Accuracy and Feasibility of Real-time Continuous Glucose Monitoring in Critically Ill Patients After Abdominal Surgery and Solid Organ Transplantation.

OBJECTIVE: Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery. RESEARCH DESIGN AND METHODS: We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL). RESULTS: We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (<1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%. CONCLUSIONS: Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.

Outcomes in Patients Perceived as Receiving Excessive Care by ICU Physicians and Nurses: Differences Between Patients < 75 and ≥ 75 Years of Age?

BACKGROUND: The benefit of the ICU for older patients is often debated. There is little knowledge on subjective impressions of excessive care in ICU nurses and physicians combined with objective patient data in real-life cases. RESEARCH QUESTION: Is there a difference in treatment limitation decisions and 1-year outcomes in patients < 75 and ≥ 75 years of age, with and without concordant perceptions of excessive care by two or more ICU nurses and physicians? STUDY DESIGN AND METHODS: This was a reanalysis of the prospective observational DISPROPRICUS study, performed in 56 ICUs. Nurses and physicians completed a daily questionnaire about the appropriateness of care for each of their patients during a 28-day period in 2014. We compared the cumulative incidence of patients with concordant perceptions of excessive care, treatment limitation decisions, and the proportion of patients attaining the combined end point (death, poor quality of life, or not being at home) at 1 year across age groups via Cox regression with propensity score weighting and Fisher exact tests. RESULTS: Of 1,641 patients, 405 (25%) were ≥ 75 years of age. The cumulative incidence of concordant perceptions of excessive care was higher in older patients (13.6% vs 8.5%; P < .001). In patients with concordant perceptions of excessive care, we found no difference between age groups in risk of death (1-year mortality, 83% in both groups; P > .99; hazard ratio [HR] after weighting, 1.11; 95% CI, 0.74-1.65), treatment limitation decisions (33% vs 31%; HR after weighting, 1.11; 95% CI, 0.69-2.17), and reaching the combined end point at 1 year (90% vs 93%; P = .546). In patients without concordant perceptions of excessive care, we found a difference in risk of death (1-year mortality, 41% vs 30%; P < .001; HR after weighting, 1.38; 95% CI, 1.11-1.73) and treatment limitation decisions (11% vs 5%; P < .001; HR, 2.11; 95% CI, 1.37-3.27); however, treatment limitation decisions were mostly documented prior to ICU admission. The risk of reaching the combined end point was higher in the older adults (61.6% vs 52.8%; P < .001). INTERPRETATION: Although the incidence of perceptions of excessive care is slightly higher in older patients, there is no difference in treatment limitation decisions and 1-year outcomes between older and younger patients once patients are identified by concordant perceptions of excessive care. Additionally, in patients without concordant perceptions, the outcomes are worse in the older adults, pleading against ageism in ICU nurses and physicians.

Periprocedural safety profile of peroral endoscopic myotomy (POEM)-a retrospective analysis of adverse events according to two different classifications.

BACKGROUND: Peroral endoscopic myotomy (POEM) is nowadays a standard method for treatment of achalasia; nevertheless, it remains an invasive intervention with corresponding risk of adverse events (AEs). The classification and grading of AEs are still a matter of discussion. The aim of our retrospective study was to assess the occurrence of all "undesirable" events and "true" adverse events in patients undergoing POEM and to compare the outcomes when either Clavien-Dindo classification (CDC) or American Society of Gastrointestinal Endoscopy (ASGE) lexicon classification applied. METHODS: This was a retrospective analysis of prospectively managed database of all patients who had undergone POEM between December 2012 and August 2018. We assessed the pre-, peri-, and early-postoperative (up to patient's discharge) undesirable events (including those not fulfilling criteria for AEs) and "true" AEs according the definition in either of the classifications. RESULTS: A total of 231 patients have successfully undergone 244 POEM procedures (13 × re-POEM). Twenty-nine procedures (11.9%) passed uneventfully, while in 215 procedures (88.1%), a total of 440 undesirable events occurred. The CDC identified 27 AEs (17 minor, 10 major) occurring in 23/244 (9.4%) procedures. The ASGE lexicon identified identical 27 AEs (21 mild or moderate, 6 severe or fatal) resulting in the severity distribution of AEs being the only difference between the two classifications. Only the absence of previous treatment was found to be a risk factor [p = 0.047, OR with 95% CI: 4.55 (1.02; 20.25)] in the combined logistic regression model. CONCLUSION: Undesirable events are common in patients undergoing POEM but the incidence of true AEs is low according to both classifications. Severe adverse events are infrequent irrespective of the classification applied. CDC may be more appropriate than ASGE lexicon for classifying POEM-related AEs given a surgical nature of this procedure.

