KT from DD with AKI and partial/complete recovery was associated with a lower risk of transplant loss (log-rank P = 0.04) and recipient mortality (log-rank P = 0.042) than ongoing AKI. KT from a donor with ongoing stage 3 AKI was associated with a higher risk of all-cause graft loss  and mortality  than stage 3 AKI with renal recovery. Persistent AKI, but not recovered AKI, significantly increases the risk of DGF. Utilizing kidneys from donors with improving AKI is generally safe. KT from donors with persistent AKI stage 3 results in a higher risk of transplant failure and recipient mortality. Therefore, meticulous pretransplant evaluation of such kidneys and intensive surveillance after KT is recommended.The influence of acute kidney injury (AKI) and renal recovery in deceased donor (DD) on long-term kidney transplant (KT) outcome has not previously been elucidated in large registry study. Our retrospective cohort study included all DDKT performed in Thailand between 2001 and 2018. Donor data was reviewed case by case. AKI was diagnosed according to the KDIGO criteria. Renal recovery was defined if DD had an improvement in AKI to the normal or lower stage. All outcomes were determined until the end of 2020. This study enrolled 4234 KT recipients from 2198 DD. The KDIGO staging of AKI was as follows: stage 1 for 710 donors (32.3%), stage 2 for 490 donors (22.3%) and stage 3 for 342 donors (15.6%). AKI was partial and complete recovery in 265 (17.2%) and 287 (18.6%) before procurement, respectively. Persistent AKI was revealed in 1906 KT of 990 (45%) DD. The ongoing AKI in DD significantly increases the risk of DGF development in the adjusted model (HR 1.69; 95% CI 1.44–1.99;  In the general population, AKI is a well-known risk factor for the further development of cardiovascular problems and chronic kidney disease (CKD), known as the AKI-CKD continuum4. The increase in donor terminal serum creatinine (SCr) is also integrated into the US kidney donor profile index (KDPI) as a harmful factor for transplant survival5. Several recent studies revealed an association between DD AKI status and the development of delayed graft function (DGF)9, but there was no definitive impact of donor AKI on long-term graft survival10. However, some studies still showed conflicting results11. Most of these large studies were conducted in developed western countries that had several differences in context with developing countries11.Acute kidney injury (AKI) is the common complication in deceased donors (DD) who suffered hemodynamic instability and hormonal change after brain death12. Data from the Thai Transplant Registry during 2016–2020 found that 30–40% of DD had terminal SCr > 1.5 mg/dL13, which is higher than western countries14. DDs in our country are younger, have a lower prevalence of diabetes mellitus (DM), hypertension (HT), and cerebrovascular accident (CVA) than in developed countries, but we have a higher prevalence of donor hypotension, the need for cardiopulmonary resuscitation (CPR), and relatively longer cold ischemic time (CIT)16. The authentic incidence of donor AKI in Thailand or in the developing country model had not been previously assessed. Several DD with AKI in Thailand received an effective resuscitation and subsequent recovery before procurement. The outcome of improving AKI in DD is not elucidated in the large registry data. The present study reviewed our local transplant data to determine the impact of AKI and recovery status on transplant and recipient outcome in Thailand.The shortage of DD numbers is a major barrier to KT in Thailand, thus the utilization of kidneys from DD with AKI can effectively represent the donor poolWe conducted a retrospective cohort study, which enrolled all deceased donor kidney-only transplants (DDKTs) in Thailand between 1 January 2001 and 31 December 2018. The national Thai data were recovered from the database of the Thai Red Cross Society for donor data and the Thai Transplant Registry for recipient characteristics and KT outcomes. This study was approved by the Ethics Committees of the Thai Transplant Society and the Siriraj Hospital Faculty of Medicine, Mahidol University, Bangkok, Thailand (COA No. Si 394/2020), with a waiver of informed consent. Study data were collected from electronic database without violation of patients’ identities. The study was performed in accordance with international guidelines for human research protection.17 and the revised Schwartz formula for pediatric donors18. The kidney donor profile index was also calculated based on the Thai Eq.16. The diagnosis and staging of AKI were defined by the KDIGO guideline; both SCr and urine output criteria19. There was no DD that required dialysis in our registry because the kidney was generally discarded.DD data was reviewed case by case for demographic data, hemodynamic profiles, need for vasopressors and CPR, change in kidney function, and urine volume throughout the pre-donation period. Donor hypotension was defined as a systolic blood pressure lower than 90 mm Hg for a consecutive 2-h period. The estimated glomerular filtration rate (eGFR) of the best SCr was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) for adult donorsRenal recovery from AKI in DD was also reviewed in all cases and defined based on the change in the KDIGO SCr level criteria. 'Partial recovery' was defined if serum creatinine decreased to the lower stage of AKI but not to the baseline level. 'Complete recovery' was defined in the case of reduction of SCr to the baseline value. Demographic data, comorbidities, duration of dialysis of KT recipients (KTRs) were gathered. The outcome of interest for the analysis included all-cause transplant loss, death-censored graft loss, and death by the end of 2020.U test, as appropriate. A two-tailed p-value < 0.05 was statistically significant.The donor, recipient and transplant factors are shown as percentage (%) number and percentage (%), or mean ± standard deviation (SD) for the normally distributed data and as median and interquartile range for nonnormally distributed data. Comparison of categorical variables was analyzed using Chi-square tests, while continuous variables were compared using Student's t test or the Mann–Whitney p value. Cox proportional-hazard regression analysis—adjusted for significant donor factors , recipient factors  and transplant factors —was used to assess the associations between each variable and transplant or recipient survival. All analyzes were performed using PASW Statistics for Windows .Kaplan–Meier analysis was used to compare survival between groups and was reported as logarithmic rank This study was approved by the Ethics Committees of the Thai Transplant Society and the Siriraj Hospital Faculty of Medicine, Mahidol University, Bangkok, Thailand (COA No. Si 394/2020), with a waiver of informed consent. Study data were collected from electronic database without violation of patients’ identities. The study was performed in accordance with international guidelines for human research protection.p = 0.04) but other comparable profiles. CIT was significantly higher in KT from the AKI donor .After applying the exclusion criteria, 4234 DDKTs of 2198 donors were enrolled . According to the KDIGO guideline, the AKI staging was determined by serum creatinine criteria, urine output criteria and both criteria in 1420 (64.6%), 15 (0.7%) and 107 (4.9%) DD, respectively. For AKI staging in DD, 710 (32.3%) DD had AKI stage 1490 (22.3%) developed AKI stage 2, and 342 (15.6%) suffered from AKI stage 3 . The majority  of DDKT also received kidneys from DD with AKI. Most DD had normal baseline kidney function , height , prevalence of HT , CVA  and Thai KDPI > 80% than those without AKI . DD who had AKI also had higher best serum creatinine (SCr) , which resulted in lower best estimated glomerular filtration rate (eGFR) . Noradrenaline and adrenaline were prescribed more for DD with AKI . The incidence of DGF is significantly higher in AKI stage 3 than in no AKI, stage 1 and 2 AKI, respectively    or complete recovery . There was no difference in the incidence of DGF among each staging of DD AKI with partial or complete recovery and those without AKI. Persistent AKI stage 3 in DD resulted in a significantly higher incidence of DGF than AKI stage 1 or 2 . Stage 1 and 2 of ongoing donor AKI also had a higher incidence of DGF than receiving kidney from donor without AKI . From multivariate analysis, the risk of DGF occurrence was significantly increased when KT from donor with stage 3 AKI  or persistent AKI   and by renal recovery status .The early loss of allograft within the first 3 months was revealed in 121 (2.9%) KT. There was no difference in the incidence of early graft loss by donor AKI status  and death-censored graft survival (log-rank p = 0.16) between KT from DD with and without AKI  and death-censored graft failure  by DD AKI status. (Supplement Table During the study period with a median follow-up time of 62.1 IQR 36.3–104.6) months, there were 1164 (27.5%) transplant losses; 673 KT (15.9%) with graft loss and 491 (11.6%) death with functioning graft. Kaplan–Meier analysis showed comparable overall transplant (log-rank 6.3–104.6P = 0.39) and death-censored graft loss (log-rank P = 0.17) among each staging of AKI staging , 2 , and 3  compared to KT from donor without AKI. There was also a comparable risk of death-censored graft failure to KT from DD without AKI, with of 1.14 (95% CI 0.9–1.45), 1.24 (95% CI 0.96–1.61), 0.92 (95% CI 0.67–1.26) for stage 1, 2 and 3, respectively  than ongoing AKI, however, the difference in death-censored graft survival was not evidenced (log-rank P = 0.14)  . Kaplan–Meier analysis showed comparable survival of KTR between KT of DD with and without AKI (log-rank p = 0.69)  than ongoing AKI  according to the status of DD AKI. There was no significant difference in mortality risk between each stage of AKI, with HR of 0.93 (95% CI 0.75–1.15), 1.01 (95% CI 0.80–1.28), 0.79 (95% CI 0.60–1.05) for stage 1, 2 and 3, respectively (Supplement Table P = 0.066)  from multivariate analysis ; 491 (11.6%) died with a functioning graft and 120 (2.8%) passed away after graft loss. The primary known cause of mortality in our population was infection 52.7%), followed by cardiovascular disease (22.1%) and cancer (7.7%). These rates were comparable between KT from DD with AKI and those without AKI p = 0.85. Kaplan–.4%; 491 2.7%, folTo increase the number of organs of DD, the use of kidneys from donor with AKI is a noteworthy alternative option. Nevertheless, the effectiveness and safety of such a strategy are still questionable. In this study, we revealed a higher incidence of DGF when KT from a donor with persistent AKI, not for AKI with recovery. We found no association between donor AKI and worse transplant outcome. The sub-analysis revealed no definite impact of donor stage 1 and 2 of AKI, however, KT from DD with persistent AKI stage 3 had significantly higher all-cause graft failure and mortality than AKI with recovery.11. Despite the healthier donor without the use of the donor after circulatory death, there was a higher incidence of donor hypotension, the need for cardiopulmonary resuscitation and vasopressors, including adrenaline, and a relatively longer cold ischemic time in Thailand20. The explanations were lack of designated donor care team, insufficient medical personnel and resources, delay in detection and donation process for potential donor.The prevalence of donor AKI in our country of 70.2% is much higher than the previous reports from western countries, which are approximately 10–38%1, a reduction in urine volume does not appear in most cases. The results of almost previous studies that diagnosed AKI by individual SCr level are generally reliable11. We found that AKI is more common in DD who had underlying HT, brain death from CVA, and higher KDPI. This result is not different from the general setting in which patients with comorbid diseases tended to develop AKI during hemodynamic instability21. Donors with higher BMI, which require a higher volume of fluid resuscitation, were also at risk of the occurrence of AKI22. Thus, marginal and large donor needs must be managed with careful attention.The diagnosis of donor AKI in our study was primarily based on SCr criteria, only 0.7% reached only urine output criteria. Since diabetes insipidus is the inevitable consequence after brain death23. Our multivariate analysis confirmed a significant association between donor AKI and the occurrence of DGF. However, the prevalence of DGF in our country is relatively high but comparable to several developing countries26. The high rate of DGF in Thailand can be attributed to several factors, including a high prevalence of donor AKI, prolonged cold ischemic time, and a shortage of dedicated surgeons and nephrologists for KT care. We observed no significant impact of overall AKI and the staging of AKI on both all-cause transplant loss and death-censored graft