The final part of the CRESS trilogy - how to evaluate the quality of stability studies.

High quality laboratory results are critical for patient management. However, poor sample quality can impact these results and patient safety. To ensure reliable and accurate results laboratories must be aware of each analyte's stability under various storage conditions and matrices to guarantee correct and dependable outcomes. This knowledge allows laboratories to define the allowable delay between sample collection and centrifugation/analysis for all analytes to guarantee appropriate results quality and interpretation. The EFLM Working Group for the Preanalytical Phase (WG-PRE) therefore established a 4-step plan to tackle this issue, aiming to standardize and harmonize stability studies for improved comparison and meta-analysis. The plan included the development of checklists and how-to guides for performing and reporting stability studies as well as a central resource of stability data. This manuscript deals with the issue of evaluating publications and incorporating them into a central resource. To evaluate stability studies, the CRESS checklist was used to structure 20 sections used to judge the quality of studies. Each section has 4 levels of quality, with scores converted to numerical values and weighted based on expert opinion. Based on this, a final score ranging from A to D was determined. The procedure was then tested on six manuscripts and checked for agreement between expert judgements. The results demonstrated that the proposed evaluation process is a useful tool to distinguish between best in class manuscripts and those of lower quality. The EFLM WG-PRE strongly believes that the provided recommendations and checklists will help improving stability studies both in quality and standardisation.

Preservation of urine specimens for metabolic evaluation of recurrent urinary stone formers.

OBJECTIVES: Stability of concentrations of urinary stone-related metabolites was analyzed from samples of recurrent urinary stone formers to assess necessity and effectiveness of urine acidification during collection and storage. METHODS: First-morning urine was collected from 20 adult calcium-stone forming patients at Tomas Bata Hospital in the Czech Republic. Urine samples were analyzed for calcium, magnesium, inorganic phosphate, uric acid, sodium, potassium, chloride, citrate, oxalate, and urine particles. The single-voided specimens were collected without acidification, after which they were divided into three groups for storage: samples without acidification ("NON"), acidification before storage ("PRE"), or acidification after storage ("POST"). The analyses were conducted on the day of arrival (day 0, "baseline"), or after storage for 2 or 7 days at room temperature. The maximum permissible difference (MPD) was defined as ±20 % from the baseline. RESULTS: The urine concentrations of all stone-related metabolites remained within the 20 % MPD limits in NON and POST samples after 2 days, except for calcium in NON sample of one patient, and oxalate of three patients and citrate of one patient in POST samples. In PRE samples, stability failed in urine samples for oxalate of three patients, and for uric acid of four patients after 2 days. Failures in stability often correlated with high baseline concentrations of those metabolites in urine. CONCLUSIONS: Detailed procedures are needed to collect urine specimens for analysis of urinary stone-related metabolites, considering both patient safety and stability of those metabolites. We recommend specific preservation steps.

Efficiency, efficacy and subjective user satisfaction of alternative laboratory report formats. An investigation on behalf of the Working Group for Postanalytical Phase (WG-POST), of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM).

OBJECTIVES: Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats. METHODS: We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics. RESULTS: Efficacy remained at a very high level both in the new formats as well as in the classical formats. We found no significant difference in any of the groups. Efficiency improved in all groups when using the sparkline cumulative format and marginally when showing the improved tabular format. When asking medical questions, efficiency and efficacy remained similar between report formats and groups. All alternative reports were subjectively more attractive to the majority of participants. CONCLUSIONS: Showing cumulative reports as a graphical display led to faster detection of general information on the report with the same level of correctness. Considering the familiarity bias of the classical single report formats, the borderline-significant improvement of the alternative tabular format and the non-inferiority of the z-log format, suggests that single reports might benefit from some improvements derived from basic information design.

Extreme diet without calcium may lead to hyperoxaluria and kidney stone recurrence-A case study.

BACKGROUND: The aim of the study was to present a case study of a 56-year-old woman with hyperoxaluria induced by calcium-free diet that resulted in kidney stone recurrence. METHODS: A 24-hour urine collection and serum tests for kidney stone risk factors identification were performed. The monitoring of urine risk factors was done by untimed urine samples and 24-hour urine collections. Polarized light microscopy was performed for kidney stone analysis. RESULTS: The results of urine collection showed hyperoxaluria of 0.551 mmoL per 24 hours. After adding calcium-containing products to the diet the oxaluria decreased to reference range value of 0.352 mmoL/24 hours and all untimed oxalate to creatinine ratios returned to reference ranges. Polarized light microscopy revealed 100% calcium oxalate kidney stone composition (It was 50% Weddellite and 50% Whewellite). CONCLUSIONS: The case study shows the importance of calcium intake in the prevention of calcium oxalate kidney stone recurrence. Particularly, unsuitable diet without calcium can induce kidney stone recurrence. Knowledge of diet habits is important for interpretation of kidney stone risk factors and their inhibitors excreted in urine.

