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juniperpublishers-rr · 3 years

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Late Infectious Complications after Liver Transplantation in Children- Juniper Publishers

Juniper Publishers- Open Access Journal of Annals of Reviews & Research

Late Infectious Complications after Liver Transplantation in Children- Juniper Publishers

Authored by Anita Verma

Introduction

Infectious complications in children after liver transplantation are a major cause of morbidity and mortality. Most of the life-threatening infections are seen in the first few months after the operation and are related to their stay in the intensive care unit, invasive monitoring, anastomotic leaks and higher levels of immunosuppressive medications. Infections that happen after six months of liver transplant operation are considered as late infections. True incidence of the type of infections is difficult to establish as most of these patients are usually not managed in the liver transplant centre and the data may not be always provided to the transplant centre by local hospitals. Hence this subject has been only a matter of few research publications [1].

After 6 month we can divide liver transplant recipients into three groups, in term of their risk to acquire infections: Group 1: patients with good allograft function and low immunosuppression (comprising about 80% of the patient population). This group usually have very low risk of infections. Most common infections in this group of patients are community-acquired and include respiratory viruses: e.g., influenza, para-influenza, respiratory syncytial virus, human metapneumovirus, swine flu virus, coronaviruses. The common bacterial infections are Streptococcus pneumoniae (drug resistant), Haemophilus influenzae, MRSA, Mycobacterium tuberculosis. Gastrointestinal pathogens - Noravirus, Rotavirus, Compylobacter, Salmonella. Rarely atypical organisms such as Mycoplasma and Legionella. Paediatirc liver transplant recipients particularly young children who are unable to receive live vaccines before transplant are also prone to vaccine-preventable diseases- variciella, measles and mumps. Second category of patients (Group 2, about 10-15% of patient population), who have on going biliary complications secondary to anastomotic strictures or cholangiopathies secondary vascular problems are more likely to get infections due to endogenous flora coliforms, enterococci and emerging carbapenem resistant enterobacteraceae (CRE). Invasive procedures like cholangiography, percutaneous or endoscopic predispose further these patients to environmental pathogens like Pseudomonas hence it is important to consider the antibiotic cover for this type of organisms when using empiric antimicrobial therapies. Patients with recurrent cholangitis are exposed to repeated courses of antibiotics which make them prone to fungal infections. Hence antifungal cover depending on local epidemiology should be considered when response to standard antimicrobials is less than optimal. Third category of patients (Group 3, about 2-5% of patient population) who have difficult to treat allograft rejection requiring higher levels of immunosuppresion and or use of biological agents like mono or polyclonal antibodies. This group can present with severe opportunistic infections involving- P jiroveci, Cryptococcus neoformans, Nocardia and invasive fungi such as Aspergillus, Mucor and other molds. Reactivation of viruses- Herpes group: CMV, HSV encephalitis, EBV and Herpes zoster.

Treating physicians should also keep in mind travel associated pathogens, specific exposures to uncommon pathogens related to work, recreational activities and pets. We evaluated the incidence, risk factors and pathogens for late IC in 181 paediatric LTR between 2004 to 2008 at King’s College Hospital, London. Follow-up end points were 2-year, death or re-transplantation. Overall incidence of late infections was 21.4% (39/181); predominant infections were due to viruses 19%, most common viral infection was due to cytomegalovirus (CMV) 10.4%, followed by respiratory tract viruses i.e. influenza, Swine flu, rhinovirus, adenovirus & gastrointestinal virus- noravirus. One patient each had cholangitis due to Candida albicans, bacteraemia (E.faecium), conjunctivitis (S aueus) and diarrhoea (Compylobacter).

Late Cytomegalovirus (CMV) Infection in Liver Transplant Recipients

Although late CMV infection is well studied in adult LTR but there is paucity of data in paediatric patients. The risk factors for late CMV infection described are prolonged antiviral prophylaxis, recurrent rejection while on antiviral prophylaxis and increased immunosuppression especially use of antilymphocyte products [2]. Late CMV presentation can manifest as non-specific viral syndrome (fever, leukopenia, atypical lymphocytosis & thrombocytopenia) or involvement of visceral organ (common sites include the gastrointestinal tract, liver, and lungs) and the site of involvement varies according to the type of transplant. This is the first centre we analysed highest number of pedaitric LTR for late CMV complications. The overall 1st CMV infection after transplant was in 51%, 67%, 66% 10% in D-R+, D+R-, D+R+ & D-R- respectively. The overall incidence of late CMV infection in three high risk group (D-R+, D+R-, D+R+ excluding low risk patients D-R-) was 18/131 (13.7%). Most of these patients were young and had late post-transplant complications. Late rejection was seen in 25% of patients mainly in D+R- & D-R+ group. The most important finding was, D-R+ group showed very high rate of hepatitis (36%) on liver biopsies in comparison to 15 % in other two groups.