loss. These findings are consistent with several previous studies that employed adjusted models and a recent systematic review23. Kidney transplantation from elderly DD with AKI resulted in worse transplant survival. However, our study lacked the statistical power to definitively address this issue, as only 4% of our DD were over the age of 6027. Given that the DD in our registry were relatively healthier than the reports in high-income countries, the reversibility of AKI is more probable, resulting in equivalent long-term survival.Donor AKI was a significant risk factor for DGF, particularly in the case of stage 3 AKI, as supported by prior studies and a recent systematic review28. This might be explained by ischemic preconditioning. On the other hand, a recent study from the French Registry revealed that donor AKI, including both ongoing or recovery groups, had higher risk of graft failure than without AKI11. However, our studies showed a favorable outcome for donor AKI with partial or complete recovery, beginning with a comparable incidence of DGF and long-term graft and recipient survival. The inconsistent findings in the French study could be attributed to the younger age of the donors with less comorbidities in the Thai Registry. Generally, almost all recovery AKI is likely a pre-renal cause which had no structural damage to the renal parenchyma. Therefore, from our finding, kidney utilization of kidneys from a donor with improving AKI is generally safe in both short- and long-term outcomes.One of the most important objectives of our study focused on recovery status of donor AKI. The delay in donor detection and suboptimal initial donor resuscitation in primary care hospitals are the leading cause of DD AKI in our country. However, after proper resuscitation, AKI began to improve in several donors. The outcome of donor AKI with partial recovery was not well elucidated from the large registry data. Previous studies from Korea showed that improving donor AKI had superior graft survival than ongoing, and even without AKI6. Our earlier studies from the Thai Transplant Registry demonstrated inferior graft and patient survival in the DGF group. KT recipients who experienced DGF, with challenges in adjusting immunosuppression, faced a higher risk of infection, which emerged as the leading cause of death in our recipients30. We did not support the discard of organs from DD with AKI; however, intensive surveillance of post-transplant infection and complications should be performed.In contrast, persistent AKI was associated with inferior transplant survival from Kaplan–Meier analysis; however, this turned out to be non-significance after adjusting with other factors. We also found that ongoing AKI stage 3 had worse transplant and recipient survival than AKI with recovery. With a significantly higher incidence of DGF in persistent stage 3 of AKI, this finding may not be surprising and was consistent with a previous study from the UKOur study has several strengths. First, the diagnosis of AKI was established by both SCr level and urine output criteria. Second, all donor data was thoroughly reviewed case by case. Third, we enrolled all DDKTs in a national database to reduce bias. Our data had a relatively high incidence of donor AKI and a low rate of loss to follow-up. Finally, we have nearly complete data of donor, recipient, and transplant parameters and put them all in multivariate analysis to figure out the impact of AKI. However, our study has some limitations. First, we did not have complete data on organ waste, so we did not analyze this issue. Since we have no available pretransplant biopsy, kidneys from a high-KDPI donor with AKI were sometimes discarded or used in a dual KT manner. Second, even though we enrolled all KTs in our country over an 18-year period, the study drew on a relatively smaller sample compared to western countries. However, our data might be more suitable for application in developing countries that have donor and recipient profiles comparable to the Thai population.Persistent donor AKI, but not AKI with recovery, significantly increased the risk of DGF. Utilization of kidneys from donors with recovered AKI is generally considered safe. KT from the donor with AKI had an equivalent outcome to those of the donor without AKI. However, KT from donors with persistent AKI stage 3 had a higher risk of graft loss and mortality compared to those with improving AKI. Therefore, we recommend careful evaluation of such kidneys before transplantation and intensive surveillance for infection after KT.Supplementary Information.


Além disso, estas condições representam encargos econômicos e sociais substanciais.3 Segundo a Sociedade Brasileira de Cardiologia, a recomendação geral para a prática de exercícios físicos é de 150 minutos semanais, distribuídos entre três a cinco sessões.2 Um dos principais objetivos da reabilitação cardiovascular é melhorar a aptidão cardiorrespiratória através da incorporação de EA.3 Além disso, a prática criteriosa de atividade física visa mitigar a hipertensão, o risco de eventos cardiovasculares e a mortalidade geral em pacientes cardiovasculares.3A reabilitação cardiovascular é uma ferramenta promissora em beneficiar pacientes com DCV, por meio de exercícios aeróbicos (EA) como aliados essenciais na melhoria da aptidão cardiorrespiratória, resistência muscular, função cardiovascular e qualidade de vida geral.Vale ressaltar que métodos individualizados para prescrição de EA, como por exemplo, através do consumo máximo de oxigênio e limiares ventilatórios identificados por meio do teste cardiopulmonar de exercício (TCPE), são amplamente reconhecidos. Contudo, nos países em desenvolvimento, onde os custos associados a estes testes podem ser proibitivos e existe escassez de profissionais altamente qualificados, a prescrição de EA é muitas vezes baseada em testes de campo, como o Teste de Caminhada de 6 Minutos (TC6) e o Teste de Fala (TF).3 fizeram em seu recente artigo publicado nos Arquivos Brasileiros de Cardiologia. Este estudo buscou analisar a frequência cardíaca (FC) durante as etapas do TF e no pico do TC6 como parâmetro para prescrição de EA, comparada com a FC no primeiro e segundo limiares ventilatórios (LV1 e LV2) do TCPE. Para a realização do estudo foram avaliados 22 pacientes com idade entre 40 e 80 anos com diagnóstico de DCV crônica clinicamente estável. Participaram de três dias de avaliação: o primeiro dia consistiu em anamnese  e TCPE, considerado padrão ouro para avaliação da função cardiopulmonar e prescrição de intensidade de exercício. Isso permitiu identificar as variáveis mais adequadas e recomendadas, como consumo de oxigênio de pico (VO2pico), carga horária, FC máxima, reserva de FC e VT1 e VT2.5O segundo dia envolveu o TC6 e o terceiro dia incluiu o TF, que é validado e acessível, baseado em um protocolo de carga incremental e utiliza a percepção de conforto de fala como marcador de intensidade do exercício.3Neste cenário, foi o que Althoff et al. 2023 Em relação aos resultados, vale ressaltar que a FC no LV1 foi semelhante à FC no TF  e TF±  e correlacionou-se moderadamente com TF+ . A FC no VT2 foi semelhante à do TF , mas apresentou forte correlação . A FC máxima durante o TC6 foi significativamente diferente da FC em TF+, TF± e VT1 , mas semelhante ao TF .2pico nos estágios TF e VT em pacientes com DCV. Esses achados sugerem que os estágios do TF podem ser empregados na prescrição de EA, alinhando-se com algumas evidências existentes na literatura científica.9 Além disso, o estudo demonstrou que o TC6 não é tão adequado para prescrição de EA quanto o TF. Apesar do conhecimento de que o TC6 é um teste submáximo, seu uso pode ser incentivado em um ambiente de baixo custo, uma vez que ainda fornece informações clinicamente relevantes, mesmo que não seja projetado especificamente para prescrição de exercícios.O aspecto distintivo deste estudo é o fornecimento de uma alternativa custo-efetiva que pode auxiliar na prescrição de exercícios no contexto da reabilitação cardíaca.Por meio desses resultados, observamos a possibilidade de identificar correlações no TF entre a FC no LV1 e TF+ e TF±, indicando semelhanças entre a FC e o VOEste estudo sugere que o TF pode ser uma alternativa viável para a prescrição de EA, particularmente em ambientes com recursos limitados. Demonstrou correlações entre os estágios do TF e os limiares derivados do TCPE, indicando sua utilidade potencial na prescrição de EA para pacientes com DCV. Além disso, o TC6, embora menos adequado, continua a ser uma opção custo-efetiva, fornecendo informações clínicas valiosas em contextos de reabilitação cardíaca. Este estudo oferece informações valiosas para a prescrição de EA em ambientes de saúde desafiadores. 3Cardiovascular diseases (CVDs) represent a concerning reality, leading to a high morbidity and mortality rate in many countries, with a global total of 18 million deaths. Moreover, these conditions pose substantial economic and social burdens.3 According to the Sociedade Brasileira de Cardiologia, the general recommendation for engaging in physical exercise is 150 minutes per week, distributed across three to five sessions.2 One of the foremost objectives in cardiovascular rehabilitation is to enhance cardiorespiratory fitness through the incorporation of AE.3 Furthermore, the judicious practice of physical activity aims to mitigate hypertension, the risk of cardiovascular events, and overall mortality in cardiovascular patients.3Cardiovascular rehabilitation holds significant promise in benefiting patients with CVDs, with aerobic exercises (AE) as pivotal allies in improving cardiorespiratory fitness, muscular endurance, cardiovascular function, and overall quality of life.It is worth noting that individualized methods for prescribing AE, such as maximal oxygen consumption and ventilatory thresholds identified through cardiopulmonary exercise testing (CPET), are widely recognized. However, in developing countries, where the costs associated with these tests can be prohibitive, and a shortage of highly skilled professionals exists, the prescription of aerobic exercises is often based on field tests, such as the 6-Minute Walk Test (6MWT) and the Talk Test (TT).3 published their recent article in Arquivos Brasileiros de Cardiologia. This study sought to analyze heart rate (HR) during the stages of the TT and at the peak of the 6MWT as a parameter for prescribing AE, compared with HR at the first and second ventilatory thresholds (VT1 and VT2) of the CPET. To conduct the study, 22 patients aged between 40 and 80 years with a diagnosis of clinically stable chronic CVD were evaluated. They attended three assessment days: the first day consisted of anamnesis  and CPET, considered the gold standard for assessing cardiopulmonary function and prescribing exercise intensity. This allowed for the identification of the most appropriate and recommended variables, such as peak oxygen uptake (VO2peak), workload, maximum HR, HR reserve, and VT1 and VT2.5 The second day involved the 6MWT, and the third day included the TT, which is validated and accessible, based on an incremental load protocol and uses speech comfort perception as an exercise intensity marker. 3In this scenario, Althoff et al. 2023 Regarding the results, it is worth noting that the HR at VT1 was similar to the HR at TT (p = 0.987) and TT± (p = 0.154) and moderately correlated with TT+ . The HR at VT2 was similar to that at TT (p = 0.383) but showed a strong correlation . The peak HR during the 6MWT was significantly different from the HR at TT+, TT±, and VT1  but similar to TT (p = 0.68).2peak in TT and VT stages in patients with CVDs. These findings suggest that TT stages can be employed for AE prescription, aligning with some existing evidence in the scientific literature.9Furthermore, the study demonstrated that the 6MWT is not as suitable for AE prescription as the TT. Despite the knowledge that 6MWT is a submaximal test, its use can be encouraged in a low-cost setting, given that it still provides clinically relevant information, even if it is not specifically designed for exercise prescription. The distinctive aspect of this study is the provision of a cost-effective alternative that can assist in exercise prescription within the context of cardiac rehabilitation.Through these results, we observe the possibility of identifying correlations in the TT between HR at VT1 and TT+ and TT±, indicating similarities between HR and VOThis study suggests that TT may be a viable alternative for AE prescription, particularly in resource-limited settings. It demonstrated correlations between TT stages and CPET-derived thresholds, indicating its potential utility in AE prescription for CVD patients. Additionally, the 6MWT, while less suitable, remains a cost-effective option, providing valuable clinical information in cardiac rehabilitation contexts. This study offers valuable insights for AE prescription in challenging healthcare environments.


