Gene bookmarking by the heat shock transcription factor programs the insulin-like signaling pathway.

Maternal stress can have long-lasting epigenetic effects on offspring. To examine how epigenetic changes are triggered by stress, we examined the effects of activating the universal stress-responsive heat shock transcription factor HSF-1 in the germline of Caenorhabditis elegans. We show that, when activated in germ cells, HSF-1 recruits MET-2, the putative histone 3 lysine 9 (H3K9) methyltransferase responsible for repressive H3K9me2 (H3K9 dimethyl) marks in chromatin, and negatively bookmarks the insulin receptor daf-2 and other HSF-1 target genes. Increased H3K9me2 at these genes persists in adult progeny and shifts their stress response strategy away from inducible chaperone expression as a mechanism to survive stress and instead rely on decreased insulin/insulin growth factor (IGF-1)-like signaling (IIS). Depending on the duration of maternal heat stress exposure, this epigenetic memory is inherited by the next generation. Thus, paradoxically, HSF-1 recruits the germline machinery normally responsible for erasing transcriptional memory but, instead, establishes a heritable epigenetic memory of prior stress exposure.

Neuronal IL-17 controls Caenorhabditis elegans developmental diapause through CEP-1/p53.

During metazoan development, how cell division and metabolic programs are coordinated with nutrient availability remains unclear. Here, we show that nutrient availability signaled by the neuronal cytokine, ILC-17.1, switches Caenorhabditis elegans development between reproductive growth and dormancy by controlling the activity of the tumor suppressor p53 ortholog, CEP-1. Specifically, upon food availability, ILC-17.1 signaling by amphid neurons promotes glucose utilization and suppresses CEP-1/p53 to allow growth. In the absence of ILC-17.1, CEP-1/p53 is activated, up-regulates cell-cycle inhibitors, decreases phosphofructokinase and cytochrome C expression, and causes larvae to arrest as stress-resistant, quiescent dauers. We propose a model whereby ILC-17.1 signaling links nutrient availability and energy metabolism to cell cycle progression through CEP-1/p53. These studies describe ancestral functions of IL-17 s and the p53 family of proteins and are relevant to our understanding of neuroimmune mechanisms in cancer. They also reveal a DNA damage-independent function of CEP-1/p53 in invertebrate development and support the existence of a previously undescribed C. elegans dauer pathway.

Efficacy of high-flow nasal oxygenation compared with tracheal intubation for oxygenation during laryngeal microsurgery: a randomised non-inferiority study.

BACKGROUND: Oxygenation via a high-flow nasal cannula (HFNC) can be an alternative to tracheal intubation during short apnoeic procedures. This randomised, non-inferiority study assessed the efficacy of HFNC compared with tracheal intubation in laryngeal microsurgery. METHODS: Patients (≥20 yr old) undergoing laryngeal microsurgery under general anaesthesia and neuromuscular blockade were randomised to either the HFNC or tracheal intubation groups. The primary endpoint was lowest pulse oxygen saturation (SpO2) during the first 30 min of surgery. Secondary endpoints included incidence of desaturation (SpO2 <95%), hypercarbia (transcutaneous carbon dioxide [CO2] ≥8.7 kPa), and rescue intervention. RESULTS: Amongst 130 patients randomised, 118 were included in the analysis. The lowest SpO2 was 100 (98-100)% in the HFNC group (n=56) and 100 (100-100)% in the tracheal intubation group (n=62), with a mean difference of -1.4% (95% confidence interval: -2.4% and -0.3%), failing to confirm non-inferiority with a non-inferiority margin of 2%. The peak transcutaneous CO2 and end-tidal CO2 at the end of surgery were higher in the HFNC group compared with the tracheal intubation group. Incidences of desaturation, hypercarbia, and rescue intervention were more frequent in patients receiving HFNC compared with tracheal intubation. CONCLUSIONS: HFNC oxygenation was not non-inferior to tracheal intubation for maintaining oxygen saturation during laryngeal microsurgery. Considering more frequent desaturation, hypercarbia, and requirement for rescue intervention compared with tracheal intubation, HFNC should be used with cautious monitoring even for short duration airway surgery. CLINICAL TRIAL REGISTRATION: NCT03629353.

Randomized Trial Comparing Early and Late Administration of Rocuronium Before and After Checking Mask Ventilation in Patients With Normal Airways.

