A Case Report of a Diaphragmatic Defect Developing Into a Late-Presenting Congenital Diaphragmatic Hernia With Severe Respiratory Failure.

Diaphragmatic hernia is a congenital malformation, often discovered in the neonatal period, and its occurrence in adults is very rare. This patient, who was completely asymptomatic until the age of 62, had developed an intestinal obstruction and went into respiratory failure after surgery for an external auditory canal carcinoma. He was subsequently diagnosed with a late-presenting congenital diaphragmatic hernia (CDH), thus requiring surgical treatment. Anesthesiologists and critical care physicians should keep in mind the possibility of CDH as well as diaphragmatic relaxation when an unexplained elevation of the diaphragm is observed perioperatively.

Cardiac Tamponade Caused By Carbon Dioxide Insufflation During Robot-Assisted Thoracic Surgery: A Case Report.

Various complications can occur during robot-assisted thoracic surgery for mediastinal tumors owing to carbon dioxide (CO2) insufflation. This study reports the case of a 43-year-old woman who underwent robot-assisted surgery for an anterior mediastinal tumor with the subxiphoid approach. Shortly after starting CO2 insufflation, the blood pressure decreased significantly. Subsequent examination of the mediastinum revealed a left-sided pericardial injury. Cardiac tamponade due to entry of CO2 gas into the pericardial cavity was suspected. A deliberate incision was made in the right pericardium, ultimately resolving the cardiac tamponade and substantially improving the patient's blood pressure.

Hypersensitivity of myelinated A-fibers via toll-like receptor 5 promotes mechanical allodynia in tenascin-X-deficient mice associated with Ehlers-Danlos syndrome.

Deficiency of an extracellular matrix glycoprotein tenascin-X (TNX) leads to a human heritable disorder Ehlers-Danlos syndrome, and TNX-deficient patients complain of chronic joint pain, myalgia, paresthesia, and axonal polyneuropathy. We previously reported that TNX-deficient (Tnxb-/-) mice exhibit mechanical allodynia and hypersensitivity to myelinated A-fibers. Here, we investigated the pain response of Tnxb-/- mice using pharmacological silencing of A-fibers with co-injection of N-(2,6-Dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314), a membrane-impermeable lidocaine analog, plus flagellin, a toll-like receptor 5 (TLR5) ligand. Intraplantar co-injection of QX-314 and flagellin significantly increased the paw withdrawal threshold to transcutaneous sine wave stimuli at frequencies of 250 Hz (Aδ fiber responses) and 2000 Hz (Aß fiber responses), but not 5 Hz (C fiber responses) in wild-type mice. The QX-314 plus flagellin-induced silencing of Aδ- and Aß-fibers was also observed in Tnxb-/- mice. Co-injection of QX-314 and flagellin significantly inhibited the mechanical allodynia and neuronal activation of the spinal dorsal horn in Tnxb-/- mice. Interestingly, QX-314 alone inhibited the mechanical allodynia in Tnxb-/- mice, and it increased the paw withdrawal threshold to stimuli at frequencies of 250 Hz and 2000 Hz in Tnxb-/- mice, but not in wild-type mice. The inhibition of mechanical allodynia induced by QX-314 alone was blocked by intraplantar injection of a TLR5 antagonist TH1020 in Tnxb-/- mice. These results suggest that mechanical allodynia due to TNX deficiency is caused by the hypersensitivity of Aδ- and Aß-fibers, and it is induced by constitutive activation of TLR5.

Presepsin and platelet to lymphocyte ratio predict the progression of septic subclinical acute kidney injury to septic acute kidney injury: a pilot study.

