In Which Patients Does the 2023 Duke-ISCVID Criteria for Infective Endocarditis Increase the Diagnosis of "Definite Endocarditis"?-A Preliminary Analysis in the Prospectively Evaluated DERIVE Cohort.

Background/Objectives: Recently, an update of the Duke criteria for the diagnosis of infectious endocarditis has been published: the 2023 Duke-ISCVID criteria. To gain an insight into which proportion of patients are affected by the new criteria, and which criteria might be the most relevant for the expected increase in sensitivity, we analysed data from a registry of cardiovascular infections. Methods: The 2023 Duke-ISCVID criteria were applied to patients who were diagnosed with and treated for endocarditis after having been classified as "possible" endocarditis according to the 2015 ESC Modified Duke criteria. In patients thus newly classified as "definite endocarditis", diagnostic factors leading to this reclassification were described. Results: Of 397 patients, 48 (12%) did not fulfil the definition "definite infectious endocarditis" according to the 2015 ESC Modified Duke criteria. Of these, six (13%) fulfilled the definition when the 2023 Duke-ISCVID criteria were applied. A main factor triggering this reclassification was the consideration of microorganisms identified using valve PCR. Conclusions: As expected, the sensitivity of the new 2023 Duke-ISCVID criteria is increased in this cohort, mainly through the incorporation of new diagnostic methods in the criteria. Further studies are required to assess the effect on specificity in detail.

Evaluating the Duke Criteria for infectious endocarditis in a single-center retrospective study.

The Duke Criteria have shaped the way infectious endocarditis (IE) is diagnosed in the last 30 years. This study aims to evaluate their current validity and importance in the diagnostic of IE. A retrospective cohort study was conducted on 163 consecutive patients who presented at the University Hospital in Ulm (Germany) with clinical suspicion of IE between 2009 and 2019. With patients' medical records we differentiated between definitive endocarditis (DIE), possible endocarditis (PIE) and rejected endocarditis (RIE) and assessed the validity of the Duke Criteria in comparison to the final discharge diagnosis. We then tried to identify new potential parameters as an addition to the current valid Duke Criteria. The validity of the Duke Criteria improves with the length of hospitalization (especially cardiac imaging criterion, RIE 33.3%, PIE 31.6% and DIE 41.9%, p = 0.622 at admission and RIE 53.3%, PIE 68.4%, DIE 92.2%, p < 0.001 at discharge). At admission, overall sensitivity and specificity were respectively 29.5 and 91.2% in the DIE group. At discharge, sensitivity in the DIE group rose to 77.5% and specificity decreased to 79.4%. Of all screened metrics, microhematuria (p = 0.124), leukocyturia, (p = 0.075), younger age (p = 0.042) and the lack of rheumatoid disease (p = 0.011) showed a difference in incidence (p < 0.2) when comparing DIE and RIE group. In multivariate regression only microhematuria qualified as a potential sixth minor criterion at admission. Even with the latest technological breakthroughs our findings suggest that the Duke Criteria continue to hold value in the accurate assessment of IE. Future efforts must shorten the time until diagnosis.

Comparison of the 2015 and 2023 European Society of Cardiology versions of the Duke criteria among patients with suspected infective endocarditis.

BACKGROUND: Diagnosing infective endocarditis (IE) poses a significant challenge. This study aimed to compare the diagnostic accuracy of the 2015 and 2023 Duke clinical criteria introduced by the European Society of Cardiology (ESC) in a cohort of patients suspected of having IE. METHODS: Conducted retrospectively at two Swiss University Hospitals between 2014-2023, the study involved patients with suspected IE. Each hospitals' Endocarditis Team categorized case as either IE or not IE. The performance of each iteration of the Duke-ESC clinical criteria was assessed based on the agreement between definite IE and the diagnoses made by the Endocarditis Team. RESULTS: Among the 3127 episodes with suspected IE, 1177 (38%) were confirmed to have IE. Using the 2015 Duke-ESC clinical criteria, 707 (23%) episodes were deemed definite IE, with 696 (98%) receiving a final IE diagnosis. With the 2023 Duke-ESC clinical criteria, 855 (27%) episodes were classified as definite IE, of which 813 (95%) were confirmed as IE. The 2015 and 2023 Duke-ESC clinical criteria categorized 1039 (33%) and 1034 (33%) episodes, respectively, as possible IE. Sensitivity for the 2015 Duke-ESC and the 2023 Duke-ESC clinical criteria was calculated at 59% (95% CI: 56-62%), and 69% (66-72%), respectively, with specificity at 99% (99-100%), and 98% (97-98%), respectively. CONCLUSIONS: The 2023 ESC criteria demonstrated significant improvements in sensitivity compared to the 2015 version, although one-third of episodes were classified as possible IE by both versions.

