Rejected

Scalp nerve block has been proven to be an alternative choice to opioids in multimodal analgesia. However, for the infratentorial space-occupying craniotomy, especially the suboccipital retrosigmoid craniotomy, scalp nerve block is insufficient.

Letermovir potently inhibits the cytomegalovirus (CMV)-terminase complex. Letermovir primary prophylaxis given for the first three months after allogeneic hematopoietic cell transplantation (HCT) has been shown to reduce clinically significant CMV infection and is well tolerated. Until now, only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis (SP) of CMV infection or diseases after HCT. Here we report the outcome of 80 consecutive CMV-seropositive adult patients included in the French compassionate program and who received letermovir as a SP after at least one CMV episode (infection or disease) since HCT. Letermovir was initiated at a median of 170 (49-1829) days after transplant and given orally for a median of 118 (26-396) days at the usual daily dose of 480 mg once daily and adjusted to 240 mg once daily when co-administered with cyclosporine. The donors were seronegative in 53% of the cases. Fifty patients had a current or previous graft-versus-host disease (GvHD) and 14 had experienced CMV disease since transplant. Four (5.5%) patients developed CMV breakthrough infections (n=1) or diseases (n=3) after the initiation of letermovir. In three of these four patients, further investigation of virological resistance showed a CMV UL56 mutation C325Y or W, conferring the high-level letermovir resistance. One or more adverse reactions were declared by the local investigator in 15 (19%) patients. Only two patients stopped letermovir SP because of an adverse reaction (pruritus: 1; cytopenia: 1). In our experience, letermovir given as a SP may prevent a new CMV reactivation in a high-risk patient population and can be administered for several weeks, providing a bridge between the pre-emptive or therapeutic treatment of a CMV episode and CMV-specific immune reconstitution, giving time for tapering immunosuppressants. Prospective studies are required to confirm these results.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is involved in various intracellular signaling pathways that mediate addiction, chronic pain, and other diseases, but its intracellular domain structures remain undetermined. The presence of seventeen native cysteines in α7 nAChR provides opportunities for extracting structural information through site-directed labeling of chemical probes in strategic locations, but it also creates uncertainties in channel function when those native cysteines must be mutated. Using site-directed mutagenesis and two-electrode voltage clamp electrophysiology measurements, we found that α7 nAChR's function was well tolerated for mutations of all 13 cysteines as long as two pairs of disulfide-bond cysteines remained in the extracellular domain. Furthermore, surface plasmon resonance measurements showed that the cysteine mutations did not affect α7 nAChR binding to the intracellular protein PICK1. The study suggests that a high native cysteine content does not necessarily preclude the use of single cysteine labeling for acquiring structural information of functional proteins.

To study the technical notes and clinical efficacy of full-endoscopic thoracic intervertebral discectomy via transforaminal approach. We included 16 patients with thoracic disc herniation treated by full-endoscopic thoracic discectomy via transforaminal approach between January 2017 and September 2018 in ours department of orthopedics. The average age is 53.7 years. The compressionare classified by nature: 5 cases of soft thoracic disc herniation, 7 cases of calcified or ossified thoracic disc herniation, and 4 cases of osteophyte protrusion of the posterior edge of the adjacent vertebral body of the diseased disc. All patients had symptoms of thoracic myelopathy before operation, and 7 of them had radiculopathy. Via transforaminal approach under local anesthesia, enlarged foraminoplasty and full-endoscopic thoracic discectomy were used for treatment. Observe the changes of postoperative imaging, pain symptoms and recovery of spinal cord function at 1 week, 3 months, 6 months and 1 year after operation. Back pain and radicular pain were scored with VAS, neurological function was assessed with Nurick score and mJOA score, and thoracic spine function was assessed with Oswestry disability index (ODI). All operations were successfully completed, and no intraoperative conversion of surgical methods occurred. Postoperative thoracic MRI and CT examinations of all patients showed that the spinal cord was fully decompressed without any residual compression. Back pain and radicular pain were all relieved obviously in all patients, and spinal cord function was obviously restored. Transient intercostal neuralgia occurred in 2 cases after operation, and no other surgical complications occurred. Full-endoscopic or fluoroscopic foraminoplasty and full-endoscopic thoracic discectomyvia transforaminal approach under local anesthesia is a safe and effective treatment for soft and hard thoracic disc herniation located on the ventral side of the spinal cord.

