How platinum-induced nephrotoxicity occurs? Machine learning prediction in non-small cell lung cancer patients.

BACKGROUND AND OBJECTIVE: Platinum-induced nephrotoxicity is a severe and unexpected adverse drug reaction that could lead to treatment failure in non-small cell lung cancer patients. Better prediction and management of this nephrotoxicity can increase patient survival. Our study aimed to build up and compare the best machine learning models with clinical and genomic features to predict platinum-induced nephrotoxicity in non-small cell lung cancer patients. METHODS: Clinical and genomic data of patients undergoing platinum chemotherapy at Wan Fang Hospital were collected after they were recruited. Twelve models were established by artificial neural network, logistic regression, random forest, and support vector machine with integrated, clinical, and genomic modes. Grid search and genetic algorithm were applied to construct the fine-tuned model with the best combination of predictive hyperparameters and features. Accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were calculated to compare the performance of the 12 models. RESULTS: In total, 118 patients were recruited for this study, among which 28 (23.73%) were experiencing nephrotoxicity. Machine learning models with clinical and genomic features achieved better prediction performances than clinical or genomic features alone. Artificial neural network with clinical and genomic features demonstrated the best predictive outcomes among all 12 models. The average accuracy, precision, recall, F1 score and area under the receiver operating characteristic curve of the artificial neural network with integrated mode were 0.923, 0.950, 0.713, 0.808 and 0.900, respectively. CONCLUSIONS: Machine learning models with clinical and genomic features can be a preliminary tool for oncologists to predict platinum-induced nephrotoxicity and provide preventive strategies in advance.

Establishing a New Normal for Hospital Care: A Whole of Hospital Approach to Coronavirus Disease 2019 (COVID-19).

Singapore's hospitals had prepared to receive patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), planning various scenarios and levels of surge with a policy of isolating all confirmed cases as inpatients. The National University Hospital adopted a whole of hospital approach to coronavirus disease 2019 (COVID-19) with 3 primary goals: zero hospital-acquired COVID-19, all patients receive timely necessary care, and maintenance of staff morale. These goals to date have been met. A large influx of COVID-19 cases required significant transformation of clinical and operational processes. Isolation room numbers almost tripled and dedicated COVID-19 cohort wards were established, elective care was postponed, and intensive care units were augmented with equipment and manpower. In the wake of the surge, establishing a new normal for hospital care requires maintaining vigilance to detect endemic COVID-19, establishing contingency plans to ramp up in case of another surge, while returning to business as usual.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

An evaluation of the I-gel supraglottic airway in 70 pediatric patients.

The I-gel is a supraglottic airway device which is commonly used in adult patients undergoing general anesthesia. In this study, we evaluated the speed of insertion, adequacy of ventilation, leak pressure, gastric tube insertion, and problems when using the I-gel in children. We included 70 patients aged between 1 and 16 years old with ASA physical status classification I or II, undergoing elective surgery requiring general anesthesia, for which use of a supraglottic airway would be appropriate. The overall insertion success rate was 96 % with a median insertion time of 25 (18-34) [7-100] s. Seventeen patients (24.3 %) experienced problems including the need for change of airway device, laryngospasm, device displacement, blood on device after removal, and postoperative sore throat. In conclusion, there was a moderate rate of problems when using the I-gel in children, and it was necessary to change the airway in a few patients to optimize ventilation.

Cerebrospinal fluid of postherpetic neuralgia patients induced interleukin-6 release in human glial cell-line T98G.

Chronic intractable pain caused by postherpetic neuralgia (PHN) can be alleviated by intrathecal (i.t.) steroid therapy. We investigated the possibility that interleukin-6 (IL-6) release in an in vitro system could be a potential marker for evaluating the effectiveness of i.t. steroid therapy in PHN patients. We studied 32 patients who received a course of i.t. injection of water-soluble dexamethasone. Their therapeutic index was calculated as such: ((Pain score before treatment - Pain score after treatment)÷Pain score before treatment)×100%, and they were divided into two groups, therapy effective (index>50%) and ineffective (index<50%). Cerebrospinal fluid (CSF) from the patients was used to stimulate cultures of T98G glioblastoma cells, and the subsequent IL-6 release was measured by enzyme-linked immunosorbent assay (ELISA). Our results showed that the CSF triggered IL-6 release from T98G cells in a volume-dependent manner. IL-6 release was significantly lower when using CSF from the therapy effective patient group (p<0.001) compared to the therapy ineffective group. In particular, therapy effective patients had less IL-6 release even before treatment as compared to therapy ineffective patients. In the therapy effective group, in vitro steroid treatment suppressed the CSF's IL-6 releasing effect almost completely, whereas in the therapy ineffective group, the IL-6 release was significantly reduced but remained detectable. These in vitro tests may provide an objective evaluation on the efficacy of i.t. steroid therapy administered to PHN patients.

