Significance and outcome of living-donor liver transplantation in acute mushroom intoxication.

INTRODUCTION: Mushroom intoxication (MT) can lead to acute liver injury which may result in Mushroom intoxication-related liver failure (M-ALF) requiring liver transplantation (LT). In the present study, we want to share the experience of our institute regarding living-donor LT (LDLT) due to mushroom poisoning. AIM: The aim of this study is to identify the predictors of poor prognosis in patients with ALF secondary to mushroom intoxication requiring LDLT. MATERIALS AND METHODS: All patients with MT between 2008 and 2016 were evaluated. Demographics, symptoms, interval between symptoms and admission to our institute, laboratory data, model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) scores, clinical course, and outcomes of supportive therapy and LT were evaluated. There were two groups in the study: Group A = responsive to supportive therapy (n = 9) versus Group B = unresponsive to supportive therapy (n = 9). RESULTS: During the study, a total of 18 patients were admitted with M-ALF. Twelve (66.7%) of them were female, and the mean age was 39.9 ± 18.2 years. All of the nine patients in Group A fully recovered with supportive therapy. In Group B, one patient died during waiting period for LT and 8 patients received LDLT LDLT. Three of the eight patients who were transplanted died in the postoperative early period within postoperative 5 days. The patients in Group B had significantly higher MELD/PELD scores and encephalopathy rate than in Group A (P < 0.05). International normalized ratio (INR), bilirubin, ammonium levels, and platelet count were significantly different between groups (P < 0.05). The patients in Group B had significantly longer interval before admission to our institute (P < 0.05). CONCLUSION: The presence of encephalopathy, higher MELD/PELD, INR, bilirubin, ammonium levels, and lower platelet count was related to poor prognosis in MT. LDLT provides a good therapeutic option in patients with M-ALF. The time is a crucial factor in successful treatment of MT. Early admission to a tertiary referral center with expertise in LT results in a better prognosis and increased survival following M-ALF.

Alterations in lipid peroxidation and T-cell function in women with hyperemesis gravidarum.

The objective of this study was to investigate serum adenosine deaminase (ADA) activity as a marker of T lymphocyte activation and parameters of oxidative stress and antioxidant defence in hyperemesis gravidarum (HG). Serum ADA activity, malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels were investigated in 40 pregnant women with the HG and 40 with healthy pregnancies, in a descriptive study. Although serum ADA and CAT were measured to be higher in HG group, the difference was not significant. Serum MDA and GPx levels were significantly elevated in women with HG when compared with those without HG. The significance of changes in lipid peroxidation and T-cell activation in the pathogenesis of HG and whether this is a cause or a compensatory reaction to HG requires further investigations with larger multicentre trials.

Cross-cultural adaptation, reliability, and validity of the Turkish version of PedsQL 3.0 Arthritis Module: a quality-of-life measure for patients with juvenile idiopathic arthritis in Turkey.

PURPOSE: The aim of this study was to describe the cultural adaptation, validity, and reliability of a Turkish version of the pediatric quality-of-life inventory (PedsQL) 3.0 Arthritis Module in a population with juvenile idiopathic arthritis (JIA). METHODS: A total of 169 patients with JIA and their parents were enrolled in the study. The Turkish version of the childhood health assessment questionnaire (CHAQ) was used to evaluate the validity of related domains in the PedsQL 3.0 Arthritis Module. Both the PedsQL 3.0 Arthritis Module and CHAQ were filled out by children over 8 years of age and by the parents of children 2-7 years of age. RESULTS: Internal reliability was poor to excellent (Cronbach's alpha coefficients 0.56-0.84 for self-reporting and 0.63-0.82 for parent reporting), and interobserver reliability varied from good to excellent (intraclass correlation coefficient (ICC) 0.79-0.91 for self-reporting and 0.80-0.88 for parent reporting) for the total scores of the PedsQL 3.0 Arthritis Module. Parent-child concordance for all scores was moderate to excellent (ICC 0.42-0.92). The PedsQL 3.0 Arthritis Module and CHAQ were highly positively correlated, with coefficients from 0.21 to 0.76, indicating concurrent validity. CONCLUSIONS: We demonstrated the reliability and validity of quality-of-life measurement using the Turkish version of the PedsQL 3.0 Arthritis Module in our sociocultural context. The PedsQL 3.0 Arthritis Module can be utilized as a tool for the evaluation of quality of life in patients with JIA aged 2-18 years.

