Short-term safety and effectiveness of sugammadex for surgical patients with end-stage renal disease: a two-centre retrospective study.

Sugammadex is a novel reversal agent for aminosteroid neuromuscular blocking drugs, especially rocuronium. Given its renal excretion, sugammadex is not recommended for patients with end-stage renal disease; however, reports exist of its use in this group of patients. This two-institutional retrospective observational study aimed to review the safety profile and effectiveness of sugammadex in surgical patients with end-stage renal disease who required pre-operative renal replacement therapy. Adult surgical patients with end-stage renal disease requiring pre-operative renal replacement therapy, who received sugammadex between April 2016 and January 2019, were studied. The primary outcome was the incidence of postoperative tracheal re-intubation within 48 h. The secondary outcome was the incidence of deferred tracheal extubation in the operating theatre. One hundred and fifty-eight patients were identified from 125,653 surgical patients: 48 patients (30%) underwent renal transplantation and 110 (70%) underwent non-renal transplantation procedures. There were 22 instances (14%) of deferred tracheal extubation due to surgical and/or pre-existing medical conditions. Out of the 136 patients who had the tracheal tube removed at the end of the procedure, three patients had their trachea re-intubated within 48 h: two patients developed pulmonary oedema resulting from volume overload; and one patient had worsening sepsis. No incidence of recurrence of neuromuscular blockade was observed. Of note, 24 (18%) patients were found to have incomplete neuromuscular blockade reversal with neostigmine but administration of sugammadex led to successful tracheal extubation. In conclusion, sugammadex appears to be safe and effective in adult patients with end-stage renal disease receiving pre-operative renal replacement therapy.

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine.

The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates (n = 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring M. tuberculosis drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of inhA gene promoter mutations, a diversity of mutation types in the rpoB resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.

Intraoperative arterial blood pressure lability is associated with improved 30 day survival.

BACKGROUND: Arterial blood pressure lability, defined as rapid changes in arterial blood pressure, occurs commonly during anaesthesia. It is believed that hypertensive patients exhibit more lability during surgery and that lability is associated with poorer outcomes. Neither association has been rigorously tested. We hypothesized that hypertensive patients have more blood pressure lability and that increased lability is associated with increased 30 day mortality. METHODS: This was a retrospective single-centre study of surgical patients from July 2008 to December 2012. Intraoperative data were extracted from the electronic anaesthesia record. Lability was calculated as the modulus of the percentage change in mean arterial pressure between consecutive 5 min intervals. The number of episodes of lability >10% was tabulated. Multivariate logistic regression was performed to determine the association between lability and 30 day mortality using derivation and validation cohorts. RESULTS: Inclusion criteria were met by 52 919 subjects. Of the derivation cohort, 53% of subjects were hypertensive and 42% used an antihypertensive medication. The median number of episodes of lability >10% was 9 (interquartile range 5-14) per patient. Hypertensive subjects demonstrated more lability than normotensive patients, 10 (5-15) compared with 8 (5-12), P<0.0001. In subjects taking no antihypertensive medication, lability >10% was associated with decreased 30 day mortality, odds ratio (OR) per episode 0.95 [95% confidence interval (CI) 0.92-0.97], P<0.0001. This result was confirmed in the validation cohort, OR 0.96 (95% CI 0.93-0.99), P=0.01, and in hypertensive patients taking no antihypertensive medication, OR 0.96 (95% CI 0.93-0.99), P=0.002. Use of any antihypertensive medication class reduced this effect. CONCLUSIONS: Intraoperative arterial blood pressure lability occurs more often in hypertensive patients. Contrary to common belief, increased lability was associated with decreased 30 day mortality.

Characterization of multi-drug resistant Mycobacterium tuberculosis from immigrants residing in the USA using Ion Torrent full-gene sequencing.

SUMMARY: Drug-resistant Mycobacterium tuberculosis bacterium (MTB) is spreading worldwide. Three drug-resistant isolates were detected in Burmese, Hmong, and Indian immigrants currently residing in Milwaukee, Wisconsin, USA. Ion Torrent full-gene sequencing and complete genetic analysis was performed within 5 days and compared to results from traditional drug sensitivity testing (DST). Genetic characterization of seven, full-length resistance-associated genes revealed two MDR and one highly resistant strain with important drug-resistant mutations that were confirmed by traditional DST. The rapid turnaround from sample-to-sequence underscores the public health value of Ion Torrent full-gene sequencing of MDR/XDR genes from epidemiologically significant clinical isolates.