OBJECTIVE: This study aimed to determine whether presepsin and inflammation-based prognostic scores can predict the progression of septic subclinical acute kidney injury (AKI) to septic AKI among intensive care unit (ICU) patients. RESULTS: Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio (PLR), Prognostic Index, and Prognostic Nutritional Index were measured at baseline. Presepsin values and these indices were compared between septic AKI and septic subclinical AKI patients. There were 38 septic AKI patients and 21 septic subclinical AKI patients. Receiver operating characteristic curve analyses revealed the following cut-off values for AKI (relative to subclinical AKI): 708.0 (pg/ml) for presepsin on Day 1 (AUC, 0.69; sensitivity, 82%; specificity, 52%), 1283.0 (pg/ml) for presepsin on Day 2 (AUC, 0.69; sensitivity, 55%; specificity, 80%), and 368.66 for PLR (AUC, 0.67; sensitivity, 71%; specificity, 62%). Multivariate logistic regression analyses revealed PLR to be a predictor of septic subclinical AKI (odds ratio, 1.0023; 95% confidence interval, 1.0000-1.0046; p = 0.046). Presepsin and PLR predicted the progression of septic subclinical AKI to septic AKI and the prognosis of subclinical septic AKI patients.

Presepsin values and prognostic nutritional index predict mortality in intensive care unit patients with sepsis: a pilot study.

OBJECTIVE: Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. RESULTS: Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001-1.0013 (p = 0.0320).

Presepsin and prognostic nutritional index are predictors of septic acute kidney injury, renal replacement therapy initiation in sepsis patients, and prognosis in septic acute kidney injury patients: a pilot study.

BACKGROUND: Sepsis is the most common cause of acute kidney injury (AKI) among critically ill patients. This study aimed to determine whether presepsin is a predictor of septic acute kidney injury, renal replacement therapy initiation (RRTi) in sepsis patients, and prognosis in septic AKI patients. METHODS: Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, Prognostic Index, and Prognostic Nutritional Index (PNI) were measured at baseline, and total scores ("inflammation-presepsin scores [iPS]") were calculated for category classification. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with and without septic AKI or RRTi and between survivors and non-survivors. RESULTS: Receiver operating characteristic curve analyses identified the following variables as predictors of septic AKI and RRTi in sepsis patients: presepsin on Day 1 (AUC: 0.73) and Day 2 (AUC: 0.71) for septic AKI, and presepsin on Day 1 (AUC: 0.71), Day 2 (AUC: 0.9), and Day 5 (AUC: 0.96), Δpresepsin (Day 2 - Day 1) (AUC: 0.84), Δpresepsin (Day 5 - Day 1) (AUC: 0.93), and PNI (AUC: 0.72) for RRTi. Multivariate logistic regression analyses identified presepsin on Day 2 as a predictor of prognosis in septic AKI patients. CONCLUSIONS: Presepsin and PNI were found to be predictors of septic AKI, RRTi in sepsis patients, and prognosis in septic AKI patients.

Urinary neutrophil gelatinase-associated lipocalin was a predictor from the day after intensive care unit entry, but not on the day of intensive care unit entry.

BACKGROUND AND AIMS: Sepsis is the main cause of death from infection. This study aimed to determine whether neutrophil gelatinase-associated lipocalin (NGAL) values better predict mortality in septic patients when combined with inflammation-based prognostic scores. MATERIAL AND METHODS: Forty-four adult patients diagnosed according to the Sepsis-3 definition and who were admitted to the ICU were prospectively examined from June 2018 to November 2018. Urine samples were collected from each patient with a urethral balloon bag to measure NGAL after ICU entry at the following time points: immediately after and 2, 3, and 4 days after ICU entry. The Glasgow Prognostic Score, the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio, the Prognostic Nutritional Index, the Prognostic Index (PI), the Sequential Organ Failure Assessment (SOFA), and quick SOFA were examined immediately after ICU entry. Predictors of mortality were assessed by receiver operating characteristics curve (ROC) analysis, log-rank test, and multivariate logistic regression analysis. RESULTS: NGAL on day 4 (AUC: 0.94) and ΔNGAL from day 4 to day 1 (AUC: 0.9) for 28-day mortality; NGAL on day 4 (AUC: 0.94) and inflammation-NGAL score (iNS) NGAL-PI (AUC: 0.69) for 60-day mortality; ΔNGAL from day 3 to day 1 (AUC: 0.82) for 90-day mortality; and iNS NGAL-NLR (AUC: 0.71) and iNS NGAL-PI (AUC: 0.68) for in-hospital mortality were found to be predictors of mortality by ROC curve analysis. NLR (p = 0.02) for 28-day mortality; NGAL on day 2 (p = 0.031), ΔNGAL from day 2 to day 1 (p = 0.013), and NLR (p < 0.0001) for 60-day mortality; NGAL on day 2 (p = 0.017), ΔNGAL from day 2 to day 1 (p = 0.014), and NLR (p = 0.033) for 90-day mortality; and NGAL on day 2 (p = 0.007) for in-hospital mortality were found to be predictors of mortality by log-rank test. iNS NGAL-NLR (OR, 0.024; p = 0.019) for 60-day mortality and NGAL from day 3 to day 1 (OR, 1.005; p = 0.013) for 90-day mortality were found to be predictors of mortality by multivariate logistic regression analysis. CONCLUSIONS: NGAL and ΔNGAL were predictors of mortality in sepsis patients on day 2 after ICU entry and thereafter, but not on day 1.

