Interscalene Brachial Plexus Block with Liposomal Bupivacaine versus Standard Bupivacaine with Perineural Dexamethasone: A Noninferiority Trial.

BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery. To extend block duration, provide adequate analgesia, and minimize opioid consumption, the use of adjuvants such as dexamethasone as well as the application of perineural liposomal bupivacaine have been proposed. This randomized, double-blinded, noninferiority trial hypothesized that perineural liposomal bupivacaine is noninferior to standard bupivacaine with perineural dexamethasone in respect to average pain scores in the first 72 h after surgery. METHODS: A total of 112 patients undergoing ambulatory shoulder surgery were randomized into two groups. The liposomal bupivacaine group received a 15-ml premixed admixture of 10 ml of 133 mg liposomal bupivacaine and 5 ml of 0.5% bupivacaine (n = 55), while the bupivacaine with dexamethasone group received an admixture of 15 ml of 0.5% standard bupivacaine with 4 mg dexamethasone (n = 56), respectively. The primary outcome was the average numerical rating scale pain scores at rest over 72 h. The mean difference between the two groups was compared against a noninferiority margin of 1.3. Secondary outcomes were analgesic block duration, motor and sensory resolution, opioid consumption, numerical rating scale pain scores at rest and movement on postoperative days 1 to 4 and again on postoperative day 7, patient satisfaction, readiness for postanesthesia care unit discharge, and adverse events. RESULTS: A liposomal bupivacaine group average numerical rating scale pain score over 72 h was not inferior to the bupivacaine with dexamethasone group (mean [SD], 2.4 [1.9] vs. 3.4 [1.9]; mean difference [95% CI], -1.1 [-1.8, -0.4]; P < 0.001 for noninferiority). There was no significant difference in duration of analgesia between the groups (26 [20, 42] h vs. 27 [20, 39] h; P = 0.851). Motor and sensory resolutions were similar in both groups: 27 (21, 48) h versus 27 (19, 40) h (P = 0.436) and 27 [21, 44] h versus 31 (20, 42) h (P = 0.862), respectively. There was no difference in opioid consumption, readiness for postanesthesia care unit discharge, or adverse events. CONCLUSIONS: Interscalene nerve blocks with perineural liposomal bupivacaine provided effective analgesia similar to the perineural standard bupivacaine with dexamethasone. The results show that bupivacaine with dexamethasone can be used interchangeably with liposomal bupivacaine for analgesia after shoulder surgery.

The Optimal Cell Salvage Settings to Maximize Hematocrit and Minimize Potassium Using the Cobe BRAT2 Autologous Blood Recovery Unit.

OBJECTIVE: The objective was to determine the optimal cell saver device settings (infusion rate and wash rate) at which hematocrit is preserved and potassium and lactate are removed from banked red blood cells (RBC). DESIGN: Red cells were washed using the Cobe BRAT 2 Autologous Blood Recovery Unit and sampled for electrolyte composition and hematocrit pre- and postwash. SETTING: This was a single-center study. INTERVENTIONS: Red cells were washed using six infusion rates (100-1,000 mL/min) and six wash rates (100-1,000 mL/min) for a total of 36 combinations. Hematocrit, potassium, glucose, and lactate were evaluated before and after washing. MEASUREMENTS AND MAIN RESULTS: At wash rates ≤400 mL/min, hematocrit increased independent of infusion rate. At wash rates ≥400 mL/min, slower infusion rates were associated with higher hematocrit compared to faster infusion rates (p < 0.0001 for a wash rate 400-800 mL/min, p < 0.0005 for a wash rate 1,000 mL/min). Maximal wash speeds were associated with decreasing hematocrit. Infusion and wash rate were both independent predictors of potassium change; slower rates were associated with a larger decrease in potassium. Glucose decreased proportionally as infusion and wash rate decreased. Lactate did not show an association with either infusion or wash rate. CONCLUSION: Red-cell washing produces higher hematocrit and lower potassium as infusion rate and wash rate decrease. A 340-mL unit of RBC can be processed in 4.26 minutes without loss of hematocrit or an increase in potassium when both infusion and wash rates are set to 400 mL/min.

Bacteremia in kidney transplant recipients: Burden, causes, and consequences.