Low intraoperative tidal volume ventilation with minimal PEEP is associated with increased mortality.

BACKGROUND: Anaesthetists have traditionally ventilated patients' lungs with tidal volumes (TVs) between 10 and 15 ml kg(-1) of ideal body weight (IBW), without the use of PEEP. Over the past decade, influenced by the results of the Acute Respiratory Distress Syndrome Network trial, many anaesthetists have begun using lower TVs during surgery. It is unclear whether the benefits of low TV ventilation can be extended into the perioperative period. METHODS: We reviewed the records of 29 343 patients who underwent general anaesthesia with mechanical ventilation between January 1, 2008 and December 31, 2011. We calculated TV kg(-1) IBW, PEEP, peak inspiratory pressure (PIP), and dynamic compliance. Cox regression analysis with propensity score matching was performed to examine the association between TV and 30-day mortality. RESULTS: Median TV was 8.6 [7.7-9.6] ml kg(-1) IBW with minimal PEEP [4.0 (2.2-5.0) cm H2O]. A significant reduction in TV occurred over the study period, from 9 ml kg(-1) IBW in 2008 to 8.3 ml kg(-1) IBW in 2011 (P=0.01). Low TV 6-8 ml kg(-1) IBW was associated with a significant increase in 30-day mortality vs TV 8-10 ml kg(-1) IBW: hazard ratio (HR) 1.6 [95% confidence interval (CI) [1.25-2.08], P=0.0002]. The association remained significant after matching: HR 1.63 [95% CI (1.22-2.18), P<0.001]. There was only a weak correlation between TV kg(-1) IBW and dynamic compliance (r=-0.006, P=0.31) and a weak-to-moderate correlation between TV kg(-1) IBW and PIP (r=0.32 P<0.0001). CONCLUSIONS: Use of low intraoperative TV with minimal PEEP is associated with an increased risk of 30-day mortality.

Influence of increased left ventricular myocardial mass on early and late mortality after cardiac surgery.

BACKGROUND: Increased left ventricular mass (LVM) is a well-recognized predictor of cardiovascular morbidity and mortality in epidemiological studies, but its impact on mortality after cardiac surgery is poorly defined. We hypothesized that patients with increased LVM index (LVMI) were more likely to have greater 30 day and 1 yr mortality. METHODS: With IRB approval, intraoperative transoesophageal echocardiography images of 844 cardiac surgical patients were reviewed. LVMI was calculated using the American Society of Echocardiography recommended formula. Outcome variables studied were 30 day and 1 yr mortality. RESULTS: Mortality within 30 days occurred in 28 patients (3.3%) and within 1 yr in 91 patients (10.8%). An almost linear relationship was found between increasing LVMI and the risk of mortality within 30 days of cardiac surgery. The odds ratio (OR) of dying within 30 days of surgery was 1.15 (95% confidence interval 1.01-1.31) per 20 g m(-2) increase in LVMI. This finding remained statistically significant in multivariate analysis controlling for the effects of age, weight, gender, surgery type, LV function, and functional status [OR=1.36 (1.11-1.66) per 20 g m(-2) increase]. Increased LVMI was not found to be a statistically significant predictor of 1 yr mortality. CONCLUSIONS: Increased LVMI, but not LV systolic function as measured by the fractional area of contraction (FAC) was identified as a strong independent predictor of perioperative mortality after adult cardiac surgery. The relationship between LVMI and risk of 30 day mortality was nearly linear. Furthermore, decreased FAC, and not LVMI, was a strong independent predictor of 1 yr mortality.

A clinical specimen collection and transport medium for molecular diagnostic and genomic applications.

Pathogen detection and genetic characterization has dramatically changed in recent years. Clinical laboratories are transitioning from traditional culture and primer-specific sequencing to more robust and rapid nucleic acid testing such as real-time PCR and meta-genomic characterization, respectively. Specimen collection is the first step in any downstream molecular diagnostic procedure. PrimeStore Molecular Transport Medium (MTM) is an optimized blend of nucleic acid stabilizing reagents that includes a non-specific internal positive control that can be amplified using real-time RT-PCR for tracking the integrity of a specimen from the point of collection to detection. PrimeStore MTM is shown here to effectively kill pathogens, including highly pathogenic H5 influenza virus, inactivate nucleases and to protect and preserve released RNA at ambient temperature for up to 30 days for downstream real-time and traditional RT-PCR detection and genetic characterization. PrimeStore MTM is also compatible with a variety of commercial extraction kits. PrimeStore is suited for routine clinical specimens and has added utility for field collection in remote areas, triage centres, border crossings and during pandemics where cold-chain, transport, and dissemination of potentially infectious pathogens are a concern.