The anti CMV prophylaxis protocol included IV ganciclovir 5mg/kg twice daily for 2 weeks for D+R- starting at day 7 posttransplant, followed by CMV DNA monitoring till patient is discharged or when symptomatic for other groups. Late CMV disease was present in 5/131 (3.8%) patients. Less than 2% patients required the second line treatment with foscarnet. Late CMV infection was associated with increased morbidity but no mortality. Antiviral prophylaxis only delays the onset of viral replication, and therefore, it does not prevent the development of a primary infection, which is relatively common after prophylactic therapy has been completed [3]. In a study of 67 high-risk CMV liver transplant recipients (9 patients on oral ganciclovir, 58 patients on valganciclovir for 92 days), primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylactic therapy was stopped with similar incidences between the two treatment groups [2].

Patient who develop allograft rejection during prophylaxis are at an increased risk for developing delayed-onset CMV disease after cessation of prophylaxis, which has led to increased mortality [4-6]. Risk of delayed onset CMV disease could be prevented by minimization of immunosuppression or by prolonging CMV prophylaxis i.e., 6 months instead of 3 months. However, these measures are associated with risk of; graft rejection, drug toxicity, increased cost, emergence of drug resistance [7]. In adult patient’s antiviral prophylaxis has been proven to be of benefit as without antiviral therapyrisk of CMV infection was reported to be 44-65%, in high risk CMV LT-recipients during first 12 month [8,9]. Meta-analysis on prophylaxis with ganciclovir or valganciclovir vs placebo showed significant reduction of - CMV infection, CMV disease & mortality in solid organ transplant recipients. Few other studies have reported improved survival and reduction of biopsy proven rejection [10,11].

However, there is no consensus on duration of antiviral prophylaxis. Prolonged duration of treatment could result in ganciclovir resistance. Resistance should be suspected if viral load persists while on antivirals, this could be confirmed by testing for genotypic mutations within the viral genes UL97 and/or UL54. Ganciclovir-resistant CMV disease was reported in up to 7% of high risk CMV recipients while none in CMVseropositive recipients in a group of solid organ transplant recipients [12]. Ganciclovir resistant patients could be treated with foscarnet or cidofovir with or without immunoglobulin and reducing immunosuppression [13]. Other antiviral agents that could become available are oral maribavir, CMX-001, artesunate, and everolimus [14]. Increased understanding, as well as the use of newer diagnostic tests, antiviral therapy, and preventative strategies, have led to marked improvements in the prevention and management of many of the complications associated with post-transplant CMV infections in children.

Influenza Infection

The 2nd most common late viral infection was respiratory virus influenza. Reported incidence in SOT recipients is 2- 4%. In our data of 181 LTR 3% were admitted to hospital because of influenza infection. It is mainly upper respiratory tract (RT) disease, lower RT disease is estimated to occur in 1-5% of LTR. Parainfluenza & influenza were associated with high morbidity and mortality in very young LTR [15]. Oseltamivir is an effective agent with protective efficacy of 75% [16]. It is very important to consider early diagnosis and treatment for influenza infection in SOT recipients as it reduces the severity of influenza, shorten duration of viral shedding, reduce the frequency of lower RT complications e.g. bronchiolitis and pneumonia. Prevention is the most important strategy for influenza management-all LTR should have annual vaccine, 6 months after transplant surgery, if used before that immune response to vaccination could be suboptimal [17,18].

