B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling.

Breast cancer mortality results from incurable recurrences thought to be seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling RTC survival is therefore essential for improving patient outcomes. Here, we derive a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant therapy in patients and is enriched for extracellular matrix-related pathways. In vivo CRISPR-Cas9 screening of dormancy-associated candidate genes identifies the galactosyltransferase B3GALT6 as a functional regulator of RTC fitness. B3GALT6 is required for glycosaminoglycan (GAG) linkage to proteins to generate proteoglycans, and its germline loss of function in patients causes skeletal dysplasias. We find that B3GALT6-mediated biosynthesis of heparan sulfate GAGs predicts poor patient outcomes and promotes tumor recurrence by enhancing dormant RTC survival in multiple contexts, and does so via a B3GALT6-heparan sulfate/HS6ST1-heparan 6-O-sulfation/FGF1-FGFR2 signaling axis. These findings implicate B3GALT6 in cancer and nominate FGFR2 inhibition as a promising approach to eradicate dormant RTCs and prevent recurrence.

Learning curve of i-gel insertion in novices using a cumulative sum analysis.

The i-gel, a popular second-generation supraglottic airway device, has been used in a variety of airway management situations, including as an alternative to tracheal intubation for general anesthesia, rescue in difficult airway settings, and out-of-hospital cardiac arrest resuscitation. We aimed to investigate the number of experiences needed to achieve a rapid, highly successful first attempt i-gel insertion in novices with a cumulative sum analysis. We also looked at how learning affected success rates, insertion time, and bleeding and reflex (limb movement, frowning face, or coughing) incidences. This prospective observational study included 15 novice residents from March 2017 to February 2018 in a tertiary teaching hospital. Finally, 13 residents with 35 [30-42] (median [interquartile range]) cases of i-gel insertion were analyzed. The cumulative sum analysis showed that 11 of 13 participants had an acceptable failure rate after 15 [8-20] cases. With increasing experience, success rate (P = 0.004), insertion time (P < 0.001), and incidence of bleeding (P = 0.006) all improved. However, the incidence of reflex did not change (P = 0.43). Based on our results, we suggest that 20 cases are preferable for novices to develop skills in using the i-gel in airway management.

AutoFlow® versus volume-controlled ventilation for laparoscopic gynecological surgery using LMA® ProSeal™: a randomized controlled trial.

BACKGROUND: During laparoscopic gynecological surgery, increased peak airway pressure (PAWP) can cause airway leak upon ventilation with the LMA® ProSeal™. We hypothesized that compared with the use of volume-controlled ventilation (VCV), the use of the AutoFlow® mode would decrease PAWP and airway leak during laparoscopic gynecological surgery with LMA ProSeal. METHODS: This single-center, randomized, controlled trial allocated 80 adult women undergoing elective laparoscopic gynecological surgery to one of two groups, namely, the AutoFlow group or the VCV group. Ventilation settings for both groups were 8 ml/kg of tidal volume and 5 cmH2O of positive end-expiratory pressure, and respiratory rate was adjusted to maintain end-tidal carbon dioxide at 35-40 mmHg. Airway leak, PAWP, and other ventilatory parameters and vital signs were recorded at four timepoints (1, 1 min after insertion of the gastric tube; 2, 2 min after intravenous administration of rocuronium 0.6-0.8 mg/kg; 3, 1 min after initiation of pneumoperitoneum; and 4, 1 min after changing to the Trendelenburg position). The primary outcome was PAWP during pneumoperitoneum and in the Trendelenburg position, whereas the secondary outcomes included PAWP at other timepoints and airway leak development. We used the Mann-Whitney U test for PAWP and Fisher's exact test for comparing airway leak among the groups. RESULTS: Data from 40 patients in the AutoFlow group and 39 in the VCV group were used for analysis. PAWP at pneumoperitoneum pressure and in the Trendelenburg position was significantly lower in the AutoFlow group than in the VCV group [median (interquartile range), 16 (15-18) cmH2O vs. 18 (17-19) cmH2O; P < 0.001]. Similarly, patients in the AutoFlow group showed lower PAWP at the other three timepoints measured. Airway leak occurred in four patients in the AutoFlow group and in two patients in the VCV group; however, this incidence was not significantly different (P = 0.68). CONCLUSIONS: Even though AutoFlow ventilation decreased PAWP, it did not reduce the incidence of airway leak compared with VCV during laparoscopic gynecological surgery with the LMA ProSeal. TRIAL REGISTRATION: UMIN Clinical Trials Registry, identifier UMIN000023173 .

A learning curve of LMA® ProSeal™ insertion: a prospective analysis of cumulative sum method.

