Transcription
Please, uh, let your colleague in, okay? Because I will be on the camera. I will not be able to see things coming in and out. So, let's go to the first case.
This is a 60-year-old female who presented to the emergency department with confusion. No background history. And the medical register contacted you because the full blood count shows a platelet count of 60. This will be 10 and follow. All right. Okay. So, this is power 10. Let's see a few more fields. Okay, let's go to power 50 now. This is power. Dr. Amir, what's the uh kidney function? Patient is in AKI1. Okay. All right. So, do we have any biomedical scientist with? No. Okay. I'm the biomedical scientist. I see this blood film and uh I put some comments on it that there is thrombocytopenia and I refer this patient, this blood film, to clinical hematology. Now, clinical hematologist, please report this blood film. You are sitting in a course exam. Dr. Amir, can I go ahead with this? Yes.
So, uh, the blood film shows genuine thrombocytopenia and then, uh, I can see, uh, some, uh, fragments as well as spherocytes. And, uh, as far as the white cells are concerned, I think, uh, I couldn't see any abnormal thing. The neutrophils, the ones that I saw, had normal granulation. Um, so, on the basis of the blood film and the AKI, I think, uh, it is most likely a case of TTP and we should urgently send an MTS 13 levels. We should also do that and other hematic screen because I can see, um, the sparides. Not sure. Anyone else? Anyone else want to report this? I can try. Yes, go ahead. You are clinical hematology sitting in Epcot exam. Report this blood.
Okay. So, there is, um, anemia with, um, aniscytosis. Uh, I can see poly, obvious poly chromasia, nucleated red blood cells, um, and, um, uh, uh, red blood cell fragments about, uh, three to four, um, per high power field, um, some target cells, uh, and spherocytes. Um, there's genuine thrombocytopenia and no evidence of platelet clumps. Um, white blood cells appear morphologically normal. So, in the context of, um, anemia with polychromasia and thrombocytopenia and NRBCs, this, I want to exclude, this is a picture of MAHA and I want to exclude TTP by sending agent TS3.
So, do you think you have passed this question, both of you? Uh, good morning. Um, can I report what I see in this field? Yes, report please. Uh, I haven't joined from the start, but here in this field, I can see hemogost cell, that's what the colleague said about the occasional spherocytes. And so, he ghost cells with few sites would give me the suspicion of G6PD. I don't know also if, if you have said anything about the background of the patient because I didn't know from the start. But no background. Patient was admitted with confusion. With what? Patient is admitted with confusion. Okay. Uh, I just wanted to report, uh, what I saw in this field about the hemogost cells together with the occasional sphere would raise the possibility also of a G6PD deficiency crisis and acute attack. Thank you.
This is not G6PD patient. This patient is admitted with confusion, thrombocytopenia. You can see red cell aniscytosis, NRBC red. Yes, this is MAHA TTP. But as an FRC path exam candidate, if you say that I will send at TS13 level for this patient and do nothing else, you will fail this question and you will fail the exam as well because you have missed the emergency. When you are suspecting TTP, what should you do according to the BSS guidelines? Who were the two candidates who reported the blood? Yes, Dr. Amir. Uh, Mrs. Romana. Uh, sorry. Yeah, I, I missed the emergency management. I think we should call, uh, the treating team immediately, inform them that we have seen, uh, fragments and, um, sorry, I didn't go through the BCSH. Who is the treating team? Uh, the emergency department. But what I think we have to actually arrange for the plasma exchange. So, I'll inform. Guidelines say, what does the guidelines say? Uh, sorry, Dr. Amir, I didn't go through the guidelines, that's why I'm a bit confused. But I know, uh, in, in practice, we actually saw, uh, two cases of TTP and, uh, uh, if, so, there was one patient who was in another center and we had to bring him immediately to the center where plasma exchange was available. So, we immediately send the blue light ambulance. And if you are appearing in FRC path exam, then you have to follow UK guideline. UK guideline says that if you suspect TTP, you should discuss the case with the TTP consultant. Okay. At MTS 13, one may take 1 hour, 4 hours, half a day. Maybe the ambulance to puncture on the way of the helicopter to which you are sending this sample may held down. Okay. So, you should discuss the case first with the TTP. This is the BSH TTP algorithm which says, discuss with TTP consultant and agree on diagnosis. Okay. Please read the BSH guidelines algorithm if you are planning BSH, if you are planning, sorry, the efforts about things. So, confusion, thrombocytopenia, you can see anemia as well. Someone asks about renal function, patient is in AKI1, suspected MAHA TTP, you will discuss the case with the TTP consultant. We agreed on the diagnosis, we transferred the patient to TTP center where she was plasma exchange. Now she is Okay. If you miss the emergency, they will ask you to come e in emergency again. Okay. Which means you have to appear in exam again. Okay. What next?