Cystatin C may be better than creatinine for digoxin dosing in older adults with atrial fibrillation.

BACKGROUND: Patients taking digoxin are older with high probability of having low muscle mass, and current clinical practice in digoxin dosing relies only on estimated glomerular filtration rate from serum creatinine (eGFRcrea). The aim of the study is to compare eGFRcrea and estimated glomerular filtration rate from serum cystatin C (eGFRcys) in older adult patients with atrial fibrillation (AF) overdosed with digoxin. METHODS: A total of 80 consecutive patients overdosed with digoxin and 33 controls with AF from Department of Internal Medicine were included in the prospective observational study. The median of age of participants was 81 years in both the overdosed and the control group. The eGFRs were calculated using The Chronic Kidney Disease Epidemiology (CKD- EPI) equations using standardized methods for serum creatinine and cystatin C measurement. RESULTS: The median (IQR) of eGFRcrea was higher than that of eGFRcys (45 mL/min/1.73 m2 (35-59) vs 30 (21-38), respectively; P < .0001) in overdosed patients. The median (IQR) of eGFRcrea was higher than that of eGFRcys (61 mL/min/1.73 m2 (49-72) vs 40 (30-56), respectively; P < .0001) in control group of patients. Serum predose digoxin concentration in overdosed patients was inversely associated with eGFRcys (ρ = -0.26, P < .05). CONCLUSION: Physicians should consider GFR when changing digoxin dosing. eGFRcys was lower in both the overdosed and the control group. eGFRcys would lead to lower digoxin doses and thus prevent overdose.

The fat mass, estimated glomerular filtration rate, and chronic inflammation in type 2 diabetic patients.

BACKGROUND: The aim of the study was to analyze the degree of obesity and its associations with age, gender, inflammation, an estimated glomerular filtration rate (eGFR), and liver function in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 874 consecutive adult Caucasian T2DM patients from outpatient diabetic clinic were included in the study. The relative fat mass (RFM) and body mass index (BMI) were used as obesity markers. Serum creatinine and cystatin C were used for the GFR estimation. Serum high-sensitive C-reactive protein (hsCRP) was used as the indicator of inflammation. RESULTS: The median, interquartile range (IQR) of RFM in females was higher than that in males (44.8 (42.3-47.2) % vs 31.3 (28.8-34.1) %, respectively; P < .0001). The median (IQR) of BMI in females was no higher than that in males (30 (27-34) kg/m2 vs 30 (27-34), respectively; P = .5152). The obesity prevalence was 99% in males and 98% in females according to RFM. BMI recognized obesity in 51% males and 53% females. RFM was positively associated with hsCRP in both males (rs  = .296, P < .0001) and females (rs  = .445, P < .0001). ALT was positively correlated with eGFRcys in both males (rs  = .379, P < .0001) and females (rs  = .308, P < .0001). CONCLUSION: The RFM equation leads to higher obesity prevalence compared to BMI. Women have higher RFM compared to men. The kidney function was positively correlated with ALT serum concentrations.

Rosuvastatin-induced rhabdomyolysis due to medication errors.

Case (description): A 74 years old Caucasian suffering from chronic kidney disease presented with progressive asthenia and diffuse myalgia. It was revealed that the patient used three different rosuvastatin-containing preparations in a total daily dose of 120 mg for 76 days. Laboratory investigations revealed a marked elevation of serum urea, creatinine, myoglobin, creatine kinase (CK) and transaminases. Two serious medication errors have been identified as possible major factors that synergistically contributed to the development of rosuvastatin-induced rhabdomyolysis. First, 40 mg of rosuvastatin dose was prescribed to the patient, although the estimation of glomerular filtration rate (eGFR) declined below 40 ml/min/1.73 m2. Moreover, the patient used 3 different rosuvastatin formulations simultaneously in a total dose of 120 mg/day. The heterozygous CYP2C9*1/*3 genotype and warfarin co-administration could further contribute to the development of rhabdomyolysis. A number of preventive measures, notably in drug policy, are suggested to overcome unintended intoxications. Conclusion: Rosuvastatin-induced myopathy is a rare, but serious adverse effect. This case report highlights the need for a proper treatment and dose adjustment during chronic medical therapy, the need for adequate patient education and application of adequate drug policy measures in the era of fragmented health care delivery and polypragmasia.