BACKGROUND: During induction of general anesthesia, it is common practice to delay neuromuscular blockade until the ability to deliver mask ventilation has been confirmed. However, the benefits of this approach have never been scientifically validated. We thus compared the early and late administration of rocuronium before and after checking mask ventilation to investigate the efficiency of mask ventilation and the time to tracheal intubation in patients with normal airways. METHODS: Patients (n = 114) were randomized to receive IV rocuronium either before (early rocuronium group, n = 58) or after (late rocuronium group, n = 56) checking mask ventilation. Expiratory tidal volumes (VTs) were measured at 10, 20, 30, 40, 50, and 60 seconds after apnea during mask ventilation. We graded the ease of mask ventilation and measured the time from apnea to tracheal intubation. The primary outcome was the average of mask VTs measured at 10, 20, 30, 40, 50, and 60 seconds after apnea. The main secondary outcome was the time from apnea to tracheal intubation. STATA was used for statistical analysis. RESULTS: The average of mask VTs measured at 10, 20, 30, 40, 50, and 60 seconds after apnea was larger in the early rocuronium group than in the late rocuronium group (552 mL breath [165 mL breath] vs 393 mL breath [165 mL breath], mean difference, 160 mL breath; 95% CI, 98-221 mL breath; P < .001, unpaired t test). Because the interaction between time and group was significant in mask VTs measured at 10, 20, 30, 40, 50, and 60 seconds after apnea (P < .001, linear mixed effects model), pairwise comparisons were performed at the 6 time points. The differences in VTs between the groups were significant at 10, 20, 30, 40, and 50 seconds after apnea (P < .001 each, contrast statements in STATA). The time from apnea to tracheal intubation was shorter in the early rocuronium group than in the late rocuronium group (116 seconds [42 seconds] vs 195 seconds [41 seconds]; mean difference, -79 seconds; 95% CI, -96 to -64 seconds, P < .001). CONCLUSIONS: The early administration of rocuronium before checking mask ventilation resulted in a larger mask VT and earlier tracheal intubation than the late administration of rocuronium after checking mask ventilation in patients with normal airways.

Tube or tubeless: an anesthetic strategy for upper airway surgery.

Since the patient's airway is shared between an anesthesiologist and a surgeon, airway management during upper airway surgery can be challenging. Beyond the conventional method of general anesthesia, high-flow nasal oxygenation (HFNO) has recently been used as a key technique for tubeless anesthesia. HFNO provides humidified, heated oxygen up to 70 L/min, which promises improved oxygenation and ventilation, allowing for prolonged apneic oxygenation. In previous physiological and clinical studies, HFNO has been demonstrated that tubeless anesthesia safely provide an uninterrupted surgical field during laryngeal surgeries. Although tubeless anesthesia remains uncommon, it can be a good alternative to conventional anesthesia if an anesthesiologist and a surgeon select appropriate patients together with sufficient experience. A safe strategy for tubeless anesthesia, along with appropriate backup plans, including endotracheal intubation and high-frequency jet ventilation, should be considered for upper airway surgery.

Feasibility of ventilator-assisted tubeless anesthesia for video-assisted thoracoscopic surgery.

General anesthesia providing one-lung ventilation (OLV) with double-lumen endotracheal intubation has been considered inevitable for thoracic surgery. However, with the recent trend of less invasive surgical technique and enhanced recovery after surgery, tubeless anesthesia has been performed in various thoracic surgeries. The aim of this study was to establish a feasible and safe strategy of ventilator-assisted tubeless anesthesia in video-assisted thoracoscopic surgeries (VATS) based on single-institution experiences. We retrospectively reviewed the medical records of patients who underwent tubeless VATS from November 2019 to December 2021. Perioperative anesthetic and surgical variables as well as complications were reported. Seventeen patients with a median age of 29 and American Society of Anesthesiologists physical status I to II underwent video-assisted pulmonary wedge resection under monitored anesthesia care (MAC) using propofol and remifentanil. Mechanical ventilation was applied in synchronized intermittent mandatory ventilation with pressure support mode through facemask if respiratory support was required. During the operation, none of the patients showed hypoxemia or involuntary movement interfering operation. No patients were converted to general anesthesia or open thoracotomy unintentionally. All patients were discharged on median 2 days postoperatively without complications. Ventilator-assisted tubeless VATS is a feasible and safe option in low-risk patients undergoing video-assisted pulmonary wedge resection.

Effects of ischemic conditioning on head and neck free flap oxygenation: a randomized controlled trial.

