Prediction of the Cervical Epidural Space Depth from the Skin Using Cervical X-Ray, During Cervical Epidural Block with Paramedian Approach.

Objective: The purpose of this study is to compare the actual needle depth measured during cervical epidural block (CEB) with the predicted needle depth measured through a cervical flexion x-ray image at the paramedian approach. Methods: The study was conducted based on the medical records of patients who underwent CEB at the pain clinic of Haeundae Paik Hospital. The actual needle distance (AD) was recorded after each successful CEB. The distance from the spinolaminar line to the skin, predicted median depth (PMD), was measured using lateral x-ray images. The medial to lateral distance (MLD), which is the distance from the midline of the spine to the needle insertion point, was measured using anteroposterior (AP) x-rays. The predicted paramedian depth (PPD) was calculated using the Pythagorean formula. The PMD represents the expected depth of the median approach, while the PPD represents the expected depth of the paramedian approach. The PMD, PPD, and AD were compared with each other. Results: Concordance correlation coefficient (CCC) and Bland-Altman analysis were obtained for PMD and PPD. The CCC value of PMD was measured as 0.829, and the CCC value of PPD was measured as 0.830. In the Bland-Altman analysis, PPD was measured at -0.13 ± 8.37 mm, and PMD was measured at 1.29 ± 8.38 mm. Conclusion: When performing CEB through the paramedian approach, the depth can be predicted using a cervical flexion x-ray. At this time, the PMD can also be used to predict the depth during the paramedian approach.

Transurethral resection of the prostate syndrome with severe lactic acidosis due to the use of sorbitol-mannitol irrigating fluid: A case report.

We report a case of transurethral resection of the prostate (TURP) syndrome with mild hyponatremia, severe lactic acidosis, and hypotension. A 73-year-old man with benign prostatic hyperplasia underwent monopolar TURP. Two episodes of hypotension occurred during the operation. These were corrected after injection of a bolus of ephedrine. After the operation, the hypotension persisted and lactic acidosis worsened. Abdominal distension was evident postoperatively. Abdominal ultrasound and computerized tomography revealed a large amount of fluid in the abdominal cavity. We suspected the leakage of sorbitol-containing irrigating fluid. After percutaneous drainage, the lactic acidosis resolved and hypotension stabilized.

Varicella-Zoster Virus Reactivation During the Incubation Period for Scrub Typhus: A Case Report.

BACKGROUND Herpes zoster caused by the reactivation of latent varicella-zoster virus is thought to result from the waning of specific cell-mediated immunity. Scrub typhus, an acute infectious disease caused by Orientia tsutsugamushi, affects multiple organs and is characterized by microangiopathies that result in significant vascular leakage and subsequent end-organ injury. Very few cases of reactivation of the varicella-zoster virus following scrub typhus occurrence have been reported. Furthermore, no previous studies have directly investigated whether Orientia tsutsugamushi infection is a potential risk factor for herpes zoster. CASE REPORT We present the case of a 64-year-old woman without a previous illness who simultaneously developed herpes zoster of the thoracic dermatome and scrub typhus. Clinical symptoms of scrub typhus appeared during the treatment course for herpes zoster symptoms. Based on positive virus antibody test results, the patient was diagnosed with scrub typhus. This is a unique case of reactivation of the varicella-zoster virus that occurred during a silent incubation period for scrub typhus. CONCLUSIONS This report indicates the possibility of reactivation of latent varicella-zoster virus following Orientia tsutsugamushi infection, although the relationship between the 2 remains undetermined. Physicians should be aware that scrub typhus might be a potential determinant of varicella-zoster virus reactivation.

Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance.

The heterotypic CIC structures formed of cancer and immune cells have been observed in tumor tissues. We aimed to assess the feasibility of using heterotypic CICs as a functional biomarker to predict NK susceptibility and drug resistance. The heterotypic CIC-forming cancer cells showed a lower response to NK cytotoxicity and higher proliferative ability than non-CIC cancer cells. After treatment with anticancer drugs, cancer cells that formed heterotypic CICs showed a higher resistance to anticancer drugs than non-CIC cancer cells. We also observed the formation of more CIC structures in cancer cells treated with anticancer drugs than in the non-treated group. Our results confirm the association between heterotypic CIC structures and anticancer drug resistance in CICs formed from NK and cancer cells. These results suggest a mechanism underlying immune evasion in heterotypic CIC cancer cells and provide insights into the anticancer drug resistance of cancer cells.

Neuropathic Pain Component in Patients with Cervical Radicular Pain: A Single-Center Retrospective Study.