The efficacy of minocycline against methotrexate-induced pulmonary fibrosis in mice.

OBJECTIVES: In addition to its antimicrobial effects, inhibitory effects of minocycline have been demonstrated, including against inflammation, apoptosis, proteolysis, angiogenesis, and tumor metastasis. In this study, we aimed to determine the beneficial effects of minocycline on lung histology and its antioxidant activity in a murine model of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight Swiss albino mice were randomly allocated into four groups of seven animals per group. Group I (control group) received intraperitoneal injection of saline. Group II (methotrexate group) received methotrexate orally 3 mg/kg for 28 days. Group III (minocycline group) received methotrexate orally 3 mg/kg and 15 mg/kg of intraperitoneally injected minocycline for 28 days. Group IV (minocycline group) received 15 mg/kg of intraperitoneally injected minocycline for 28 days. Twenty-eight days later, the animals were euthanized. Thereafter, lung tissue samples were harvested. Histological findings of airways were evaluated by light microscopy. The levels of malondialdehyde (MDA), the product of reactive oxygen in lung tissue, and catalase, an antioxidant enzyme, were also determined. RESULTS: In the light microscopic examination, the lung tissues of the control group showed normal histological features. In the methotrexate group, the degree of lung damage (grade 3 fibrosis) was higher than the control and other groups (p: 0.001). In the minocycline-treated group, improvement in lung tissue was noted (median fibrosis score: 3 (MTX group) vs 1 (MTX plus minocycline group); p: 0.001). Only the minocycline group showed normal histological features. Although minocycline reduced the MDA levels in lung tissue, an increase in catalase activity was detected (p: 0.018 and p: 0.014, respectively). CONCLUSIONS: The administration of minocycline may be effective in MTX-induced lung fibrosis in mice. However, further studies with high-dose and long-term treatments are needed.

Depression and anxiety in cancer patients and their relatives.

PURPOSE: To investigate the depression and anxiety levels and the factors that affect patients receiving chemotherapy and their relatives with the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scoring system. METHODS: 330 patients and 330 relatives of these patients were enrolled in this study. The study forms including the questions regarding the patient demographic characteristics, BDI, and STAI were completed during face-to-face interviews by trained interviewers for the determination of the psychological status of the patients and their relatives. BDI and STAI were validated for Turkish population by studies made before. RESULTS: According to BDI scale, 96 (29.1%) patients had mild and 60 (18.2%) had severe depression. Seventy-one (21.5%) relatives had mild and 24 (7.3%) had severe depression. Anxiety evaluation was made by STAI scale and a statistical difference emerged between patients and relatives (patients: 44.93±8.8 vs relatives: 43.27±8.5, p=0.015). The depression and anxiety levels were higher in women, in people with low socio-economic level, in people having a time period between diagnosis and participation in the study longer than 6 months, and in people having relapsing disease. CONCLUSION: Since there are many emotional and psychological disorders in patients and their relatives, much attention should be paid in order to diagnose and treat their psychiatric disorders and enough information about their disease should be given.

The relationship of insulin resistance and metabolic syndrome with known breast cancer prognostic factors in postmenopausal breast cancer patients.