Actually, I'm, I'm sorry, I'm a little bit late in joining it. Actually, I lost the link. Okay. And next is another slide which is a 60-year-old patient admitted with confusion again in the emergency department. The CT scan shows intracranial hemorrhage. This is power 10 of the patient. Let's go to power 50. It was in a low bar leukocytosis. Only I could appreciate only this feature of this map. It was leukocytosis. I could not comment on platelets. It was not clear to me. Apparently, there is, uh, the count is very less. Platelet count is very less, most probably. But I would like to review it in under high power. This is power 50 going on. Okay. Yes. It's a better view. There's thrombocytopenia and sites are positive and there are blastoid cells. Now, this blood film came to me again because I am the biomedical scientist and, uh, I reported as leukocytosis, suspected LPD, likely CLL, and I refer this blood film to you guys because you are a clinical hematologist. I may not have this much knowledge. So, you have seen the blood power 10 and you are seeing power 50. Please report the blood. Dr. Ram, can I go ahead? Yes.
So, uh, firstly, starting with the red cells, uh, there is an isopolytosis which is somewhat. What is the main or threatening abnormality in this blood cell? So, the threatening abnormality is, uh, the, you know, the abnormal white cells. Mention white cell, white cells first. So, uh, the white cells appear in monomorphic and they, uh, some of them have prominent nuclei. So, I think it is a case of, uh, acute leukemia. I'm not sure about the platelet count. The plates look okay. So, the platelet count in this patient was 162. Okay. The, the hemoglobin is 102 and white cell count is 56. Sorry, white cell count is what? 56. 56. Okay. Okay. Now, report this blood please. So, uh, the white cells, uh, appear, there's a monomorphic population, uh, of, uh, mononuclear cells, uh, with prominent nuclei, uh, some have abundant cytoplasm as well. I can't see any Auer rods or anything like that. Uh, and, uh, red cells also have an isopolytosis with elliptocytes, some echinocytes, a few, um, spherocytes as well. And on the basis of this, I think it is either acute leukemia or, um, leukemic form of some LPD. Appears most likely acute leukemia. Yeah. So, I can see some vacuolation in, in a few white cells. So, it is most likely acute leukemia. I'll send this for procyto. Mhm. And I'll inform the consultant as well who is covering the lab. What to do with the patient? The patient. So, you said, yeah. Yeah. So, you said that the patient has intracranial hemorrhage. Yeah. So, close automatically confirm acute myeloid leukemia. Yes. When you report the blood film, you will comment on the, uh, most prominent abnormality first. This blood film shows multiple blasts which you can see. You cannot say that they are myeloid or lymphoid. You always confirm that on the flow, because sometimes we think these are myeloid blasts, they turn out to be lymphoid ones, or sometimes we think this is lymphoid blast, they turn out to be myeloid ones. Okay. This patient has a lot of red cell abnormality which you have seen. There are elliptocytes and this patient has mild thrombocytopenia. Blood film, um, you can mention that or you can say count normal because that is blood as normal on the blood count as well. So, most likely this patient is of acute leukemia. This patient needs urgent flow cytometry to be sent to diagnostic center. Once the patient also needs, uh, bone marrow. This patient has intracranial hemorrhage. You cannot stick a needle into someone who is lying in emergency with intracranial. Sorry, Dr. I don't know what's the cause of intracranial hemorrhage because the platelet count is appears normal, it is not a severe thrombocytopenia. So, I'm not sure why there is intracranial hemorrhage. Anyone has any idea? May I say something? May I say