Sepsis affects kidney graft function and one-year mortality of the recipients in contrast with systemic inflammatory response.

Background: Infections remain a major cause of morbidity and mortality after kidney transplantation. The aim of our study was to determine the effect of sepsis on kidney graft function and recipient mortality. Methods: A prospective, observational, single-center study was performed. Selected clinical and biochemical parameters were recorded and compared between an experimental group (with sepsis, n = 34) and a control group (with systemic inflammatory response syndrome, n = 31) comprising kidney allograft recipients. Results: Sepsis worsened both patient (HR = 14.77, p = 0.007) and graft survival (HR = 15.07, p = 0.007). Overall one-year mortality was associated with age (HR = 1.08, p = 0.048), APACHE II score (HR = 1.13, p = 0.035), and combination immunosuppression therapy (HR = 0.1, p = 0.006), while graft survival was associated with APACHE II (HR = 1.25, p = 0.004) and immunosuppression. In sepsis patients, mortality correlated with the maximal dose of noradrenalin (HR = 100.96, p = 0.008), fungal infection (HR = 5.64, p = 0.024), SAPS II score (HR = 1.06, p = 0.033), and mechanical ventilation (HR = 5.97, p = 0.033), while graft survival was influenced by renal replacement therapy (HR = 21.16, p = 0.005), APACHE II (HR = 1.19, p = 0.035), and duration of mechanical ventilation (HR = 1.01, p = 0.015). Conclusion: In contrast with systemic inflammatory response syndrome, septic kidney allograft injury is associated with early graft loss and may represent a significant risk of mortality.

Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial.

OBJECTIVE: Endoscopic pyloromyotomy (G-POEM) is a minimally invasive treatment option with promising uncontrolled outcome results in patients with gastroparesis. DESIGN: In this prospective randomised trial, we compared G-POEM with a sham procedure in patients with severe gastroparesis. The primary outcome was the proportion of patients with treatment success (defined as a decrease in the Gastroparesis Cardinal Symptom Index (GCSI) by at least 50%) at 6 months. Patients randomised to the sham group with persistent symptoms were offered cross-over G-POEM. RESULTS: The enrolment was stopped after the interim analysis by the Data and Safety Monitoring Board prior to reaching the planned sample of 86 patients. A total of 41 patients (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male) were randomised (21 G-POEM, 20-sham). Treatment success rate was 71% (95% CI 50 to 86) after G-POEM versus 22% (8-47) after sham (p=0.005). Treatment success in patients with diabetic, postsurgical and idiopathic gastroparesis was 89% (95% CI 56 to 98), 50% (18-82) and 67% (30-90) after G-POEM; the corresponding rates in the sham group were 17% (3-57), 29% (7-67) and 20% (3-67).Median gastric retention at 4 hours decreased from 22% (95% CI 17 to 31) to 12% (5-22) after G-POEM and did not change after sham: 26% (18-39) versus 24% (11-35). Twelve patients crossed over to G-POEM with 9 of them (75%) achieving treatment success. CONCLUSION: In severe gastroparesis, G-POEM is superior to a sham procedure for improving both symptoms and gastric emptying 6 months after the procedure. These results are not entirely conclusive in patients with idiopathic and postsurgical aetiologies. TRIAL REGISTRATION NUMBER: NCT03356067; ClinicalTrials.gov.

Changes in Sepsis Biomarkers after Immunosuppressant Administration in Transplant Patients.