PURPOSE: The aim of this study was to investigate the effect of metabolic syndrome and insulin resistance at the time of diagnosis on the known prognostic factors of breast cancer in postmenopausal breast cancer patients. METHODS: The study included 71 patients with a recent diagnosis of postmenopausal breast cancer, admitted at the Medical Oncology outpatient clinic of the Izmir Ataturk Training and Research Hospital between June 2010 and June 2011. We determined whether the patients had metabolic syndrome and insulin resistance at diagnosis, and recorded known prognostic factors, such as tumor size, axillary lymph node involvement, presence of distant metastasis, tumor grade, estrogen receptor (ER), progesterone receptor (PR), and CerbB-2 status. RESULTS: Among 71 patients, 25 (35%) had metabolic syndrome at the time of diagnosis, and 33 (46%) had insulin resistance with Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR)>2.7. No statistically significant difference was found in the prognostic values of breast cancer, i.e. tumor size, axillary lymph node involvement, distant metastasis, tumor grade, ER, PR, and CerbB-2 status between the patients with and without metabolic syndrome. There was no statistically significant difference in the prognostic factors of breast cancer at the time of diagnosis between 33 patients with insulin resistance and 38 patients without insulin resistance. CONCLUSION: Several previous studies showed a negative relationship between metabolic syndrome and insulin resistance and prognostic factors of breast cancer in postmenopausal breast cancer patients. However, our study failed to show such a relationship. The relationship between metabolic syndrome and insulin resistance and postmenopausal breast cancer was not well demonstrated due to the small number of patients, unknown duration of the metabolic syndrome and insulin resistance, and shorter follow-up period. Further studies are required to demonstrate the effect of metabolic syndrome and insulin resistance on the prognosis of breast cancer, including larger number of patients and longer follow-up periods.

The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma.

PURPOSE: Metastatic renal cell carcinoma (mRCC) bears a poor prognosis. We investigated the prognostic significance of some hematologic parameters of patients with mRCC. METHODS: We retrospectively reviewed the records of 53 patients with mRCC . The mean follow up time was 34 months (range 5-142).We assessed the prognostic value of hematologic parameters (leukocytes ,neutrophils, lymphocytes, platelets, neutrophil to lymphocyte ratio/NLR, platelet to lymphocyte ratio/PLR), and other clinical parameters with univariate and multivariate analysis. RESULTS: Memorial Sloan-Kettering Cancer Center (MSKCC) risk group , lung metastases, sunitinib treatment, lymphocyte count, NLR, and anemia significantly correlated with median overall survival (OS) on univariate analysis. The median OS in patients with a NLR < 3.4 was 32.2 months , significantly higher than the 13.9 months in patients with a ratio ≥ 3.4 (p = 0.006). Multivariate analysis revealed that MSKCC risk group and the NLR were independent predictors of OS. CONCLUSION: Hematologic parameters may be associated with OS in mRCC. However, further studies are needed to establish their routine use.

The effect of biocompatible carriers with vitamin D and platelet-rich plasma (PRP) on bone defects.

Introduction: In oral and maxillofacial surgery, hard tissue augmentation is provided by materials that accelerate the healing, act as a template for reconstructing bony defects, and stimulate bone production and growth. This study investigated the effects of biocompatible carriers containing active vitamin D and platelet-rich plasma (PRP) on bone defects created in rat calvaria. Material and Methods: This experimental animal study utilized fifty-two male Sprague Dawley rats divided into six groups and conducted histopathological, microtomographic, and biochemical comparisons by adding vitamin D, which has an accelerating effect on bone development. We examined the calvarial defects, sacrificing the rats in equal numbers (eight in each group and four to obtain PRP) at the first, second, fourth, and eighth weeks. The newly formed bone was assessed using histopathologic, microtomographic, and macroscopic methods as well as the biochemical analysis performed in the plasma samples. Expression of fibroblast growth factor 23 (FGF23), vitamin D receptor (VDR), and receptor activator of nuclear factor-kappa B (RANK), which determine bone formation, were investigated. The amounts of ossification, bone volume, and mineral densities were significantly higher in the fourth and eighth weeks as the biocompatible material was delivered with calcitriol. Results: The histological and macroscopic examinations revealed that the defect area shrank and was colonized with new cells in the "calcitriol + chitosan + PRP" group. The expression of RANK, FGF23, and VDR antibodies was more intense in the "calcitriol + chitosan + PRP" group than in other groups of the experiment and controls. Conclusion: Active vitamin D, PRP, and chitosan formulation positively contributed to the repair of bone defects and induced remarkable clinical improvement. This new delivery approach could be promising for healing bone defects following surgical operations in hard bony tissues. HIPPOKRATIA 2023, 27 (2):48-56.