Objectives: The number of lung transplants is increasing year by year in China and globally. With the widespread use of donation after brainstem death (DBD) donor lungs and donation after circulatory death (DCD) donor lungs, donor-derived infection (DDI) poses a major challenge in lung transplantation. Using donor lungs infected or colonized with carbapenem-resistant Enterobacteriaceae (CRE) may have serious implications in lung-transplant recipients. Currently, traditional microbial culture along with antimicrobial susceptibility testing cannot fully meet the need for rapid and accurate diagnosis of CRE infection in a donor before organ harvest. Methods: The Xpert Carba-R device  was used to detect and differentiate Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-encoded metallo-β-lactamase (VIM), active-on-imipenem (IMP), and OXA-48 carbapenemase genotypes in bronchial lavage fluid from donor lungs before organ harvest. Positive detection of 1 or more of these genotypes indicated a potentially CRE-infected donor lung, and these organs were removed from the lung transplantation cohort. Donor lungs negative for all KPC, NDM, VIM, IMP, and OXA-48 genotypes determined by the Xpert Carba-R device were used for lung transplantation. The incidence of CRE-associated DDI and infection-related complications were compared in the Xpert Carba-R screening group and an historic control group. Results: In this study, 21 donor lungs were tested with the Xpert Carba-R device to detect and differentiate carbapenemase genotypes. Among them, 4 were positive for 1 or more carbapenemase genotypes and were discarded, and the remaining 17 donor lungs showing no carbapenemase gene presence were used for lung transplantation. No CRE-associated DDI occurred in these 17 lung-transplant recipients. Conclusions: Rapid and accurate detection of the carbapenemase gene in donor lungs at the point of care before transplantation using the Xpert Carba-R device reduced the risk of CRE-associated DDI in lung-transplant recipients.


For treatment of ventriculitis, vancomycin and meropenem are frequently used as empiric treatment but cerebrospinal fluid (CSF) penetration is highly variable and may result in subtherapeutic concentrations. Fosfomycin has been suggested for combination antibiotic therapy, but data are sparse, so far. Therefore, we studied CSF penetration of fosfomycin in ventriculitis.Adult patients receiving a continuous infusion of fosfomycin (1 g/h) for the treatment of ventriculitis were included. Routine therapeutic drug monitoring (TDM) of fosfomycin in serum and CSF was performed with subsequent dose adaptions. Demographic and routine laboratory data including serum and CSF concentrations for fosfomycin were collected. Antibiotic CSF penetration ratio as well as basic pharmacokinetic parameters were investigated.Seventeen patients with 43 CSF/serum pairs were included. Median fosfomycin serum concentration was 200 [159–289] mg/L and the CSF concentration 99 [66–144] mg/L. Considering only the first measurements in each patient before a possible dose adaption, serum and CSF concentrations were 209 [163–438] mg/L and 104 [65–269] mg/L. Median CSF penetration was 46 [36–59]% resulting in 98% of CSF levels above the susceptibility breakpoint of 32 mg/L.Penetration of fosfomycin into the CSF is high, reliably leading to appropriate concentrations for the treatment of gram positive and negative bacteria. Moreover, continuous administration of fosfomycin appears to be a reasonable approach for antibiotic combination therapy in patients suffering from ventriculitis. Further studies are needed to evaluate the impact on outcome parameters.The online version contains supplementary material available at 10.1186/s12941-023-00572-4. In acute hydrocephalus, external ventricular drains (EVD) are often used as temporary devices for the therapeutic diversion of cerebrospinal fluid (CSF). As a percutaneously placed catheter, EVDs are prone to bacterial colonization that can lead to ventriculitis, requiring antibiotic therapy . As oppoStaphylococcus spp. and Pseudomonas spp. As recently discussed [Staphylococcus spp. which makes it suitable for the treatment of device associated central nervous system (CNS) infections. Therefore, the local antibiotic therapy standard for EVD associated ventriculitis includes adding fosfomycin where timely removal or replacement of EVD is not possible. Fosfomycin is eliminated renally and shows a half-life of approximately 2 h in adults with normal renal function. With a small volume of distribution (Vd), small molecular size and almost no protein-binding fosfomycin is distributing widely into all body compartments. Preliminary results have shown that fosfomycin penetrates well into the CSF even in the absence of meningeal inflammation [As initial empirical therapy, meropenem and vancomycin are indicated  but curriscussed  fosfomycammation , 8. Evenammation , 9, thisammation , 11. As This analysis was reported to the Ethics Committee of the Hamburg Chamber of Physicians . Due to the non-interventional nature of this study and anonymous recording of data, written informed consent was waived.Patients included were diagnosed with ventriculitis and treated with fosfomycin by continuous infusion as combination therapy with meropenem and vancomycin as initial empiric therapy. TDM measurements were performed in regular intervals during EVD diagnostics from serum and CSF. Antibiotic dosages were adjusted according to TDM results from serum and CSF samples. Moreover, antibiotic regimens were deescalated, adjusted, or discontinued after species identification or at the discretion of the treating physician.Diagnosis of ventriculitis was generally applied according to the CDC/NHSN surveillance definition . Since cdeath (1), persistent vegetative state (2), severe (3), moderate (4) and low disability (5) [Demographic and clinical data were obtained from the patients’ electronic records . We recorded data on antibiotic serum and CSF concentrations. Renal function was determined by the estimated glomerular filtration rate (eGFR) calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) . Moreovelity (5) .Pseudomonas spp. and Enterococcus spp., a target concentration above 128 mg/L was aimed for. This represented a pragmatic approach adapted from the published wild-type MIC distributions although neither an epidemiological cut-off value (ECOFF) nor a breakpoint has been defined in these cases by the EUCAST, yet [Fosfomycin  was reconstituted with water and used with a final concentration of 100 mg/mL. It was administered by continuous intravenous infusion (CI) with an initial dose of 1 g/h. Considering a potential disequilibrium effect in CSF two times the minimal inhibitory concentration (MIC) was targeted. Regarding the general European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint for susceptibility (32 mg/L) 64 mg/L was targeted. For AST, yet . FosfomyAST, yet .Fosfomycin serum samples were collected and centrifuged , subsequently. The serum supernatant and CSF samples were stored at dry ice until being further processed. Serum samples were analyzed by LC–MS/MS according to the procedure described by Martens-Lobenhoffer et al. . CSF samData management, non- compartmental calculations for fosfomycin clearance (CL) and area under the curve (AUC) were performed by using Microsoft Excel 365 . CL Eq.  and AUC 2) were either calculated by linear or non-linear regression methods included in Prism 9 .Visualization, statistical evaluation as well as determination of coefficients of correlation  and a preserved renal function with a mean estimated GFR of 110 ± 32 ml/min/1.73m2. Fosfomycin dosing was started with 24 g/24 h and adapted to a mean fosfomycin dosing regimen of 20 g/24 h during the course of the therapy.The patients showed a regular body composition  and 13 CSF values (30%) were above 128 mg/L. In total, 98% of the observed CSF concentrations were above the MIC of 32 mg/L for susceptible isolates  of the patients prior to fosfomycin treatment start with a mean sodium value of 153 mmol/L in this subgroup.As opposed to meningitis, reaching sufficient bactericidal concentrations in ventriculitis may be difficult. Diffusion of anti-infectives into the CNS is dependent on different factors such as their lipophilicity, protein binding and molecular size . Moreovein-vitro and in-vivo analyses [in-vitro data showing pharmacodynamic indexes such as either time-dependent pharmacodynamics for species such as Staphylococcus aureus or Enterococcus spec. [Pseudomonas aeruginosa or Escherichia coli [. With the chosen dosing regimen fosfomycin (d1 24 g/d) penetration into the CSF was reliably reaching CSF concentrations well above the defined EUCAST breakpoint of 32 mg/L for susceptible bacteria such as Staphylococcus aureus. The AUC/MIC ratio for an MIC of 32 mg/L was 74 for CSF specimens. This is in concordance with in-vitro data showing bacteriostasis at mean AUC/MIC ratios of 22.7 and a 1-log kill for 83.3 when targeting the group of Enterobacterales [To the best of our knowledge, this is the first study analyzing the penetration whilst using fosfomycin by a CI regimen. Application of fosfomycin by CI or prolonged infusion has been