Sepsis biomarkers change continuously during the postoperative period. We aimed to demonstrate the influence of immunosuppressants after transplantation (Tx) on presepsin, procalcitonin, CRP, white blood cells, and IL-6. A group of 140 patients after major surgery (86 non-Tx, 54 Tx) without any signs of sepsis or infectious complications was followed for 7 days. The changes in biomarkers were analyzed with respect to the type of surgery, organ, and induction immunosuppressant used (antithymocyte globulin, corticosteroids, or basiliximab/rituximab). Concentrations (95th percentiles) of presepsin and procalcitonin were higher in the Tx group (presepsin: Tx < 2380 vs. non-Tx < 1368 ng/L, p < 0.05; procalcitonin: <28.0 vs. 3.49 µg/L, p < 0.05). In contrast, CRP and IL-6 were lower in the Tx group (CRP: Tx < 84.2 vs. non-Tx < 229 mg/L, p < 0.05; IL-6: <71.2 vs. 317 ng/L, p < 0.05). Decreases in CRP and IL-6 were found for all immunosuppressants, and procalcitonin was increased after antithymocyte globulin and corticosteroids. Negligible changes were found for white blood cells. Different responses of presepsin, procalcitonin, CRP, and IL-6 were therefore found in patients without any infectious complications after major surgery or transplantation. Immunosuppression decreased significantly IL-6 and CRP in comparison to non-Tx patients, while procalcitonin was increased after corticosteroids and antithymocyte globulin only. Cautious interpretation of sepsis biomarkers is needed in the early posttransplant period. This work was conducted as a noninterventional (nonregistered) study.

Liver stiffness measured by two-dimensional shear-wave elastography predicts hepatic vein pressure gradient at high values in liver transplant candidates with advanced liver cirrhosis.

Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis.

Amanita phalloides intoxication: mechanism of toxicity, clinical manifestations and therapeutic approaches.

Ingestion of Amanita phalloides is the most common cause of fatal mushroom poisoning. The clinical picture of intoxication varies from mild subclinical manifestation to lethal fulminant course with the development of acute liver failure. Early diagnosis of Amanita phalloides poisoning is crucial for the outcome but i tis difficult because it is often mistaken as gastroenteritis or due to other mushroom poisoning. The diagnosis is based on the history of recent mushroom ingestion followed by gastrointestinal symptoms, typical time course and laboratory markers and is proven with mycological examination or toxicological examination. Specific treatment consists of detoxification procedures, supportive measures, administration of drugs and therapy in the specialized intensive care unit in the case of acute liver failure. In selected patients with acute liver failure urgent liver transplantation is the only life-saving option.

Evaluation of surgical risk in patients with liver cirrhosis.

The prevalence of liver cirrhosis in population is increasing, as well as its prevalence among patients admitted to hospital for elective surgery. These patients are at risk of high postoperative morbidity and mortality. Perioperative risk assessment of patients with liver cirrhosis is a complex procedure. It consists of evaluation of general condition of the patient, including comorbidities and nutritional status, evaluation of the grade of liver disease, and urgency of the surgical procedure. There are no specific guidelines. Proper risk assessment before surgery, considering alternative ways of treatment, is a cornerstone of optimal postoperative course and prevention of complications in patients with liver cirrhosis.

Single mutidrug resistant enterobacteriacae donor-derived infection in four solid organ transplant recipients: a case report.

BACKGROUND: Bacteraemia of the donor is not considered to be contraindication of organ procurement. On the other hand, infection of solid organ transplant recipients remains to be a major cause of their morbidity and mortality. When using organs from bacteraemic donors, individual risks need to be assessed and the appropriate antibiotic treatment applied. CASE PRESENTATION: In this case series we report several serious donor-derived infectious complications in four out of five recipients of different organs from one single donor in the early posttransplant period. Donor-transmitted multi-drug resistant strains of Escherichia coli and Klebsiella pneumonia was confirmed by both serologic and molecular testing. CONCLUSIONS: To prevent donor-derived infections, careful microbiological screening followed by targeted antibiotic treatment is essential. Although such complications can never by completely prevented, a high index for potential bacterial infection in organ donors and transplant recipients should be routinely employed.

Erratum to: Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety.

The Given Names and Family Names were all inadvertently inverted. The correct order is: Jan Martinek, Hana Svecova, Zuzana Vackova, Radek Dolezel, Ondrej Ngo, Jana Krajciova, Eva Kieslichova, Radim Janousek, Alexander Pazdro, Tomas Harustiak, Lucie Zdrhova, Pavla Loudova, Petr Stirand, Julius Spicak. The original article was corrected.

Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) is becoming a standard treatment for achalasia. Long-term efficacy and the rate of post-POEM reflux should be further investigated. The main aim of this study was to analyze safety and mid-term (12 and 24 months) clinical outcomes of POEM. METHODS: Data on single tertiary center procedures were collected prospectively. The primary outcome was treatment success defined as an Eckardt score < 3 at 12 and 24 months. A total of 155 consecutive patients with achalasia underwent POEM; 133 patients were included into the analysis (22 patients will be analyzed separately as part of a multicenter randomized clinical trial). RESULTS: POEM was successfully completed in 132 (99.2%) patients, and the mean length of the procedure was 69.8 min (range 31-136). One patient underwent a drainage for pleural effusion; no other serious adverse events occurred. Treatment success at 3, 12, and 24 months was observed in 95.5% (CI 89.6-98.1), 93.4% (86.5-96.8), and 84.0% (71.4-91.4) of patients, respectively. A total of 11 patients (8.3%) reported initial treatment failure (n = 5) or later recurrence (n = 6). The majority of relapses occurred in patients with achalasia type I (16.7 vs. 1.1% achalasia type II vs. 0% achalasia type III; p<0.05). At 12 months, post-POEM reflux symptoms were present in 29.7% of patients. At 3 months, mild reflux esophagitis was diagnosed in 37.6% of patients, and pathological gastroesophageal reflux was detected in 41.5% of patients. A total of 37.8% of patients had been treated with a proton pump inhibitor. CONCLUSION: POEM resulted in greater than 90% treatment success at 12 months which tends to decrease to 84% after 2 years. More than one-third of the patients had mild reflux symptoms and/or mild esophagitis.

Serial measurement of presepsin, procalcitonin, and C-reactive protein in the early postoperative period and the response to antithymocyte globulin administration after heart transplantation.

Differentiation between systemic inflammatory response syndrome and sepsis in surgical patients is of crucial significance. Procalcitonin (PCT) and C-reactive protein (CRP) are widely used biomarkers, but PCT becomes compromised after antithymocyte globulin (ATG) administration, and CRP exhibits limited specificity. Presepsin has been suggested as an alternative biomarker of sepsis. This study aimed to demonstrate the role of presepsin in patients after heart transplantation (HTx). Plasma presepsin, PCT, and CRP were measured in 107 patients serially for up to 10 days following HTx. Time responses of biomarkers were evaluated for both noninfected (n=91) and infected (n=16) patients. Areas under the concentration curve differed in the two groups of patients for presepsin (P<.001), PCT (P<.005), and CRP (P<.001). The effect of time and infection was significant for all three biomarkers (P<.05 all). In contrast to PCT, presepsin was not influenced by ATG administration. More than 25% of noninfected patients had PCT above 42 µg/L on the first day, and the peak concentration of CRP in infected patients was reached on the third post-transplant day (median 135 mg/L). Presepsin seems to be as valuable a biomarker as PCT or CRP in the evaluation of infectious complications in patients after HTx.

[Intestinal transplantation in Czech Republic]. / Transplantace tenkého streva v Ceské republice.

Intestinal transplantation represents a suitable treatment for patients with intestinal failure who then develop life-threatening complications of total parenteral nutrition and for some patients with complex abdominal disorders not suitable for conventional treatment. METHODS: prior to launch of the clinical program, preparation started in 2006 initially with extensive experimentation carried out on pigs. The clinical phase involved a specialized, multidisciplinary team who examined 23 patients being considered for transplantation. Seven patients were put on a waiting list and one female, due to the improvement of her medical status, was unlisted. The first ever intestinal transplantation was done in 2014. RESULTS: three out of six transplanted patients are alive with 380 days of actual survival; median 131 days (63-763). Two patients are on a full oral diet and nutritionally independent with an excellent quality of life. One female is nutritionally independent but with the need for partial supplemental parenteral rehydration due to the stomal output. CONCLUSION: intestinal transplantation is a suitable treatment for highly selected patients with intestinal failure who meet specific listing criteria.