Bacteremia is an important complication after kidney transplantation. We examined bacteremia and its outcomes in a large cohort of kidney transplant recipients. Kidney transplants from 1-Jul-2004 to 1-Dec-2014 at the Toronto General Hospital were eligible for study inclusion. Bacteremia was defined as two blood culture positives for common skin contaminants or one blood culture positive for other organisms. The cumulative incidence of first bacteremia was estimated using the Kaplan-Meier method, and risk factors were examined in a Cox proportional hazards model. The risk of graft failure or death was assessed in a time-dependent Cox model. Over follow-up, 154 of 1333 patients had at least one bacteremia episode. The cumulative incidence of first bacteremia was 6.8% (6 months) and 11.9% (5 years). Risk factors included recipient diabetes mellitus, time on dialysis, dialysis modality, delayed graft function, donor age, and donor eGFR. Bacteremia increased the risk of total graft failure (hazard ratio 2.11 [95% CI: 1.50, 2.96]), death-censored graft failure (1.73 [0.99, 3.02]), and death with graft function (2.52 [1.63, 3.89]). In conclusion, bacteremia is common after kidney transplantation and impacts both graft and patient survival. Identifying high-risk patients for targeted preventive strategies may reduce the burden and adverse consequences of this important complication.

Anaesthetic care of patients undergoing primary hip and knee arthroplasty: consensus recommendations from the International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) based on a systematic review and meta-analysis.

BACKGROUND: Evidence-based international expert consensus regarding anaesthetic practice in hip/knee arthroplasty surgery is needed for improved healthcare outcomes. METHODS: The International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) systematic review, including randomised controlled and observational studies comparing neuraxial to general anaesthesia regarding major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, genitourinary, thromboembolic, neurological, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, from 1946 to May 17, 2018 were queried. Meta-analysis and Grading of Recommendations Assessment, Development and Evaluation approach was utilised to assess evidence quality and to develop recommendations. RESULTS: The analysis of 94 studies revealed that neuraxial anaesthesia was associated with lower odds or no difference in virtually all reported complications, except for urinary retention. Excerpt of complications for neuraxial vs general anaesthesia in hip/knee arthroplasty, respectively: mortality odds ratio (OR): 0.67, 95% confidence interval (CI): 0.57-0.80/OR: 0.83, 95% CI: 0.60-1.15; pulmonary OR: 0.65, 95% CI: 0.52-0.80/OR: 0.69, 95% CI: 0.58-0.81; acute renal failure OR: 0.69, 95% CI: 0.59-0.81/OR: 0.73, 95% CI: 0.65-0.82; deep venous thrombosis OR: 0.52, 95% CI: 0.42-0.65/OR: 0.77, 95% CI: 0.64-0.93; infections OR: 0.73, 95% CI: 0.67-0.79/OR: 0.80, 95% CI: 0.76-0.85; and blood transfusion OR: 0.85, 95% CI: 0.82-0.89/OR: 0.84, 95% CI: 0.82-0.87. CONCLUSIONS: Recommendation: primary neuraxial anaesthesia is preferred for knee arthroplasty, given several positive postoperative outcome benefits; evidence level: low, weak recommendation. RECOMMENDATION: neuraxial anaesthesia is recommended for hip arthroplasty given associated outcome benefits; evidence level: moderate-low, strong recommendation. Based on current evidence, the consensus group recommends neuraxial over general anaesthesia for hip/knee arthroplasty. TRIAL REGISTRY NUMBER: PROSPERO CRD42018099935.

Xenocorneal transplantation.

PURPOSE OF REVIEW: Donor shortage in corneal transplantation is a significant problem in Asian countries and is an emerging issue worldwide. This review will discuss current knowledge of the pathogenesis of the rejection mechanism, recent advances in xenocorneal transplantation, and feasibility of porcine xenocorneal graft. RECENT FINDINGS: α-Gal epitopes which are expressed on the porcine cornea, however less than in other vascularized organs. A small animal model provided evidence of complement-mediated or antibody-mediated rejection in porcine xenocorneal transplantation. Recent progress in genetic engineering of the pig or biomedical engineering for removal of the α-Gal epitope appears to have resulted in reduction of antibody-mediated rejection. Porcine corneal xenograft is not rejected hyperacutely in all animal models. T cells predominantly mediate xenocorneal rejection through various animal models. Survival of lamellar fresh porcine grafts is longer than that of full-thickness fresh porcine grafts. Decellularized porcine grafts also demonstrate significantly longer survival than fresh grafts do. SUMMARY: Recent studies have documented the potential of the porcine corneal graft as a substitute for use in human allograft and have highlighted the mechanisms of rejection of xenocorneal transplantation. Antibody-mediated or complement-mediated xenogeneic rejection should be further explored in a large animal model.