Carbapenem resistant Enterobacteriaceae (CRE)

Excessive use of antibiotics has led to emergence of multidrug resistant gram-negative bacteria. The emerging problems with the CRE is becoming an issue in LTR, because of not only it is harboured in gut for long but can spread rapidly to other patients if stringent infection control precautions are not followed. We encountered an outbreak of infection with Carbapenem resistant Enterobacteriaceae (CRE) in our unit lately. A very stringent infection control protocol including; quarantine of all new admission from other hospitals in to single rooms till results of screening swabs (rectal swabs) are negative for CRE [19-21] hand hygiene, environmental cleaning, and antibiotic stewardship helped to control the outbreak. Further continuation of active surveillance prevented the silent dissemination of these superbugs in this immunosuppressed population.

Conclusion

In conclusion the late infections after transplantation requiring hospital admission are not uncommon. Most severe infections occur in patients with biliary complications and during periods of increased immunosuppression. Careful monitoring and treatment could limit morbidity and avoid mortality.

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For more articles in Open Access Journal of Reviews & Research please click on: https://juniperpublishers.com/arr/index.ph

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madokasoratsugu · 3 years

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therefore you and me post-production notes (or: murphy’s law as a project that has been two years in the making)

ive had this idea for ‘therefore you and me’ and Fritz ever since i first played CindPhenon. nothing ever fell into place until i played Evermore though, so here we are!

drafting this project was pretty easy tbh (see: hubris). the parallel imagery and everything about the lyrics was right up my alley aha.

fun thing with the lyrics: TadanoCo uses ‘要る (iru)’ in the line ‘Which do you want (iru)? Or do you want neither (iranai; aka negative form of ‘iru’)?’

‘ 要る ‘ as a verb can mean ‘to be wanted’ or ‘to be needed’.

hence, the line can also be read: ‘Which do you need? Or do you need neither?” or any other variation of the verb’s usage.

it’s halfway through drawing the lineart that murphy’s law began. 1) i drew ~15 panels on the wrong dimensions, and had to redraw them all (lol), re-grey tone (LOL), and re-ink (LOLOL). it was not a fun three days.

then i lost momentum because of lunar new year (happy late lunar new year btw! happy year of the ox :”) )

anyway: the moment i regained momentum for the project again, i hit a roadblock in the form of overconfident, sloppy drafting (see: hubris is my downfall).

because of the lack of clear drafting for certain panels (and changes to previous panels), i had to redraft two different sections of the PV while keeping in mind that there was the bridge still to be drafted. fun !

i decided to simplify the bridge. can you believe it was supposed to be another animation. i can’t. so i scrapped it.

(slight tangent. Evermore’s release honestly cleared up a lot of uncertainty regarding the direction of the PV and whether or not to include Fritz’s mother (who I still fondly call Beatrice). im really happy the PV never came to fruition before Evermore’s release, as im not sure i would have done half as good a job without Evermore’s content.)

back to the hubris of proceeding with a messy draft - there was a lot of push and pull internally for me as to how much i should keep to the original PV and how much i should just put my spin on things. i ended up doing a bit of half-and-half, i think.

but really, it only delayed things as i ended up redrafting and having multiple drafts of certain panels haha//

the last two choruses were honestly my favourite parts to draw. the shift from Varg’s clothes and colours to Fritz, Fritz’s acceptance of Varg and the soft way Varg looks at Fritz (and no one else). there’s something cathartic about acceptance and acknowledgement. i think that’s what i aimed to really capture.

also: in between drawing all the panels, murphy’s law 2) my Evermore itchio game file ? got deleted off my computer ?

it’s a very old, barely functional brick so im lowkey unsurprised but at the same time it was a crazy experience and setback when i needed to reference certain scenes. oh, and Steam decided to not download Evermore too. i still haven’t fixed that one. haha. ha.

i have screenshot posters to thank for uploads of certain CGs, although im still pretty sure its best not to post a ton of those publicly at one shot?

also, i had to scrap the recreation of the famous ‘did you love Varg’ scene because of this aha. looking back now, i think it worked out.