Presepsin Values Predict Septic Acute Kidney Injury, Acute Respiratory Distress Syndrome, Disseminated Intravascular Coagulation, and Shock.

BACKGROUND: Sepsis remains a major cause of mortality in critically ill patients. This study aimed to determine whether presepsin is a predictor of septic acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and shock. METHODS: A total of 83 adult patients diagnosed with sepsis were prospectively examined. Presepsin values were measured immediately after intensive care unit (ICU) admission and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, Prognostic Index, and Prognostic Nutritional Index were also examined at baseline. For category classification, total scores were calculated (hereafter, "inflammation-presepsin scores [iPS]") as follows: a score of 1 was assigned if the presepsin value and inflammation-based prognostic scores at baseline were above cutoffs determined by receiver operating characteristic (ROC) curve analysis for 28-day mortality; a score of 0 was assigned if they were below the cutoffs (total score range, 0-2 points). Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with septic AKI, ARDS, DIC, or shock and those without these disorders. RESULTS: ROC curve analyses identified the following variables as predictors: presepsin on Days 1 and 2 for septic AKI; presepsin on Days 1 to 3; and iPS-GPS for septic ARDS; and presepsin on Day 2 and Δpresepsin (Day 2-Day 1) for septic DIC. Multivariate analysis revealed presepsin on Day 2 to be a predictor of septic DIC. CONCLUSION: Presepsin is a predictor of septic AKI, ARDS, and DIC. Combining presepsin values with GPS improved the specificity for predicting septic ARDS relative to using baseline presepsin values alone.

Evaluation of alveolar recruitment maneuver on respiratory resistance during general anesthesia: a prospective observational study.

BACKGROUND: Alveolar recruitment maneuvers enable easily reopening nonaerated lung regions via a transient elevation in transpulmonary pressure. To evaluate the effect of these maneuvers on respiratory resistance, we used an oscillatory technique during mechanical ventilation. This study was conducted to assess the effect of the alveolar recruitment maneuvers on respiratory resistance under routine anesthesia. We hypothesized that respiratory resistance at 5 Hz (R5) after the maneuver would be decreased after the lung aeration. METHODS: After receiving the ethics committee's approval, we enrolled 33 patients who were classified with an American Society of Anesthesiologists physical status of 1, 2 or 3 and were undergoing general anesthesia for transurethral resection of a bladder tumor within a 12-month period from 2017 to 2018. The recruitment maneuver was performed 30 min after endotracheal intubation. The maneuver consisted of sustained manual inflation of the anesthesia reservoir bag to a peak inspiratory pressure of 40 cmH2O for 15 s, including 5 s of gradually increasing the peak inspiratory pressure. Respiratory resistance was measured using the forced oscillation technique before and after the maneuver, and the mean R5 was calculated during the expiratory phase. The respiratory resistance and ventilator parameter results were analyzed using paired Student's t-tests, and p < 0.05 was considered statistically significant. RESULTS: We analyzed 31 patients (25 men and 6 women). R5 was 7.3 ± 1.6 cmH2O/L/sec before the recruitment maneuver during mechanical ventilation and was significantly decreased to 6.4 ± 1.7 cmH2O/L/sec after the maneuver. Peak inspiratory pressure and plateau pressure were significantly decreased, and pulmonary compliance was increased, although the values were not clinically relevant. CONCLUSION: The recruitment maneuver decreased respiratory resistance and increased lung compliance during mechanical ventilation. TRIAL REGISTRATION: Name of registry: Japan Medical Association Center for Clinical Trials. TRIAL REGISTRATION NUMBER: reference JMA-IIA00136. Date of registration: 2 September 2013. URL of trial registry record: https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=3582.

