Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. @*Materials and Methods@#In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. @*Results@#Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. @*Conclusion@#Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

Diagnosis and treatment of nerve injury following venipuncture - A report of two cases -

Background@#Venipuncture is one of the one of the most commonly performed, minimally-invasive procedures; however, it may lead to peripheral nerve injury. Here, we describe the diagnosis, treatment, and prognosis of two self-reported cases of nerve injury during venipuncture with the aim of drawing attention to possible needle-related nerve injuries.Case: Two anesthesiologists in our hospital experienced an injury of the lateral antebrachial cutaneous branch of the musculocutaneous nerve during venipuncture. Immediately, they underwent ultrasound examinations and nerve blocks with oral medication, resulting in full recovery. @*Conclusions@#Ultrasonography is important for the early and confirmative diagnosis of a nerve injury during venipuncture, and for immediate treatment with a nerve block. Moreover, it is imperative for both the practitioner and the patient to be aware of the possible complication of nerve injury after venipuncture.

Cdo Is Required for Efficient Motor Neuron Generation of Embryonic Stem Cells

Background and Objectives@#The directed differentiation of pluripotent stem cells into motor neurons is critical for the development of disease modelling and therapeutics to intervene degenerative motor neuron diseases. Cell surface receptor Cdo functions as a coreceptor for Sonic hedgehog (Shh) with Boc and Gas1 in the patterning of ventral spinal cord neurons including motor neurons. However, the discrete function of Cdo is not fully understood. @*Methods@#and Results: In this study, we examined the role of Cdo in motor neuron generation by utilizing in vitro differentiation of Cdo＋/＋ and Cdo−/− embryonic stem cells (ESCs). In response to Shh, Cdo−/− ESCs exhibited impaired expression of motor neuron specification markers while dorsal interneuron specification markers were significantly increased, compared to Cdo＋/＋ ESCs. Reactivation of Shh signalling pathway with Smoothened (Smo) agonist (SAG) restored motor neuron specification in Cdo−/− ESCs. In addition, electrophysiological analysis revealed the immature electrical features of Cdo−/− ESCs-derived neurons which was restored by SAG. @*Conclusions@#Taken together, these data suggest that Cdo as a Shh coreceptor is required for the induction of motor neuron generation by fully activating Shh signalling pathway and provide additional insights into the biology of motor neuron development.

Ultrasound-guided treatment of common peroneal neuropathy caused by Baker’s cyst: a clinical note - A case report -

Baker’s cysts are usually located in the posteromedial side of the knee and seldom cause neuropathy. We describe the rare case of a 57-year-old woman with a popliteal cyst who presented with limping gait and pain in her lower leg. She was electronically diagnosed with common peroneal neuropathy and transferred to our pain clinic. On ultrasound examination, about 2.0 × 1.2 cm sized popliteal cyst was found to extend to the fibular head, compressing the common peroneal nerve. Therefore, ultrasound-guided aspiration of the cyst and a common peroneal nerve block were performed. Immediately after the procedure, the pain, dysesthesia, and limping gait were relieved. Although her pain and dysesthesia were relieved, she underwent the surgery because of limping gait. In this case, we found the Baker’s cyst, the cause of the common peroneal neuropathy, and treated it immediately by just simple ultrasound examination and aspiration.

Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Hypotension due to compression of the inferior vena cava by intrathoracic herniation of peritoneal fat during laparoscopic surgery: A case report

Vena cava syndrome is caused by central venous obstruction and can be divided into superior vena cava syndrome and inferior vena cava (IVC) syndrome. Symptoms and signs of IVC syndrome vary from no symptoms to lower limb edema, hypotension, and typical venous stasis changes of the lower extremities, such as brownish discoloration of the skin, woody edema, and ulceration. Carbon dioxide pneumoperitoneum, lithotomy-Trendelenburg position, and abdominal obesity could increase intra-abdominal pressure. We report a patient undergoing laparoscopic surgery who showed intrathoracic herniation of peritoneal fat induced by elevated intra-abdominal pressure due to the reasons mentioned above, resulting in IVC syndrome and hypotension perioperatively. The patient was treated with a conservative approach because he was asymptomatic except for hypotension on the first postoperative day.