studied by analyses  and was analyses –23. Thisus spec.  or AUC/Mhia coli –27. Withcterales . Unfortucterales .2), increased AUC and serum concentrations (> 400 mg/L) using the initial standard fosfomycin dose were seen.Because our cohort included one patient with renal insufficiency (eGFR < 50 mL/min/1.73mPseudomonales or other non-fermenting bacteria could not be attained in all specimens of our cohort, even though 24 g/d by continuous infusion was used empirically.The penetration ratio of 46% in our cohort is within the range of 30–60% as reported earlier by Silica et al.  who usedMore recently, CSF protein levels could be associated with an improved CSF penetration ratio of meropenem in patients with ventriculitis , whereasFosfomycin CI was generally well tolerated as it was infused via a central line. In cases where increased serum sodium levels occurred during treatment, hypernatremia was already present prior to fosfomycin start. This is in concordance with Putensen et al. who also found a moderate incidence for hypernatremia of 14.3% . BesidesOur study has certain limitations. We performed an analysis from clinically obtained samples that were collected at irregular time intervals from patients with ventriculitis presenting different underlying pathologies. However, our data therefore represents “real-world” conditions from a mixed cohort of patients. Moreover, there is currently no guideline regarding required antibiotic CSF concentrations for the treatment of ventriculitis. Thus, we suggest that concentrations one to two times the MIC of the targeted pathogen are sufficient as inflammation occurs within the CSF and the surrounding tissue. On the other hand, tissue concentrations obtained by microdialysis as reported for meropenem can exceed the CSF concentrations by a factor of three . Hence, Fosfomycin administration by continuous infusion is a feasible way in patients with ventriculitis resulting in appropriate drug concentrations in CSF. Our patient cohort showed a high fosfomycin CSF penetration rate of 46%, making it a potential treatment option for susceptible gram negative and positive pathogens. Future studies are needed to systematically investigate fosfomycin treatment in infections of the central nervous system regarding efficacy and patient outcome.Additional file 1: Additional Figure and Table; Figure 1: Fosfomycin concentration in serum and CSF over time, Table 1: Fosfomycin concentration in CSF and penetration ratio per GOS


Helicobacter pylori (H. pylori) infection in South Korea. Herein, we evaluated the treatment outcomes of tailored clarithromycin-based triple therapy (TT) in patients infected with H. pylori.Tailored therapy has been widely used for patients with We enrolled 460 patients without A2142G and A2143G point mutations by dual priming oligonucleotide-based polymerase chain reaction who had taken TT and undergone the urease breath test to evaluate eradication in clinical practice. Eradication rates according to the treatment duration and dose of clarithromycin were analyzed.P = 0.788). In 210 patients with TT-half CLA, the eradication rates were 84.2% (139/165) in those with a 7-day TT-half CLA and 88.9% (40/45) in those with a 10-day or 14-day TT-half CLA (P = 0.436).Among 460 patients , 250 patients underwent TT with full-dose clarithromycin (TT-full CLA), and 216 patients underwent TT with half-dose clarithromycin . The eradication rates were 88.0% (220/250) in patients with TT-full CLA and 85.2% (179/210) in patients with TT-half CLA. In 250 patients with TT-full CLA, the eradication rates were 86.8% (33/38) in patients with 7-day TT-full CLA and 88.2% (187/212) in patients with 10-day or 14-day TT-full CLA (H. pylori infection without A2142G and A2143G point mutations by DPO-PCR in clinical practice, treatment extension above 7-day TT with full CLA did not improve the eradication rates. Future studies on the treatment outcomes of TT-half CLA considering effectiveness and compliance are warranted.For patients with  Helicobacter pylori (H. pylori) is associated with variable gastric diseases including peptic ulcer disease, gastric adenocarcinoma, gastric preneoplastic diseases, and gastric mucosa-associated lymphoid tissue lymphoma  and had undergone urease breath test for eradication verification after taking more than 80% of the prescribed medication in the Chonnam National University Hospital between Jan 2019 and July 2021. Among 622 patients, 151 patients with the A2142G and/or A2143G point mutations of the 23S rRNA gene were excluded from the study, as they received other treatment regimens other than TT. We also excluded 11 patients who did not take TT. Finally, 460 patients were included in this study. We extracted the data of demographics or clinical characteristics and eradication success rates according to the eradication regimens from the medical chart review. The Institutional Review Board of Chonnam National University Hospital approved this study (IRB Number: CNUH-2022-351). We followed the ethical principles of the Declaration of Helsinki.This was a retrospective observational study. We identified 622 patients older than 18 years of age and younger than 80 years of age, in whom H. pylori infection by detecting the deoxyribonucleic acid (DNA) extraction. The amplified DNA products were identified using an ultraviolet transilluminator in electrophoresis. A single 621-bp DNA product was considered a wild-type H. pylori. The presence of the A2142G and 2143G mutations resulted in DNA bands at 475-bp and 19-bp, respectively.We obtained two gastric biopsy specimens from the antrum and body of patients during EGD, for which a DPO-based multiplex PCR test  was performed to diagnose In this study, all patients were treated with acid suppressants [proton pump inhibitor (PPI)- or potassium-competitive acid blocker (P-CAB)]-based triple therapy, which consisted of 1000 mg of amoxicillin twice a day, 500 mg or 250 mg of clarithromycin twice a day, and acid suppressants  for 7, 10, or 14 days, respectively.13C-urea breath test  to find out whether H. pylori eradication was successful or not. Eradication was defined as a negative result obtained in the test.At least 4 weeks after treatment completion, the patients visited the hospital to take a standard t-test. Two-tailed P-values of <0.05 were considered statistically significant. All statistical analyses were conducted using SPSS 27.0 for Windows .Continuous variables are expressed as the median and interquartile range (IQR), and categorical variables are expressed as numbers with percentages (%). Eradication rates according to the treatment duration (7 vs. 10 or 14 days) and dose of clarithromycin [full CLA (500 mg of clarithromycin twice a day) vs. half CLA (250 mg of clarithromycin twice a day)] were analyzed using Fisher's exact H. pylori eradication was gastric low-grade dysplasia , followed by carcinoma in situ or early gastric cancer . The overall eradication rates were 86.7% (399/460).We enrolled 460 patients without the A2142G and A2143G point mutations of 23S rRNA certified by the DPO-PCR test. H. pylori in terms of treatment duration; 86.8% (33/38) in the 7-day TT-full CLA, and 88.2% (187/212) in the 10-day or 14-day TT full-CLA (P = 0.788).Among the 250 patients who had received TT-full CLA, 212 patients received 10-day or 14-day TT-full CLA, and 38 patients received 7-day TT-full CLA. The overall eradication rates were 88.0% (220/250). There was no significant difference in the eradication rates of H. pylori were 84.2% (139/165) in the 7-day TT-half CLA and 88.9% (40/45) in the 10-day or 14-day TT-half CLA (P = 0.635).There were 210 patients who had received TT with half-dose clarithromycin . The overall eradication rates were 85.2% (179/210). Among them, 165 patients received TT 7-day TT-half CLA. The eradication rates of P = 0.806, P = 0.806). Moreover, in 10-day or 14-day TT, there was no significant difference in the eradication rates between TT-full CLA and TT-half CLA (P > 0.999).We compared the eradication rates among four groups . The eradication rates were not significantly different among the four groups  for H. pylori eradication, it is necessary to analyze the eradication rate in patients with clarithromycin-sensitive H. pylori. Clinicians need to choose antibiotic doses in terms of efficacy, antibiotics-related adverse events, and compliance. A large-scale observational study demonstrated that the adverse events increased with higher doses of clarithromycin  were used for the eradication regimen. The metabolism of PPI is affected by the enzymatic activity, cytochrome P450 enzymes, and CYP2C19 with genetic differences. Conversely, P-CAB is not dependent on the CYP2C19 genotype and provides the long-standing inhibition of gastric acid secretion. While vonoprazan showed higher eradication rates compared with PPI . Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.SHC and MSP contributed to the data collection and drafting of the manuscript. DK, H-SY, and H-SK participated in the review and editing of the draft. S-YP contributed to the study conceptualization, design, writing the original draft, and critical revision of the draft. All authors contributed to the article and approved the submitted version.