Urinary neutrophil gelatinase-associated lipocalin values alone and combined with Prognostic Index predict septic AKI, DIC, and shock: a pilot study.

OBJECTIVE: Sepsis is a syndrome involving life-threatening organ dysfunction. The present study aimed to determine whether septic AKI, ARDS, DIC, and shock can be predicted more readily by combining uNGAL values and inflammation-based prognostic scores, over the use of uNGAL values alone. RESULTS: ROC curve analyses yielded the following cut-off values: AKI: 438.5 (ng/ml) for uNGAL at Day 1 (AUC, 0.8), 476.9 (ng/ml) for uNGAL at Day 2 (AUC, 0.86), 123.8 (ng/ml) for uNGAL at Day 3 (AUC, 0.81), 133.6 (ng/ml) for uNGAL at Day 4 (AUC, 0.78), 1.0 for iNS NGAL-NLR (AUC, 0.75), 2.0 for iNS NGAL-PI (AUC, 0.77), DIC; 648.5 (ng/ml) for uNGAL at Day 1 (AUC, 0.77); shock; 123.8 (ng/ml) for uNGAL at Day 3 (AUC, 0.71) and 9 for SOFA (AUC, 0.71). Multivariate logistic regression analyses revealed iNS NGAL-PI to be a significant independent predictor of AKI (OR, 20.62; 95% CI, 1.03-412.3; p = 0.048).

Efficacy of Goreisan in Preventing Transurethral Resection Syndrome in Transurethral Resection of the Prostate: A Randomized-Controlled Study.

Objectives: Nonconductive irrigation fluids used during transurethral resection (TUR) of the prostate can cause fluid overload and dilutional hyponatremia. TUR syndrome is generally defined as serum sodium at or below 125 mmol/L with cardiovascular and neurologic symptoms. The aim of this study was to evaluate the effects of Goreisan, a traditional Japanese Kampo medicine, on serum sodium levels and the occurrence of TUR syndrome in patients undergoing TUR of the prostate. Design: This was a randomized-controlled trial. Settings/Location: This trial was conducted at the Osaka Medical College Hospital and Keneikai Sanko Hospital. Subjects: Fifty patients scheduled for TUR of the prostate were included. Interventions: Patients in the Goreisan group (n = 23) received 2.5 g Goreisan orally on the night before surgery and on the morning of surgery. The control group (n = 27) did not receive Goreisan. Surgical procedures, perioperative management, and patient monitoring were otherwise the same in both groups. Outcome Measures: The primary outcome was occurrence of TUR syndrome. The secondary outcome was serum sodium level. Results: Serum sodium remained above 125 mmol/L in all patients, so none of the patients met the criteria for TUR syndrome. However, the Goreisan group had significantly higher intraoperative sodium levels (p < 0.001) and significantly higher intraoperative (p = 0.008) and postoperative (p = 0.02) hemoglobin levels than the control group. Conclusions: These findings indicate that preoperative Goreisan administration can help maintain serum sodium levels in patients undergoing TUR of the prostate.

Mechanical allodynia in mice with tenascin-X deficiency associated with Ehlers-Danlos syndrome.

Tenascin-X (TNX) is a member of the extracellular matrix glycoprotein tenascin family, and TNX deficiency leads to Ehlers-Danlos syndrome, a heritable human disorder characterized mostly by skin hyperextensibility, joint hypermobility, and easy bruising. TNX-deficient patients complain of chronic joint pain, myalgia, paresthesia, and axonal polyneuropathy. However, the molecular mechanisms by which TNX deficiency complicates pain are unknown. Here, we examined the nociceptive behavioral responses of TNX-deficient mice. Compared with wild-type mice, TNX-deficient mice exhibited mechanical allodynia but not thermal hyperalgesia. TNX deficiency also increased pain sensitivity to chemical stimuli and aggravated early inflammatory pain elicited by formalin. TNX-deficient mice were significantly hypersensitive to transcutaneous sine wave stimuli at frequencies of 250 Hz (Aδ fiber responses) and 2000 Hz (Aß fiber responses), but not to stimuli at frequency of 5 Hz (C fiber responses). In addition, the phosphorylation levels of extracellular signal-related kinase, an active neuronal marker, and the activity of NADPH-diaphorase, a neuronal nitric oxide activation marker, were enhanced in the spinal dorsal horns of TNX-deficient mice. These results suggest that TNX deficiency contributes to the development of mechanical allodynia and hypersensitivity to chemical stimuli, and it induces hypersensitization of myelinated A fibers and activation of the spinal dorsal horn.