Flap failure after microvascular reconstructive surgery is a rare but devastating complication caused by reperfusion injury and tissue hypoperfusion. Remote ischemic conditioning (RIC) provides protection against ischemia/reperfusion injury and reduces tissue infarction. We hypothesized that RIC would enhance flap oxygenation and exert organ-protective effects during head and neck free flap reconstructive surgery. Adult patients undergoing free flap transfer surgery for head and neck cancer were randomized to receive either RIC or sham-RIC during surgery. RIC consisted of four cycles of 5-min ischemia and 5-min reperfusion applied to the upper or lower extremity. The primary endpoint, tissue oxygen saturation of the flap, was measured by near-infrared spectroscopy on the first postoperative day. Organ-protective effects of RIC were evaluated with infarct size of rat hearts perfused with plasma dialysate from patients received RIC or sham-RIC. Between April 2018 and July 2019, 50 patients were randomized (each n = 25) and 46 were analyzed in the RIC (n = 23) or sham-RIC (n = 23) groups. Tissue oxygen saturation of the flap was similar between the groups (85 ± 12% vs 83 ± 9% in the RIC vs sham-RIC groups; P = 0.471). Myocardial infarct size after treatment of plasma dialysate was significantly reduced in the RIC group (44 ± 7% to 26 ± 6%; P = 0.018) compared to the sham-RIC group (42 ± 6% to 37 ± 7%; P = 0.388). RIC did not improve tissue oxygenation of the transferred free flap in head and neck cancer reconstructive surgery. However, there was evidence of organ-protective effects of RIC in experimental models.Trial registration: Registry number of ClinicalTrials.gov: NCT03474952.

Hypertrophic osteoarthropathy in renal cell carcinoma - A case report.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a rare clinical condition including an abnormal periosteal reaction in the long bones that causes painful swelling and tenderness of the extremities, digital clubbing, arthritis, synovitis, and joint effusions. Most cases are associated with tumorous conditions and most commonly with lung cancer. HOA has been rarely reported in association with other cancers. CASE: A patient with a history of recurrent renal cell carcinoma was referred to our clinic with bilateral leg pain, knee joint effusion, and arthritis. Simple radiography and bone scintigraphy confirmed a diagnosis of HOA. Oral non-steroidal anti-inflammatory drugs, joint fluid aspiration, and intra-articular injection of pain medications were found to be effective in the management of HOA pain. CONCLUSIONS: HOA prognosis depends on the underlying disease, therefore, cancer treatment is critical. This case demonstrates the need to consider HOA in patients with various malignancies who present with bone or joint pain of the extremities.

Repeated intermittent hypoxic stimuli to operative lung reduce hypoxemia during subsequent one-lung ventilation for thoracoscopic surgery: A randomized controlled trial.

BACKGROUND: An intervention to potentiate hypoxic pulmonary vasoconstriction may reduce intrapulmonary shunt and hypoxemia during one-lung ventilation. Previous animal studies reported that repeated intermittent hypoxic stimuli potentiated hypoxic pulmonary vasoconstriction, but no clinical study has examined the effects of this intervention on hypoxemia during one-lung ventilation. We thus performed a single-center, parallel-group, double-blind, randomized controlled trial to investigate whether repeated intermittent hypoxic stimuli to the operative lung reduce hypoxemia during the subsequent one-lung ventilation for thoracoscopic surgery. METHODS: Patients undergoing one-lung ventilation were randomized into two groups (n = 68 each). Before one-lung ventilation, in the intermittent hypoxia group, the nondependent lung was not ventilated for 2 min and then ventilated for 2 min while the dependent lung was continuously ventilated. This was repeated five times. In the continuous normoxia group, both lungs were ventilated for 20 min. We measured SpO2, PaO2, FiO2, PaCO2, SaO2, and central venous oxygen saturation during one-lung ventilation. The primary outcome was the number of patients with hypoxemia defined as a SpO2 <95% during one-lung ventilation, which was analyzed with a chi-squared test. RESULTS: Hypoxemia was less frequent in the intermittent hypoxia group than in the continuous normoxia group during OLV [6/68 (8.8%) vs 17/68 (25.0%), risk ratio (95% CI) 0.35 (0.15-0.84), p = 0.012]. The PaO2 (p = 0.008 for 30 min and 0.007 for 60 min) and PaO2/FiO2 (p = 0.008 for both) were higher 30 and 60 min after starting one-lung ventilation, and the alveolar-arterial pressure gradient (p = 0.010) and shunt index (p = 0.008) were lower 30 min after starting one-lung ventilation in the intermittent hypoxia group than in the continuous normoxia group. Postoperative adverse events did not differ significantly between groups. CONCLUSIONS: Repeated intermittent hypoxic stimuli to the operative lung seemed to potentiate hypoxic pulmonary vasoconstriction, and thus reduced hypoxemia during the subsequent one-lung ventilation.