Higher KDPI was linked to delayed graft function and worse kidney function, but not among expanded-criteria donor transplantations. No significant association was found between KDRI, KDPI, and patient survival. In conclusion, increasing KDRI and KDPI are linked to worse graft function, although their ability to discriminate long-term graft failure remains limited.The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to predict transplant outcomes in a Greek cohort. The efficacy of KDRI, KDPI, and donor’s age in predicting death-censored graft failure was primarily assessed. Overall, 394 donors and 456 recipients were included. Death-censored graft survival was significantly worse with increasing KDRI , KDPI , and donor’s age . The unadjusted discriminative ability was similar for KDPI (C-statistic: 0.54) and donor’s age (C-statistic: 0.52). The KDPI threshold of 85 was not predictive of graft failure ( End-stage kidney disease (ESKD) represents a rising global health concern, associated with impaired quality of life and high mortality rates . Kidney In this context, the OPTN (US Organ Procurement and Transplantation Network) adopted a new kidney allocation system in 2014, aiming to ameliorate the donor–recipient longevity matching. To this end, the KDPI (Kidney Donor Profile Index) has been developed as a mapping of the Kidney Donor Risk Index (KDRI), based on 10 donor parameters, expressing the relative graft failure risk for a given donor compared to the risk attributed to the average donor from the prior calendar year . To enabTo date, the KDRI and KDPI lack wide external validation in populations outside the USA and their implementation in non-US patients may be complicated by significant differences in transplant programs, donor age, and comorbidities across regions . The preThis was a single-center retrospective cohort study, conducting a chart review of all deceased-donor kidney-only transplantations that were performed in Laiko General Hospital, Athens, Greece, between 1 January 2008 and 31 December 2018. Living-donor transplantations and cases with missing data in study outcomes were excluded. Kidney transplant recipients were actively followed up until December 31, 2021. For losses to follow-up, relative data were retrieved through medical records and hospital discharges.Donors were categorized as standard-criteria donors (SCD) and expanded-criteria donors (ECD). Specifically, ECD were defined as those with an age greater than 60 years or as those aged between 50 and 60 years, fulfilling at least two of the following criteria: history of arterial hypertension, serum creatinine above 1.5 mg/dL, and cerebrovascular accident as the cause of death .The following donor characteristics were collected: age, sex, ethnicity, body mass index (BMI), history of arterial hypertension and diabetes mellitus, hepatitis C status, serum creatinine, cause of death, and donation after circulatory death. BMI was calculated as weight (in kilograms) divided by the square of height (in meters). The main exposures were the values of the donor KDRI (Kidney Donor Risk Index) and KDPI that were compared to the donor age alone in regard to graft function and survival after transplantation. Specifically, the KDRI score was estimated based on ten donor characteristics as suggested by the OPTN. The donor characteristics used in the estimation of KDRI are presented in The main collected baseline recipients’ characteristics were the following: age, sex, BMI, diabetes mellitus status, duration of dialysis, and EPTS score. The EPTS score ranges from 0 to 100%, with lower values predicting longer graft survival . The indp-value threshold of 0.05. The normality of continuous variables was examined by the visual inspection of histograms, along with the significance of the Kolmogorov–Smirnov test [t-test; otherwise, the median and interquartile range (IQR) were reported and the non-parametric Mann–Whitney U-test was applied to enable comparisons [Statistical analysis was conducted in R-4.0.5  and was in accordance with the principles of the Declaration of Helsinki. All recipients were fully informed about the study procedures and provided written informed consent.ρ: 0.924, p-value < 0.001).The analysis was based on a total of 394 (251 SCD and 143 ECD) kidney donors and 456 recipients. The main patients’ baseline characteristics are summarized in The median age of kidney recipients was 52 years (IQR: 43 to 59) and was higher among ECD recipients. The main induction therapy was basiliximab (74.6%), while the most commonly administered maintenance immunosuppression regimen was the combination of mycophenolate mofetil, a calcineurin inhibitor, and corticosteroids (87.3%). No significant difference in EPTS score was noted between SCD and ECD. The median follow-up period was 6.3 years (IQR: 3.6 to 10).p-value: 0.558). DGF was linked to significantly higher KDPI  and KDRI  scores. Moreover, in standard-criteria donor transplantations, DGF was associated with significantly greater values of both KDPI  and KDRI , while no significant associations were observed in ECD transplantations.Overall, DGF complicated the course of 169 cases. No significant difference in DGF rates was observed between SCD and ECD transplantations , third , and fifth  post-transplant year . The outcomes of the Cox proportional hazards regression analysis regarding the association of KDPI, KDRI, and donor age with death-censored graft survival are presented in p-value: 0.016) in the overall population. Thus, patients with donor KDPI > 79 (4th quartile) were estimated to be at a threefold higher risk compared to those with donor KRPI < 25 (1st quartile) . No significant difference was observed when patients with donor KDPI > 79 were compared to those with a donor KDPI of 25–54  or 54–79 . A KDPI value above 85 (vs. <85) was not predictive of graft loss  (2 (IQR: 2 to 19). This difference was not significantly associated with donor’s KDPI .Overall, the study included 62 pairs (124 recipients) who received a graft from the same deceased donor. Of them, during the follow-up, 16 recipients experienced graft loss; 54 pairs remained with functioning grafts, while graft loss was observed in both recipients in only one pair. Kidney function in the first year was inversely associated with donor’s KDPI  . The medThe present study retrospectively examined the prognostic value of KDRI and KDPI in a Greek transplant cohort, evaluating both SCD and ECD. The outcomes proposed that increasing KDPI is associated with significantly worse death-censored graft failure, with values in the fourth quartile of its distribution being linked to a threefold higher risk of graft loss compared to the first quartile. However, the prognostic value of KDPI was lost when donors were sub-grouped as SCD and ECD ones, while the overall discriminative ability was estimated to be modest. Donor age also emerged as an independent negative prognostic factor of graft survival, presenting a similar C-statistic to KDPI.Regarding KDRI, it was observed that higher donor KDRI values were significantly associated with worse allograft survival. The median KDRI was calculated at 1.02, which is comparable to the median KDRI of the original US derivation cohort  (1.05) bThe KDPI cut-off of 85 has been arbitrarily chosen since 15% of US deceased donors were expected to meet the ECD definition . In the Similar outcomes regarding the prognostic value of KDPI were derived from other studies on the European population. Specifically, the analysis of a German transplant cohort  suggesteWe observed that DGF was associated with significantly higher KDPI values among SCD, but not among ECD transplantations. This was probably related to the wider range of KDPI values in this subgroup, most likely related to the donor age. A similar finding was obtained by the study of Jun et al. , suggestOne of the main factors that contributed to the transition from the ECD/SCD dichotomy to the new allocation system, including KDPI/KDRI in the USA, was the ‘longevity matching’ concept in view of discard-rate decrease . In a EuThe development of KDPI is considered an important improvement over the dichotomized classification of donors to SCD ones, as it represents a more detailed and descriptive tool, able to reflect a greater amount of variability of donor characteristics. However, data from various European cohorts converge toward the conclusion that KDPI has limited efficacy in predicting long-term graft survival ,20,21,22The main strength of the present study relies on its long follow-up period, enabling the assessment of hard outcomes, such as graft failure and patient survival. A variety of multivariable models were applied, aiming to limit the effects of potential donor and recipient-specific confounders. Specifically, possible confounders were sequentially added to models, aiming to test the robustness of the estimated effects when different recipient factors were taken into account. However, the interpretation of the findings is limited by the retrospective observational nature of the study since residual confounding cannot be safely excluded. It should be also noted that it was a single-center study with a moderate sample size, which may jeopardize the generalizability of the results. Lastly, the lack of ethnicity variety and the exclusion of donors after circulatory death may have influenced the observed outcomes by limiting the variability of KDPI due to the aforementioned factors.Τhe present analysis of a Greek transplant cohort provides evidence that although KDRI and KDPI are predictive of kidney function, they offer limited efficacy in accurately discriminating grafts with worse long-term survival. Therefore, the KDRI and KDPI scores may serve as adjunct clinical tools for the prediction of transplantation outcomes providing prognostic information about graft function, although they may be insufficient to guide decisions regarding kidney graft allocation in Greece. Further studies are needed to verify these findings, while large-scale cohorts may focus on the development of a modified prognostic index tailored to the Greek population. The derivation of an adapted KDPI may enhance its ability to predict transplantation outcomes, although whether such a marker would be able to ameliorate decision-making and optimize organ utilization remains to be investigated.