Maternal thyroid-stimulating hormone reference ranges for first trimester screening from 11 to 14 weeks of gestation.

BACKGROUND: To establish maternal thyroid-stimulating hormone (TSH) reference ranges for first trimester screening from 11 + 0 to 13 + 6 weeks of gestation. METHODS: A total of 10 592 singleton and 201 twin consecutive Caucasian pregnant women who underwent simultaneously prenatal first trimester Down's syndrome screening and thyroid function screening from January 2010 to November 2017 were included in the study. Women with positive antithyroid peroxidase antibody (TPOAb) and positive personal history of thyroid disease were previously excluded. TSH was measured by immunochemiluminescent assay on ci 16200 Abbott Architect analyzer. Nonparametric percentile method (also known as CLSI C28.A3) was used for the determination of reference ranges. RESULTS: We established reference ranges of TSH for the period of gestation from 11 + 0 to 13 + 6 weeks of pregnancy as 0.16-3.43 mU/L for singleton Caucasian pregnancies and 0.02-2.95 mU/L for twin Caucasian pregnancies. The median (IQR) of TSH for singleton pregnancies was higher than that for twin pregnancies (1.25 mU/L (0.83-1.81) vs 0.84 (0.37-1.47), respectively; P < .0001). CONCLUSIONS: Each first trimester screening center should be aware of which type of immunoassay their laboratory uses. TSH reference ranges in women during the first trimester of pregnancy are lower than those for general population. Twin pregnancies have lower TSH than singleton pregnancies.

Incorporating thyroid markers in Down syndrome screening protocols.

OBJECTIVE: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd.

Comparison of biochemical response between the minimally invasive and standard open posterior lumbar interbody fusion.

BACKGROUND: The mini-invasive open posterior lumbar fusion procedure (mini PLIF) procedure is an alternative to standard open procedure (open PLIF) and is intended to reduce surgery-related trauma. The measuring of suitable biochemical factors enables objective comparison of the invasiveness of spinal surgery procedures. METHODS: Prospectively collected data on myoglobin, creatine kinase, interleukin-6, C-reactive protein levels and intensity of low back pain and radicular pain in one-level mini PLIF and open PLIF procedures were analysed. The mini PLIF and the open PLIF groups included 27 and 23 patients, respectively. The collection of blood samples and clinical data were performed preoperatively and on postoperative days 1, 3 and 7. The non-paired t-test was used for statistical evaluation. RESULTS: We did not found any statistically significant differences of myoglobin and creatine kinase levels between the groups. In the open PLIF group the IL-6 levels were significantly higher than in the mini PLIF group on postoperative day 3. CRP levels showed significant lower stress response in favour of the mini PLIF group on postoperative days 3 and 7. Levels of post-op low back pain on day 3 were significantly lower in mini PLIF group. Also intensity of radicular pain on day 1 and 3 were lower also mini PLIF group. CONCLUSION: The extent of myonecrosis was comparable in both techniques. The analysis of the IL-6 and CRP levels showed significantly lower systemic inflammatory response in mini PLIF technique. The mini PLIF technique provides transiently lower postoperative pain levels.

Chemotherapy treatment patterns and neutropenia management in gastric cancer.