Evaluation of the HANDOC Score and the 2023 International Society of Cardiovascular Infectious Diseases and European Society of Cardiology Duke Clinical Criteria for the Diagnosis of Infective Endocarditis Among Patients With Streptococcal Bacteremia.

BACKGROUND: Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. METHODS: This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high risk for IE. RESULTS: Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-ß-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high risk for IE was 95% (95% confidence interval [CI], 90%-98%), the specificity 82% (95% CI, 78%-85%), and the negative predictive value (NPV) 98% (95% CI, 96%-99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity (95% CI) for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57%-72%), 81% (74%-86%), and 73% (65%-79%), respectively, with specificity (95% CI) at 100% (98%-100%), 99% (98%-100%), and 99% (98%-100%), respectively. CONCLUSIONS: The HANDOC score showed an excellent NPV to identify episodes at high risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia.

An Unusual Presentation of an Enterococcus faecalis Endocarditis With Wrist and Forearm Infection: A Case Report.

In this case, an unusual presentation of Enterococcus faecalis (E.faecalis) endocarditis and clinical signs of wrist and forearm infection are reported. Before the patient was diagnosed with E.faecalis endocarditis, the patient managed to be treated with both prednisolone, various antibiotics, and colchicine on suspicion of gout, erysipelas, and deep tissue infection. Growth of E.faecalis in blood cultures raised the suspicion of endocarditis, and transesophageal echocardiography revealed vegetations on the aortic and the mitral valves with a perforation of the anterior mitral leaflet. Since the patient responded well to antibiotic treatment and there was no progression of the size of the vegetations or the perforation, it was decided by the endocarditis team to refrain from surgery. E. faecalis endocarditis can be difficult to diagnose because the patients are often elderly, and symptoms may be subtle and misleading. In the present case, the diagnostic process was based on the Danish IE guidelines, which state that E. faecalis is a typical IE bacterium. Accepting E. faecalis as a typical infective endocarditis bacterium may lead to an earlier diagnosis and treatment.

Infective endocarditis is rare in patients with hematologic malignancy and neutropenia.

BACKGROUND: Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic. METHODS: Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke-ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non-HSCT). RESULTS: Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified. CONCLUSIONS: Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient-centered outcomes.

Kocuria kristinae-Induced Infective Endocarditis: Unveiling an Emerging Threat in Clinical Practice.

Infective endocarditis (IE) remains a formidable challenge in clinical practice due to several causative agents, each presenting with unique diagnostic and therapeutic dilemmas. Kocuria kristinae, a coagulase-negative, catalase-positive Gram-positive coccus, has recently emerged as an uncommon but increasingly recognized pathogen in the cause of IE. This case report highlights the clinical characteristics, risk factors, and challenges associated with Kocuria kristinae-induced IE. We conducted a comprehensive literature review and identified several case reports on Kocuria kristinae as a causative agent. Due to its indolent nature and the subtle presentation of symptoms, along with its ability to form biofilms, delayed diagnosis of Kocuria is often seen, thereby emphasizing the need for heightened clinical suspicion. The predisposing factors for Kocuria kristinae infection include underlying cardiac abnormalities, prosthetic heart valves, and immunocompromised states. Additionally, antimicrobial susceptibility patterns and optimal treatment strategies remain unclear, warranting further investigation. This abstract presents the case of a 75-year-old male with IE secondary to Kocuria kristinae on a prosthetic mitral valve. We aim to highlight the need for increased awareness among clinicians to facilitate early recognition and prompt initiation of targeted therapeutic interventions. Unraveling the intricacies of Kocuria kristinae's pathogenicity is crucial for refining diagnostic approaches and optimizing patient outcomes.