Correction to: Stiripentol alleviates neuropathic pain in L5 spinal nerve-transected mice.

In the original publication of the article, the value "40-µm thickness" was incorrect in the legend of Figure 4. The correct value is 10-µm thickness.

Stiripentol alleviates neuropathic pain in L5 spinal nerve-transected mice.

PURPOSE: Antiepileptic drugs are used not only for the treatment of epilepsy but also for that of neuropathic pain. However, their action mechanisms have not always been well explained. Stiripentol, an effective antiepileptic drug indicated as a therapeutic for Dravet syndrome, was recently shown to act as an inhibitor of lactate dehydrogenase in astrocytes. In this present study, we examined the effect of stiripentol on neuropathic pain in L5 spinal nerve-transected mice. METHODS: We carried out behavioral tests using calibrated von Frey filaments and the immunohistochemistry of glial fibrillary acidic protein, an astrocyte marker, in L5 spinal nerve-transected mice after intrathecal administration of drugs. RESULTS: Like other anticonvulsants such as gabapentin and carbamazepine, stiripentol alleviated mechanical hyperalgesia induced by L5 spinal nerve transection in a dose-dependent manner, when intrathecally administered to mice 7, 14, and 28 days after L5 spinal nerve transection. Likewise, α-cyano-4-hydroxycinnamic acid, a broad inhibitor of monocarboxylate transporters, diminished mechanical hyperalgesia induced by L5 spinal nerve transection. Simultaneous administration of L-lactate negated the analgesic effect elicited by stiripentol, carbamazepine or α-cyano-4-hydroxycinnamic acid, but not that by gabapentin. None of the anticonvulsants affected the immunoreactivity of glial fibrillary acidic protein. CONCLUSIONS: This present study demonstrated that stiripentol was effective against neuropathic pain and suggested that the astrocyte-neuron lactate shuttle was involved in such pain.

Yokukansan Alleviates Cancer Pain by Suppressing Matrix Metalloproteinase-9 in a Mouse Bone Metastasis Model.

Bone cancer pain control is difficult because it includes various characteristics of pain such as nociceptic and neuropathic pain. In this study, we investigated the effect of yokukansan (YKS), one of the traditional Japanese herbal medicines, on cancer pain in mouse bone metastasis model. Oral administration of YKS significantly alleviated pain behavior measured by quantitative body weight bearing. Furthermore, the pain behavior was also significantly alleviated by intrathecal and intraperitoneal administration of matrix metalloproteinase- (MMP-) 9 inhibitor, but not of MMP-2 inhibitor. MMP-9 expression was significantly elevated in the bone tissue on day 3 after carcinoma cell injection and in the ipsilateral spinal cord on day 7, which was suppressed by YKS administration. Taken together, these results suggest that YKS alleviates cancer pain via suppressing MMP-9 expression in bone metastasis model in mice.

Sudden, Sharp Turn in an AIDS Patient's Course Following the Onset of Fulminant Type 1 Diabetes.

A previously healthy 40-year-old Japanese male was urgently admitted with a 2-month history of dysphagia, 30-kg weight loss, and fever. Human immunodeficiency virus (HIV) antibodies and cytomegalovirus antigenemia were positive. Pneumocystis pneumonia and cytomegalovirus pneumonia were suspected. The patient was diagnosed with acquired immune deficiency syndrome (AIDS). Cytomegalovirus antigenemia became negative 20 days after the positive result. On hospital day 41, he experienced cardiopulmonary arrest. The clinical diagnosis was fulminant type 1 diabetes mellitus. He later developed hypoglycemia and was diagnosed with adrenal insufficiency accompanied by septic shock. He died of multiple organ failure 29 h post-admission to our ICU.