Demonstration of opsonic activity and in vivo protection against group B streptococci type III by Streptococcus pneumoniae type 14 antisera.

The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective.

Mathematical model for describing cerebral oxygen desaturation in patients undergoing deep hypothermic circulatory arrest.

BACKGROUND: Surgical treatment for aortic arch disease requiring periods of circulatory arrest is associated with a spectrum of neurological sequelae. Cerebral oximetry can non-invasively monitor patients for cerebral ischaemia even during periods of circulatory arrest. We hypothesized that cerebral desaturation during circulatory arrest could be described by a mathematical relationship that is time-dependent. METHODS: Cerebral desaturation curves obtained from 36 patients undergoing aortic surgery with deep hypothermic circulatory arrest (DHCA) were used to create a non-linear mixed model. The model assumes that the rate of oxygen decline is greatest at the beginning before steadily transitioning to a constant. Leave-one-out cross-validation and jackknife methods were used to evaluate the validity of the predictive model. RESULTS: The average rate of cerebral desaturation during DHCA can be described as: Sct(o(2))[t]=81.4-(11.53+0.37 x t) (1-0.88 x exp (-0.17 x t)). Higher starting Sct(o(2)) values and taller patient height were also associated with a greater decline rate of Sct(o(2)). Additionally, a predictive model was derived after the functional form of a x log (b+c x delta), where delta is the degree of Sct(o(2)) decline after 15 min of DHCA. The model enables the estimation of a maximal acceptable arrest time before reaching an ischaemic threshold. Validation tests showed that, for the majority, the prediction error is no more than +/-3 min. CONCLUSIONS: We were able to create two mathematical models, which can accurately describe the rate of cerebral desaturation during circulatory arrest at 12-15 degrees C as a function of time and predict the length of arrest time until a threshold value is reached.

Cat scratch disease: a bacterial infection.

Histopathologic examination of lymph nodes from 39 patients with clinical and pathological criteria for cat scratch disease revealed delicate pleomorphic Gram-negative bacilli in 34 of the 39 nodes. They were within the walls of capillaries in or near areas of follicular hyperplasia and within microabscesses. They were best seen with the Warthin-Starry silver impregnation stain. Organisms in lymph node sections exposed to convalescent serum from three patients and to immunoperoxidase stained equally well with all three samples. The organisms did not react with hyperimmune sera to Legionella pneumophila nor to several species of Rickettsia. These bacilli appear to be the causative agents of cat scratch disease.

Characterization of novel Mycobacterium tuberculosis pncA gene mutations in clinical isolates from the Ukraine.

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis cases in the Ukraine are increasing. Pyrazinamide (PZA) is critically important for first- and second-line tuberculosis (TB) treatment regimes. However, PZA drug susceptibility testing is time consuming and technically challenging. The present study utilized Next-generation sequencing (NGS) to identify mutations in the pncA gene from clinical isolates and to assess the prevalence of pncA gene mutations in MDR/XDR-TB patients. Clinical isolates were inactivated in molecular transport media and shipped from Kharkiv, Ukraine, to San Antonio, TX. Whole-genome and targeted pncA gene sequencing was carried out using Illumina MiSeq instrumentation. Mutations were noted in 67 of 91 (74%) clinical isolates comprising substitutions, insertions, and deletions in the pncA coding and upstream promoter region. Of 45 mutation types, there were 11 novel, i.e., to date unknown, pncA mutations identified of which 3 were confirmed PZA resistant. Seven isolates contained mixed base mutations, whereas 4 harbored doubled mutations. Data reported here further support use of NGS for pncA gene characterization and may contribute in significant fashion to PZA therapy, especially in MDR- and XDR-TB patients.

Management of patients undergoing multivalvular surgery for carcinoid heart disease: the role of the anaesthetist.