Listeria monocytogenes is a foodborne pathogen which causes life-threatening septicemia and meningoencephalitis. Defective cell-mediated immunity is a well-known risk factor of human listeriosis. We herein present a case of 64-year-old Japanese woman with relapsed and refractory follicular lymphoma (FL). Salvage chemoimmunotherapy with cyclophosphamide, vincristine, prednisolone, and obinutuzumab was followed by obinutuzumab maintenance therapy, when a follow-up computed tomography scan revealed recurrent lymphadenopathy. One month later, the patient presented with fever and headache. L. monocytogenes was recovered from an anaerobic blood culture. Cerebrospinal fluid analysis confirmed the presence of meningoencephalitis. The invasive listeriosis was successfully treated with meropenem for three weeks. There were several predisposing factors of invasive listeriosis in our case. Cell-mediated immunity was severely impaired by prior cytotoxic chemotherapy and low-dose prednisolone. Use of a proton pump inhibitor facilitated entry of the microorganism into the host. Under these circumstances, patients with relapsed and refractory FL are susceptible to invasive listeriosis even if they avoid high-level contaminated food products. Of note, physical examination at initial presentation detected periorbital vesiculopustular eruptions with surrounding erythema. Cutaneous listeriosis is a rare but recurrent manifestation which might be occasionally overlooked. Skin eruptions should be carefully examined for early diagnosis.

To evaluate the effectiveness of a group intervention in Primary Care in patients with fibromyalgia (FM) based on pain neuroscience education (PNE).

Ectropion, or eyelid eversion, is the most common form of eyelid malposition. By impairing the eyelid's protective function, ectropion can cause epiphora, lagophthalmos, keratinization, chronic irritation, pain, and ulceration. There are 5 types of ectropion, each with a different cause: congenital, paralytic, involutional, cicatricial, and mechanical. The most common presentation in dermatology is involutional eversion with a mechanical or tractional element. Several options exist for the surgical repair of ectropion and choice of technique will depend on the main pathogenic component. We review the basic anatomy of the eyelid and describe examination techniques for assessing risk and preventing ectropion and for identifying the main pathogenic component in order to select the most suitable repair technique.

The cholecystokinin 2 receptor (CCK2R) is expressed in the central nervous system and peripheral tissues, playing an important role in higher nervous and gastrointestinal functions, pain sensation, and cancer growth. CCK2R is reversibly activated by cholecystokinin or gastrin, but whether it can be activated permanently is not known. In this work, we found that CCK2R expressed ectopically in CHO-K1 cells was permanently activated in the dark by sulfonated aluminum phthalocyanine (SALPC / AlPcS4, 10-1,000 nM), as monitored by Fura-2 fluorescent calcium imaging. Permanent CCK2R activation was also observed with AlPcS, but not PcS. CCK2R previously exposed to SALPC (3 and 10 nM) was sensitized by subsequent light irradiation (> 580 nm, 31.5 mW·cm). After the genetically encoded protein photosensitizer mini singlet oxygen generator (miniSOG) was fused to the N-terminus of CCK2R and expressed in CHO-K1 cells, light irradiation (450 nm, 85 mW·cm) activated in-frame CCK2R (miniSOG-CCK2R), permanently triggering persistent calcium oscillations blocked by the CCK2R antagonist YM 022 (30 nM). From these data, it is concluded that SALPC is a long-lasting CCK2R agonist in the dark, and CCK2R is photogenetically activated permanently with miniSOG as photosensitizer. These properties of SALPC and CCK2R could be used to study CCK2R physiology and possibly for pain and cancer therapies.

We aimed to rank the most common locations of pain among Google users globally and locally and analyze secular and seasonal trends in pain-related searches in the years 2004-2019. We used data generated by Google Trends (GT) to identify and analyze global interest in topics ( = 24) related to locations of pain and how these progressed over time. We analyzed secular trends and time series decomposition to identify seasonal variations. We also calculated the interest in all topics with reference to the relative search volume (RSV) of "Abdominal pain". Google users were most commonly interested in "Headache" (1.30 [times more frequently than "Abdominal pain"]), "Abdominal pain" (1.00), and "Back pain" (0.84). "Headache" was the most frequent search term in = 41 countries, while "Abdominal pain" was the most frequent term in = 27 countries. The interest in all pain-related topics except "Dyspareunia" increased over time. The sharpest increase was observed for "Abdominal pain" (5.67 RSV/year), and "Toothache" (5.52 RSV/year). Most of the topics revealed seasonal variations. Among pain-related topics, "Headache," "Abdominal pain," and "Back pain" interested most Google users. GT is a novel tool that allows retrospective investigation of complaints among Internet users.