The AA group patients who developed a PO-AKI presented more risk factors compared to those who did not (2 (2-4) vs. 1 (1-2), p = 0.031) with a cut-off of 3 risk factors in the ROC curve . The hospital length of stay was higher in the crystalloid group (p < 0.05) with a consequent saving in hospital costs. Perioperative AA infusion may help reduce the incidence of PO-AKI after major urological minimally invasive surgery.Post-operative acute kidney injury (PO-AKI) is a serious complication that may occur after major abdominal surgery. The administration of intravenous perioperative amino acids (AAs) has been proven to increase kidney function and has some beneficial effects to prevent PO-AKI. The aim of this study was to establish if the perioperative infusion of AAs may reduce the incidence of PO-AKI in patients undergoing major urological minimally invasive surgery. From a total of 331 patients, the first 169 received perioperative crystalloid fluids and the following 162 received perioperative AA infusions. PO-AKIs were much higher in the crystalloid group compared to the AA group (34 vs. 17,  Post-operative acute kidney injury (PO-AKI) is defined as a decrease in kidney function occurring within seven days from surgery and is one of the most frequent post-operative complications after major abdominal surgery. In major laparoscopic urologic surgery, PO-AKIs have been described to occur in 15.5% of cases ,3, are aIn recent years, minimally invasive surgeries such as laparoscopic and robotic surgery have been increasingly used by urologists worldwide . DependiThe occurrence of PO-AKIs is strongly associated with the risk of mortality, co-occurrence of other post-operative complications, increased length of hospital stay and progressive chronic kidney disease . This anProtein intake in animal models has been proven to be a protective factor for AKIs due to a direct increase in renal blood flow . MoreoveThe aim of the present study was to evaluate if the perioperative administration of intravenous amino acids may reduce the occurrence of PO-AKIs in patients submitted to major laparoscopic urological surgery. This was a before–after clinical study conducted at the Galliera Hospital of Genoa from January 2022 to May 2023. All patients signed an informed consent form on personal data storage and the local ethics committee approved the study . 2), regardless of the main cause, was the only exclusion criterion. Patients who developed a PO-AKI due to obstructive uropathy were also excluded.Three hundred and thirty-one patients older than 18 years undergoing any major urological, minimally invasive surgery were consecutively studied. The presence of preoperative severe kidney chronic diseases . All patients were treated following a standardized multidisciplinary Enhanced Recovery After Surgery (ERAS) protocol as previously described [For each patient, the following anamnestic data were recorded: age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, preoperative serum creatinine and hemoglobin. Furthermore, the following comorbidities were evaluated to identify the presence of risk factors for developing PO-AKI: age > 75 years, female sex, hypertension, hyperlipidemia, liver diseases, peripheral vascular diseases, smoking history, diabetes, anemia and cardiovascular diseases . The cumAt admittance to operating room, after positioning a large caliber peripheral venous access 16 G), all patients in the AA group received continuous infusion of Sintamin 10% at 100 mL/h, before anesthesia induction. The intravenous infusion of Sintamin was continued at the same rate for the entire duration of surgery and was reduced to 50 mL/h after recovery from anesthesia throughout post-operative day 1. Other additional crystalloids were administrated per clinical need depending on the patient’s hemodynamics and intraoperative blood loss, always following the restrictive goal-directed fluid therapy imposed by the ERAS protocol [6 G, all The crystalloid group was managed with the same restrictive goal-directed fluid therapy imposed by the ERAS protocol using mostly Ringer’s lactate as the intravenous crystalloid. Post-operatively, the patients of crystalloid group continued the infusion of Ringer’s lactate at 50 mL/h until the end of post-operative day 1. All patients started drinking water 2 h after extubation and were allowed free oral water intake 6 h later. ®  or a LexionSystem®  throughout the whole surgical procedure in both the laparoscopic and robotic-assisted procedures. The intraoperative abdominal pressure induced by pneumoperitoneum was settled at 10 mmHg and maintained using an AirSeal Intelligent Flow SystemPrimary outcomes were the incidence and gravity of PO-AKI, defined according to the Kidney Disease Improving Global Outcomes criteria based on creatinine values and urinary output variations .Secondary outcomes were admittance to the intensive care unit, in-hospital length of stay, 30 days re-admission and any kind of complication. The safety of amino acid administration was evaluated by adverse reaction development or an increase in intra-operative blood loss in partial nephrectomies. A cost-effectiveness assessment was conducted by comparing administration of amino acids with Ringer’s Lactate. By assuming an effect size = 0.20 (with arcsine transformations of the square root differences between AKI proportions for two distinct patient groups before/after treatment), alpha = 0.05 and power (1 − Beta) = 0.8, a minimum overall sample size of 196 patients was required.All the variables are expressed as median and interquartile range (IQR) for continuous variables, or as a percentage (%) for categorical variables. The Shapiro–Wilk test was used to evaluate the normal distribution of continuous variables. The Mann–Whitney U-test or Fisher’s exact test was used to evaluate differences between groups for continuous or categorical variables, respectively. The cumulative probability for lack of PO-AKI was calculated. Logistic regression was used to identify independent variables potentially associated with PO-AKI assumed as the dependent variable. p < 0.05. Statistical analyses were performed by using SPSS, version 27.0 , software packages. A p-value < 0.05 was considered statistically significant. Statistical significance was assumed at two-tailed p = 0.028). There were no differences in the duration of surgery, intraoperative mean arterial pressure or intraoperative blood loss between groups , with a significantly lower incidence of KDIGO 1 and 2 PO-AKI in the AA than the crystalloid group (14 vs. 30 p = 0.016), whereas no difference was observed in the incidence of KDIGO 3 class of PO-AKIs (3 vs. 5 p = 0.724). Considering the overall population of crystalloid and AA groups, no difference was found in the cumulative number of PO-AKI risk factors (1 (1-2) vs. 1 (1-2) p = 0.310). The median number of risk factors was not significantly different between the patients who developed PO-AKI and those who did not (2 (1-2) vs. 1 (1-2) p = 0.196)  .p = 0.995). In contrast, within the AA group, those patients who developed PO-AKI had a significantly higher number of risk factors than those who did not (2 (2-4) vs. 1 (1-2), p = 0.031). The best cut-off for the number of risk factors to identify PO-AKI determined by ROC analysis was ≥3 .Within the crystalloid groups, there was no significant difference in the median number of risk factors between patients who developed PO-AKI and those who did not (1 (0-2) vs. 1 (1-2), p = 0.477). Direct logistic regression was used to assess the impact of a number of factors on the likelihood of developing PO-AKI. The model contained five independent variables . The full model containing all predictors was statistically significant, X2 = 6.553, p = 0.010. Only intravenous amino acid infusion made a unique statistically significant contribution to the model with an OR = 0.480, CI:0.250–0.923, p = 0.028 controlling for all other factors in the model  vs. 4 days (4–6) p = 0.034). The cumulative number of days of hospitalization was 923 for the 169 patients in the crystalloid group and 752 for the 162 patients in the AA group with a reduction of 171 days and a net estimated saving in hospital costs of EUR 68,400 in eight months. The amount of savings clearly exceeded the increased cost of administering amino acids instead of crystalloids during hospitalization, as the costs for the whole period of 8 months were estimated to be about EUR 1156 . Furthermore, considering an observed median hospital stay of 4 days, the reduction in the duration of hospitalizations by 171 days may have allowed 42 more patients to undergo oncological surgery over the same time period. In-hospital length of stay was higher in the crystalloid group than in the AA group . p = 0.087) or off-clamp partial nephrectomies (261 mL (100–380) vs. 234 mL (50–265) p = 0.768), and no allergic reactions were reported. Regarding safety, there were no differences between crystalloid and AA groups in terms of intraoperative bleeding assessed by estimated blood loss (200 mL (95–400) vs. 150 mL (50–300) The main findings of this before–after clinical study are that the perioperative administration of amino acids reduced (1) the incidence of mild-to-moderate PO-AKI and (2) the in-hospital length of stay and its related costs. A possible explanation of our results could be the normal hyperemic response of the kidneys to a protein workload to enhance the elimination of nitrogenous wastes. Indeed, eating a high protein meal is known to have a great influence on renal perfusion by causing vasodilatation of afferent arteries and a reduction in vascular resistances through local receptors (glutamate receptor N-methyl-D-aspartate) and humoral factors , finally leading to an increase in renal blood flow and the glomerular filtration rate (eGFR) by up to 35% from the baseline ,13,16.In agreement with these assumptions, studies on animal models showed that the resulting increase in renal blood flow after a protein meal can protect the kidneys against acute ischemic insults ,8. LikewIn the present study, a significantly lower number of PO-AKIs was detected in the AA than the crystalloid group thanks to a reduced occurrence of mild-to-moderate AKIs in class KDIGO 1 and 2. We interpreted this result by considering that some of our patients possibly had pre-existing subclinical renal damage at hospital admittance with a reduced renal functional reserve, despite the absence of any rise in the serum baseline creatinine level . NeverthThe perioperative increase in renal blood flow and consequently the eGFR via amino acid infusion is only possible in kidneys with a sufficient residual recruitable nephron mass. In fact, patients with less than three risk factors seem to benefit more from perioperative amino acid infusion. Therefore, in the case of severe pre-existing structural nephropathy, amino acid infusion may not be able to reduce the incidence of PO-AKI. This result is supported by the reduction in the incidence of KDIGO 1 and 2 but not KDIGO 3 in the AA group.There was a statistically significant sex difference between crystalloid and AA groups. Recent animal studies focused on sex differences and AKI, although with some conflicting data, and described an increased susceptibility to AKI development in males due to the presence of testosterone which increases endoplasmic reticulum stress ,19.A reduction in PO-AKI leads to a faster enhanced recovery after surgery and a reduced in-hospital length of stay, which may be translated into a global economic saving and the possibility of increasing the monthly number of surgeries. Finally, it should be emphasized how amino acid infusion increases renal perfusion without increasing intraoperative blood loss even in partial off-clamp nephrectomies. The present study has limitations. First, it was a single-center, before–after design without randomization. Second, consecutive patients underwent major urologic minimally invasive surgery without considering the impact of different types of surgery on renal function. Nevertheless, the absolute and relative numbers of surgery types were similar between groups with the exception of radical prostatectomy. Third, the low occurrence of PO-AKI KIDGO 3 might have affected the results. Fourth, this study was not designed to investigate the underlying mechanisms of intravenous amino acid infusion efficacy and basic experiments, and larger clinical studies are needed to support our results. Fifth, the lack of determination of fractional sodium excretion and urine sediments might have obscured chronic kidney conditions. Sixth, the effects of medications affecting the renin–angiotensin system were not investigated. The results of the present study suggest that perioperative intravenous amino acid infusion in major minimally invasive urological surgery is safe and might be helpful in reducing the incidence of PO-AKI, the hospital length of stay and related hospital costs, thus potentially shortening pre-operative waiting lists. Further randomized trials focusing on selected surgical interventions are needed to better define the efficacy and safety of perioperative intravenous amino acid infusion for the prevention of PO-AKIs and other complications.