The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma.

The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma.83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and anti-Bax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted. Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003). Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome.

Micro-metastases into the uterine leiomyoma from invasive ductal breast cancer under adjuvant tamoxifen therapy: case report.

Metastasis of breast cancer to the uterus is extremely rare. However, breast cancer is the leading tumor metastasizing from extragenital organs to the uterus. The most common signs of uterine metastasis are bleeding and mass effect. Tamoxifen use is known to increase risk of endometrial cancer. Immunohistochemical staining with GCDFP can be useful in differentiating primary uterine tumors from breast cancer metastasis. Metastasis to the uterus has been reported to worsen the prognosis. Although hysterectomy has been effective on survival, treatment modality to be used in the presence of other systemic metastases is not clear. Locoregional treatments can be used in oligometastatic cases. In addition, removal of solitary organ metastasis together with bone metastasis provides improvement in survival.

The toxicity and efficacy of Nordic-FLOX regimen as adjuvant treatment of stage III colon cancer.

PURPOSE: To evaluate the toxicity and efficacy of oxaliplatin combined with the Nordic regimen of bolus 5-fluorouracil (5-FU) and leucovorin (LV) (Nordic-FLOX) as adjuvant treatment in stage III colon cancer patients. METHODS: Fifty-three patients with resected stage III colon cancer were treated with adjuvant bolus Nordic-FLOX regimen (oxaliplatin 85 mg/m(2) on day 1, bolus 5-FU 500 mg/ m(2) and bolus LV 60 mg/m(2) days 1 and 2) every 2 weeks for 12 cycles. RESULTS: The probability of disease-free survival (DFS) at a median follow-up time of 29 months was 72%. Relapse was seen in 13 (24.5%) patients. The probability of 3-year overall survival (OS) at 36 months was 85%. Grade IV neutropenia was noticed in 15.1% of the patients, grade III-IV neurotoxicity was not encountered, while grade II neurotoxicity was 17%. Gastrointestinal toxicity (mild diarrhea) was seen in 11.3% of the patients. CONCLUSION: Adjuvant treatment of stage III colon cancer with the Nordic-FLOX regimen can be an alternative regimen to infusional and other bolus regimens due to its easy administration, lower toxicity, and similar efficacy.

Aborted donor hepatectomy in living donor liver transplantation: lessons learned.

BACKGROUND: Aborted donor hepatectomy (ADH) during any stage of living donor hepatectomy (LDH) is a rare event. We describe our experience and discuss the lessons from these events. METHODS: From September 2005 to January 2019, 77 of 2 031 (3.79%) LDH were aborted at various stages of surgical procedure due to donor or recipient related reasons. Demographic and clinical data of aborted donor candidates and the clinical course of their potential recipients were analysed. RESULTS: LDH of 77 donor candidates was aborted due to donor (n = 53) or recipient (n = 24) related reasons. The most common donor related reason was the quality of liver parenchyma (n = 31). The most common recipient related reason was haemodynamic instability (n = 11). Twenty-three recipients underwent either living donor liver transplantation (LDLT) (n = 21) or deceased donor liver transplantation (DDLT) (n = 2) at a median of 6 days following ADH. In one aborted due to a donor reason and two aborted for recipient reasons, LDLT was performed using the same donor candidates. Thirty-six recipients had no liver transplantation (LT) and died a median of 17.5 days following ADH. CONCLUSIONS: We believe that ADH will decrease with experience and meticulous preoperative clinical and radiological evaluations. Abandoning the donor hepatectomy is always a valid option at any stage of the surgery when the unexpected is encountered.

A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study).