Background and Objectives: Evidence regarding the prevalence of neuropathic pain in patients with cervical radicular pain is limited. This study aimed to investigate the prevalence of neuropathic pain components in patients with cervical radicular pain using established screening tools and identify the relationship between neuropathic pain components and clinical factors. Materials and Methods: Data from 103 patients (aged ≥ 20 years) with cervical radicular pain who visited our pain clinic were analyzed retrospectively. Demographic characteristics, history of neck surgery, pain intensity using numeric rating score, dominant pain site, duration of symptoms, and neck disability index were assessed. The prevalence of neuropathic pain components was defined according to the Douleur Neuropathique 4 questions and painDETECT questionnaire tools. Patient characteristics were compared using the chi-square test or Fisher's exact test for categorical variables and the independent t-test or Mann−Whitney U test for continuous variables. The correlation between neck disability index and other variables was analyzed using Pearson's correlation coefficient. Results: Of the 103 patients, 29 (28.1%) had neuropathic pain components. The neck disability index was significantly higher (p < 0.001) for patients in the neuropathic pain group (23.79 ± 6.35) than that in the non- neuropathic pain group (18.43 ± 7.68). The Douleur Neuropathique 4 questions (r = 0.221, p < 0.025) and painDETECT questionnaire (r = 0.368, p < 0.001) scores positively correlated with the neck disability index score. Conclusions: The prevalence of neuropathic pain components in patients with cervical radicular pain was low. The patients in our study showed a strong correlation between functional deterioration and their neuropathic pain screening score. This study may be useful in understanding the characteristics of cervical radicular pain.

Atypical Course of Vertebral Artery Identified by Ultrasound Prescan before Performing a Stellate Ganglion Block.

Ultrasound provides direct visualization of blood vessels and soft tissues around the sympathetic chain and potentially minimizes injury to these critical anatomic structures when performing stellate ganglion block (SGB). We report an atypical left vertebral artery course detected during an ultrasound prescan before performing a SGB. The left vertebral and inferior thyroid arteries were identified on the longus colli muscle's ventral surface at the C6 level. This report was the first to demonstrate ultrasound images of a vulnerable vertebral artery to intravascular injection. The study emphasized the importance of identifying the sonoanatomy before performing procedures involving the anterior cervical vertebrae.

Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

Effect of Remifentanil on Postoperative Vomiting After Strabismus Surgery in Preschool Children: A Prospective Randomized Controlled Trial.

Background: Strabismus surgery and the use of opioid are risk factors of postoperative vomiting. We evaluated whether there is a dose-dependent effect of remifentanil on the incidence of postoperative vomiting. Methods: Sixty pediatric patients who were scheduled for strabismus surgery were enrolled. Patients were randomly divided into three groups; Group H (high-dose remifentanil group), Group L (low-dose remifentanil group), and Group C (control group). After endotracheal intubation, patients in the Group H and L received an intravenous bolus dose of remifentanil of 1.0 µg/kg and 0.5 µg/kg over 2 min, respectively. Group H and L patients received a continuous infusion of remifentanil (0.1 µg/kg/min) during the surgery. The patients in Group C did not have any dose of remifentanil. Intravenous fentanyl (1 µg/kg) was administered to the patients for postoperative pain control. Results: The primary outcome was a difference of the incidence of postoperative vomiting within 24 hours after surgery. There was no significant difference in incidence of postoperative vomiting between three groups. The degree of emergence agitation and postoperative pain did not show any significant difference between three groups. Conclusions: The intraoperative administration of remifentanil did not show dose-dependent effect on postoperative vomiting in pediatric strabismus surgery.

Spontaneous intracranial hypotension following spinal anesthesia initially misdiagnosed as postdural puncture headache.

Spontaneous intracranial hypotension (SIH) is not rare, but its diagnosis remains challenging. SIH tends to be misdiagnosed as postdural puncture headache when orthostatic headache develops subsequent to spinal anesthesia because both have similar symptoms. We report the case of a 35-year-old man with orthostatic headache following spinal anesthesia, who did not respond to conventional therapy for postdural puncture headache. SIH was confirmed after epidural fluid collection was identified at the thoracic spine level on magnetic resonance myelography. Physicians must consider SIH despite a history of neuraxial block. Diagnostic work-up is necessary to identify potential cerebrospinal fluid leakage in refractory cases.

Leriche Syndrome Misdiagnosed as Complex Regional Pain Syndrome in a Patient with Neuropathic Pain Caused by a Chip Fracture: A Case Report.

