Rejected

Selecting a bowel preparation for patients with renal impairment or diabetes requires special consideration. We aimed to describe the effect of baseline renal impairment or diabetes on the safety, efficacy, and tolerability of low-volume sodium picosulfate, magnesium oxide, and citric acid (SPMC) ready-to-drink oral solution bowel preparation.

This study evaluated the clinical manifestation of COVID-19 and adverse outcomes in patients with comorbidities (outcome: death).

Neuropathic pain (NP) is caused by primary injury or dysfunction of the peripheral and the central nervous system. Long non-coding RNAs were critical regulators involved in nervous system diseases, however, the precise regulatory mechanism remains unclear. This study aims to uncover the essential role of LINC01119 in NP progression and further clarify the underlying regulatory mechanism at post-transcriptional level. LINC01119 was significantly upregulated in rats of spare nerve injury (SNI) group compared to sham group. Functionally, silencing of LINC01119 significantly alleviated the neuropathic pain-induced hypersensitivity and reduced the increase in IL-6, IL-1β, and TNF-α caused by SNI. Mechanistically, Brain-derived neurotrophic factor (BDNF) was identified as the functional target of LINC01119. Besides, an RNA binding protein, ELAVL1 could directly interact with LINC01119, and this formed LINC01119- ELAVL1 complex binds to BDNF mRNA, strengthening its RNA stability and increasing the expression level of BDNF at both transcript and protein levels. Clinically, serum LINC01119 was verified as a promising diagnostic biomarker for NP patients. LINC01119 induces NP progression via binding with ELAVL1 and increasing BDNF mRNA stability and expression level. Therefore, LINC01119 may serve as a promising diagnostic marker and therapeutic target for NP treatment.

One of the most intriguing and mysterious phenomena observed during the COVID-19 pandemic has been represented by the occurrence of the multisystem inflammatory syndrome in children and adolescents (MIS-C). Patients with this condition have some overlapping signs and symptoms with those of Kawasaki disease (KD), but also display clinical features that are uncommon or less frequent in this illness, such as diarrhea, abdominal pain and myocardial involvement. The sickest patients may develop multiorgan failure and shock, usually due to myocarditis. Management is based on the administration of intravenous immunoglobulin, glucocorticoids and, in the most severe instances, anakinra. It is still debated whether MIS-C and KD represent different illnesses or are part of the same disease spectrum. The aim of the present review is to analyze critically the evidence in favor of the latter hypothesis and to provide the authors' personal interpretation of the relationship between the two conditions.

Multiple vertebral compression and rib fractures in elderly patients with pre-existing chronic obstructive pulmonary disease is a common scenario associated with significant morbidity and mortality. Severe pain prevents normal ventilation and leads to atelectasis, consolidation, and pneumonia. Subsequently, these patients frequently develop respiratory failure and require intubation and critical care. Therefore, adequate analgesia is often a life-saving intervention. Anesthetic management of a 78-year-old kyphotic patient with T6, T7, and T9 rib fractures on the right and T10-12 vertebral compression fractures sustained in an accidental fall is presented. She had inadequate pain control and was unable to take a deep breath or cough. Her respiratory status was deteriorating, with tachypnea and worsening hypoxia, necessitating bi-level positive airway pressure (BiPAP) support. Since thoracic epidural analgesia was contraindicated owing to compressive vertebral fractures and to the pending respiratory failure, we opted for a unilateral erector spinae plane (ESP) block at the T7 level and bilateral retrolaminar (RL) blocks at the T10 level. Following the procedure, the pain was immediately relieved and the patient was able to take deep breaths. Shortly thereafter, her respiratory status improved, with the respiratory rate coming back close to the baseline. The patient was subsequently weaned from BiPAP support and discharged from the intensive care unit. While the combination of ESP and RL blocks is not routinely used in patients with multiple rib and vertebral compression fractures, our report indicates that it may be an excellent alternative for analgesia in situations where thoracic epidural and/or paravertebral blocks are contraindicated and when timely intervention could be potentially life-saving.