BACKGROUND: The management of patients with carcinoid heart disease poses two major challenges for the anaesthetist: carcinoid crisis and low cardiac output secondary to right ventricular (RV) failure. Carcinoid crises may be precipitated by the administration of catecholamines and histamine-releasing drugs. METHODS: We analysed a series of 11 patients [six males, median (range) age 60 (42-73) yr] with severe symptomatic carcinoid heart disease who underwent multivalve surgery (right-sided valves, n=8; right- and left-sided valves, n=3) between 2001 and 2007. RESULTS: All patients received octreotide intraoperatively [650 (300-1050) microg] to prevent carcinoid symptoms and vasoplegia. Those patients on a greater preoperative octreotide regime required additional intraoperative octreotide [median (range) dose 320 (300-850) vs 750 (650-1050) mug]. Similarly, the use of greater doses of aprotinin (> 5 KIU) was associated with greater requirements for octreotide [475 (300-700) vs 750 (320-1050) microg] and higher glucose levels (> or =8.5 mmol litre(-1)). Catecholamines were generally required in those patients who presented with a worse New York Heart Association functional class. Overall mortality was 18% (n=2) and only one episode of mild intraoperative carcinoid crisis was observed. CONCLUSIONS: Carcinoid crisis and RV failure still remain the primary challenges for the anaesthesiologist while managing patients with carcinoid heart disease. Our study supports the administration of catecholamines to wean patients off cardiopulmonary bypass, particularly in the presence of myocardial dysfunction. Those patients on higher octreotide dosages may require close intraoperative glucose monitoring. Despite high operative mortality, surgical outcome has been improved potentially due to earlier patient referral and better perioperative management.

Xpert(®) MTB/RIF detection of Mycobacterium tuberculosis from sputum collected in molecular transport medium.

BACKGROUND: The Xpert(®) MTB/RIF assay is widely used for Mycobacterium tuberculosis detection. However, specimen transport remains a challenge. PrimeStore Molecular Transport Medium(®) (PS-MTM) inactivates specimens and stabilizes DNA/RNA at ambient temperature for subsequent molecular detection. OBJECTIVE: To compare the detection of M. tuberculosis concentrations in PS-MTM using Xpert and real-time polymerase chain reaction (RT-PCR), and smear-positive sputum specimens collected using a flocked swab. METHODS: Dilutions of M. tuberculosis in PS-MTM and phosphate buffered saline (PBS) were analyzed using the Xpert assay and commercial RT-PCR. Smear-positive (1+ to 3+) sputum specimens (n = 17) were transferred by flocked swab into PS-MTM and PBS, and were compared to standard 1.0 ml sputum Xpert analysis. RESULTS: Using the Xpert assay, cycle threshold values from high M. tuberculosis concentrations in PS-MTM (>10(3) colony forming units [cfu]/ml) were increased compared to control. In contrast, M. tuberculosis samples containing <10(3) cfu/ml, i.e., low concentrations, suspended in PS-MTM resulted in detection down to 10 cfu/ml. Xpert detection efficiency in PS-MTM treated samples (63.2%) was improved compared to PBS controls (34.9%). Xpert detected M. tuberculosis in all sputum specimens collected by flocked swabs in PS-MTM, and correlated with routine Xpert detection. CONCLUSIONS: PS-MTM enhances M. tuberculosis detection at low concentrations of M. tuberculosis, and provides a simplified and efficient collection method for Xpert detection.

Molecular detection of Mycobacterium tuberculosis from sputum transported in PrimeStore(®) from rural settings.

SETTING: Mopani District, South Africa. OBJECTIVE: To explore remote, molecular detection of Mycobacterium tuberculosis from sputum transported using PrimeStore(®) Molecular Transport Medium (PS-MTM) compared to settings where microscopy or Xpert(®) MTB/RIF is used as the baseline test. DESIGN: Two sputum specimens were collected from patients with cough of ⩾ 2 weeks at clinics in rural South Africa. Shortly after expectoration and before processing using Xpert, microscopy and liquid culture, a flocked swab was swirled in each of these specimens and placed in PS-MTM. Swabs were stored and transported to the United States at ambient temperature for real-time PrimeMix(®) polymerase chain reaction (PM-PCR). RESULTS: Of 132 patients, 23 (17%) were positive on microscopy, 39 (30%) on Xpert and 44 (33%) by PS-MTM/PM-PCR. Concordance of PS-MTM/PM-PCR with positive microscopy and Xpert was respectively 96% and 85%. Of 107 microscopy-negative samples, 22 (21%) were positive using PS-MTM/PM-PCR, while 11/91 (12%) Xpert-negative samples were PS-MTM/PM-PCR-positive. PS-MTM/PM-PCR positivity was significantly higher than smear microscopy positivity (P < 0.001), but similar to Xpert (P = 0.33). CONCLUSION: PCR testing of specimens transported in PS-MTM would enhance TB diagnosis in settings where smear microscopy is the baseline diagnostic test, and could provide an alternative in settings where Xpert testing is not available.