Elevated prepronociceptin, nociceptin/orphanin FQ and nocistatin concentrations in rat chronic constriction nerve injury and diabetic neuropathic pain models.

Nociceptin/orphanin FQ (N/OFQ) and nocistatin are derived from the same precursor peptide, prepronociceptin. N/OFQ and nocistatin have been postulated to participate in pain modulation. In this study, we investigated whether the prepronociceptin, N/OFQ and nocistatin concentrations in the brain and spinal cord would be altered in chronic constriction injury and diabetic rat neuropathic pain models. Total brain and spinal cord lysates as well as serum from rats that had undergone chronic constriction injury and streptozocin-induced diabetic neuropathy were used to determine the concentrations of three peptides using competitive radioimmunoassay. We found that N/OFQ and prepronociceptin concentrations were significantly raised in both rat neuropathic pain models. Nocistatin was raised in the brains of post traumatic neuropathy pain rats. Overall, our data have demonstrated for the first time that prepronociceptin, N/OFQ and nocistatin concentrations are significantly altered at different tissues of two rat neuropathy pain models.

[The i-gel, a new supraglottic airway].

The i-gel, invented by Muhammed Aslam Nasir, is a new supraglottic airway, consisting of a mask and a tube. One notable feature of the i-gel is that the rim of the mask is designed to conform to the anatomical shape of the larynx. This enables the device to provide an airtight seal without the cuff mechanism. The mask is made of styrene ethylene butadiene styrene (SEBS), and changes its form, based on each patient's laryngeal anatomy. The tube consists of a breathing and a drain tube. It is possible to intubate the trachea through the breathing tube, and to insert a gastric tube through the drain tube. We used the i-gel in 20 adults who were breathing spontaneously under general anesthesia. In all, but one, patients, insertion was successful at the first attempt, with the mean insertion time of 12 s (range 8-25 s). It was also always possible to insert a gastric tube through the i-gel. No airway complications occurred during the anesthesia, and spontaneous breathing could be maintained. No blood was detected on the device, after uneventful removal in all the patients. We believe that the i-gel is useful in maintaining a clear airway during general anesthesia.

Use of the Pentax-AWS in 293 patients with difficult airways.

BACKGROUND: Several case reports have shown that the Pentax-AWS (Hoya Corporation, Tokyo, Japan), a new video laryngoscope, is useful in patients with difficult airways. METHODS: We assessed the effectiveness of the Pentax-AWS in two groups. Group 1 included 270 patients in whom direct laryngoscopy using a Macintosh laryngoscope had been difficult. Group 2 included 23 patients with predicted difficult intubation and difficult mask ventilation without previous use of the Macintosh laryngoscope. RESULTS: In group 1, the view of the glottis with the Macintosh laryngoscope was Cormack and Lehane grade 2 in 14 patients, grade 3 in 208 patients, and grade 4 in 48 patients. In 256 patients in whom the grade was 3 or 4 with the Macintosh laryngoscope, the view with the Pentax-AWS was either grade 1 or 2 in 255 patients (99.6%; 95% confidence intervals 97.8-100%). Tracheal intubation was successful with the Pentax-AWS in 268 of 270 patients (99.3%; 95% confidence interval 97.4-100%), and it failed (after two attempts) in two patients. In group 2, tracheal intubation was successful in 22 of 23 patients, and it failed in one patient. The reasons for failed intubation using the Pentax-AWS were failure to position the blade toward the glottic side of the epiglottis, inability to maneuver the endotracheal tube away from the arytenoids and into the trachea, and bleeding and swelling of the oropharynx. CONCLUSION: The success rate of tracheal intubation using the Pentax-AWS was high in patients with difficult laryngoscopy with a Macintosh laryngoscope and in patients with predicted difficult intubation.

Success of tracheal intubation with intubating laryngeal mask airways: a randomized trial of the LMA Fastrach and LMA CTrach.

BACKGROUND: The LMA CTrach system (The Laryngeal Mask Company, Singapore) is a development of the LMA Fastrach system (The Laryngeal Mask Company, Singapore), with integrated fiberoptic bundles and a detachable liquid crystal display viewer. This randomized study of 271 patients compared tracheal intubation with these two systems. METHODS: In both groups, ventilation was optimized after insertion of the laryngeal mask conduit before proceeding further: intubation with the LMA Fastrach, and optimizing the conduit placement and view and then intubation with the LMA CTrach. The first-attempt and overall success rates of tracheal intubation, and the times required, were recorded. RESULTS: Tracheal intubation was successful on the first attempt in 93.3% of patients with the LMA CTrach and 67.9% of patients with the LMA Fastrach (P < 0.001). The success rates within three attempts were 100% with the LMA CTrach and 96.4% with the LMA Fastrach (P = 0.06). The median (interquartile range) time for the complete tracheal intubation process was 116 (82-156) s with the LMA CTrachand 100 (74-121) s with the LMA Fastrach (P = 0.002). There was no correlation between the grade of conventional laryngoscopy and success of intubation with either system. CONCLUSIONS: The ability to view the glottis and optimize placement of the LMA CTrach under vision enabled a higher first-attempt success rate of tracheal intubation with the LMA CTrach. However, more time is required with the LMA CTrach, there are failed views in some patients, and its cost effectiveness remains unclear.