Intrathecal Morphine Administration Does Not Affect Survival After Liver Resection for Hepatocellular Carcinoma.

Introduction. Opioids may influence tumor recurrence and cancer-free survival in hepatocellular carcinoma (HCC). The relationship between intrathecal morphine administration, tumor recurrence, and patient survival after hepatectomy for HCC is unknown. Patients and Methods. This single-center, retrospective study included 1837 liver resections between July 2002 and December 2012; 410 cases were incorporated in the final univariate and multivariate analysis. Confirmatory propensity matching yielded 65 matched pairs (intrathecal morphine vs none). Primary outcomes were recurrence of HCC and survival. Secondary outcomes included characterization of factors associated with recurrence and survival. Results. Groups were similar except for increased coronary artery disease in the no intrathecal morphine group. All patients received volatile anesthesia. Compared with no intrathecal morphine (N = 307), intrathecal morphine (N = 103) was associated with decreased intraoperative intravenous morphine administration (median difference = 12.5 mg; 95% confidence interval [CI] = 5-20 mg). There was no difference in blood loss, transfusion, 3- or 5-year survival, or recurrence in the univariate analysis. Multivariate analysis identified covariates that significantly correlated with 5-year survival: intrathecal morphine (hazard ratio [HR] = 0.527, 95% CI = 0.296-0.939), lesion diameter (HR = 1.099, 95% CI = 1.060-1.141), vascular invasion (HR = 1.658, 95% CI = 1.178-2.334), and satellite lesions (HR = 2.238, 95% CI = 1.447-3.463). Survival analysis on the propensity-matched pairs did not demonstrate a difference in 5-year recurrence or survival. Discussion and Conclusion. Multivariate analysis revealed a significant association between intrathecal morphine and 5-year survival. This association did not persist after propensity matching. The association between intrathecal morphine and HCC recurrence and survival remains unclear and prospective work is necessary to determine whether an association exists.

A Quantitative Severity Scale for Retinopathy of Prematurity Using Deep Learning to Monitor Disease Regression After Treatment.

Importance: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, but treatment failure and disease recurrence are important causes of adverse outcomes in patients with treatment-requiring ROP (TR-ROP). Objectives: To apply an automated ROP vascular severity score obtained using a deep learning algorithm and to assess its utility for objectively monitoring ROP regression after treatment. Design, Setting, and Participants: This retrospective cohort study used data from the Imaging and Informatics in ROP consortium, which comprises 9 tertiary referral centers in North America that screen high volumes of at-risk infants for ROP. Images of 5255 clinical eye examinations from 871 infants performed between July 2011 and December 2016 were assessed for eligibility in the present study. The disease course was assessed with time across the numerous examinations for patients with TR-ROP. Infants born prematurely meeting screening criteria for ROP who developed TR-ROP and who had images captured within 4 weeks before and after treatment as well as at the time of treatment were included. Main Outcomes and Measures: The primary outcome was mean (SD) ROP vascular severity score before, at time of, and after treatment. A deep learning classifier was used to assign a continuous ROP vascular severity score, which ranged from 1 (normal) to 9 (most severe), at each examination. A secondary outcome was the difference in ROP vascular severity score among eyes treated with laser or the vascular endothelial growth factor antagonist bevacizumab. Differences between groups for both outcomes were assessed using unpaired 2-tailed t tests with Bonferroni correction. Results: Of 5255 examined eyes, 91 developed TR-ROP, of which 46 eyes met the inclusion criteria based on the available images. The mean (SD) birth weight of those patients was 653 (185) g, with a mean (SD) gestational age of 24.9 (1.3) weeks. The mean (SD) ROP vascular severity scores significantly increased 2 weeks prior to treatment (4.19 [1.75]), peaked at treatment (7.43 [1.89]), and decreased for at least 2 weeks after treatment (4.00 [1.88]) (all P < .001). Eyes requiring retreatment with laser had higher ROP vascular severity scores at the time of initial treatment compared with eyes receiving a single treatment (P < .001). Conclusions and Relevance: This quantitative ROP vascular severity score appears to consistently reflect clinical disease progression and posttreatment regression in eyes with TR-ROP. These study results may have implications for the monitoring of patients with ROP for treatment failure and disease recurrence and for determining the appropriate level of disease severity for primary treatment in eyes with aggressive disease.