Indolethylamine-N-methyltransferase activity in psychiatric patients and controls.

The level of INMT activity was determined in the sera of 29 psychiatric patients and 11 healthy controls from St. Louis; and in 13 psychiatric patients and 15 healthy controls from Chicago. The level of enzyme activity in the serum of paranoid schizophrenics in the St. Louis group was significantly higher than in other types of schizophrenics. The mean level of enzyme activity in the serum in nonschizophrenic psychiatric patients in the Chicago group was significantly higher than that in the same group of patients from St. Louis. The serum level of INMT activity in all psychiatric patients and schizophrenic patients from St. Louis was positively correlated with severity of delusions. The only significant difference in the Chicago patients was that the occurrence of depressive features was greater in the group of patients with a low serum INMT level than in the group with a high enzyme level.

Immunoglobulin levels in psychiatric patients.

In a study of 19 schizophrenic patients, 7 nonschizophrenic patients, and 31 controls, the authors found significantly higher mean serum levels of 1) immunoglobulin A in schizophrenic women then in control women and in schizophrenic blacks than in either schizophrenic whites or black controls. 2) immunoglobulin D in schizophrenic blacks than in schizophrenic whites, 3) immunoglobulin M in controls than in nonschizophrenic patients, and 4) immunoglobulin G (IgG) in schizophrenics whose urine was positive for phenothiazines than in schizophrenics whose urine was negative for phenothiazines. High serum levels of IgG were associated with no or mild hallucinations and low levels with moderate or severe hallucinations. Black female patients had significantly more severe hallucinaions than white female patients. The authors discuss the possible implications of these findings.

Intravenous immunoglobulin in neonatal group B streptococcal disease. Pharmacokinetic and safety studies in monkeys and humans.

Numerous studies have suggested that opsonic antibody is important in neonatal immunity to group B streptococci. Immunoglobulin G is primarily transferred from the mother to the fetus across the placenta in the last few weeks of pregnancy. Premature babies may, therefore, not acquire sufficient opsonic antibody to protect them from infection with group B streptococci. Although maternal immunization may provide adequate maternal opsonic antibody, premature infants with antibody deficiency may remain susceptible to infection. Intravenous immunoglobulin administered to term pregnant rhesus monkeys did not provide reliable levels of serum opsonic activity to group B streptococci in their offspring. Pharmacokinetic and safety studies were also performed in human neonates. Significant elevations in group B streptococcal-specific IgG did occur in human neonates given 500 mg/kg intravenous immunoglobulin and the infusions appeared safe and well tolerated. The availability of intravenous immunoglobulin with functional activity against group B streptococci may provide a rapid and effective method of delivering opsonic antibody to neonates.

Immunoglobulin therapy of neonatal group B streptococcal infections: an overview.

Group B streptococci (GBS) are a major cause of sepsis and meningitis in newborn babies. Neonatal GBS infections are often rapidly progressive, suggesting that the immunity to GBS is deficient. Studies have shown that opsonic antibody is required for efficient phagocytosis and killing of GBS, and neonatal GBS infections have been associated with diminished levels of anti-GBS antibody. Intravenous immunoglobulin (IVIG) has been shown to provide protective immunity in experimental GBS infection models. However, lot to lot variation in opsonic antibody levels occurs in standard IVIG preparations. Recently hyperimmune anti-GBS IVIG has been prepared with high levels of opsonic and protective antibody to GBS. Hyperimmune IVIG preparations will allow physicians to give higher quantities of specific anti-GBS antibody without having to administer large fluid volumes or large amounts of nonspecific immunoglobulin. In addition specific immunoglobulin preparations will ensure that the IVIG contains reliable antibacterial activity. Although human studies are limited they suggest that IVIG therapy in neonates may be safe and effective in treating neonatal sepsis. However, further studies are necessary to determine the role of IVIG in preventing or treating neonatal infections.