(another tangent: using referencing as an excuse, i actually took the opportunity to replay Fritz’s route for the third time. i ended up checking nothing at all and falling in love with the masquerade scene again.)

up till the very end, im still not sure if everyone got that the line “You are love itself.” was meant to be said by Lucette to Fritz. i colour-coded Lucette with her own unique blue for the PV, which was the same hue as the line. i hope that it got across, aha.

with that said, video production was a whole entanglement in and of itself. i think murphy’s law really took up a hammer and swung hard at this stage.

timing was actual hell. im usually not this bad at it, but this project in particular was tricky bc TadanoCo uses a lot of background beats that aren’t overt, which his PV also matches - i think? or maybe im just not good at recognising beats from lack of video/music production haha//

hence there were certain scenes i was stuck at and kept revising because i wasnt clear where the beat was meant to be, what transitions i should use, and when the transitions should be.

subtitling was actually really fun! until i rendered my first version and realised all the subtitles were completely off and blurry.

turns out my project properties were different from my video properties, hence the off-alignment. huh. didnt know those were Actual Things(tm).

also, quick tip to all vid-making amateurs like me out there: you may have to double the dimensions of the font’s media properties if you dont want them to come out fuzzy. another thing i didnt know lol.

anyway all this lead to: me needing to spend another evening to redo subtitles. haha. it was not a fun two back-to-back 3am nights + extra evening afterward.

in between all this was countless rendering tests to guess-and-check what’s causing numerous errors in the video btw.

and with those rendering tests came: glaring mistakes in the panel art that i only now spotted and had to fix, and refix, and refix again. then reimport into sony vegas, put it into the video, render and double check if it’s alright. rinse and repeat countless times ! haha ! PV making is fun !

i think i nearly redid a certain scene with the exact same panels once. like i said: not a fun two 3am nights.

that said: i dont know how all this technical issues (and more) popped up and were resolved over two 3am nights and one evening. im not about to question it either.

at this point: panel art - fixed ! subtitling all redone ! render works fine, everything checks out.

i make the mistake of uploading it directly to yt instead of leaving it unlisted first.

murphy’s law 3) when im watching the vid on yt, the yellow parts in the second verse were completely unable to be seen.

panic put it on unlisted. people are already watching it and leaving (very sweet) comments. panic delete it.

btw if you’re one of the first three commenters reading this: thank you for the quick response !! it means a lot and made me really flustered in a good way :”))

cue me re-colouring those scenes, redo-ing the section and oops, is that a panel in the masquerade scene where Fritz literally is missing his mask ???

i think i lost my mind entirely at this point. from then on i was fueled by spite to complete this cursed project.

at thereforeFINAL.mp4, (version five of the full PV, version maybe 10-11 of all the rendered videos, including tests) finally. finally it is done.

i upload it.

the end !

(except, not really. because here you are at post-production notes detailing the worst luck i’ve ever had with PV making.

i learnt a lot from this though, and honestly on hindsight i should have learnt all these from my first PV but nothing went wrong at this magnitude so i kinda just...shelved it aha//

but really, im relieved it turned out well, and that i took the time to redo scenes until i was satisfied. for a PV that’s been waiting in the background for two years now, i think this is the least it deserves.

if the comic about Fritz and Varg (which i referenced in one of the last choruses, i wonder if anyone caught that?) was meant to be a love letter to Fritz’s route, i think this PV ought to be a tribute to the character himself.

although - hm, this isn’t quite as good a tribute to Fritz as it is to his route, maybe? i don’t know, haha ! maybe it’s just myself wanting to make excuses to create more for him//

i was thinking of continuing on about the PV and it’s significance to Fritz and Varg, but hm. maybe not on this post. maybe some other one, some other time.

but at it’s core, at it’s simplest, most raw - i think i just wanted to explore what it means to Fritz to ‘want’ and to ‘need’ with this PV.

thank you for watching the PV, and thank you for reading this.

- blu.)

#linear notes #notes #bluh bluh text #long post

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juniperpublishers-rr · 3 years

Text

Late Infectious Complications after Liver Transplantation in Children- Juniper Publishers

Authored by Anita Verma

Introduction

Late Cytomegalovirus (CMV) Infection in Liver Transplant Recipients

Influenza Infection

Carbapenem resistant Enterobacteriaceae (CRE)

Conclusion

To know more about juniper publishers please click on: Juniper Publishers

For more articles in Open Access Journal of Reviews & Research please click on: https://juniperpublishers.com/arr/index.php

To know more about Open Access Journals please click on: https://juniperpublishers.com/index.php

#Juniper Publishers Review #Juniper Publishers e-pub #Juniper Publishers Address #juniper publishers

0 notes