INTRODUCTION: Leriche syndrome is an aortoiliac occlusive disease caused by atherosclerotic occlusion. We report a case of Leriche syndrome with a fracture that was suspected as complex regional pain syndrome (CRPS), as the post-traumatic pain gradually worsened in the form of excruciating neuropathic pain. CASE REPORT: A 52-year-old woman with a history of hypertension was referred to the Department of Pain Medicine from a local orthopedic clinic because of suspected CRPS for excruciating neuropathic pain for one month. She complained of gait dysfunction and severe pain in the right foot following an incident of trauma with the right first toe. The average pain intensity assessed using the visual analog scale (VAS) was 90 (0: no pain, 100: the worst pain imaginable), and the neuropathic pain was evident as a score of 6/10 on Douleur neuropathique 4. Allodynia, hyperalgesia, blue discoloration of the skin, asymmetric temperature change (1.38 °C), and edematous soft tissue changes were observed. Ultrasonography showed a chip fracture in the first distal phalanx of the right first toe. The diagnosis was most probably CRPS type I according to the Budapest research criteria for CRPS. However, multiple pain management techniques were insufficient in controlling the symptoms. A month and a half later, an ankle-brachial index score of less than 0.4 suggested severe peripheral artery disease. Computed tomography angiography showed total occlusion between the infrarenal abdominal aorta and the bilateral common iliac arteries. Therefore, she underwent aortic-bifemoral bypass surgery with a diagnosis of Leriche syndrome. Three months after the surgery, the average pain intensity was graded as 10 on the VAS (0-100), the color of the skin of the right first toe improved and no gait dysfunction was observed. CONCLUSION: A chip fracture in a region with insufficient blood flow could manifest as excruciating neuropathic pain in Leriche syndrome.

Effect of depth of anesthesia on the phase lag entropy in patients undergoing general anesthesia by propofol: A STROBE-compliant study.

The PLEM100 (Inbody Co., Ltd., Seoul, Korea) is a device for measuring phase lag entropy (PLE), a recently developed index for the quantification of consciousness during sedation and general anesthesia. In the present study, we assessed changes in PLE along with the level of consciousness during the induction of general anesthesia using propofol. PLE was compared with the bispectral index (BIS), which is currently the most commonly used index of consciousness.After obtaining Institutional Review Board approval and written informed consent, we enrolled 15 patients (8 men, 7 women; mean age: 37 ±â€Š9 years; mean height: 168 ±â€Š8 cm; mean weight; 68 ±â€Š11 kg) undergoing nasal bone reduction. PLE and BIS sensors were attached simultaneously, and general anesthesia was induced via target-controlled infusion (TCI) of propofol. PLE and BIS scores were recorded when the calculated effect site concentration shown on the TCI pump was equal to the target concentrations of 1.5, 2.0, 2.5, 2.8, 3.0, 3.2, 3.4, and 3.5 µg/mL (and at each 0.1 µg/mL increase, thereafter). Observer's Assessment of Alertness/Sedation (OAA/S) scores were also recorded until unconsciousness was achieved. Throughout the anesthesia period, all pairs of PLE and BIS data were collected using data acquisition software.The partial correlation coefficients between OAA/S scores and PLE, and between OAA/S scores and BIS were 0.778 (P < .001) and 0.846 (P < .001), respectively. Throughout the period of anesthesia, PLE and BIS exhibited a significant positive correlation. The partial correlation coefficient prior to the loss of consciousness was 0.838 (P < .001), and 0.669 (P < .001) following the loss of consciousness. Intra-class correlation between the 2 indices was 0.889 (P < .001) and 0.791 (P < .001) prior and following the loss of consciousness, respectively.PLE exhibited a strong and predictable correlation with both BIS and OAA/S scores. These results suggest that PLE is reliable for assessing the level of consciousness during sedation and general anesthesia.

Effect of phenylephrine infusion on hypotension induced by the beach chair position: A prospective randomized trial.

BACKGROUND: The beach chair position (BCP), used during shoulder surgery, is associated with hypotension, bradycardia, and risk of cerebral hypoperfusion. Phenylephrine is commonly used as a first treatment of choice of intraoperative hypotension during surgery. We evaluated the hemodynamic effects of 2 doses of intravenous phenylephrine infusion administered before being placed in BCP for arthroscopic shoulder surgery. The primary endpoint was the incidence of hypotension after positional change. METHODS: Sixty-six patients were randomized to receive either intravenous normal saline (group NS) or intravenous phenylephrine infusion (0.5 µg/kg/min, group LP or 1.0 µg/kg/min, group HP) for 5 minutes before being placed in the BCP. Mean arterial pressure(MAP), heart rate, stroke volume variation, and cardiac index were measured before and after positional change. RESULTS: The total incidence of hypotension after the BCP was 93.65%, but was not significantly different among the 3 groups. However, there was a significant difference in trends between the groups for MAP for 5 minutes after BCP (P = .028). Comparison of changes in MAP at 1 minute compared to post-induction MAP was significantly different between group HP and group NS (P = .014). CONCLUSION: Infusion of 0.5 and 1.0 µg/kg/min of phenylephrine for 5 minutes before the BCP has no preventive effect for incidence of hypotension. However, this study showed that 1.0 µg/kg/min of phenylephrine infusion for 5 minutes can attenuate the severity of hypotension.