something? I can see very clearly, uh, features of hemolysis on this peripheral blood smear, especially fragments. I think these are 1 plus 2 plus fragments. So, there is a feature of hemolysis on peripheral which is in favor of intracranial bleed as well. And there is thrombocytopenia, I think it is clear thrombocytopenia. Now, the question is that what is the underlying cause of his thrombocytopenia and whether there is malignancy? This is, I was thinking over, okay, whether it is a malignancy or this patient has, no, no previous history of any malignancy. Previously fit well, just complained of body for two days. Uh, GP gave some antibiotics and then he was admitted to the emergency department because of world finding difficulty and in the ED, emergency department, he was totally confused. Then when we did the CT scan, it shows intracranial. Now, these blasts have absorbing capacity. Blasts absorb the von Willebrand factor multimer. It leads to deficiency of von Willebrand protein and that leads to secondary hemorrhage. Whenever there are high count, high blood count, high white cell count, high platelet count, high red cell count, they absorb von Willebrand factor, causing acquired von Willebrand disease. That's why this patient has a tendency to bleed. Okay. Thank you, sir. Would it be, uh, better if he had his marrow done? Because it will also give some clues about the underlying cause. Marrow? Yes. But this scenario is saying that this patient has intracranial hemorrhage. Would you stick a needle into someone that has intracranial hemorrhage? You will give this patient some platelets. Some is not suitable for him. Disorder. Once the hematoma is stabilized, then you can do marrow. You will discuss this patient with the neurosurgeons as well. Maybe they want to do some procedure in this patient. So, what genetic test would you send for this patient as per BS guideline 2022? What I have got from the, uh, presentation is that, uh, I think, uh, thrombocytopenia should be evaluated further. No, the main ideology, main ideology underlying the condition is thrombocytopenia. I think this patient has leukemia, that's why the platelet count has gone low. But my question is, what genetic panel would you send in acute myeloid leukemia according to, according to BS 2022 guideline? BM ML, rather. What else? There is a table given in the BSS guideline that tells you that if you have acute myeloid leukemia, you should send these four categories of tests. That is a question that comes. AML with myelodysplastic differentiation. So, you have to send karyotyping, number one. Yes. Yes. Molecular for FLT3 ITD, NPM1, and CEBPA. This is category two. Category three is NGS panel. Category four is PH or PCR for 821, inversion 16, and KMT2A. Okay, these, these four categories of tests you have to send, uh, for every acute myeloid leukemia. Okay. This patient is stabilized and now you are planning treatment for this patient. Patient has no background history, previously. What are the choices of treatment? Come on. Give him some, give her some treatment. Yes. But, uh, actually, I have not gone through the treatment in such, so much detail. So, that is why I was not participating in this part of the question. How old is the patient? 60 year old, no background. Do we have any, any of the flow or the genetic panels for FLT3 or anything? So, after stabilization, once the, um, hematoma was addressed, this patient had NPM1 mutated AML. We can start with hydroxycarbamide to control the count if her cell count is high, and then we can, um, um, start with induction chemotherapy. The standard is DA, um, daunorubicin, cytarabine, 3 plus 7, if CD33 positive, we can give gemtuzumab ozogamicin. Would you transfer after remission? Or, uh, for NPM1, we need to check the MRD after second cycle. If it's still MRD positive, then we need to go for transplant. Yeah. Okay. Correct.