Anesthetic management of a patient with glucose-6-phosphate dehydrogenase deficiency undergoing robot-assisted laparoscopic surgery: A case report

The authors describe the successful perioperative management of a 3-year-old boy from Dubai with glucose-6-phosphate dehydrogenase (G6PD) deficiency, who underwent robot-assisted laparoscopic pyeloplasty for complete right ureteropelvic junction obstruction. G6PD deficiency is a genetic disorder predisposing patients to hemolytic anemia from oxidative stress. Important considerations in anesthetic management include avoiding oxidative stress, which can be caused by various conditions, and monitoring for hypercapnia, which can cause acidosis and hemolysis. Laparoscopic surgery is usually associated with hypercapnia and therefore an increased risk for respiratory acidosis. During surgery in this particular case, efforts were made to avoid carbon dioxide retention and to keep the patient warm. General anesthesia was induced with thiopental sodium, rocuronium, and fentanyl, and maintained with sevoflurane. There were no signs of hemolysis in the perioperative period and he was discharged owing to his improved condition.

Intraoperative ventilation and hemodynamic change due to bladder perforation during transurethral resection of a bladder tumor: A case report

Transurethral resection is the most efficacious and safest urologic procedure for the treatment of benign prostatic hypertrophy, prostate cancer, and bladder cancer. Complications of transurethral resection include hemorrhage, infection, transurethral resection syndrome, and bladder perforation. Early detection of bladder perforation is important because it can cause critical ventilation and hemodynamic changes. In this case, we detected bladder perforation as the cause of ventilation and hemodynamic change intraoperatively and treated it by immediate surgical repair.

Intraoperative ventilation and hemodynamic change due to bladder perforation during transurethral resection of a bladder tumor: A case report

Transurethral resection is the most efficacious and safest urologic procedure for the treatment of benign prostatic hypertrophy, prostate cancer, and bladder cancer. Complications of transurethral resection include hemorrhage, infection, transurethral resection syndrome, and bladder perforation. Early detection of bladder perforation is important because it can cause critical ventilation and hemodynamic changes. In this case, we detected bladder perforation as the cause of ventilation and hemodynamic change intraoperatively and treated it by immediate surgical repair.

Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase

Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K+ (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca2+-activated K+, inward rectifier K+ and ATP-sensitive K+ channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca2+ channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, alpha-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.

Regulation of Adenosine-activated GIRK Channels by Gq-coupled Receptors in Mouse Atrial Myocytes

Adenosine (Ado) is an important mediator of the endogenous defense against ischemia-induced injury in the heart. The action of Ado is mediated by activation of G protein-gated inwardly rectifying K+ (GIRK) channels. In turn, GIRK channels are inhibited by reducing phosphatidylinositol 4,5-bisphosphate (PIP2) through Gq protein-coupled receptors (GqPCRs). We previously found that GIRK channels activated by acetylcholine, a muscarinic M2 acetylcholine receptor agonist, are inhibited by GqPCRs in a receptor-specific manner. However, it is not known whether GIRK channels activated by Ado signaling are also regulated by GqPCRs. Presently, this was investigated in mouse atrial myocytes using the patch clamp technique. GIRK channels were activated by 100 micrometer Ado. When Ado was repetitively applied at intervals of 5~6 min, the amplitude of second Ado-activated GIRK currents (I(K(Ado))) was 88.3+/-3.7% of the first I(K(Ado)) in the control. Pretreatment of atrial myocytes with phenylephrine, endothelin-1, or bradykinin prior to a second application of Ado reduced the amplitude of the second I(K(Ado)) to 25.5+/-11.6%, 30.5+/-5.6%, and 96.0+/-2.7%, respectively. The potency of I(K(Ado)) inhibition by GqPCRs was different with that observed in acetylcholine-activated GIRK currents (I(K(ACh))) (endothelin-1>phenylephrine>bradykinin). I(K(Ado)) was almost completely inhibited by 500 micrometer of the PIP2 scavenger neomycin, suggesting low PIP2 affinity of I(K(Ado)). Taken together, these results suggest that the crosstalk between GqPCRs and the Ado-induced signaling pathway is receptor-specific. The differential change in PIP2 affinity of GIRK channels activated by Ado and ACh may underlie, at least in part, their differential responses to GqPCR agonists.