PURPOSE: LMA® ProSeal™ (pLMA) has been used as an alternative to tracheal tubes. It is unclear how many cases are required to achieve proficiency in performing pLMA insertion among novice residents. Therefore, we analyzed the learning curve of pLMA insertion using a cumulative sum (CUSUM) chart and assessed the effects of learning. METHODS: In this single-center, prospective, observational study, we included 15 novice residents. Staff anesthesiologists recorded success or failure; insertion time; and incidences of bleeding or reflex including cough, hiccups, and limb movement. A successful pLMA insertion was defined as effective ventilation within two attempts with an insertion time of ≤ 120 s. Regarding CUSUM, we set acceptable and unacceptable failure rates as 20% and 40%, respectively. Further, α and ß errors were designated as 0.1. We stratified the number of cases encountered by each resident into four groups of 10 cases each (1-10, 11-20, 21-30, and ≥ 31 cases) and evaluated the effects of learning. RESULTS: Each resident encountered 44 ± 5 (mean ± SD) cases of pLMA insertion, and 14/15 achieved proficiency in performing pLMA insertion after 20 ± 8 cases. Success rate (76%, 86%, 91%, and 93%; P < 0.001) and insertion time (45 s, 35 s, 31 s, and 26 s; P < 0.001) significantly improved with increased experience; however, incidences of bleeding (16%, 10%, 8%, and 10%; P = 0.124) and reflex (5%, 3%, 3%, and 3%; P = 0.54) remained unchanged. CONCLUSION: Experience with 20 ± 8 cases is needed to achieve proficiency in performing pLMA insertion for novice residents in a tertiary teaching hospital.

Pectoral nerve II block, transversus thoracic muscle plane block, and dexmedetomidine for breast surgery in a patient with achondroplasia: a case report.

BACKGROUND: Patients with achondroplasia have various airway deformations and spinal anatomic abnormalities; therefore, performing general anesthesia and neuraxial anesthesia in such patients can be challenging. CASE PRESENTATION: A 56-year-old, 112-cm, 30-kg woman was scheduled to undergo partial mastectomy and sentinel lymph node biopsy for cancer of the right breast. She had short limbs, scoliosis, thorax deformation, and chronic moderate to severe mitral regurgitation of the mitral valve. We performed pectoral nerve II block and transversus thoracic muscle plane block and administered intravenous dexmedetomidine. The surgery was completed without the administration of any additional analgesics or sedatives. CONCLUSIONS: We successfully performed breast surgery using pectoral nerve II block, transversus thoracic muscle plane block, and sedation with dexmedetomidine in a patient with achondroplasia. We found that the combination of peripheral nerve blocks is a useful option in patients who have difficulties with both general anesthesia and neuraxial anesthesia.

Age is a predictive factor in the femoral nerve positioning: an anatomical ultrasound study.

Precise identification of the femoral nerve (FN) is essential for an ultrasound-guided femoral nerve block. We hypothesized that the distance between the FN and the femoral artery (FA) is correlated with patient age. In this prospective observational study, we evaluated the FN-FA (from the lateral edge of the FA to the medial edge of the FN) distance [0.42 ± 0.42 (mean ± standard deviation) cm] in 102 patients using ultrasound. In addition, we calculated the cross-sectional area of the iliopsoas muscle using computed tomography or magnetic resonance imaging. Multiple regression analyses revealed that age was significantly and positively correlated with the FN-FA distance (R2 = 0.72, p < 0.001) and that this correlation was greater than that between height, weight, or gender and the FN-FA distance. Further, the cross-sectional area of the iliopsoas muscle per weight was significantly correlated with age (R2 = 0.54, p < 0.001) and the FN-FA distance (R2 = 0.50, p < 0.001). These findings may help refine the ultrasound techniques used for the femoral nerve block.

[A Case Report of Mirror Syndrome after Fetoscopic Laser Photocoagulation for Twin to Twin Transfusion Syndrome].

Mirror syndrome is a rare obstetric condition where a mother "mirrors" the edema of her hydropic fetus and placenta. We present the successful resolution of mirror syndrome following fetoscopic laser photocoag- ulation for twin to twin transfusion syndrome (TTTS). A 36-year-old woman was pregnant with monocho- rionic twins. She was diagnosed with TTTS at the 23rd week of pregnancy and transported to our hospi- tal by ambulance for treatment Her human chorionic gonadotropin serum concentration was 144,437 IU - ml'. Fetoscopic laser photocoagulation was performed under local anesthesia with dexmedetomidine. How- ever, her restlessness disturbed the procedure and conversion to general anesthesia was required, which facilitated successful completion of the surgical proce- dure. Postoperatively, her vital signs were stable, and after 30 min, the saturation decreased to 80%. She was intubated, sedated with propofol, and transported to the intensive care unit A transthoracic ultrasound examination showed no cardiomyopathy. A chest X-ray suggested pulmonary edema. Pulmonary edema disap- peared immediately, and she was extubated after 36 hr. Postoperatively, the twins had a good prognosis. There are several reports of mirror syndrome after fetoscopic laser photocoagulation for TTTS. Recovery from mirror syndrome can improve following the reso- lution of fetal hydrops in TTTS using fetoscopic laser photocoagulation.

Unexpected Systolic Anterior Motion of the Mitral Valve Diagnosed by Transthoracic Echocardiography after the Induction of General Anesthesia.