OBJECTIVE: It has been suggested that lipid-lowering treatment with the use of statins adversely affects the steroid hormones. However, the safety of lipid lowering treatment targeting very low levels of LDL with respect to the steroid hormones has not been established. RESEARCH DESIGN AND METHODS: A prospective, randomized, multicenter trial was conducted involving 98 patients. The patients were randomized into 2 groups: group-I received 10 mg of atorvastatin plus 10 mg of ezetimibe and group-II 80 mg of atorvastatin for the first 3 months. After crossover, the first group received 80 mg of atorvastatin and the second group 10 mg of atorvastatin plus 10 mg of ezetimibe for the following 3 months. Cortisol, DHEAS, testosterone, and estradiol levels were measured at the enrollment and at the end of the 1st, 2nd, 3rd, and 6th months. RESULTS: Along with a decrease in LDL level, the levels of DHEAS, testosterone, and estradiol decreased in both groups (p<0.001). While cortisol levels were maintained in the group given 10 mg of atorvastatin plus 10 mg of ezetimibe, it decreased significantly after the crossover to 80 mg of atorvastatin (p<0.001). The group initially given 80 mg of atorvastatin measured a lower level of cortisol for the first 3 months and it returned to normal levels after switching to 10 mg of atorvastatin plus 10 mg of ezetimibe. CONCLUSION: Eighty milligrams of atorvastatin decreased all adrenal and gonadal steroids, whereas 10 mg of ezetimibe combined with 10 mg of atorvastatin had at least no impact on cortisol levels.

Torsion of wandering spleen.

Wandering spleen is characterized by ectopic localization of spleen owing to the lack or weakening of the major splenic ligaments. In present study, two cases with torsion of wandering spleen were reported. The first case was a 30-year-old female who was admitted to emergency department with acute abdominal pain and vomiting. Abdominal Ultrasonography and computed tomography showed a round solid hypodense mass that was located in the left hypochondriac region of abdomen. At laparotomy, the patient was found to have torsion of a wandering spleen with complete infarction and pancreatic tail infarction. Splenectomy and distal pancreatectomy were performed. The second patient was a 19-year-old female. She was admitted to emergency department with abdominal pain. Axial computed tomography (CT) showed pelvic mass that indicated a possibility of a wandering spleen. The wandering spleen was removed with its long pedicle because of infarction. Torsion of wandering spleen must be considered in differential diagnosis of acute abdomen when a palpable painful abdominal mass is present on physical examination, and the spleen is absent in its normal anatomical location on radiological examination (Fig. 4, Ref. 8). Full Text (Free, PDF) www.bmj.sk.

Surgical treatment of phytobezoars causes acute small intestinal obstruction.

PURPOSE: Our aim was to perform a clinical analysis of small intestinal obstructions caused by surgically treated phytobezoars. METHODS: Twenty-four patients, with small intestinal obstructions caused by phytobezoars, underwent surgery in our department between 1998 to 2008, were reviewed retrospectively. RESULTS: Twenty (83.3%) of 24 patients had previous gastric surgery. Preoperative computed tomography (CT) was performed in nine patients and seven (77.8%) patients, showed results consistent with a bezoar and subsequently, underwent surgery on the same day. The remaining patients had no preoperative diagnosis of a phytobezoar were typically followed-up for postoperative adhesion intestinal obstruction. Only those patients who showed no response to nonoperative treatment options underwent surgery. The phytobezoar was fragmented and milked into the cecum in 11 (45.8%) patients or extracted via longitudinal enterotomy in 12 (50%) patients; the remaining patient (4.2%) was treated via laparoscopy. Three patients had gastric phytobezoars, which were extracted via gastrotomy. There was no postoperative mortality. Two patients with previous enterotomy had either postoperative wound infection or wound infection and evisceration. CONCLUSIONS: Phytobezoars should be considered in the differential diagnosis of acute small intestinal obstruction in patients with prior gastric surgery, poor dentition, or consume fiber-rich foods. Abdominal CT is useful for both diagnosis and for the decision to perform emergency surgery. When possible, the phytobezoar should be fragmented and milked into the cecum. Laparoscopic fragmentation may be useful in such cases (Tab. 3, Ref. 28). Full Text (Free, PDF) www.bmj.sk.