Eyes Wide Shut: A Cohort Study Questioning the Role of Fundoscopy in Infective Endocarditis Diagnosis.

In this retrospective/prospective study, we assessed the role of fundoscopy in 711 episodes with suspected infective endocarditis (IE); 238 (33%) had IE. Ocular embolic events (retinal emboli or chorioretinitis/endophthalmitis) and Roth spots were found in 37 (5%) and 34 (5%) episodes, respectively, but had no impact on IE diagnosis.

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis.

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.

External Validation of the 2023 Duke-International Society for Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis.

BACKGROUND: The 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required. METHODS: We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria. RESULTS: A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P < .001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P < .001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact. CONCLUSIONS: The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE.

Endocarditis.

Infectious endocarditis (IE) is a universally fatal condition if left unmanaged, requiring urgent evaluation and treatment. Fever, new heart murmur, vegetations found by echocardiogram, and bacteremia are the most common symptoms and findings. Blood cultures and echocardiography are obligatory diagnostic modalities and should be used with the modified Duke criteria, the accepted diagnostic aid, when establishing a diagnosis of IE. When IE is suspected, consultations with cardiology, infectious disease, and cardiothoracic surgery teams should be made early. Staphylococci, Streptococci, and Enterococci are common pathogens, necessitating bactericidal antimicrobial therapy. Importantly, up to 50% of patients with IE will require cardiothoracic surgical intervention.

18F- FDG PET/CT in reclassifying the probable diagnosis of IE - A review.

In the diagnosis of infective endocarditis (IE), Modified Duke's criteria, coupled with clinical suspicion, serve as the guiding framework. For cases involving prosthetic valve endocarditis and infections affecting implantable devices, the use of metabolic imaging with 18 F-FDG PET/CT scans has gained prominence, as per the recommendations of the European Society of Cardiology guidelines. This imaging modality enhances sensitivity and specificity by identifying infective foci within the heart and extracardiac locations. Early utilization of these scans is crucial for confirming or ruling out IE, although caution is required to mitigate false positive responses, especially in the presence of ongoing inflammatory activity. A standardized ratio of ≥2.0 between FDG uptake around infected tissues and the blood pool has demonstrated a sensitivity of 100 % and specificity of 91 %. It is noteworthy that the sensitivity of FDG PET/CT varies, being lower for native valve and lead infections but considerably higher for prosthetic valve and pulse generator infections. This review provides a comprehensive overview of the advantages offered by FDG PET/CT in achieving a definitive diagnosis of IE.

Evaluation of the 2023 Duke-ISCVID and 2023 Duke-ESC Clinical Criteria for the Diagnosis of Infective Endocarditis in a Multicenter Cohort of Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB). METHODS: This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018-23) or IE expert clinicians (2014-17). RESULTS: Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% vs 7%, P = .026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% vs 5%, P = .461). CONCLUSIONS: The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria.

Did the updated Duke criteria missed Erysipelothrix rhusiopathiae from the list of typical microorganisms causing infective endocarditis?

Infectious endocarditis is a severe condition still characterized by a high morbidity and mortality rate. An early diagnosis may positively impact the outcome, so we need our diagnostic tools to match with the ever-changing epidemiologic and microbiologic landscape of infectious diseases. We read with great interest the update to the Modified Duke Criteria for the diagnosis of Infectious Endocarditis recently proposed by the International Society for Cardiovascular Infectious Diseases and decided to propose the addition of Erysipelothrix rhusiopathiae to the list of typical microorganisms causing Endocarditis. This pathogen is widespread distributed in the world, has a zoonotic origin, harbors virulence factors and a multidrug resistance phenotype. Moreover, its retrieval from blood seems to have an important correlation with the presence of Endocarditis. The inclusion of E. rhusiopathiae in the list of typical microorganisms may represent a further refinement of the Modified Duke Criteria, which represent a fundamental tool in the management of patients with suspected endocarditis.

Transesophageal Echocardiography vs. Transthoracic Echocardiography for Methicillin-Sensitive Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus Endocarditis.

