 days one month prior to her admission, unbeknownst to the medical team on admission. A chlamydia DNA probe test was positive, and the diagnosis of Fitz-Hugh-Curtis syndrome was made.

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Rimegepant for the treatment of migraine.

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide relief in severe migraine, but are not universally effective and carry a significant side-effect profile with frequent redosing requirement. Prophylactic therapy may reduce the occurrence of acute migraine attacks in selected patients, but does not completely eliminate it. More recently, CGRP antagonism has been studied and shown to be effective in both abortion and prevention of migraine. Novel medications, targeting CGRP, divide into CGRP antibodies and receptor antagonists (gepants). Rimegepant, a second-generation gepant, has shown efficacy in several clinical trials in treating acute migraine. Ongoing trials are also evaluating its role in migraine prophylaxis, and results are promising. It is also generally safer for use than existing options, does not appear to increase the chance of developing chronic migraines, and carries a very tolerable side effects profile. It is a part of a growing arsenal in migraine treatment, and may present the silver bullet for treatment of this disease.

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