Now, this is the third patient. This is a 35-year-old patient with persistent leukocytosis. Hemoglobin 140, platelet count 250, white cell count is 14. He has leukocytosis since more than 2 years. This is power 10. 15. Right. This neutin came to me as a biomedical scientist and, um, I have seen some cells which has blasts like this one and I have carried it as LPD. And I have referred this blood film to clinical hematologist to report it and act accordingly. Please report the blood. What abnormality do you see in this blood? May I, sir? Yes, go ahead. Uh, this is a very blood smear and RBC morphology is unremarkable and these are normal normocytic red cells. Thrombocytopenia is, thrombocytopenia and, uh, leukocytosis count seems to be normal within the normal range with relative neutrophilia. It could be reactive or I would like to check the, uh, more smears for neutrophilia whether it is reactive due to infection, inflammation, or any other. [Music] Cause. To me, they appear in the. Oh, yes, they seem to be. All right. So, what would you do in this patient then? This patient has count of three since more than two years. I would like to know the eosinophil count and whether, uh, this patient had, uh, serial records of eosinophil count to differentiate between reactive and clonal disorder. Okay. So, you have given advice to the GP, for example, this is a GP blood film that exclude the reactive causes of the eosinophilia, which you have done. Now, he is asking you to please exclude the clonal cause of this. What test would you like to send for the clonal cause of this? For that purpose, I think bone marrow examination is especially bone marrow biopsy. Anything else before biopsy? Yes. Uh, PDGFR alpha gene, uh, PDGFR beta, FGFR, all these. Then there is a use in eosinophilic panel. Okay. I have not, I'm sorry. Operation blood core. PDGR alpha beta and, uh, we also send levels as in the patient to see if, if there is, if it is positive or not. If these two tests are negative, then you will learn for bone marrow. What are the clonal causes of this? One is myeloproliferative neoplasm, chronic eosinophilia. Then it could be due to hypereosinophilic syndrome and, uh, reactive causes of not. You have the clonal causes. These two were in my mind. I think the myelocytosis also comes. Okay. So, there are two broad categories. Either it is chronic leukemia or myeloid lymphoid neoplasm with eosinophilia. Okay. If there is no cause for this patient and it has been labeled as idiopathic eosinophilia here, and now he has symptoms as well. Idiopathic hypereosinophilic syndrome, IHS. What are the treatment different treatment options for hypereosinophilic syndrome? Anti-steroids. Start the steroids if there is no, no parasitic infection and if there is no response, we can go for depending on, um, if there is PDGF alpha, we can go for low-dose imatinib or we can go if there is a alpha GF, then it is not idiopathic hypereosinophilic syndrome. Yeah, yeah, correct. Then it is hypereosinophilia with special target. Yes. So, my question was, if the patient has been labeled as idiopathic hypereosinophilic syndrome, then you mentioned start with steroid. What if steroid fails? Um, we, we can go for other immunosuppressants. I think, uh, anti-CD52, we can use or anti-IL5. So, first line is steroid. Second one is imatinib, which is a trial drug. Then you have immunosuppressive and cytoreduction. Then in the end, you will give them anti-CD22, anti-CD52 antibody, alemtuzumab. So, in every blood film in the exam, you will be asked three or four small questions. For example, this is your eosinophilia blood film. They will ask you, uh, to report the blood and then they will ask you, okay, what investigation you will do to find out the cause of thrombocytosis? Or what are the hematological conditions associated with eosinophilia? They can ask you as well, uh, please mention the treatment of the eosinophilia where special targets are present. And they can also ask, what is the treatment drugs for idiopathic hypereosinophilic syndrome? So, in the exam, there will always be three or four small questions in your section. Another thing is that whenever you see that your full count contains high eosinophil count, always start with power four. Okay, power four because maybe this patient has any, um, worm inside. Okay, so which you will pick on power four. He's an affiliate in the exam. Never miss power. Or if the patient has eosinophilia plus travel history as well, it means this is a worm. So, find somewhere it will be on the corners or somewhere. In the Nikas blood film that we receive in our hospitals, they are full of worms. But in the exam, unfortunately, each blood film contains one worm or two worms hiding somewhere. So, you should be vigilant to see, to look for the worms. If this is a case of eosinophilia plus patient has a travel history, then it is indeed a worm somewhere is hiding. Okay. There is no worm in this patient, but this is a general tip for the exam. If you see, um, your past, search for a first wire power. All right.
This is another case. 60-year-old male patient with high white cell count. This is the power 10 of the patient. Go to the thin side. The full blood count shows hemoglobin of 110, white cell count of 93, and platelet count of 190. This is the power 10. Let's say I'm the biomedical scientist again. I'm a first-year biomedical scientist. I receive this blood. I label it as a CLL and refer this blood film to you guys. You are the clinical hematologist. And let's go to power 50 now. Any clinical hematologist who want to report this blood film? Can I go for that? Yes, please report the blood film.