Background: High cerebrospinal fluid (CSF) sampling frequency is considered a risk factor for external ventricular drain (EVD)-associated infections. To reduce manipulation at the proximal port and potentially minimize the risk of an infection, we aimed to analyze whether CSF parameters sampled from the far distal collection bag could provide reliable results compared to the proximal port. Methods: We included patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. CSF sampling, including microbiological analysis, was performed simultaneously from the proximal port and the collection bag. Spearman’s correlation coefficients were calculated to assess the correlation of CSF cell count, protein, lactate and glucose between the two sample sites. Results: We analyzed 290 pairs of CSF samples in 77 patients. Ventriculitis was identified in 4/77 (5%) patients. In 3/4 patients, microbiological analysis showed the same bacterial species at both sample sites at the same time. Spearman’s correlation coefficient showed that CSF cell count (r = 0.762), lactate (r = 0.836) and protein (r = 0.724) had a high positive correlation between the two collection sites, while CSF glucose (r = 0.663) showed a moderate positive correlation. Conclusion: This study shows that biochemical CSF parameters can be reliably assessed from the EVD collection bag. External ventricular drain (EVD) placement is considered one of the most important life-saving treatment strategies in neurosurgical patients, particularly when dealing with patients facing acute hydrocephalus. The external ventricular drain provides continuous monitoring of intracranial pressure (ICP) and effective ICP reduction by a constant cerebrospinal fluid (CSF) release.Despite its high diagnostic and treatment potential, EVDs are also associated with a high rate of infections ,2,3,4,5.Previous studies have explored CSF sampling from a more distal site, at the EVD drip chamber, aiming to reduce manipulation at the proximal port and potentially decrease the risk of EVD-associated infections while preserving data integrity ,11. ThesWe retrospectively analyzed consecutive patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. We included only patients who were 18 years or older with at least two concurrent CSF samples from the proximal port and the collection bag obtained on the same day. Patients who received an EVD due to meningitis or ventriculitis were excluded from our study.We assessed the following variables: patient’s demographics, indication for EVD insertion (subarachnoid hemorrhage (SAH), tumor, trauma, intracerebral hemorrhage (ICH) or other), CSF cell count, protein, glucose, lactate and microbiological analysis of CSF from both collection sites and type of EVD-associated infection according to our previously published definition .The EVD insertion technique and drainage system  were appEVD insertion was performed by a neurosurgical consultant or resident in the operating room or in the ICU under sterile conditions. The procedures were performed under appropriate sedation and analgesia, with the patient in the supine position and the head of the bed elevated by 30–40 degrees. The area of insertions was shaved and prepared under sterile conditions. After identifying Kocher’s point, a 2 cm straight incision at the pupilar line was performed. A self-retaining retractor was placed, and a small burr hole was drilled. After coagulating and incising the dura, a regular non-antibiotic coated ventricular catheter  was passed toward the ipsilateral medial canthus and ipsilateral tragus into the frontal horn of the lateral ventricle. Subsequently, the catheter was tunneled under the galea and secured by multiple sutures.According to our clinical protocol, CSF sampling was performed by the neurosurgeon assigned to the ICU from the 3-way stopcock at the proximal port twice a week. Additionally, since the EVD collection bag has to be changed every day, daily CSF samplings from the removed collection bag were performed as well. From each site, we withdrew 2 mL CSF to assess cell count, protein, glucose and lactate, and 4 mL for the microbiological analysis.We used the definition of EVD-associated infections according to our previously published study  7]. Acc. Acc7]. p-value < 0.05 was considered statistically significant for all performed tests.Statistical analysis was performed using SPSS software version 28.0 . Categorical data were presented as counts and percentages, and continuous parameters as median and range. To assess the correlation of CSF cell count, protein, lactate and glucose between two CSF samples, Spearman’s correlation coefficients were calculated. Interpretation of Spearman’s correlation coefficients was performed according to established ranges as previously described by Mukaka et al. . A p-valWe analyzed 290 pairs of CSF samples in 77 patients treated with an EVD at a median age of 58 years (range: 18–80 years). There were 44 (57%) female patients. The reason for EVD placement was hydrocephalus due to SAH in 60 (78%) patients, intracerebral tumor in 8 (10%) patients and other diseases in 9 (12%) patients .The median CSF cell count, glucose and lactate from the proximal port was 57 cells/µL , 71 mg/dL (range: 11–113 mg/dL) and 2.8 mmol/L (range: 1.2–18.6 mmol/L), respectively. Quantitative protein values were available from 107 samples and showed a median value of 32 mg/dL (range: 0–1856 mg/dL).The median CSF cell count, glucose, lactate and protein from the collection bag was 26 cells/µL (range: 0–2830 cells/µL), 69 mg/dL (range: 2–114 mg/dL), 2.9 mmol/L (range: 0.6–11.8 mmol/L) and 55.3 mg/dL (range: 4.3–797 mg/dL), respectively.CSF cell count and glucose, acquired from the proximal site, showed median 1.84 (range: 0–910) and 1.01 (range: 0.39–6.2) times higher values compared to the distal site. In contrast, CSF lactate and protein showed median 0.93 (0.42–5.8) and 0.99 (range: 0–25.32) times lower values.p < 0.001), lactate  and protein  had a high positive correlation between the two collection sites. In contrast, CSF glucose  showed a moderate positive correlation  patients had no infections, with 9/77 (12%) classified as contamination and 4/77 (5%) patients as ventriculitis.Staphylococcus epidermidis  being the most frequent species. Staphylococcus spp. was identified in all nine contamination cases. In the ventriculitis group, Candida albicans and Escherichia coli 4 MRGN were identified separately in three consecutive microbiological analyses in one patient, respectively. In the other two cases, the microbiological analysis revealed Serratia marcescens and Klebsiella pneumoniae.The results of the positive microbiological analysis from the proximal EVD port showed 19 bacterial species in 17 samples, with Candida albicans and Staphylococcus epidermidis) and in one with contamination (Staphylococcus hominis and Staphylococcus epidermidis), two species were identified in the same microbiological analysis.In one patient with ventriculitis  as the most frequent species. In three out of four cases of ventriculitis, microbiological analysis identified the same species as from the proximal EVD port on the same day. Moreover, in one case, Serratia marcescens was identified 2 days prior to the positive result of the proximal sample. We have summarized all microbiological results from the proximal EVD port and the collection bag and compared them to each other in The microbiological analysis of the CSF from the collection bag showed This study aimed to investigate whether CSF parameters acquired from the EVD collection bag would show comparable results to CSF parameters collected from the proximal port of the EVD system. We showed that CSF cell count, lactate and protein levels had a high positive correlation between the two sample sites. Therefore, these parameters could be reliably assessed from CSF drawn at the more distal EVD collection bag to potentially decrease EVD-associated infections by reducing manipulation at the proximal site of the EVD system ,6,7.polymerase chain reaction (PCR) or metagenomic next-generation sequencing, have been introduced into the clinical setting [There are various guidelines available on how to effectively utilize CSF parameters in the diagnosis of specific diseases affecting the central nervous system, including conditions like bacterial infections . These r setting ,15,16. YSince a one-time CSF parameter analysis in neurosurgical patients is not specific enough to detect EVD-associated infections, clinicians at the neurosurgical ICU need to rely on the sequential analysis of CSF parameters to prevent a delay in antibiotic treatment and to guide treatment decisions ,18. Our In contrast to these studies, our study showed only a moderate positive correlation of glucose values between the two collection sites. According to Deisenhammer et al., CSF glucose degrades during storage, which could explain our results . AnotherCompared to glucose, the stability of CSF lactate and protein concentrations seems to be less affected by storage time. While the data on the stability of these CSF parameters are scarce, it has been shown in previous studies that a time delay of 2.5 h in sample processing did not influence the analytical results . MoreoveIn regard to the CSF cell count, it appears that the in vitro biochemical process has been analyzed in more detail. Historical studies have shown that due to the hypotonic state of CSF, leukocytes lyse if they are exposed for an extended time period . This ceIn summary, our data show that CSF parameters can be reliably assessed from the EVD collection bag. CSF sampling by this approach has the potential to reduce manipulation of the proximal site of the EVD system and, thus, theoretically reduce EVD-associated infections to a certain degree. However, since this is the first study analyzing the reliability of this CSF sampling approach, more studies are needed to validate our results.To our knowledge, this is the first study analyzing the analytic value of CSF parameters from the EVD collection bag. Moreover, the continuously applied standard CSF sampling protocol with a high amount of CSF sample pairs is the major strength of our study.While we could show a moderate to high positive correlation of CSF values between the two collection sites, it must be pointed out that laboratory reference values are validated for CSF specimens acquired from the proximal site. Thus, future studies are needed to assess appropriate reference values for CSF parameters acquired from far distal collection sites.Although we included neurosurgical patients only, our cohort still comprised a heterogeneous group of cases with a history of SAH in 78% of our patients. Moreover, due to our low infection rate , we did not perform a comparison analysis of the microbiological results between the two collection sites. Thus, the comparison of the microbiological results should be interpreted with caution since this part of the study was purely descriptive.Clinicians still depend on the sequential analysis of CSF parameters to detect EVD-associated infections due to (1) the lack of specific parameters and (2) the delayed availability of microbiological results. Moreover, microbiological analysis may be influenced by empiric antibiotic treatment. With the aim of reducing manipulation at the proximal port of the EVD system, we analyzed whether CSF parameters could be reliably detected from the far distal collection bag. Our results showed a high correlation of CSF cell count, lactate and protein between the two collection sites. Therefore, we are convinced that an increased CSF sampling frequency from the far distal collection bag is possible, with the potential to prevent a loss of information and minimize the risk of EVD-associated infections. This approach could guide the treating clinician to improve treatment strategies.However, in cases of abnormal CSF values, CSF parameter analysis should always be performed from the proximal site to verify the analytical results. More importantly, future studies should focus on the development of newer techniques to expedite the determination of EVD-associated infections.