Localization of nocistatin-binding sites in mice brain and spinal cord using a biotinylated nocistatin probe.

Nocistatin and nociceptin/orphanin FQ are two neuropeptides processed from the same precursor prepronociceptin. They have opposing roles in nociception and several other biological functions. Whereas the location and structure of the nociceptin/orphanin FQ receptors has been defined, the location of the nocistatin receptors remains unknown. In the course of this study, we synthesized a novel probe for histochemistry by linking biotin to the N terminus of nocistatin, and purified this with high-pressure liquid chromatography and confirmed the structure by mass spectrometer. Using this probe, we found nocistatin-binding sites in the cerebral cortex and the dorsal horn nucleus of the spinal cord. We also found that the nocistatin-binding sites were in the cell body, whereas the nociceptin/orphanin FQ binding sites were on the fibrous processes.

Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls.

BACKGROUND: Variants of certain haemostatic genes (such as that encoding factor V Leiden) are involved in the development of venous thrombosis, but studies of such variants in coronary disease have reported apparently conflicting results. We did meta-analyses on seven such haemostatic genetic variants for which the available evidence on each comprises at least 5000 coronary disease cases and at least 5000 controls. METHODS: Meta-analyses were done of 191 studies in relation to factor V G1691A (ie, factor V Leiden), factor VII G10976A, prothrombin G20210A, plasminogen activator inhibitor-1 (PAI-1) [-675] 4G/5G, and three platelet glycoprotein (GP) receptor variants (GPIa C807T, GPIbalpha T[-5]C, GPIIIa C1565T), involving a total of 66 155 coronary disease cases and 91 307 controls. We explored potential sources of heterogeneity. FINDINGS: In a combined analysis of all studies, the per-allele relative risks (RR) for coronary disease of factor V 1691A and of prothrombin 20210A were 1.17 (95% CI 1.08-1.28) and 1.31 (1.12-1.52), respectively. Combined analyses of studies of the PAI-1 [-675] 4G variant yielded a per-allele relative risk for coronary disease of 1.06 (1.02-1.10), but there was an indication of publication bias in these studies. Combined analyses of the factor VII 10976A, GPIa 807T, GPIbalpha [-5]C, and GPIIIa 1565T variants showed no significant overall associations with coronary disease, yielding per-allele RRs of 0.97 (0.91-1.04), 1.02 (0.97-1.08), 1.05 (0.96-1.13), and 1.03 (0.98-1.07), respectively. INTERPRETATION: The 1691A variant of the factor V gene and the 20210A variant of the prothrombin gene, both of which increase circulating thrombin generation, might each be moderately associated with the risk of coronary disease. Further studies are merited to assess these associations in greater detail (including any gene-gene and gene-environment interactions) and to determine any implications with regard to potential therapies designed to reverse patients' prothrombotic phenotype, such as selective plasma factor V or factor Xa inhibition.

Monitoring oxygenator expiratory isoflurane concentrations and the bispectral index to guide isoflurane requirements during cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to measure the changes in isoflurane requirements during the rewarming phase of cardiopulmonary bypass with moderate hypothermia. DESIGN: An observational study. SETTING: University hospital, single center. PARTICIPANTS: Forty patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass. INTERVENTIONS: Isoflurane requirements were quantified by measuring the concentrations in the oxygenator expiratory gas. Anesthesia was guided by bispectral index monitoring. MEASUREMENTS AND MAIN RESULTS: Isoflurane concentrations required to maintain the bispectral index between 40 and 50 during the rewarming phase of cardiopulmonary bypass were measured. There was a progressive increase in expiratory isoflurane requirements during rewarming from 30 degrees C to 37 degrees C, with a Pearson correlation coefficient of 0.78. There was a significant difference in the concentration required at 30 degrees C (0.41% +/- 0.14%) compared with 37 degrees C (1.00% +/- 0.12%). CONCLUSION: Isoflurane requirements are reduced during hypothermic cardiopulmonary bypass. Monitoring anesthetic concentrations in the oxygenator expiratory gas may be a useful adjunct to monitoring the depth of anesthesia.