Comparison of Inflammatory Response to Transgastric and Transcolonic NOTES.

Aims. The aim of our study was to determine the physiologic impact of NOTES and to compare the transgastric and transcolonic approaches. Methods. Thirty pigs were randomized to transgastric, transcolonic, or laparoscopic peritoneoscopy. Blood was drawn and analyzed for C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1ß, IL-6, WBCs, and platelets. Results. Endoscopic closure with an OTSC was successful in all 20 animals. The postoperative course was uneventful in all animals. CRP values rose on day 1 in all animals and slowly declined to baseline levels on day 14 with no differences between the groups (P > 0.05, NS). The levels of TNF-α were significantly increased in the transcolonic group (P < 0.01); however this difference was already present prior to the procedure and remained unchanged. No differences were observed in IL1-ß and IL-6 values. There was a temporary rise of WBC on day 1 and of platelets on day 7 in all groups (P > 0.05, NS). Conclusions. Transgastric, transcolonic, and laparoscopic peritoneoscopy resulted in similar changes in systemic inflammatory markers. Our findings do not support the assumption that NOTES is less invasive than laparoscopy.

[AB0 incompatible kidney transplantation - first experiences]. / Transplantace ledviny pri inkompatibilite krevní skupiny - úvodní zkusenosti programu.

Living donor AB0 incompatible kidney transplantation represents a new tool how to improve the access to transplantation. Majority of European protocols are based on desensitization with rituximab, triple drug immunosuppression, intravenous immunoglobulins and specific immunoads option (IA) which eliminates isohaemaglutinins. AB0i kidney transplant program was initiated in our centre in 2011 and 21 patients have received grafts from incompatible donors until recently. Highest accepted isohaemaglutinins titers before rituximab were 1 : 64 and corresponding pretransplant immunoadsorption procedures varied from 2 to 9. In 5 patients 1-2 IA procedures were performed also after transplantation. With the advent of paired exchange program the AB0i transplantation is offered to patients with unsuccessful matching run or with aim to improve HLA match between donor and recipient. The main complications were postoperative bleeding and urinary tract infections in patients at risk. Majority of protocol biopsies exhibited positivity of C4d staining. Neither graft loss nor patient death were noticed.

[Caecal ligation and puncture in the minipig - a model of sepsis induction]. / Cékální ligace a punkce u miniprasat - metoda studia sepse.

BACKGROUND: Sepsis belongs among the most serious conditions and animal models of sepsis are the basic tools to investigate the pathophysiological response to this condition. MATERIAL AND METHODS: A total of 16 adult minipigs with identical baseline parameters were randomized into two groups. In the sepsis group (n = 10), sepsis was induced using caecal ligation and puncture (CLP). The control group (n = 6) underwent laparotomy without CLP. Selected clinical and laboratory parameters as well as histological findings between the sepsis and control group were subsequently compared. RESULTS: All animals undergoing CLP developed diffuse peritonitis and sepsis. Compared to the control group, experimental animals showed significant increase of body temperature and heart rate (while) requiring noradrenaline to maintain their perfusion pressure. No significant differences in the monitored biochemical parameters (including C-reactive protein levels) between the two groups were found. Histological findings in organs of experimental animals were consistent with changes of organs seen in sepsis, i.e., centrilobular liver necroses, acute tubular renal necrosis, serous fibrinopurulent exudate, myocardial malacias, and pulmonary edema. CONCLUSION: Experimental caecal ligation with a predefined size of the perforation in the intestinal wall is a suitable model for assessing the pathophysiological changes occurring in the body in sepsis.

[Acute liver failure: present recommendations]. / Akutní selhání jater: soucasná doporucení.

Acute liver failure is a life threatening illness whose mortality rate remains high. For the survival an early diagnosis is crucial as well as the use of specific and supportive therapy and the determination of patient's need for urgent liver transplantation. At the first signs of the disease progression it is necessary to contact a transplantation centre. The patient with acute liver failure should be admitted to intensive care unit of a hospital capable to perform liver transplantation. Liver transplantation is limited by the availability of organs. It is possible to expand the time required for spontaneous liver regeneration or transplantation by using liver supporting systems. The therapy of the acute liver failure is multidisciplinary and should be performed in specialized centers.