Comparison of two methods for the rapid radiochemical analysis of air dust samples in emergency situations.

The reliable determination of airborne radionuclides in air is a key aspect in decision-making for the protection against public exposure in the event of a nuclear or radiological emergency. Nowadays, this needs to be done in real time and at the international level. These needs require the development of fast response protocols and the harmonisation of results. This work presents two fast radiochemical methods for the simultaneous separation of alpha and beta emitters in aerosols and their performance in a series of samples.

The Alvarado Score is accurate in pregnancy: a retrospective case-control study.

BACKGROUND: Acute appendicitis is the most frequent abdominal condition that requires non-obstetric surgical intervention during pregnancy. This study aims to scan pregnant patients operated on for acute appendicitis to evaluate the efficiency of using the Alvarado Score (AS) for diagnosis. METHODS: Our study included 48 pregnant patients who were pre-diagnosed with acute appendicitis and operated on at our department of general surgery from January 2010 to July 2016 and whose files were accessed. Fifty-three non-pregnant female patients of reproductive age who were operated on for appendicitis during the same period were included in the study as the control group. The patients in both groups were divided into two groups based on their AS total score being 7 and ≥ 7. RESULTS: The mean age of the 48 pregnant patients was 28 (19-42) years, while the mean age of the 53 control patients was 31 (18-45) years. Among pregnant and non-pregnant women, about a third of patients had an AS < 7 (16 of 48 versus 18 of 53). There was no significant difference when the AS scores of both groups were compared (p = 0.947). Using pathology results as reference test, the sensitivity and specificity of the AS in pregnant women was 79 and 80%. CONCLUSIONS: As a result, when the data collected by our study are evaluated, we see that pregnancy does not have a negative effect on the efficacy of AS. Therefore, the AS system can be an easy, non-invasive auxiliary diagnostic tool with high diagnosis accuracy rates that can be used in pregnant patients suspected of having acute appendicitis.

Living Donor Re-transplantation for Repeated Acute Liver Failure.

Emergency liver transplantation (LT) for acute liver failure (ALF) is a life-saving treatment. Occurrence of this situation in the same patient twice is very rare. Herein, we describe a patient who underwent two emergency LTs for ALF, both from living donors. When she was 26 years old, she underwent a right lobe living donor LT (LDLT) from her sister for ALF due to use of herbal weight loss medications. The next 3 years were uneventful but another ALF developed during a terminal stage pregnancy (37th week). Despite medical treatment, her liver functions worsened, and the baby was delivered by caesarean section. The second time, her brother was the donor and she recovered after the emergency right lobe re-LDLT. Both patient and baby were well at the 2-month follow-up. As far as we know, there is no reported similar case, and we concluded that LDLT is a paramount treatment option for both primary and secondary ALFs.

Results of an international comparison of activity measurements of 68Ge.

An international key comparison, identifier CCRI(II)-K2.Ge-68, has been performed. The National Institute of Standards and Technology (NIST) served as the pilot laboratory, distributing aliquots of a 68Ge/68Ga solution. Results for the activity concentration, CA, of 68Ge at a reference date of 12h00 UTC 14 November 2014 were submitted by 17 laboratories, encompassing many variants of coincidence methods and liquid-scintillation counting methods. The first use of 4π(Cherenkov)ß-γ coincidence and anticoincidence methods in an international comparison is reported. One participant reported results by secondary methods only. Two results, both utilizing pure liquid-scintillation methods, were identified as outliers. Evaluation using the Power-Moderated Mean method results in a proposed Comparison Reference Value (CRV) of 621.7(11)kBqg-1, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6mL ampoules to the BIPM to link the comparison to the International Reference System (SIR) which may lead to the evaluation of a Key Comparison Reference Value and associated degrees of equivalence.