Augmentation of curved tip of left-sided double-lumen tubes to reduce right bronchial misplacement: A randomized controlled trial.

BACKGROUND: During intubation with a blind technique, a left-sided double-lumen tube (DLT) can be misdirected into the right bronchus even though its curved tip of the bronchial lumen turns to the left. This right bronchial misplacement may be associated with the tip angle of DLTs. We thus performed a randomized trial to test the hypothesis that the DLT with an acute tip angle enters the right bronchus less frequently than the tube with an obtuse tip angle. METHODS: We randomized surgical patients (n = 1427) receiving a polyvinyl chloride left-sided DLT. Before intubation, the curved tip was further bent to an angle of 135° and kept with a stylet inside in the curved-tip group, but not in the control group. After the tip was inserted into the glottis under direct or video laryngoscopy, the stylet was removed and the DLT was advanced into the bronchus with its tip turning to the left. We checked which bronchus was intubated, and the time and number of attempts for intubation. After surgery, we assessed airway injury, sore throat, and hoarseness. The primary outcome was the incidence of right bronchial misplacement of the DLT. RESULTS: DLTs were misdirected into the right bronchus more frequently in the control group than in the curved-tip group: 57/715 (8.0%) vs 17/712 (2.4%), risk ratio (95% CI) 3.3 (2.0-5.7), P < 0.001. The difference was significant in the use of 32 (P = 0.003), 35 (P = 0.007), and 37 (P = 0.012) Fr DLTs. Intubation required longer time (P < 0.001) and more attempts (P = 0.002) in the control group. No differences were found in postoperative airway injury, sore throat and hoarseness. CONCLUSIONS: Before intubation of left-sided DLTs, augmentation of the curved DLT tip reduced the right bronchial misplacement and facilitated intubation without aggravating airway injury.

Involvement of calcium-mediated apoptotic signals in H2O2-induced MIN6N8a cell death.

Reactive oxygen species are believed to be the central mediators of beta-cell destruction that leads to type 1 and 2 diabetes, and calcium has been reported to be an important mediator of beta cell death. In the present study, the authors investigated whether Ca(2+) plays a role in hydrogen peroxide (H(2)O(2))-induced MIN6N8a mouse beta cell death. Treatment with low concentration H(2)O(2) (50 microM) was found to be sufficient to reduce MIN6N8a cell viability by 55%, largely via apoptosis. However, this H(2)O(2)-induced cell death was near completely blocked by pretreatment with BAPTA/AM (5 microM), a chelator of intracellular Ca(2+). Moreover, the intracellular calcium store channel blockers, such as, xestospongin c and ryanodine, significant protected cells from 50 microM H(2)O(2)-induced cell death and under extracellular Ca(2+)-free conditions, 50 microM H(2)O(2) elicited transient [Ca(2+)](i) increases. In addition, pharmacologic inhibitors of calpain, calcineurin, and calcium/calmodulin-dependent protein kinase II were found to have a protective effect on H(2)O(2)-induced death. Moreover, H(2)O(2)-induced apoptotic signals, such as c-JUN N-terminal kinase activation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase cleavage were all down-regulated by the intracellular Ca(2+) chelation. These findings show that [Ca(2+)](i) elevation, possibly due to release from intracellular calcium stores and the subsequent activation of Ca(2+)-mediated apoptotic signals, critically mediates low concentration H(2)O(2)-induced MIN6N8a cell death. These findings suggest that a breakdown of calcium homeostasis by low level of reactive oxygen species may be involved in beta cell destruction during diabetes development.

Sudden severe hyperammonemia and status epilepticus -a case report-.

There are various causes to a low level of consciousness in patients in the intensive care unit. Neurological injury, infection, and metabolic disarray are considered as some of the causes. A 39 year-old female patient was transferred to our hospital with septic shock due to ascending colon perforation. The patient had previously received ovarian cancer surgery and a cycle of chemotherapy at another hospital. Emergent operation for colon perforation was successful. After the operation, she was treated in the intensive care unit for infectious and pulmonary complications. She suddenly showed deterioration in her level of consciousness and had a generalized seizure. At the time of her seizure, she had severe hyperammonemia. Brain CT showed severe cerebral edema that was absent in the CT scan taken 2 days before. Continuous renal replacement therapy was conducted but was ineffective in lowering the level of serum ammonia and the patient subsequently died.