So, yeah, the blood film is showing, um, lymphocytosis, small to medium size, um, cells, um, with, um, mature nuclear chromatin, um, scant cytoplasm with some, uh, cytoplasmic projections, and some of the lymphocytes are showing, uh, clifting of the nucleus. Um, it also shows, uh, thrombocytopenia and, um, and, um, mild anemia with, I'm not sure if this is the thick part of the film showing some sphere or. Mhm. So, um, the conclusion from that will be, um, uh, possible LPD for immunophenotyping. What do you suspect is going on here? So, there is some cytoplasmic projections and some clifting of the nucleus, which I think, um, usually goes with follicular lymphoma. Do you think this is follicular lymphoma? Anyone else has a different opinion for lymphoma before I may say something? I, I noticed madam on smear there are atypical cells with some with cytoplasmic blebs. So, I think these should be followed whether T-cell prolymphocytic leukemia or not. I should not say it right now on this point. First, I will have to see, then I will have IP done of this patient, bone marrow examination with IP, then only I can say something wrong. So, you do not make a confirmed diagnosis on blood cell. You always give your suspicion that this is likely neoplastic disorder, most likely follicular or something else. But you need flow cytometry to confirm this case. You are done with the flow cytometry and the result says CD2 positive, 3 positive, 5 negative, 10 negative, uh, 19 negative, 20 negative, um, 7 positive, 25 negative, 52 positive. So, I think it's positive for T-cell markers, negative for B-cell markers. CD7 positive. Um, I think it's always positive in, uh, T-PLL. Um, so, the CD52 is negative. Yeah. 52 is positive. Positive. Yeah. Um, yeah, I think T-PLL, this flow and TDT is negative. Yeah. TDT is negative. Yeah. So, in the exam, if they give you flow cytometry in the, in the scenario, you are very lucky, you can make a diagnosis from the flow as well before making, before seeing the blood. But if you are not lucky, they will not give you. Okay. So, what is the pathogenesis associated with this condition? I think there are always, um, we should check for, um, translocation, inversion 14. Translocation 14;18. Inversion 14. Inversion 14 and, uh, treatment option. You need anything in the treatment. Treatment options for [Music] CD52 that became blank now without your number. Yes, this, uh, this case T-PLL is CD52 positive. So, you can give them alemtuzumab. Okay. After this is the last. In the FRC part exam, things are not always difficult. They can give you a very easy case as well, like B12 deficiency, folate deficiency. People fail the exam because they think that why they would give B12 deficiency in the exam. Yeah, they can give B12 deficiency. Like they want to check every aspect of your module. Uh, can I ask you just about this case? Uh, like where in the exam, when when we see the flow and it gives us clue about the diagnosis, I mean, when you see the morphology and you suspect follicular from the morphology and then when you see the the flow metric compounds another diagnosis, do you write it like, do you write it in the, in the, in the blood film report that you suspect you like, you still put down, um, follicular as suspicion or just you make it. Okay, if they have given me a flow in this scenario, Okay, I will go through the flow first. Okay. Okay. Uh, to see what I'm suspecting in this case. If they have given me a flow, flow set, flow of T-PLL, why would I mention follicular in the, in the, uh, paper? Yeah, they would say most likely this is a case of lymphoproliferative disorder, most likely T-PLL, but I need to confirm this with further investigation like, like cytogenetic, which is inversion 14;14, or MTCP1 mutation. So, do not write it like that. If the flow is matching T-PLL, do not write in the blood film report that you are suspecting follicular. Okay, they give you a flow, already they have done the flow already for you. So, you should be able to interpret that flow. Yeah. All right. Thank you.
This is the last case. This is again a 60-year-old man who presented to the emergency department with, uh, fatigue, worsening fatigue. Hemoglobin is 90, platelet count is normal, and white cell count is four. This is power. What's the poison? No. So, in this blood film, just enumerate the abnormalities that you see. In the exam, there will be one question to you which will say, list the abnormalities in the blood film. Can I go ahead? Yes.