To determine the safety and tolerability of nusinersen treatment in ambulatory adults with spinal muscular atrophy (SMA) and investigate the treatment effect on muscle strength, physical function, and motor unit physiology. Individuals aged 18 years or older with genetically confirmed 5q SMA, three or more copies of the SMN2 gene, and the ability to ambulate 30 feet were enrolled. Safety outcomes included the number of adverse events and serious adverse events, clinically significant vital sign or laboratory parameter abnormalities. Outcome assessments occurred at baseline (prior to the first dose of nusinersen) and then 2, 6, 10, and 14 months post-treatment. Six women, seven men (mean age: 37 ± 11, range: 18-59 years) were included for analyses. The most common side effects were headache and back pain, but overall procedures and treatments were well-tolerated. No serious adverse events were reported. Maximal Voluntary Isometric Muscle Contraction Testing (MVICT) and 6-min walk test (6MWT) both showed overall stability with significant increases at 2, 6, and 10 months for the 6MWT. More consistent significant treatment effects were noted on the Hammersmith Functional Motor Scale Expanded, SMA-Functional Rating Scale, and forced vital capacity. Treatment resulted in progressively increased ulnar compound muscle action potential and average single motor unit potential amplitudes, but motor unit number estimation remained stable. Nusinersen treatment is safe and well-tolerated in ambulatory adults with SMA. Treatment resulted in improved motor function and electrophysiological findings suggest that this improvement may be occurring improved motor unit reinnervation capacity.

Chronic scrotal pain (CSP) can be a debilitating condition for patients and is often difficult to characterize.

Approximately 30% insomnia patients have associated somatic, neurological and psychiatric conditions. Clinician has to define causality of these conditions to determine a treatment plan. Secondary insomnia can result from the symptoms of a primary condition or form an impairment of central nervous system due to neurological disorder. Some associated conditions are characterized by high coincidence with insomnia, similar triggers and crossing genotype, neurophysiological and functional findings. This association with insomnia is observed in anxiety disorders, depression, chronic pain syndromes. The paper presents a concept of comorbid insomnia disorder which proposes the existence of a common neural structure which when affected causes the symptoms of both insomnia and comorbid disorder. Comorbid disorders can also be interconnected due to the overlap of the responsible nerve centers. Positive effect of specific pharmacological, psychotherapeutical and behavioral treatment on both conditions evidences this concept.

Koumine (KM), the most abundant alkaloid in , has anti-neuropathic, anti-inflammatory, and analgesic activities; thus, it has the potential to be developed as a broad-spectrum analgesic drug. However, factors determining the relationship between analgesic efficacy and the corresponding plasma KM concentration are largely unclear. The pharmacokinetics and pharmacodynamics of KM and their optimization in the context of neuropathic pain have not been reported. We investigated the pharmacokinetics and pharmacodynamics of KM after oral administration in a streptozotocin-induced rat model of diabetic neuropathic pain (DNP) using a population approach. A first-order absorption and elimination pharmacokinetics model best described the plasma KM concentration. This pharmacokinetic model was then linked to a linear pharmacodynamic model with an effect compartment based on the measurement of the mechanical withdrawal threshold. KM was rapidly absorbed (time to maximum plasma concentration: 0.14-0.36 h) with similar values in both DNP and naïve rats, suggesting that DNP did not influence the KM absorption rate. However, the area under the curve (AUC) of KM in DNP rats was over 3-fold higher than that in naïve rats. The systemic clearance rate and volume of KM distribution were significantly lower in DNP rats than in naïve rats. Blood glucose value prior to KM treatment was a significant covariate for the systemic clearance rate of KM and baseline value of the threshold. Our results suggest that streptozotocin-induced hyperglycemia is an independent factor for decreased KM elimination and its anti-allodynic effects in a DNP rat model. To the best of our knowledge, this is the first study to investigate the role of DNP in the pharmacokinetics and pharmacokinetics-pharmacodynamics of KM in streptozotocin-induced diabetic rats.

Knee pain causes functional limitations, eventually compromising the quality of life. We evaluated the efficacy of our water-dispersible turmeric formulation (60% natural curcuminoids, TurmXTRA 60N-WDTE60N), which exhibited better PK profile at low dose (250 mg) than standard turmeric extract, in alleviating symptoms of chronic knee pain.