Analgesia for spinal anesthesia positioning in elderly patients with proximal femoral fractures: Dexmedetomidine-ketamine versus dexmedetomidine-fentanyl.

Elderly patients with femoral fractures are anticipated to endure the most pain caused by positional changes required for spinal anesthesia. To improve pain relief, we compared the analgesic effects of intravenous dexmedetomidine-ketamine and dexmedetomidine-fentanyl combinations to facilitate patient positioning for spinal anesthesia in elderly patients with proximal femoral fractures. Forty-six patients were randomly assigned to two groups and received either 1 mg/kg of intravenous ketamine (group K) or 1 µg/kg of intravenous fentanyl (group F) concomitant with a loading dose of dexmedetomidine 1 µg/kg over 10 minutes, then dexmedetomidine infusion only was continued at 0.6 µg/kg/h for following 20 minutes, and titrated at a rate of 0.2 to 0.6 µg/kg/h until the end of surgery. After completion of the infusion of either ketamine or fentanyl, the patients were placed in the lateral position with the fracture site up. The pain score (0 = calm, 1 = facial grimacing, 2 = moaning, 3 = screaming, and 4 = unable to proceed because of restlessness or agitation) was used to describe the pain intensity in each step during the procedure (lateral positioning, hip flexion, and lumbar puncture), and quality score (0 = poor hip flexion, 1 = satisfactory hip flexion, 2 = good hip flexion, and 3 = optimal hip flexion) was used to describe the quality of posture. Group K showed a median pain score of 0 (0-1), 0 (0-0) and 0 (0-0) in lateral positioning, hip flexion and lumbar puncture, respectively, while group F showed a score of 3 (2.75-3), 3 (2-3) and 0 (0-1), respectively. The pain score in lateral positioning (P < .0001) and hip flexion (P < .0001) was significantly lower in group K than group F. Group K showed the significantly higher quality scores of spinal anesthesia positioning (P = .0044) than group F. Hemodynamic adverse effects, such as bradycardia, hypotension, and desaturation, were not significantly different between the groups. The administration of dexmedetomidine-ketamine showed a greater advantage in reducing pain intensity and increasing the quality with patient positioning during spinal anesthesia in elderly patients with proximal femoral fractures, without any serious adverse effects.

Modelling monogenic autism spectrum disorder using mouse cortical organoids.

Variants of the contactin-associated protein-like 2 (CNTNAP2), which is a member of the neurexin family of proteins, function as cell adhesion molecules. The loss of CNTNAP2 function leads to autism spectrum disorder in humans and to autistic behaviours in mice. However, the functional effects of these mutations at the cellular level during fetal developmental periods remain elusive. Here, we studied mouse cortical organoids (mCOs) derived from Cntnap2-/- (knockout, KO) mouse induced pluripotent stem cells (miPSCs). Our results showed that KO mCOs displayed inhibitory-neuron-specific defects. At the neural progenitor stage, the GABAergic-neurogenesis-governing transcriptional network was dysregulated in the absence of Cntnap2. Our findings suggest that, in the early fetal cortical development, the cell adhesion molecule Cntnap2 plays a crucial role in the regulation of the differentiation of GABAergic neurons in the organoid platform. The reduced number of GABAergic neurons was efficiently restored in KO mCOs by treatment with the antiepileptic drug retigabine, showing the effectiveness of Cntnap2 KO mCOs in the therapeutic targeting of ASD.

Metastable Reprogramming State of Single Transcription Factor-Derived Induced Hepatocyte-Like Cells.

We previously described the generation of induced hepatocyte-like cells (iHeps) using the hepatic transcription factor Hnf1a together with small molecules. These iHeps represent a hepatic state that is more mature compared with iHeps generated with multiple hepatic factors. However, the underlying mechanism of hepatic conversion involving transgene dependence of the established iHeps is largely unknown. Here, we describe the generation of transgene-independent iHeps by inducing the ectopic expression of Hnf1a using both an episomal vector and a doxycycline-inducible lentivirus. In contrast to iHeps with sustained expression of Hnf1a, transgene-independent Hnf1a iHeps lose their typical morphology and in vitro functionality with rapid downregulation of hepatic markers upon withdrawal of small molecules. Taken together, our data indicates that the reprogramming state of single factor Hnf1a-derived iHeps is metastable and that the hepatic identity of these cells could be maintained only by the continuous supply of either small molecules or the master hepatic factor Hnf1a. Our findings emphasize the importance of a factor screening strategy for inducing specific cellular identities with a stable reprogramming state in order to eventually translate direct conversion technology to the clinic.