Monitoring Disease Progression With a Quantitative Severity Scale for Retinopathy of Prematurity Using Deep Learning.

Importance: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, but clinical diagnosis is subjective and qualitative. Objective: To describe a quantitative ROP severity score derived using a deep learning algorithm designed to evaluate plus disease and to assess its utility for objectively monitoring ROP progression. Design, Setting, and Participants: This retrospective cohort study included images from 5255 clinical examinations of 871 premature infants who met the ROP screening criteria of the Imaging and Informatics in ROP (i-ROP) Consortium, which comprises 9 tertiary care centers in North America, from July 1, 2011, to December 31, 2016. Data analysis was performed from July 2017 to May 2018. Exposure: A deep learning algorithm was used to assign a continuous ROP vascular severity score from 1 (most normal) to 9 (most severe) at each examination based on a single posterior photograph compared with a reference standard diagnosis (RSD) simplified into 4 categories: no ROP, mild ROP, type 2 ROP or pre-plus disease, or type 1 ROP. Disease course was assessed longitudinally across multiple examinations for all patients. Main Outcomes and Measures: Mean ROP vascular severity score progression over time compared with the RSD. Results: A total of 5255 clinical examinations from 871 infants (mean [SD] gestational age, 27.0 [2.0] weeks; 493 [56.6%] male; mean [SD] birth weight, 949 [271] g) were analyzed. The median severity scores for each category were as follows: 1.1 (interquartile range [IQR], 1.0-1.5) (no ROP), 1.5 (IQR, 1.1-3.4) (mild ROP), 4.6 (IQR, 2.4-5.3) (type 2 and pre-plus), and 7.5 (IQR, 5.0-8.7) (treatment-requiring ROP) (P < .001). When the long-term differences in the median severity scores across time between the eyes progressing to treatment and those who did not eventually require treatment were compared, the median score was higher in the treatment group by 0.06 at 30 to 32 weeks, 0.75 at 32 to 34 weeks, 3.56 at 34 to 36 weeks, 3.71 at 36 to 38 weeks, and 3.24 at 38 to 40 weeks postmenstrual age (P < .001 for all comparisons). Conclusions and Relevance: The findings suggest that the proposed ROP vascular severity score is associated with category of disease at a given point in time and clinical progression of ROP in premature infants. Automated image analysis may be used to quantify clinical disease progression and identify infants at high risk for eventually developing treatment-requiring ROP. This finding has implications for quality and delivery of ROP care and for future approaches to disease classification.

Determinants of long-term graft outcome in transplant glomerulopathy.

BACKGROUND: Transplant glomerulopathy (TG) is a renal allograft disease defined by glomerular basement membrane duplication with peritubular capillary basement membrane multilayering (PTCML), and associated with anti-human leukocyte antigen antibodies and C4d. Outcome in TG is poor but variable, and prognostic factors, particularly those affecting long-term outcome, are not well known. We investigated several potentially prognostic clinical and pathologic factors in TG and evaluated estimated glomerular filtration rate (eGFR) slopes to assess graft function and early decline. METHODS: We examined all cases of TG from 2001 to 2005 with at least 4-year follow-up after biopsy, excluding those with a second confounding diagnosis. RESULTS: Among 36 cases of pure TG, mean graft age at biopsy was 8.8±6 years. C4d stain was positive in 11 (33%) cases. Clinical characteristics at biopsy were not different based on C4d. C4d was associated with greater PTCML (P=0.03), peritubular capillaritis (P=0.04), and glomerulitis (P=0.03). Death-censored graft survival was significantly associated with interstitial fibrosis (P=0.001), PTCML (P=0.001), and arteriolar hyalinosis (P=0.007), and it showed a trend with proteinuria (P=0.07) and C4d positivity (P=0.08). C4d-positive cases also showed a trend toward rapid graft loss. Analysis of eGFR slopes showed a pattern of preserved, slightly negative slope from transplant until approximately 1 year before biopsy, at which point the slope became significantly more negative (P<0.001). CONCLUSION: Interstitial fibrosis, PTCML, and arteriolar hyalinosis were significant predictors of graft survival in TG. C4d positivity was associated with a more rapid rate of function decline. eGFR slope data showed significant deterioration in graft function well before the diagnostic biopsy.