BACKGROUND: Potentially myelosuppressive doublet and triplet chemotherapy combination regimens are considered the most active treatments in gastric cancer. This multicenter prospective observational study was designed to gain insight into the chemotherapy regimens being used in Europe and to evaluate neutropenia management in patients identified as at high risk for febrile neutropenia (FN). METHODS: Eligible patients had gastric cancer, were scheduled for ≥ 3 cycles of myelosuppressive chemotherapy, and had an investigator-assessed overall FN risk ≥ 20%. Data were collected for up to ten cycles. The primary endpoint was the proportion of patients who received granulocyte colony stimulating factor (G-CSF) primary prophylaxis (defined as G-CSF initiated on days 1-7 of cycle 1). Secondary endpoints included FN incidence, chemotherapy administration, and G-CSF use. RESULTS: Of 199 patients who met the eligibility criteria and started at least one cycle of chemotherapy, mean age was 63 years, 76% were men, 83% had an ECOG score of 0 or 1, 54% had metastatic disease, and 24% had received prior chemotherapy. A total of 27 different backbone regimens were given; the most common regimen was modified docetaxel, cisplatin, and 5-fluorouracil (DCF). Despite all patients having been identified as having a ≥ 20% FN risk, only 70 (35%) received G-CSF primary prophylaxis. FN occurred in 14 patients overall (7%). Most FN events occurred in patients who received DCF/modified DCF (9/14 events, 64%). CONCLUSIONS: The results of this study reveal a high use of myelotoxic treatment regimens in gastric cancer in Europe and low adherence to clinical practice guidelines for the use of primary and secondary G-CSF prophylaxis for FN.

Comparison of approaches and measurement of continuing professional development for specialists in laboratory medicine within four European countries.

BACKGROUND: This study investigated approaches to continuing professional development (CPD) for specialists in laboratory medicine within four European countries: Croatia, the Czech Republic, Malta and the UK. METHODS: The research questions focussed on ascertaining if continued registration/licence was linked to CPD and if so, were there requirements for certain amounts and types of CPD and for CPD activities to meet specified accreditation criteria. The Professional Associations Research Network (PARN) model of CPD measurement was applied to each country's registration/licencing body's CPD requirements. RESULTS: Our results indicate a spectrum of approaches to CPD within participating countries. CONCLUSIONS: It will be necessary for European employers to be familiar with these differences and to take them into account for this increasingly mobile European workforce.

Intermittent hemodialysis is superior to continuous veno-venous hemodialysis/hemodiafiltration to eliminate methanol and formate during treatment for methanol poisoning.

During an outbreak of methanol poisonings in the Czech Republic in 2012, we were able to study methanol and formate elimination half-lives during intermittent hemodialysis (IHD) and continuous veno-venous hemodialysis/hemodiafiltration (CVVHD/HDF) and the relative impact of dialysate and blood flow rates on elimination. Data were obtained from 11 IHD and 13 CVVHD/HDF patients. Serum methanol and formate concentrations were measured by gas chromatography and an enzymatic method. The groups were relatively comparable, but the CVVHD/HDF group was significantly more acidotic (mean pH 6.9 vs. 7.1 IHD). The mean elimination half-life of methanol was 3.7 and formate 1.6 h with IHD, versus 8.1 and 3.6 h, respectively, with CVVHD/HDF (both significant). The 54% greater reduction in methanol and 56% reduction in formate elimination half-life during IHD resulted from the higher blood and dialysate flow rates. Increased blood and dialysate flow on the CVVHD/HDF also increased elimination significantly. Thus, IHD is superior to CVVHD/HDF for more rapid methanol and formate elimination, and if CVVHD/HDF is the only treatment available then elimination is greater with greater blood and dialysate flow rates.

Pseudonormokalemia case report - What does it mean to have normal blood potassium?

This case report describes a case of pseudonormokalemia, true hypokalemia. Often, only laboratory values outside the normal range gain attention and false normal results are at risk of not being noticed. However, a disease state may be masked by another pathological process. Here, a 50-year old male was admitted to the Department of Internal Medicine due to sepsis from a dental infection. Initially, serum potassium measurement revealed a normal value of 4 mmol/L (reference interval 3.8-5.1 mmol/L). Thrombocyte number was above 500x109/L. Due to our policy to recommend a repeated measurement of potassium in whole blood or heparin plasma if a patient has thrombocytosis, pseudonormokalemia was identified because the heparin plasma potassium value was only 2.9 mmol/L (reference interval 3.5-4.8 mmol/L). The physiological difference between serum and plasma concentration is no more than 0.3 mmol/L. In this case, potassium concentration were falsely elevated in the serum sample, probably caused by the high number of platelets releasing potassium during clotting. Interpretative comments in patients with thrombocytosis over 500x109/L recommending plasma potassium measurement are helpful. The best way to eliminate pseudohyperkalemia and pseudonormokalemia phenomena caused by thrombocytosis is to completely change towards heparin plasma as the standard material.

Reporting LDL cholesterol results by clinical biochemistry laboratories in Czechia and Slovakia to improve the detection rate of familial hypercholesterolemia.