In order to expand the donor pool and accessibility of the transplant procedure, it was necessary to introduce haplo-identical stem cell transplants in the Fundeni Clinical Institute from 2015. Even if the Romanian population is an ethnically compact white population, many of the patients referred for bone marrow transplant lack a suitable donor. Hematopoietic stem cell transplant from a haplo-identical donor is an alternative option for those patients without an HLA (Human Leucocyte Antigen)-matched donor (sibling or matched unrelated). This procedure was used also as a salvage option for those who experienced engraftment failure or the rejection of the first stem cell graft. In this case series, we present three such cases, with a haplo-transplant used as a salvage protocol (after an engraftment failure or rejection of the first transplanted cells). The patients we present were diagnosed with AML (acute myeloid leukemia) with MDS (myelodysplastic syndrome), MDS—RAEB 2 (myelodysplastic syndrome—refractory anemia with excess blasts 2), and SAA (severe aplastic anemia). In two of the three cases, the engraftment failure may have been due to the conditioning Fludarabine/Busulfan/Cyclophosphamide (Flu/Bu/CFA) used, combined with marrow grafts. In all three cases, the second transplant was of haplo-identical peripheral blood stem cells using Melphalan/Fludarabine (Mel/Flu) conditioning, the cells engrafted properly and the patients experienced complete chimerism, and two of them are alive with an excellent quality of life. Even if the Romanian population is an ethnically compact white population, many of the patients referred for bone marrow transplant lack a suitable donor.The chance of finding a suitable HLA-matched donor is about 60–70% in the white population and <10% for different minorities .The medium time for finding a suitable unrelated donor, from the initiation of searching until the donation of stem cells, is approximately 4 months; some patients do not have this time  .Hematopoietic stem cell (HSC) transplant from an matched unrelated donor using myeloablative conditioning (MAC) still has a high transplant mortality rate and a high long-term morbidity ,5,6,7,8.More than 95% of patients in need of an allogeneic stem cell transplant have a haplo-identical donor [Haplo-identical stem cell transplant is associated with a high incidence of graft-versus-host disease (GVHD), late engraftment and graft failure ,11. GVHD6 CD34 + cells/kg and ≤4 × 104/kg T cells in patients with severe SCID (combined immunodeficiency syndrome) [The T cell depletion of the graft leads to an imbalance between the host and donor T cells and thus results in high rates of graft failure. This imbalance may be overcome with the use of “megadose” stem cell grafts  ,13.-6/kg. The graft is depleted by the CD19 + cells (B lymphocytes) in order to decrease the risk of developing lympho-proliferative diseases after transplant (PLDL) [in vitro, using a CliniMACS device, in which the graft is depleted by both CD3 + cells (T lymphocytes) and CD19 + cells (B lymphocytes). For these cases, engraftment will appear at a CD34 + cell dose of 5.2 × 10t (PLDL)  and GVHDt (PLDL) -in vivo, using antithymocite globulin (ATG). ATG affects the host T lymphocytes and facilitates engrafting. ATG acts on donor T lymphocytes with effects on GVHD and post-transplant immunity.There are two methods for T-cell depletion:One strategy for achieving the in vivo attenuation of T cell alloreactivity is the use of high-dose post-transplant cyclophosphamide (PTCy) .PTCy may be used in reduced intensity conditioning (RIC) as well as in MAC conditioning. Its use leads to a decrease in the development of acute and chronic GVHD ,17. MAC PTCy has better results than ATG in patients with acute myeloid leukemia (AML) ,20.In order to expand the donor pool and the accessibility of the transplant procedure, it was necessary to introduce haplo-identical stem cell transplants in the Fundeni Clinical Institute (ICF) from 2015. The Bone Marrow Transplant Unit of the ICF is the only place in Romania that performs haplo-transplant procedures.Hematopoietic stem cell transplant from a haplo-identical donor is an alternative option for those patients without a human leukocyte antigen (HLA)-matched donor, sibling or unrelated, so it was included in our transplant strategy.This procedure can be also used as a salvage option for those who have experienced engraftment failure or a rejection of the first stem cell graft. In this case series, we would like to present three such cases, with haplo-transplant used as a salvage protocol.Case presentation: the first three cases  undergoing a secondary haploidentical stem cells transplant, used for salvage after engraftment failure or the rejection of the first transplanted cells ,22,23.The patient is a 28-year-old male diagnosed with AML/MDS, transplanted, and in first complete remission (CR1), with his sister as the haplo-identical donor (5/10 HLA match); this was due to the unavailability of a matched unrelated donor within the registry in a timely manner.-2/day × 5 days ;Fludarabine (Flu): 30 mg/m-Cyclophosphamide (CFA): 14.5 mg/kg bw/day × 2 days ;-Busulfan (BU): 3.2 mg/kg bw × 2 days .The first transplant was conditioned with the following (Flu/CFA/BU):-PTCy (day + 3 and day + 4);-Tacrolimus (tacro): 0.12 mg/kg/day, divided in two doses from day + 5;-Mycophenolat mofetil (MMF): 15 mg/kg/dose in 2–3 doses/day from day + 5 ,36,37,38The GVHD prophylaxis used the following (PTCy + tacro + MMF):6 CD34+/kgbody weight) of the donor on day 1. For the patient, we used G-CSF (granulocyte colony-stimulating factor) at a dose of 300 micrograms/day from day + 5. The patient did not engraft at all, so we had to use a salvage protocol; because of the the absence of a new donor, we repeated the haplo approach from the same haploidentical sister. However, the second time, we changed the conditioning and the source of the cell graft as well.The stem cells we used were harvested from the marrow : 140 mg/m-2/day on day - 5, day - 4, day - 3 and day - 2Fludarabine (Flu): 40 mg/mFor the second conditioning we used (MEL/Flu):The GVHD prophylaxis was the same as that in the first setting: PTCy + tacro+ MMF.6 CD34+/kg of body weight. He engrafted on day + 15, with complete chimera on day + 30, + 60, + 90 at 6, 9 and 12 months. Immune suppression was stopped at 5 months. , transplanted, and in second complete remission (CR2), with her haplo-identical uncle with 5/10 HLA match as the donor .-2/day × 5 days ;Fludarabine: 30 mg/m-Cyclophosphamide: 14.5 mg/kg body weight/day × 2 days ;-Busulfan: 3.2 mg/kg body weight × 2 days .The first transplant was conditioned with the following (Flu/CFA/BU):-PTCy: (day + 3 and day + 4);-Tacrolimus: (0.12 mg/kg/day divided into two doses from day + 5);-Mycophenolat mofetil: 15 mg/kg/dose in 2–3 doses/day from day +5 ,42,43,44GVHD prophylaxis was as follows (PTCy + tacro + MMF):6 CD34+/kg body weight; 2.8 × 108 TNC <total nucleated cells>/kg body weight) with G-CSF from day + 5. The patient was engrafted and the chimerism on day +30 was fully the donor’s. Shortly after, she experienced rejection, with a chimeric profile on day + 48 of only 3% donor cells. We had to re-transplant her with the same haplo-identical uncle in the absence of another donor.The first graft we used was marrow :The GVHD prophylaxis was PTCy + tacro + MMF.6 CD34+/kgbw, and we used G-CSF from day + 5. She engrafted on day + 16, with complete chimera on day + 30. She died as a result of broncho-pneumonia and multiorgan failure on day + 42 after the second transplant. , diagnosed in January 2015, with a good initial response to immune-suppression therapy. He was transplanted after a relapse in 24 February 2016 with cells from a 10/10 HLA female; she was a matched unrelated donor (MUD) with the same blood group and same positive CMV status.-2/day in day - 5, - 4, - 3 and - 2;Fludarabine: 30 mg/m-2 in day - 5, - 4, - 3 and - 2.Cyclophosphamide: 300 mg/mThe conditioning protocol for the MUD transplant was the EBMT protocol (Flu/CFA):-CsA (Cyclosporine A) from day - 1;-MTX on day + 1, + 3 and + 6;-ATG (Antithymocyte globulin): 10 mg/kg/day on day - 4, - 3, - 2 and - 1.The GVHD prophylaxis was as follows (CsA + MTX + ATG):6 CD34+/kg bw [The cell graft this time was bone marrow: 3.1 × 104+/kg bw .He was engrafted on day + 23 with G-CSF. The chimeric profile was 100% donor cells on day + 30, and 84% donor cells at 3 months. We stopped the immune suppression at 5 months, but the chimerism decreased continuously. At 6 months, he had 23% donor chimera and the CMV and parvo-virus were reactivated also. His body totally rejected his graft with these complications.6 CD34+/kg of body weight.On 23 September 2016 , he received peripheral blood stem cells from his haplo-identical sister (5/10 HLA match) using 5.23 × 10The conditioning protocol was Mel/Flu, as in the first two cases of re-transplant.The GVHD prophylaxis was PTCy + MMF + tacro.The engraftment was on day + 24 with G-CSF. The chimeric profile was 100% donor on day + 30, + 60 and + 90. He only experienced a CMV reactivation and one bacterial infection with Enterococcus sp after the transplant.He is alive and well. See .See In recent years, haplo-identical family members have become one of the valid choices for allogeneic stem cell transplant.-find a sibling donor as a first step;-additionally identify the haplotypes within the family in case a haplo-identical transplant is needed.In Romania, the algorithm used to choose a donor for a patient starts with family HLA typing in order to achieve the following:The second step is to look in international registries for a matched unrelated donor. In the case of a patient who does not have a sibling or a matched unrelated donor in a timely manner, the haplo-identical transplant is proposed.6 CD34+ cells/kg recipient; 2.17 × 106 CD34+ cells/kg recipient; 3.1 × 106 CD34+ cells/kg recipient). It is well known that an insufficient quantity of stem cells in the graft can lead to engraftment failure. This small amount of stem cells from the bone marrow graft can be explained by the fact that, in all three cases, the weights of the recipients were significantly higher than the weights of the donors. In addition, in the first two cases, the donors had a 50% HLA match with the recipients.We presented three cases using the haplo protocol in order to save the lives of patients who have experienced an engraftment failure or rejections. The engraftment failure may be due (in the first two cases) to the conditioning we used (Flu/Bu/CFA), combined with marrow grafts. The source of the hematopoietic stem cells is also an important factor in the failure of the hematopoietic stem cells (HSC) transplant. In all three cases, the amount of CD34+ in the marrow graft was poor  and another source of stem cells  were used in all three patients. The number of stem cells from the peripheral blood was superior compared to the that from the first transplant . The donor for the third patient was changed for the second transplant, unlike the first two patients. This patient had a MUD 10/10 HLA match for the first transplant, but for the second one, his haplo-identical sister with a 5/10 HLA match became the donor.HLA-haploidentical stem cells post-transplant, with a high-dose cyclophosphamide, are associated with a low rate of GVHD and non-relapse mortality .-Couban et al., 2002: superior rates of engraftment for AML patients who receive peripheral blood stem cells (PBSC). At the same time, these patients have a higher risk of acute and chronic graft versus host disease (GVHD) .-Anaseti et al., 2012: comparable survival rates and relapse rates in AML patients transplanted with PBSC MUD grafts vs. AML patients transplanted with bone marrow (BM) grafts. It is demonstrated that BM grafts have a higher rate of graft failure and PBSC grafts are accompanied by higher rates of chronic GVHD .-Schlenk et al., 2010: MSD (matched sibling donor) and MUD (matched unrelated donor) are the preferred options for HSC transplant. For patients who do not have these types of donors, haplo-identical donors can be found .Both sources of stem cell grafts  are acceptable options at the present time. All three patients grafted when peripheral blood was used as the source of the stem cells graft. This is in accordance with the medical literature that shows superior rates of engraftment for patients who receive peripheral blood stem cells (PBSC):In all three cases, the second transplant involved haplo-identical peripheral blood stem cells using Mel/Flu conditioning; the cells engrafted properly and the patients became complete chimeras, and two of them are alive with a good quality of life.