Infective endocarditis is an infection of the inner layers of the heart, seen often in intravenous drug users and patients with valvular lesions or prosthetic heart valves. This entity has high mortality and morbidity. The most common causative microorganism is Staphylococcus aureus. In this comprehensive literature review, we focused on both Staphylococcus aureus infections, i.e., methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, demographics, use of transthoracic echocardiogram and/or transesophageal echocardiogram for diagnostics, and treatments. Although clinical criteria are relevant, transesophageal echocardiogram plays a vital role in establishing and identifying the presence of infective endocarditis and its local complications, with higher sensitivity in patients with prosthetic valves. The antibiotic selection posed a great challenge for clinicians due to antibiotic resistance and the aggressive nature of Staphylococcus aureus. Early diagnosis of infective endocarditis, when suspected, and effective management by a multispecialty team can improve the outcome for the patients.

Native Mitral Valve Endocarditis Caused by a Non-HACEK Gram-Negative Pathogen in a Hemodialysis Patient.

Infective endocarditis (IE) due to non-HACEK (species other than Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia accounts for less than 2% of all IE cases but is proven to be associated with higher mortality, even more so in hemodialysis (HD) patients. Few data are available in the literature concerning non-HACEK Gram-negative (GN) IE in this immunocompromised population with multiple comorbidities. We report the atypical clinical presentation of an elderly HD patient diagnosed with a non-HACEK GN IE, namely E. coli, successfully treated with intravenous (IV) antibiotics. The objective of this case study and related literature was to highlight the limited applicability of the modified Duke criteria in the HD population, as well as the frailty of HD patients that increases their susceptibility to IE due to unexpected microorganisms that could have fatal consequences. The need for a multidisciplinary approach of an IE in HD patients is therefore imperative.

The role of early defervescence in ruling out infective endocarditis: a cohort study.

OBJECTIVES: To evaluate the role of defervescence within 4 days from antibiotic treatment initiation in ruling out infective endocarditis (IE) among patients suspected of such diagnosis. METHODS: This study was conducted at the Lausanne University Hospital, Switzerland (January 2014 to May 2022). All patients with suspected IE being febrile upon presentation were included. IE was classified according to the modified Duke criteria proposed by the 2015 European Society of Cardiology guidelines, before or after applying the criterion 'resolution of symptoms suggesting IE within 4 days of the introduction of antibiotic therapy' based solely on early defervescence. RESULTS: Among 1022 episodes with suspected IE, 332 (37%) had IE according to Endocarditis-Team evaluation; 248 were classified by clinical Duke criteria as definite and 84 as possible IE. The rate of defervescence within 4 days from antibiotic treatment initiation was similar (p 0.547) among episodes without (606/690; 88%) and those with IE (287/332; 86%); among episodes classified as definite and possible IE by clinical Duke criteria, 211 of 248 (85%) and 76 of 84 (90%), respectively, defervesced within 4 days from antibiotic treatment initiation. By using early defervescence as a rejection criterion, the 76 episodes with final IE diagnosis classified as possible by clinical criteria could be reclassified as rejected. DISCUSSION: The majority of IE episodes defervesced within 4 days from antibiotic treatment initiation; thus, early defervescence should not be used to rule out the diagnosis of IE.

The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria.

The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, polymerase chain reaction, amplicon/metagenomic sequencing, in situ hybridization), imaging (positron emission computed tomography with 18F-fluorodeoxyglucose, cardiac computed tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of "typical" microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the Duke-ISCVID Criteria available online as a "Living Document."

Native Valve Infective Endocarditis Secondary to Acute Cholecystitis in the Setting of Escherichia coli Bacteremia: A Case Report.

Infective endocarditis is an infection of the endocardium that affects the heart valves. It is usually caused by bacteremia secondary to distant infections such as urinary tract infections, surgical procedures, or other sources of pathogenic entry into the blood. It often affects damaged native valves, as well as prosthetic valves, and is primarily caused by Gram-positive bacteria, such as Staphylococcus aureus. Infective endocarditis secondary to Escherichia coli is rare, despite E. coli being one of the most common pathogens causing Gram-negative bacteremia. Between 1909 and 2002, 36 cases of native valve infective endocarditis were reported that met Duke criteria. The majority were secondary to urinary tract infections due to E. coli. Infective endocarditis secondary to E. coli bacteremia in the setting of acute cholecystitis is highly uncommon, and this case report aims to highlight this unusual presentation of infective endocarditis.