Introduction: This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. Materials and methods: The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. Results: A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). Conclusions: Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.

Thiazide-associated hyponatremia in internal medicine patients: analysis of epidemiological and biochemical profiles.

OBJECTIVES: Thiazide-associated hyponatremia (TAH) is a clinically important side effect of the therapy with thiazide and thiazide-like diuretics. This study aims to analyze epidemiological, biochemical, and symptomatological profiles (including volume status) of patients admitted with TAH. METHODS: A retrospective hospital record study was performed. Epidemiological and biochemical parameters and symptoms were compared between the thiazide (n = 143) and non-thiazide (n = 282) groups. Patients in the thiazide group were classified as hypo-, normo-, or hypervolemic. Furthermore, the comparison of epidemiological, biochemical, partially pharmacotherapeutical, and symptomatological parameters between the hypovolemic and normovolemic TAH groups was performed. RESULTS: The thiazide group showed lower s-Na (p = 0.008), s-K (p < 0.001), s-Cl (p < 0.001), measured s-osmolality (p = 0.021), and eGFR (p < 0.001); higher s-urea (p < 0.001), s-creatinine (p = 0.023), s-glucose (p < 0.001), u-osmolality (p = 0.012), u-Na (p < 0.001), u-K (p = 0.023), and u-Cl (p < 0.001). Patients using thiazide were older (p < 0.001), more likely to be female (p = 0.011), and with symptoms corresponding more to chronic hyponatremia. Compared to the normovolemic group (n = 93; 65%), the hypovolemic patients (n = 47; 32.9%) showed higher s-urea (p = 0.005), s-creatinine (p = 0.045), and s-UA (p = 0.010); lower eGFR (p = 0.032), u-Na (p = 0.015), u-Cl (p = 0.016), anorexia (p < 0.001), and a higher frequency of furosemide use (p < 0.001). CONCLUSIONS: Thiazide use is a crucial etiological cause of hypotonic hyponatremia among internal medicine inpatients, associated with more severe hyponatremia, but with no difference in the in-hospital mortality. Even in hypo-osmolar conditions of TAH, 32.9% of patients exhibited signs of volume depletion. FE-UA did not differ between the hypovolemic and the normovolemic patients in TAH conditions. Anorexia and the combination of thiazide together with furosemide, rather than thiazide use alone, were risk factors for hypovolemic hyponatremia without affecting FE-UA.

Post-collection acidification of spot urine sample is not needed before measurement of electrolytes.

Introduction: Kidney stone formers can have higher oxalate and phosphate salt amounts in their urine than healthy people and we hypothesized that its acidification may be useful. The study aims to compare results of urine concentrations of calcium, magnesium, and inorganic phosphorus in the midstream portion of first voided morning urine samples without (FMU) and with post-collection acidification (FMUa) in kidney stone patients. Materials and methods: This is a prospective single center study. A total of 138 kidney stone patients with spot urine samples were included in the study. Urine concentrations of calcium, magnesium and inorganic phosphorus were measured with and without post-collection acidification. Acidification was performed by adding 5 µL of 6 mol/L HCl to 1 mL of urine. Results: The median age (range) of all participants was 56 (18-87) years. The median paired differences between FMU and FMUa concentrations of calcium, magnesium, and inorganic phosphorus were: - 0.040 mmol/L, 0.035 mmol/L, and 0.060 mmol/L, respectively. They were statistically different: P < 0.001, P < 0.001, P = 0.004, respectively. These differences are not clinically significant because biological variations of these markers are much higher. Conclusions: No clinically significant differences in urinary calcium, magnesium, and inorganic phosphorus concentrations between FMU and FMUa in patients with kidney stones were found.

Acidification of 24-hour urine in urolithiasis risk testing: An obsolete relic?

BACKGROUND: Recommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions. MATERIAL AND METHODS: We collected urine samples from ten healthy volunteers and prepared aliquots to be stored either at room temperature or 4 °C. Some aliquots were preserved using hydrochloric acid prior to storage, some thereafter, some using the BD Urine preservation tube and some were not preserved at all. Storage duration was 0, 24, 48 or 72 h. In all samples calcium, magnesium, phosphorus, creatinine, oxalate, citrate and uric acid were measured and compared to the according reference sample. RESULTS: We could not find any significant deviation for any of the analytes and preanalytical treatment conditions compared to the associated reference sample. CONCLUSION: Preservation of 24 h urine for the metabolic evaluation in stone formers might not be necessary for sample storage up to 72 h.