We report an 87-year-old woman who presented with unexpected systolic anterior motion (SAM) of the mitral valve after the induction of general anesthesia. She was receiving medication for hypertension and cerebral infarction. There were no abnormal findings on her preoperative transthoracic echocardiography (TTE) examination. After the induction of general anesthesia, she presented with refractory hypotension. We performed TTE and diagnosed SAM of the mitral valve. Her hemodynamic state was improved by fluid infusion and administering intravenous phenylephrine. After the surgery, we performed a morphologic assessment of the patient's heart using TTE. We found a thick basal interventricular septum and a small distance from the mitral coaptation point. to the septum. This case shows that SAM of the mitral valve can occur in a patient without preoperative cardiac abnormalities. SAM of the mitral valve should be considered in the differential diagnosis of refractory hypotension, particularly in elderly patients. Perioperative TTE is a useful tool for the rapid diagnosis and treatment of hemodynamic instability.

Detection of dexmedetomidine in human breast milk using liquid chromatography-tandem mass spectrometry: Application to a study of drug safety in breastfeeding after Cesarean section.

Several analytical methods for dexmedetomidine (DEX) in human plasma have been published, but quantification of DEX in human breast milk has not been described. In this article, we describe a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method suitable for quantification of DEX in human breast milk. DEX and an internal standard were extracted in a single liquid-liquid extraction step with diethyl ether from 200µL of human breast milk. HPLC was performed on a TSK-gel ODS-100V column with isocratic elution at a flow rate of 0.3mL/min using a mobile phase of 5mM ammonium formate:0.1% formic acid in acetonitrile (60:40, v/v). Detection was performed using an API4000 mass spectrometer with positive electrospray ionization. The method was validated in the concentration range of 10pg/mL (lower limit of quantification) to 2000pg/mL. The intra- and inter-day accuracy were within ±5.8% and precision was <6.31% based on the coefficient of variation. The recoveries of DEX in human breast milk were 82.4-87.9%. Recovery and matrix effects were consistent and reproducible for human breast milk. The method is robust and was successfully used in a study of drug safety in breastfeeding in patients after administration of DEX.

Confirmation of optimal guidewire length for central venous catheter placement using transesophageal echocardiography.

STUDY OBJECTIVE: Several authors have reported rare, but severe, complications associated with the length of the intravascular guidewire during central venous catheter placement, as the wire tip can cause cardiac arrhythmia or perforation or become trapped within the vessel. Although one report investigated the optimal guidewire length using fluoroscopy, few reports have precisely measured guidewire position using transesophageal echocardiography (TEE). Here, we investigated the appropriate intravascular length of a guidewire for right internal jugular vein approach using TEE during cardiac surgery. DESIGN: A prospective observational study. SETTING: Operating room. PATIENTS: Fifty-two patients undergoing elective cardiac surgery. MEASUREMENTS: The intravascular guidewire distance from the insertion site to the superior vena cava-right atrium (SVC-RA) junction was measured by TEE. Demographic factors (height, weight, age, etc) were recorded. RESULTS: The mean distance from the access site to the SVC-RA junction was 17.8±1.3 cm (maximum/minimum =20.0/15.0 cm). There was a greater correlation with height than with weight or age. CONCLUSION: We confirmed the wire tips at all cases by ultrasonography. The distance using TEE was similar to that by fluoroscopy, but TEE was more precise. Guidewire length was weakly correlated to height. About 15 cm as minimum length should be considered the limit for guidewire length in an adult, in consideration of height, to ensure patient safety during central catheter placement for right internal jugular vein approach.

[The Usefulness of SIVA Guide® for Beginners Performing Ultrasound-guided Nerve Block with the In-plane Approach].

BACKGROUND: When performing a nerve block, the needle is usually inserted using the in-plane approach. However, it is often difficult for beginners to insert the needle. We report good results obtained using the SIVA Guide® among junior residents with no experi- ence of performing nerve blocks. METHODS: Twenty-seven junior residents partici- pated in the study. They had no previous experience of performing an ultrasound-guided nerve block. Using a phantom, the time for needle insertion to the target item at shallow layer (2 cm) and the number of minor adjustments were measured. The SIVA Guide® was fitted and measurements were taken again in the same manner. Furthermore, the time to insertion to the tar- get item in a deep layer (4 cm) and number of minor adjustments were measured. The SIVA Guide® was then fitted and measurements were taken again in the same manner. RESULTS: For both shallow and deep punctures, insertion time and the number of repeated insertions significantly improved. CONCLUSIONS: Use of the SIVA Guide® for nerve block beginners improves puncture time and the num- ber of repeated insertions, making it possible to safely perform the in-plane approach.

Socioeconomic considerations regarding a land mine victim with maxillofacial injuries.

This article describes a case we experienced while doing volunteer medical work in Cambodia for six months in 2002. By examining treatment of a 14-year-old female land mine victim with maxillofacial injuries, we report on the present socio-medical situation in Cambodia. This case suggests the lack of infrastructure, facilities, human resources, and patient education make it extremely difficult to provide patients with proper treatment, including general anesthesia. A comparison of land mine victim statistics between 2002 and 2005 reveals significant problems.