So, uh, the red cells show, uh, aniso with prominent targeting, elliptocytes, teardrop cells, occasional fragmentation, uh, uh, some crenated red cells, and, yeah, so, elliptocytes, targeting, crenated cells, teardrop cells. Uh, occasional spherocytes and occasional fragmentation. Anything else? Yes, ma'am says raining on this smear and I would like to have sickling test and SB electrophoresis of this patient. Age should also be, I think, a 60-year-old. If he has any hemoglobinopathy, it would have been mentioned in the history. This was what I wanted to say. There are quite a few cells in it and I want to ask one thing from you, sir. When we can, when we obviously to me, if these, if this much cells are present on a smear, it is, uh, it confirms almost confirms that this is hemoglobinopathy, sickle cell disease. But I think why should we undergo, in addition to sickling test, and why should we have hemoglobin electrophoresis? If sickling test is enough, then why should we go by electrophoresis? You always confirm hemoglobinopathies on two separate tests, according to the guideline. But in this patient, there is no hemoglobinopathy. These things, these are not sickle cells. You can see there is a white area inside the cell. In sickle cells, you should not see any white area inside. Okay. Yes. These are echinocytes. Echinocytes have a white area in the middle. Okay. So, what is your likely diagnosis in this patient? Dr. I think it is iron deficiency, but we should always check. All right. So, you can see there are some red cells whose MCV looks high, some of them are small, some of them are very high. Okay. That's why you said in your answer, red cells and isocytosis. In such cases, you will not say that this is iron deficiency anemia. This can be a mixed hematinic deficiency. That's why you are seeing some macrocytes and some spherocytes. So, most likely mixed hematinic deficiency. Okay. You would like to check iron profile plus hematinics in this patient. Okay. So, maximum deficiency is a common question in the FRC part two exam. And then they ask you, what advice would you give to the patient other than iron profiling, which is simple? Please rule out the causes of iron deficiency or hematinic deficiency in this patient, which will be by CT scan and OGD. Iron deficiency in a patient of age 60 is usually alarming. It can be a colonic malignancy. We just give them advice. We don't do anything, uh, any of these investigations. As he, so, yes, iron deficiency anemia, B12 deficiency, folic acid deficiency, mixed deficiency, mixed hematinic and iron deficiency. These are the questions which appear in the exam. Be ready for that. Do not make something else of this case. One of my friend had here is a leukemia in the exam and he said, why would they give hair cell leukemia? It is a very easy case. Yes. What else they should give you? Non-Hodgkin lymphoma which does not show anything on the blood. So, these are the common and daily cases that we face in the FRC path exam. It is an easy exam, but you should have some practice. Okay. So, practice you can do among yourself or by, um, or by subscribing to this man. You know this man, subscribe him. He will tell you what is happening. Any question? He knows. Thank you. Okay. Sorry. No question. Yeah, I have one question if you please. Uh, I'd like to make sure that I got it in the right way. Uh, you have too many. Oh, uh, if, um, while reporting the blood film, is it better to, uh, mention, uh, just acute leukemia and to be confirmed it by flow? No need to write the type AML or ALL. No, just keep looking. As I mentioned, that you do not make a diagnosis on blood film. You give your most likely impression on. Okay, because sometimes we say that this is acute myeloid leukemia. The cells are just like, uh, myeloid looking, but then it turns out to be, uh, lymphoid cells. Like the quiz number 40, the morphology quizzes, the quiz number 40 is about a 7-year-old boy. When you see the blasts in the blood film, it looks like myeloid blasts, but when we did the flow cytometry for that patient, it turns out to be ALL patient. Please see the morphology quiz 40 and in the YouTube channel. That's why we say that do not make a diagnosis on on the blood film. Just give your impression. If there are blasts, say this is most likely acute leukemia. We need to confirm this on flow. Yes. If you are suspecting APML on the blood film as well, you say this is most likely APML to start treatment acutely, emergency, and to send a peripheral blood sample for PML-RAR and the staining results usually come back within hours if you have HMDS or diagnostic center in your hospital. Uh, got it. For emergency cases, I have to mention the, this suspicion of emergency. It's okay. Thank you. Dr. Dr. Ramy, just one more question. If we, if we are suspecting acute myeloid leukemia, should we also always check for PML-RAR or send PML-RAR or or just if we see the promyelocytes and we are, we are sure that it is, uh, uh, an APML, then we can send for PML-RAR. If you're suspecting APML, then you should, then you should send for PML stain. If you are suspecting AML, why would we send PML stain in this patient? Yes, they will, they will take PML-RAR as a part of the cytogenetics on a bone marrow biopsy because it is included in the list that we discussed today. Uh, and it is mentioned in the BSH guideline as well that they will do PML-RAR as a part of the genetic panel. But as a first instance, I will not send PML-RAR to the, uh, HMDS to check whether this is positive or not. We are seeing a lot of leukemia patients. It means the HMDS will be full of PML-RAR stain. PML-RAR has its own specific morphology and the patient has its own specific presentation as well. Very rarely you will see a 60-year-old with APML. APML always appear in young people and they are always in their 30s and they come with bleeding, bruising. Okay. Okay. Take care. Enjoy. Have a nice one.