Evaluating Alternative Ramucirumab Doses as a Single Agent or with Paclitaxel in Second-Line Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma: Results from Two Randomized, Open-Label, Phase II Studies.

Studies JVDB and JVCZ examined alternative ramucirumab dosing regimens as monotherapy or combined with paclitaxel, respectively, in patients with advanced/metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. For JVDB, randomized patients (N = 164) received ramucirumab monotherapy at four doses: 8 mg/kg every 2 weeks (Q2W) (registered dose), 12 mg/kg Q2W, 6 mg/kg weekly (QW), or 8 mg/kg on days 1 and 8 (D1D8) every 3 weeks (Q3W). The primary objectives were the safety and pharmacokinetics of ramucirumab monotherapy. For JVCZ, randomized patients (N = 245) received paclitaxel (80 mg/m2-D1D8D15) plus ramucirumab (8 mg/kg- or 12 mg/kg-Q2W). The primary objective was progression-free survival (PFS) of 12 mg/kg-Q2W arm versus placebo from RAINBOW using meta-analysis. Relative to the registered dose, exploratory dosing regimens (EDRs) led to higher ramucirumab serum concentrations in both studies. EDR safety profiles were consistent with previous studies. In JVDB, serious adverse events occurred more frequently in the 8 mg/kg-D1D8-Q3W arm versus the registered dose; 6 mg/kg-QW EDR had a higher incidence of bleeding/hemorrhage. In JVCZ, PFS was improved with the 12 mg/kg plus paclitaxel combination versus placebo in RAINBOW; however, no significant PFS improvement was observed between the 12 mg/kg and 8 mg/kg arms. The lack of a dose/exposure-response relationship in these studies supports the standard dose of ramucirumab 8 mg/kg-Q2W as monotherapy or in combination with paclitaxel as second-line treatment for advanced/metastatic gastric/GEJ adenocarcinoma.

COVID-19 and oncological disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus named SARS-CoV-2, initially emerged in China in late 2019. The rapid global spread of this novel virus led the World Health Organization declare a pandemic with > 30,000,000 confirmed cases, 946,000 deaths and > 21,000,000 recoveries reported as of 18 September 2020, according to the Johns Hopkins Coronavirus Resource Center. Initial reports from Asia suggested that elderly patients with multiple comorbidities, specifically diabetes, hypertension, and obesity were at an increased risk of developing severe COVID-19 following a SARS-CoV-2 infection. As data on these risks have evolved, evidence has increasingly shown that patients with cancer are indeed a particularly vulnerable group. However, the effects of various confounding factors, including an older than average patient population who often have underlying comorbidities including a suppressed immune system and/ or a hypercoagulable state, have been difficult to separate from the effects of having cancer. Common presenting symptoms of SARS-CoV-2 including dyspnoea, cough, fever, fatigue, dysgeusia and, less commonly, diarrhoea and/ or a hyperinflammatory syndrome are equally confusing to clinicians as they all are common symptoms of both cancer and toxicity from anti-cancer therapy. Furthermore, the radiographic dilemma of distinguishing between immune-checkpoint inhibitor-induced pneumonitis from that caused by SARS-CoV-2 infection and conflicting data on the effects of certain therapies on patient outcomes has left clinicians with considerable angst on how to help patients with acute or worsening symptoms in an optimal way. Predicted increase in mortality follows not only from the delay in discovery and progress resulting from temporary closing of research laboratories at cancer centers but also from diversion of resources to patient care and temporary suspension of clinical trial enrolment both by companies and local institutions. The possibilities of travelling to specialized medical centers whose activities are essential for the delivery and improvement of patient care were reduced, too. Viral mutations might also occur during transmission and spread; this leads to a statement that SARS-CoV-2 will forever remain a looming threat to the oncological community. What is crucial to remember is that cancer itself is a pandemic with > 18,000,000 people dia-gnosed worldwide every year. Many societies, including the European Society for Medical Oncology and the American Society of Clinical Oncology, are providing clinical recommendations for the management of patients with cancer during this challenging time, recognizing that continuation in the precise treatment of our patients is critical for our role of physicians. PURPOSE: The aim of the presentation is to point out the contact or overlapping areas of both mentioned disease entities for the purpose of possible simplification of dia-gnostic and therapeutic management of a cancer patient with suspected or already proven  COVID-19 disease.