Rejected

Patients undergoing laparoscopic gynecologic surgery and receiving postoperative analgesia with opioids have a high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of three doses of ramosetron in this high-risk population. In this prospective, double-blind trial, 174 patients randomly received ramosetron 0.3 mg (R0.3 group; 58), 0.45 mg (R0.45 group; 58), or 0.6 mg (R0.6 group; 58) at the end of surgery. The primary outcome was the incidence of PONV during the first postoperative 48 h. Nausea severity, pain scores, adverse events, and patient satisfaction (1-4; 4, excellent) were assessed. The incidence of PONV was not different between groups (35%, 38%, and 35% in R0.3, R0.45, and R0.6 groups; 0.905). Nausea severity, pain scores, and incidence of adverse events (dizziness, headache, or sedation) were similar between groups. Compared to the R0.3 group, the R0.45 and R0.6 groups had lower incidence of premature discontinuation of fentanyl-based patient-controlled analgesia primarily because of intractable PONV (9% and 5% vs. 24%; 0.038), and higher satisfaction scores (3.4 ± 0.8 and 3.3 ± 0.7 vs. 2.4 ± 0.9; 0.005). Compared to ramosetron 0.3 mg, ramosetron 0.45 and 0.6 mg did not reduce PONV, but reduced premature discontinuation of patient-controlled analgesia and increased patient satisfaction, without increasing adverse events.

Somatostatin released from the capsaicin-sensitive sensory nerves mediates analgesic and anti-inflammatory effects via the somatostatin sst receptor without endocrine actions. Therefore, sst is considered to be a novel target for drug development in pain including chronic neuropathy, which is an emerging unmet medical need. Here, we examined the in silico binding, the sst-linked G-protein activation on stable receptor expressing cells (1 nM to 10 μM), and the effects of our novel pyrrolo-pyrimidine molecules in mouse inflammatory and neuropathic pain models. All four of the tested compounds (C1-C4) bind to the same binding site of the sst receptor with similar interaction energy to high-affinity reference sst agonists, and they all induce G-protein activation. C1 is the more efficacious (γ-GTP-binding: 218.2% ± 36.5%) and most potent (EC: 37 nM) ligand. In vivo testing of the actions of orally administered C1 and C2 (500 µg/kg) showed that only C1 decreased the resiniferatoxin-induced acute neurogenic inflammatory thermal allodynia and mechanical hyperalgesia significantly. Meanwhile, both of them remarkably reduced partial sciatic nerve ligation-induced chronic neuropathic mechanical hyperalgesia after a single oral administration of the 500 µg/kg dose. These orally active novel sst agonists exert potent anti-hyperalgesic effect in a chronic neuropathy model, and therefore, they can open promising drug developmental perspectives.

Human African Trypanosomiasis (HAT) is a neglected disease caused by the protozoan parasites Trypanosoma brucei and transmitted by tsetse flies that progresses in two phases. Symptoms in the first phase include fever, headaches, pruritus, lymphadenopathy, and in certain cases, hepato- and splenomegaly. Neurological disorders such as sleep disorder, aggressive behavior, logorrhea, psychotic reactions, and mood changes are signs of the second stage of the disease. Diagnosis follows complex algorithms, including serological testing and microscopy. Our case report illustrates the course of events of a 41-year old woman with sleep disorder, among other neurological symptoms, whose diagnosis was made seven months after the onset of symptoms. The patient had consulted two different hospitals in Kinshasa and was on the verge of being discharged from a third due to negative laboratory test results. This case report highlights the challenges that may arise when a disease is on the verge of eradication.

An 18-year-old woman with a history of hollow visceral myopathy presented with a small-bowel obstruction. High-dose opioid analgesia was required subsequently during hospital admission. She suffered two episodes of documented fasting hypoglycaemia, despite adjustment of parenteral carbohydrate administration. Investigations for non-insulin-mediated hypoglycaemia revealed a low morning cortisol of 109 nmol/L and an inappropriately low Adrenocorticotropic hormone (ACTH) level of 2.2 pmol/L. A diagnosis of secondary adrenal insufficiency was confirmed on repeat cortisol and ACTH testing. The 250 µg short Synacthen test cortisol response was normal, suggestive of acute rather than chronic ACTH deficiency. This pattern was consistent after further opioid exposure. Adrenal recovery occurred shortly after opioid cessation. Opioid-induced hypoadrenalism is likely an under-recognised clinical entity with potentially serious adverse patient outcomes. There are reported cases involving commonly prescribed opioids including fentanyl and tramadol. However, we believe this is the first reported clinical case of acute transient opioid-induced secondary hypoadrenalism associated with fasting hypoglycaemia.

The transient receptor potential akyrin type-1 (TRPA1) is a non-selective cation channel playing a pivotal role in pain sensation and neurogenic inflammation. TRPA1 channels expressed in the central nervous system (CNS) have a critical role in the modulation of cortical spreading depression (CSD), which is a key pathophysiological basis of migraine pain. ADM_09 is a recently developed lipoic acid-based TRPA1 antagonist that is able to revert oxaliplatin-induced neuropathic pain and inflammatory trigeminal allodynia. In this context, aiming at developing drugs that are able to target TRPA1 channels in the CNS and promote an antioxidant effect, permeability across the blood-brain barrier (BBB) represents a central issue. Niosomes are nanovesicles that can be functionalized with specific ligands selectively recognized by transporters expressed on the BBB. In this work, the activity of ADM_09 on neocortex cultures was studied, and an efficient formulation to cross the BBB was developed with the aim of increasing the concentration of ADM_09 into the brain and selectively delivering it to the CNS rapidly after parenteral administration.

For pain relief after total knee arthroplasty (TKA), an injection at the midthigh level may produce analgesia inferior to that of a femoral nerve block as the anterior femoral cutaneous nerves (intermediate femoral cutaneous nerve (IFCN) and medial femoral cutaneous nerve (MFCN)) are not anesthetized. The IFCN can be selectively anesthetized in the subcutaneous tissue above the sartorius muscle and the MFCN by an injection in the proximal part of the femoral triangle (FT). The primary aim was to investigate the area of cutaneous anesthesia in relation to the surgical incision for TKA and anteromedial knee area after intermediate femoral cutaneous nerve blockade (IFCNB) in combination with an injection in the proximal or distal part of the FT (proximal vs distal femoral triangle block (FTB)).

To summarize the clinical characteristics of pulmonary actinomycosis and analyze its diagnostic methods. The clinical symptoms, underlying diseases, imaging characteristics, preliminary diagnosis, diagnostic methods, treatment and prognosis of 30 patients with pulmonary actinomycetes admitted into the First Affiliated Hospital of Zhejiang University School of Medicine during the 10 years (January 2007 to November 2017) were retrospectively analyzed. The 30 patients with pulmonary actinomycetes included were from 47 to 81 years old, with an average age of (59.5±7.8) years, with a course of disease from 5 days to 48 months, and a median course of disease of 1.5 months; 18 patients (60.0%) were complicated with underlying diseases, 10 patients (33.3%) had a history of smoking, 10 patients (33.3%) had a history of alcohol abuse. The main clinical manifestations were cough in 29 cases (96.7%), followed by sputum in 22 cases (73.3%), hemoptysis in 20 cases (66.7%), fever in 12 cases (40.0%), chest pain in 5 cases (16.7%) and shortness of breath in 3 cases (10.0%). Mass, nodules, consolidation, atelectasis can be seen by imaging, there can be a low-density lesion necrosis, formation of voids or vacuoles. Among the 25 patients (83.3%) who underwent bronchoscopy, 14 cases were abnormal, 5 cases showed endotracheal polypoid neoplasms, 9 cases showed endotracheal mucosal inflammatory changes, 2 cases of them showed bronchial foreign body, and 1 case showed broncholithiasis. All cases were diagnosed by pathology. Nine cases (30.0%) were confirmed by bronchoscopic biopsy. Two cases (6.7%) underwent CT-guided percutaneous lung biopsy, 18 cases (60.0%) underwent surgical resection of pathology, and 1 case (3.3%) was diagnosed by puncture of chest wall mass. Sufficient dose and course of penicillin were effective. Surgical excision of the lesion with antibiotics for 2-4 weeks was effective. The clinical manifestation of pulmonary actinomycosis is lack of specificity, obtaining positive pathological specimens is the key to the diagnosis of this disease, the first choice is bronchoscopy and percutaneous lung biopsy.

To investigate the clinical and imaging characteristics of acute histoplasmosis. The clinical and imaging data of 10 patients with acute histoplasmosis were studied. Their clinical and imaging characteristics were analyzed. All the patients returned from a South American republic in April 2019 and were treated at the Chongqing public health medical treatment center. All the 10 patients were male, aged 30-56 years old, with an average age of 43.8 years old. Four of them were engaged in soil clearing, 2 in gas cutting, 2 in moving tools, and 2 in inspection. The disease in all the 10 patients was caused by inhaling a large amount of bacteria-bearing dust in a short time, with an incubation period of 9-13 days, and the main clinical manifestations were fever, insomnia, dizziness, headache, cough, poor appetite, rash and diarrhea. One patient's head CT showed extensive thickening and increased density of bilateral frontotemporal, parietal and occipital meninges, while the other 9 patients showed no obvious abnormalities. Chest CT findings were as follows: (1) Multiple nodular shadow: the chest CT findings of 4 patients were miliary nodular shadow with diffuse distribution in both lungs. Most of the nodules were less than 5 mm in diameter and distributed evenly or unevenly. CT findings of 6 cases showed scattered nodular shadows in both lungs, with diameters ranging from 2 to 15 mm, and obvious distribution in subpleural and inferior lobes of both lungs. (2) Consolidation shadow: in 2 cases, the size of the shadow was uneven and the density increased, mainly distributed in the subpleura and the lower lobe of both lungs. (3) Ground glass density shadow: mainly distributed around nodules, halo signs can be seen around some nodules. (4) Mediastinum and/or hilar lymph nodes were enlarged. (5) Pleural effusion: a small amount of pleural effusion was found in 4 cases. (6) Pericardial effusion in 3 cases. Abdominal CT showed splenomegaly in 8 cases and hepatomegaly in 1 case. Acute histoplasmosis has no specificity in clinical manifestations. However, there are still some features in CT manifestations, including multiple nodules in both lungs accompanied by halo, enlarged liver, spleen and mediastinal lymph nodes, and multiple serous cavity effusions.

Following full-thickness skin injuries, epithelialization of the wound is essential. The standard of care to achieve this wound "closure" in patients is autologous split-thickness skin grafting (STSG). However, patients living with STSGs report significant chronic impairments leading to functional deficiencies such as itch, altered sensation, fragility, hypertrophic scarring, and contractures. These features are attributable to the absence of functional dermis combined with the formation of disorganized fibrotic extracellular matrix. Recent work has demonstrated the existence of dermal progenitor cells (DPCs) residing within hair follicles that function to continuously regenerate mesenchymal tissue. The present work examines whether cultured DPCs could regenerate dermis within an STSG and improve overall graft function. Adult human DPCs were transplanted into a full-thickness skin wound in immune-compromised mice and closed with a human STSG. At 3 months, human DPCs (hDPCs) had successfully integrated into the xenograft and differentiated into various regionally specified phenotypes, improving both viscoelastic properties of the graft and mitigating pruritus.

Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS.