S-box to dynamically generate encrypted rounds, realizing more numbers of dynamic rounds encryption for the important information marked by NLPIR, while less numbers of dynamic rounds encryption for the non-important information that is not marked. Through linear and differential cryptographic analysis, ciphertext information entropy, “0–1” balance and National Institute of Science and Technology (NIST) tests and the comparison with other traditional and lightweight block ciphers, the results indicate that the dynamic variety of encrypted rounds can achieve different levels of encryption for different information, which can achieve the purpose of enhancing the anti-attack ability and reducing the number of encrypted rounds. Therefore, the dynamic rounds chaotic block cipher can guarantee the security of information transmission and realize the lightweight of the cryptographic algorithm.According to the keyword abstract extraction function in the Natural Language Processing and Information Retrieval Sharing Platform (NLPIR), the design method of a dynamic rounds chaotic block cipher is presented in this paper, which takes into account both the security and efficiency. The cipher combines chaotic theory with the Feistel structure block cipher, and uses the randomness of chaotic sequence and the nonlinearity of chaotic  Cryptography is the core of information security technology, which is mainly used to ensure the confidentiality and integrity of information in the transmission process . As an iThe encrypted rounds of block cipher generally depend on the compromise option between cryptographic security and operational efficiency. In most cases, the security of the block cipher will be enhanced by the increase of encrypted rounds. However, if there are too many encrypted rounds, the practicality of the block cipher will be affected. The Feistel structure, which is a classical and the most used block cipher structure, has the advantages of easy implementation, rapid diffusion, simple calculation and good security, etc. At present, the same encrypted rounds are used for all plaintext information by the Feistel structure block cipher, and it can easily lead to information leakage and decipherment due to the insufficient security of encryption of important information, and unnecessary computational burden and resource consumption caused by the excessive security of encryption of non-important information. In response to the above problems, a dynamic rounds chaotic block cipher based on keyword abstract extraction is proposed in this paper.S-box. The randomness of the chaotic sequences is employed for DNA encoding, operation, and decoding to generate and extend keys. The fireworks algorithm is used to search for the optimal chaotic sequence explosively to construct the S-box. The dynamic change of the number of encrypted rounds not only enhances the complexity of the cipher but also reduces the total number of the encrypted rounds. By adopting such a block cipher algorithm that is dynamically encrypted according to different information, it is possible to guarantee the security of information transmission and realize the lightweight of the cryptographic algorithm.On the basis of traditional Feistel structure chaotic block cipher, the abstract extraction function in the Natural Language Processing and Information Retrieval Sharing Platform (NLPIR) is used to mark important information of text plaintext automatically before block encryption. Under condition of the same cryptographic structure and components, for a small number of plaintext blocks containing important information, the encrypted rounds of which would dynamically change within the interval The main contents of this paper are arranged as follows: the first part explains the background and significance of the research. The second part analyzes the research basis and status of the chaotic block cipher. The third part introduces the automatic abstract extraction based on keywords in the NLPIR big data search and mining development platform. The fourth part presents the system design of the dynamic rounds chaotic block cipher based on keyword abstract extraction, which includes the cryptographic structure, cryptographic components and the realization method of dynamic encrypted rounds. In the fifth part, the system performances of the dynamic rounds chaotic block cipher are analyzed and tested, and the security and practicality are evaluated according to the experimental data. The contents of this paper are summarized and concluded in the sixth part.The chaotic system has some typical characteristics, such as sensitive dependence of initial parameters, topological transitivity, tensile folding transformation characteristics, mixing, periodic point, ergodicity, positive Lyapunov exponent, fractional dimension, etc. . With thAt present, the main factors hindering the development of chaotic block cipher are as follows. Firstly, the chaotic theory is in the initial stage and the content of which is not sufficient. Secondly, the structural design of the chaotic block cipher is still in the exploratory stage. Thirdly, the finite operation precision effect results in the degradation of the dynamic characteristics of the chaotic system ,7. In adS-box generation in this paper.Based on the analysis of chaotic systems that have been proposed so far, we have roughly divided the chaotic systems into two categories in the literature . DiscretAiming at the deficiencies of the one-dimensional discrete chaotic map, we have proposed a two-stage cascaded chaotic map in the literature , which iThe difference iterative equation of the cascaded chaotic map is given to beIn Equation , μ is thS-box more flexible [Lorenz is a classical three-dimensional continuous chaotic system. Apart from being non-periodic, unconvergent but bounded, and extremely sensitive to initial values, it also has the following three advantages: complex system structure makes it more difficult to predict output chaotic sequence, the solution space constituted of three initial values and three parameters is significantly higher than the low-dimensional discrete chaotic maps, and the application of three chaotic sequences makes the design of flexible ,13.The three-dimensional first order nonlinear differential equation of the Lorenz chaotic system is as follows:a, b and c are the system parameters. When a = 10, b = 28, c = 8/3, the Lorenz chaotic system is in the chaotic state [In Equation , a, b anic state .NLPIR is a set of software designed for processing the original text, which combines natural language understanding, web search, text mining technologies, and provides 11 functions, such as word segmentation tagging, abstract and keyword automatic extraction, big data clustering and hotspot analysis, big data classification filtering, and HyperText Markup Language (HTML) text extraction . In thisAutomatic abstract extraction based on keywords is shown in t in the text d, t appearing in the text d, N is the number of all texts in the corpus, and t appears in the corpus. The more frequently a word appears in a text and the less frequently it appears in other texts simultaneously, which indicates that the word has more distinguishable ability for expressing this text, so the weight value should be greater.The word frequency-inverse text frequency is used to calculate the weight of a word. Creating a plaintext corpus in text format, the word frequency reflects the word feature by counting the frequency of each word appearing in a text. The inverse text frequency reflects the importance of a word by counting the frequency of which appearing in all texts of the corpus, then the word feature expressed only by word frequency would be corrected. The ratio of the frequency of a feature word appearing in the text to the number of texts containing that feature word in the corpus is taken as the weight of the word, i.e.,ω=loThe keywords with higher word frequency are extracted using the adjacent category value of words. The left adjacent category value of a string is the number of words appearing on the left side of that, and the right adjacent category value of a string is the number of words appearing on the right side of that. The total adjacent category value of a string refers to the number of words appearing on the left and right sides of that. The greater the adjacency category value of a word, the more flexible it is to use, and the more likely it is to use in different contexts, the higher the probability to become a keyword.T appears n times in the corpus, and the appearing positions of candidate word T are T) of T isT. The positional variance of the word indicates the sparsity of the distribution of word. The smaller the positional variance, the higher the degree of concentration in each position and the stronger the locality of the string. Assuming that LE represents a local measure value of a string, the locality formula isThe positional locality of words is used to extract keywords with lower word frequency. The positional variance of the word appearing in the text is used to represent the positional locality of that. Assuming that the candidate word ) of T isD(T)=∑i=1x represents the position of the sentence in the paragraph, l represents the number of sentences in the paragraph, A piecewise function is used to quantify the influence of sentence position on the weight of the word, i.e.,SP=−α operation with The dynamic rounds chaotic block cipher of the Feistel structure is shown in F is the round function, i is the number of encrypted rounds, In Equation , F is thThe encryption and decryption process of dynamic rounds chaotic block cipher of Feistel structure is similar, and decryption is the inverse operation of encryption. It does not need to do the inversion because the round functions of encryption and decryption are the same, which makes the design of round function more flexible. The cryptographic structure is relatively simple and easy to implement.F is the core to realize the confusion and diffusion of the block cipher, which is composed of the round key S-boxes P-boxes F is obtained through the right shift operation of As shown in S-box is the key to design round function F. In the present design of S-box based on Lorenz chaotic system, the method of Runge–Kutta has been used to solve the Lorenz chaotic system and then select a chaotic sequence randomly to construct the S-box, which makes it difficult to guarantee the rationality and superiority of the selected chaotic sequence. The fireworks algorithm [x-axis, y-axis outputs of Lorenz chaotic system, and combines with reverse coding operation and edge contraction matrix transformation to construct F.As the only nonlinear component, the lgorithm  has highThe master key Equation  is digitIn the iterative operation of the round function, each round of the master key S-box, which will achieve different levels of dynamic encryption for important and non-important plaintext blocks respectively. The 4 × 4 S-box generated by the Lorenz chaotic system and fireworks algorithm is shown in S-box, and the rear two bits determine the column of S-box, so any four-bit binary input can be converted to any decimal number in the interval of Considering the security, speed, storage space and other factors, a kind of dynamic generation of encrypted rounds within two intervals of S-box, and an output of the S-box is set to In the encrypted process of each block, it has to calculate the number of dynamic rounds needed to encrypt firstly. The first four bits of the initial master key are used as the input to the As a kind of symmetric cipher, block cipher encryption and decryption use the same key, the number of rounds that the block has been encrypted can be determined according to the same way in the decryption, so that the plaintext information can be recovered.S-boxes, whose method is used when evaluating linear and differential cryptanalysis of block ciphers such as AES, Camellia, and CLEFIA.Linear analysis  and diffThe linear analysis is a known-plaintext attack, whose basic principle is to seek an effective linear approximation between plaintext, ciphertext and key. When the linear deviation of the approximation is large enough, the partial key information can be inferred from a certain amount of plaintext and ciphertext pairs.S-box whose input and output are n bits,For any given S-box is defined asThe maximum linear approximation probability  of the Sn-dimensional vector space on the binary domain, that is, the set of all possible inputs of x, a, b. S-box, and its relationship with the degree of nonlinearity x to get the output as a. Therefore, the smaller the value of the maximum linear approximation probability of the S-box, the stronger the ability to resist the linear attack.In Equation , F2n repterature . LPmaxS S-box [S-box whose output representation vector is non-zero. Then, the number of minimum linear active S-boxes isThe linear active S-box  refers tS-boxes when encrypting eight rounds is 56.In Equation , Γz′,Γz S-box in this paper is 106, the maximum linear approximation probability of the S-box is calculated to be that Since the average degree of nonlinearity of the L represents the number of encrypted rounds and S-boxes. When the block length of the block cipher is 64 bits, according to the linear complexity analysis, if the number of encrypted rounds is greater than 8, the maximum linear approximation probability would be less than the upper bound of In Equation , L repreThe differential analysis is a kind of chosen-plaintext attack. Its basic idea is to recover some or all of the keys by analyzing the impact of the differences of plaintext pairs on the difference of ciphertext pairs.S-box whose input and output are n bits,For any given S-box is defined asThe maximum differential approximation probability  of the SS-box, x to get the output as S-box, the stronger the ability to resist the differential attack [In Equation , DiffS il attack .S-box whose input difference is non-zero. Then, the number of minimum differential active S-boxes isThe differential active S box  refers tS-boxes when encrypting eight rounds is 42.In Equation , Δz,Δz′ S-box in this paper is 10, the maximum differential approximation probability of the S-box is calculated to be that Since the maximum value of the differential uniformity of L represents the number of encrypted rounds, and DS represents the number of differential active S-boxes. From this, it can be seen that there is no valid difference feature for analysis if the number of encrypted rounds is greater than 8, and the dynamic rounds chaotic block cipher proposed in this paper can resist the differential attack.In Equation , L repreThe randomness of ciphertext is an important index to measure the performance of cryptographic algorithms. If the distribution of ciphertext is not uniform or random enough, the cryptanalyst can break and obtain information through the ciphertext-only attack. In order to reflect the encryption performance of dynamic rounds chaotic block cipher as accurately as possible, the information entropy, “0–1” balance and NIST tests of ciphertext are carried out respectively in this paper.The probability of information appearing in the ciphertext is called information entropy, which is used to indicate the confusion degree of the ciphertext, and its calculation equation isn.In Equation , the proFor the test results of information entropy of different block ciphers as shown in The “0–1” balance refers to the relationship between the number of 0 and 1 in the ciphertext, which is used to indicate the randomness degree of ciphertext, and its calculation equation isn is the total number of 0 and 1. The more In Equation , k1 and For the test results of “0–1” balance of different block ciphers as shown in p-value, the better the randomness of the test sequences.In order to further verify the statistical characteristics of ciphertext, the SP800-22 test package developed by the National Institute of Standards and Technology (NIST) is used for the random performance detection . In thisAs shown in S-box through inheriting and approximating the local information of the neighborhood. the randomness of chaotic sequence and the nonlinearity of chaotic S-box are used for the dynamic generation of encrypted rounds in two intervals, realizing more numbers of dynamic rounds encryption for the important information blocks marked by NLPIR, while fewer numbers of dynamic rounds encryption for the non-important information blocks that are not marked. The example of the proposed encryption cipher is shown in The description of the proposed encryption cipher is shown in The ideal lightweight cipher should occupy a small circuit area, consume the least amount of resources and power, and perform as fast as possible. The complexity of implementation is one of the most dominant factors that affect the design approach of the cipher. It is determined by the logic gates that are required to implement a cipher, and the relevant metric is called Gate Equivalent (GE). Software implementations are optimized for throughput and energy consumption by requiring fewer cycles since voltage and clock frequency are usually fixed for microcontrollers. The performances of most lightweight block ciphers are evaluated in the literature . Table 7Considering the trade-off between security and performance, in the case of the same encrypted structure, process and round function, the dynamic rounds chaotic block cipher proposed in this paper based on the automatic abstract extraction function in the NLPIR big data search and mining development platform, which will achieve different levels of dynamic encryption for important and non-important plaintext information, respectively. Compared with traditional and lightweight block ciphers, the dynamic variety of encrypted rounds can realize the security of information transmission and the lightweight of the cryptographic algorithm. At the same time, the research and application of the dynamic rounds chaotic block cipher have important significance and research value to the design analysis theory of traditional block cipher and the further development of chaotic application theory.


The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression. Therefore, graft injury was assessed in 133 liver biopsies with normal/near normal liver enzymes from a prospective liver biopsy program. Cytokeratin-18 cell death marker (M65) and donor specific anti-HLA antibodies (DSA) were measured as non-invasive markers in paired plasma samples in addition to routine parameters. M65 was associated with subclinical graft injury but this association was too weak for reasonable clinical application. DSA positivity was associated with more graft inflammation (OR = 5.4) and more fibrosis (OR = 4.2). Absence of DSA excluded fibrosis in 87–89%, while presence of DSA excluded histological criteria for immunosuppression minimization attempts in 92–97%. While CK18 cell death marker had no diagnostic value for the detection of subclinical liver graft injury, DSA testing can help to preselect patients for immunosuppression reduction in case of DSA negativity, while DSA positivity should prompt elastography or liver biopsy for the assessment of subclinical graft injury. An individualization of immunosuppression promises a better balance of necessary control of alloreactivity and side effects of immunosuppressants. Approaches for such a personalized medicine are safer after Ltx than after other solid organ transplants, because of lower rates of chronic and antibody-mediated rejection and the highest rates of spontaneous operational tolerance.Long-term survival after liver transplantation (Ltx) did not improve for the last three decades. Approximately 25% of deaths beyond year one after liver transplantation were associated with the long-term intake of immunosuppression, e.g. malignancies and infections, while liver graft dysfunction was only responsible for 12% of deaths4. The relevance of many subclinical abnormalities remained unclear, because typical features of T cell-mediated rejection (TCMR) were less frequent late after transplantation. On the other hand, patients that achieved spontaneous operational tolerance in clinical trial had not necessarily a complete absence of inflammation in screening biopsies6. Just recently, a first consensus document describing pattern of chronic antibody-mediated rejection (cAMR) after Ltx was published7.However, it is still difficult to monitor the control of alloreactivity after liver transplantation, because liver enzymes are rather insensitive to detect subclinical graft injuries. Protocol liver biopsies, the current gold standard for the detection of subclinical graft injury, could fill this gap of sensitivity, but lack specificity, because subclinical histological abnormalities are found in the majority of livers allografts late after transplantation even in patients with a stable long term course10.Unfortunately, non-invasive markers predicting subclinical graft injury are still missing. A promising candidate is cytokeratin-18 (CK18) that is released during hepatocyte cell death. Serum levels of CK18 and its cleaved fragments can help to diagnose non-alcoholic steatohepatitis and have prognostic relevance e.g. during acute liver failure or primary biliary cholangitis21. Although graft and patient survival of DSA positive liver transplanted patients is reduced, the association between DSA positivity and graft outcome is milder than after e.g. kidney transplantation23 and DSAs can even be found in operational tolerant patients25.Donor specific anti-HLA antibodies (DSA) are well known to be associated with graft injury and rejectionThe aim of this study was to test the association of blood levels of CK18 and DSAs with defined patterns of subclinical graft injury with clinical relevance in an adult protocol liver graft biopsy program.Patients for this study were transplanted between 1990 and 2015 and liver biopsies were taken between July 2009 and November 2017. In total 402 complete pairs of cryo-conserved plasma samples and liver biopsies were collected. Sample selection for this retrospective analysis is shown in Fig. 7. Therefore, similar thresholds for liver enzyme elevations were chosen (ALT and AST and gGT < 2 × ULN and ALP < 1.5 × ULN) as in an adult prospective immunosuppression weaning trial5. Altogether 133 liver biopsies were taken while liver enzymes were within these limits  were published in a Banff consensus documentOn one side subclinical graft injury that may need more intense immunosuppression like subclinical graft hepatitis or subclinical T cell-mediated (subTCMR) or antibody-mediated rejection (AMR) should be identified in these patients with normal or only marginally elevated liver enzymes. Furthermore, an at least moderate graft fibrosis was chosen as a second histological entity for the subsequent analyses.26. Other abnormalities related to rejection like portal microvasculitis or central perivenulitis were only found in a minority of biopsies (15–18%). Similarly, relevant steatosis or steatohepatitis were only occasionally present. As expected, the graft injury and fibrosis stages in biopsies with normal/marginally elevated liver enzymes (n = 133) were significantly lower (Mann–Whitney U-test) than in those with higher liver enzyme elevation (n = 86) (data not shown). Only portal microvasculitis and steatosis/steatohepatitis were not significantly different.The results of the pathological analysis of these 133 liver biopsies with normal/marginally elevated liver enzymes are summarized in Table Histological diagnoses in descending order were indeterminate findings 46/133; 35%), subTCMR , no histological rejection , possible cAMR , subTCMR with additional hepatitis features but not suggestive for cAMR  and PSC recurrence . Of these 133 biopsies, 32  were compatible with criteria of HCMini and 23  exhibited at least moderate fibrosis. HCMini and at least moderate graft fibrosis had stable frequencies over time  of the current study fell into the cTCMR cluster, while the molecular signature of 50 biopsies (81%) fell into the NHR cluster. Although histological abnormalities increased over time, as indicated by the decrease of NHR  liver biopsies with normal/near normal liver enzymes of the current study. Based on the graft gene expression of 93 transcripts being associated with rejection and immune regulation after transplantation  of the blood parameters were performed. Although, there were some significant associations of M65 or some liver enzymes, the associations were overall too weak for further reliable clinical applications or with cut-off values within the normal range  DSA had MFI above 5,000.DSA were present in 39/133 (29%) blood samples with normal/near normal liver enzymes and in 20/80 (25%) patients. Class I DSA were found in 8/39 (21%) DSA positive samples from 4/20 (20%) DSA positive patients, while class II DSA were found in 31/39 (80%) DSA positive samples from 16/20 (80%) DSA positive patients. Specificities and MFI of DSA are outlined in Fig. 2 test; Fig. The onsets of DSA (preexisting before transplantation or de novo after transplantation) could not be determined in our study, because pre-transplant samples were not available. However, longitudinal samples after transplantation in our biorepository could help to describe the persistence of DSA after transplantation. In this sense, 8/20 (40%) patients had DSA at all available time points. 4/20 (20%) patients were tested DSA positive at the only available time point after transplantation. 6/20 30%) patients were tested DSA positive after being DSA negative at an earlier time point after transplantation. 2/20 (10%) patients were tested DSA positive and were DSA negative at a later time point. DSA frequencies significantly increased with time after transplantation  rather than tacrolimus and in parallel to liver biopsies with more graft injury and more graft fibrosis Table . The finMFI of DSA were positively correlated with hepatitis activity index , thereby mostly with lobular inflammation , graft fibrosis/LAF score , thereby especially with sinusoidal fibrosis , portal microvasculitis , ductular reaction  and nodular regenerative hyperplasia . Nonetheless, there was no significant difference of subclinical graft injury between samples with high  and low  MFI.19. DSA positivity  mostly excluded HCMini in 92%, while DSA  negativity excluded relevant graft fibrosis in 89%. The non-invasive diagnostic fidelity of DSA for graft fibrosis was not relevantly different, when only DSA with higher MFI  and/or DSA class II were considered  (odds ratio (OR) = 5.4 with 95% confidence interval (CI): 1.5–18.9), while DSA positivity  was significantly associated with graft fibrosis  Fig. C. An ass28, the association of DSA with graft injury in general is a well described phenomenon21. However, we are not aware of another study with a specific focus on non-invasive capacities of both parameters in comparison to the routine blood markers to detect subclinical graft injury in adults. This is of clinical importance for an individualization of immunosuppressive regimens, because the presence of more advanced subclinical graft injury firstly limits attempts to lower immunosuppression7 and secondly might indicate insufficiently controlled alloreactivity with a “smoldering” graft damage4.While this was the first analysis of the predictive value of CK18 levels for graft injury after liver transplantation beyond hepatitis C29. SubTCMR defined by liver enzymes below two times ULN had no progression to cTCMR or subsequent progressive fibrosis when left untreated later after transplantation30. The same thresholds were also used for the description of subclinical graft injury in other studies in adults3. Furthermore, the thresholds applied here were adapted from a prospective immunosuppression weaning trial after adult liver transplantation5 that were used similarly in an ongoing multicenter validation trials as well .The threshold of approximately two times ULN instead of the normal range to distinguish between clinical and subclinical graft injury seems rather arbitrary. However, liver enzyme elevations above this threshold were independent risk factors for a reduced patient and graft survival in the setting of early subTCMR21. The most prominent findings were portal inflammation and fibrosis. Subclinical graft injury and fibrosis progressed over time after transplantation. Thereby, biopsies without evidence of rejection declined, while indeterminate findings increased over time. In contrast, subTCMR and possible cAMR had rather stable prevalence. This single center study also confirmed the common notion that graft injury has more hepatitis features later after transplantation7. The longitudinal sequence of inflammation, fibrosis and the association of graft injury with DSAs was also described in a recent pediatric study by Varma et al.21. Furthermore, biopsies in the present study were selected mostly regarding the level of liver enzymes. Thereby, biopsies with liver enzymes above 1.5–twofold ULN were excluded.The patterns of subclinical graft injury in our transplantation center resembled what is published from other centers32. This association cannot help to unravel, whether DSA are cause or consequence of the graft injury. However, it is compatible with the two hit hypothesis, which proposes that inflammation in the graft induces upregulation of class II HLA molecules and this promotes a sensitization towards mismatched allo-HLA molecules33. In line with this hypothesis and in line with other studies, DSA were predominantly targeted against class II HLA in the current study. However, C4d deposition suggestive for AMR could not be found in any DSA positive liver biopsy.The progression of hepatitis features with time was accompanied by an increasing appearance of DSA. An increase of DSAs over time has been reported by many other but not all studies34. Nonetheless, we and other groups found an association of DSA with graft injury21. Interestingly, the present data suggest that the association of DSA with subclinical graft injury is more evident later after transplantation, because mostly DSA positive recipients showed a progressive graft injury over time while DSA negatives did not. This has been reported in other studies without a special focus on subclinical findings as well35. In addition, higher MFI were associated with more subclinical graft injury e.g. portal microvasculitis and graft fibrosis, features being associated with antibody-mediated rejection7. Mostly DSA with high MFI, e.g. above 5,000–10,000, are associated with reduced graft and patient survival36. The majority of the DSA (69%) found in this cohort of patients with normal/near normal liver enzymes had DSA with high MFI , too.The clinical relevance of DSA after liver transplantation is controversially discussed, because graft and patient survival is much less reduced in DSA positive liver recipients than after kidney transplantation27 recommend MFI thresholds of 1,000–1,500 to define DSA positivity but relevant associations of DSA with reduced graft or patient survival after liver transplantation were mostly found for DSA with higher MFI as mentioned above. The absence of DSA in the present patient cohort had an OR of 5.4 for the presence of HCMini according to the Banff guidelines7 justifying attempts to further reduce immunosuppressants. The diagnostic fidelity of DSA positivity for the exclusion of HCMini could be further increased, when only class II DSA irrespective of high or low MFI were considered. A limitation of the present study in this aspect was the high prevalence of primary autoimmune liver diseases . Of note, this association was not strong enough to be used for a reasonable clinical non-invasive prediction. Multiple studies found associations of transient elastography with liver fibrosis stage in liver biopsies and transient elastography seems to be most appropriate to assess fibrosis non-invasively as compared to AST-to-platelet ratio index and fibrosis score 439.Multiple studies analyzed potential non-invasive markers for the assessment of graft injury, mostly in the context of acute rejectionIn summary, subclinical graft injury was a common finding on the histological and transcriptional level in protocol liver graft biopsies in adults. Cytokeratin-18 cell death marker (M65) were not suitable for non-invasive monitoring of subclinical graft injury. While DSA were significantly associated with subclinical graft injury, their low overall prevalence (29%) diminished their predictive capacity. However, the presence of DSA or class II DSA could help to exclude patients for a reduction of immunosuppression without the necessity of a liver biopsy. DSA positivity even in patients with normal/near normal liver enzymes should prompt an at least non-invasive assessment of fibrosis e.g. via elastography. However, in the end liver biopsies are still inevitable to reliably confirm subclinical graft injury for individualized immunosuppression guidance after adult liver transplantation.19. Liver biopsies came from our protocol biopsiy program , or from patients with a liver biopsy because of elevated liver enzymes. A participation in the protocol biopsy program was voluntary and offered to all liver transplanted patients without contraindications, e.g. dilated bile duct, thrombocytopenia etc., even when they were transplanted before 2008. Likewise, all patients with a liver biopsy because of elevated liver enzymes were asked for a participation in the biorepository.We included all adult liver recipients without a replicative viral hepatitis (HCV-RNA or HBs-Ag negativity) who underwent at least one liver biopsy and agreed to participate in our prospective liver allograft biorepository since 2008 (age at time of liver biopsy ≥ 18 years) as described recentlyThe study was approved by the Ethics Committee of Hannover Medical School, Hannover/Germany (protocol number 933 for project Z2 of comprehensive research center 738). Written informed consent was obtained from all subjects. All experiments were performed in accordance with relevant guidelines and regulations.No organs or tissues were procured from prisoners. All liver transplantations of patients in this study were performed in Germany, where organ procurement and allocation are organized by Eurotransplant and the German Organ Transplantation Foundation.Liver biopsies were performed percutaneously under local anesthesia. An approximately 5 mm portion of the needle biopsy was immediately preserved in Allprotect Tissue Reagent (QIAGEN) and then stored at − 80° C. The remaining cylinder was fixed in 4% neutral buffered formalin and embedded in paraffin wax.19. Sections of 2 µm thickness from liver allograft biopsies with a 17-gauge needle were stained with hematoxylin and eosin, elastic van gieson stain, periodic acid–Schiff stain, silver stain, Berlin blue stain and rhodanine stain. Histological examination and scoring for the rejection activity index (RAI)7, inflammation grade and fibrosis stage (Ishak score)40, central perivenulitis, portal microvasculitis, ductular reaction7, fatty liver disease41 and liver allograft fibrosis (LAF) score26 was performed by experienced liver pathologists in a blinded fashion.Histological grading and staging was performed as described recently7 as: portal tract inflammation ≤ 1, interface hepatitis ≤ 1, central perivenulitis ≤ 1, lobular/biliary inflammation/endothelialitis = 0, portal microvasculitis = 0, periportal fibrosis ≤ 3, any LAF score ≤ 1. At least moderate fibrosis was defined as: periportal fibrosis (Ishak F) ≥ 2 and/or any LAF score component ≥ 2.The histological criteria conducive to minimization of immunosuppression (HCMini) were defined according to the last Banff consensus documentBlood samples were preferentially taken at the day of admission before the performance of the liver biopsy or within the first 24 h after the liver puncture. Blood plasma was cryo-conserved at – 80 °C.19. The recipient plasmas were screened for the presence of HLA class I/II antibodies using mixed HLA antigen-charged polysterene beads , using a multichannel flow array . A specification of HLA antibodies in sera with a positive screening result was performed using class I/class II single-antigen beads . The tests were performed according to the manufacturer's instructions. The incidence of DSA positivity was analyzed using mean fluorescence intensity (MFI) threshold of 1,000 or more for the plasma antibodies against HLA and a positive match with donor HLA typing as recommended recently27. In case of multiple DSA, the highest MFI of all DSA is reported, but not the sum or the mean of MFI of all DSA. DSA, panel reactive antibodies (PRA) or crossmatch before transplantation are not part of the clinical work-up before liver transplantation at our center and were not available.DSAs were detected as described recently8. The M65 ELISAs were used according to the manufacturer’s instructions .Caspase-generated neoepitopes of cytokeratin-18 (CK18) were measured in cryo-conserved plasma as recently publishedThe other laboratory parameters (aminotransferases and IgG) were measured in the course of the routine clinical surveillance of the patients.42.RNA was isolated from cryo-conserved liver biopsy fragments, reverse transcribed into cDNA and subsequent gene expression analysis was performed as described recently19. The Mann–Whitney U test was used to compare quantitative data between two independent groups and the Kruskal–Wallis test with Dunn’s multiple comparison post hoc test for more than two groups. Fisher’s exact test, if possible, was used to compare contingency tables with two groups and the Chi square test was used to compare more than two groups. Spearman’s rank correlation coefficient (Spearman’s rho = SR) was used for correlation analyses.Statistical analysis was performed with SPSS version 25 and GraphPad Prism 5.01 software as described recentlyP-values below 0.05 (two-tailed) were considered statistically significant in all analyses.Further material and methods are listed in the supplementary information.Supplementary file1.


With the rapid technology development, sequencing the organelle genomes becomes feasible even for small laboratories. Besides, several large-scale genome projects such as the “Earth Biogenome Project,” the “Bioscan Project,” and “1000 Medicinal Plant Genome Project”, have started. We are witnessing an influx of animal mitogenomes, chloroplast genomes, and plant mitochondrial genomes. How can the journal Part B serve the scientific community better in the face of these new developments?To answer this question, we conducted a bibliometric analysis based on journals indexed in Web of Science during the period of 1980–2019. Using “animal” and “mitochondrial genome” or “mitogenome” as the query terms, we found over 4500 out of 49000 papers published on the scope of Mitochondrial DNA Part A and Part B combined. Using “plant” and “mitochondrial genome” as the query terms, we found 29 of 1400 papers published on Part B. Using “chloroplast genome” or “plastome” as the query terms, we found 1200 of 2250 articles published on Part B. Taking these numbers together; it suggests that Part B is the most productive journal for subjects on “animal mitogenome” and “chloroplast genome,” but not for “plant mitogenome.” Why is this, and what should we do then?https://www.tandfonline.com/action/authorSubmission?journalCode=tmdn20&page=instructions. Below we outline several of the most important changes.For announcement type of paper, the length is increased to 800 words, the limit for one phylogenetic tree remains the same.supplementary materials. This change will allow the authors to publish their work with sufficient technical details. Besides, the rapid communication will accept broad-sense resource papers such as those describing software tools and databases, as long as they are within the journal’s scope.For the rapid communication type of paper, the length is increased to a maximum of 2500 words with no limit for the numbers of tables and figures, and Following the growth in submissions the journal has seen in recent years, we have further streamlined the peer-review process. Associate Editors will take expanded responsibilities to assess submissions for their suitability for the journal through managing the external review process.We have also introduced a new Public Data Policy, requiring mitogenome sequence data to be made publicly available before manuscripts are submitted to the journal. This will ensure that results and data associated with published Part B papers is made available to the public as quickly as possible.Our new ‘scoop protection’ policy ensures that authors’ submissions will be protected from the date of their original submission, should another paper on the same mitogenome sequence be published while their paper is under evaluation in the journal.There are three issues we should take into consideration to address these questions. First, the mitogenomes differ significantly across kingdoms. The animal mitogenomes are usually a dozen kilobases long. In contrast, plant mitogenomes can be up to a few megabases long. It can be easy to describe an animal mitogenome in 500 words. Still, it is pretty tight to describe a chloroplast genome or plant mitogenome. Second, initially, Part B’s paper usually focused on the assembly, annotation, and phylogenetic classification of the genome. By using software tools such as MEGA, BEAST, MrBayes, etc., it is straight forward now to carry out various analyses such as distance calculation, diversity exploration, and phylogeny construction. The results are usually an integral part of a genome paper, and many authors would like to have these results published along with the genome. Last, the definition of “resources” has been broadened. New experimental protocols, software tools, databases, integrated analytical methods are all great resources. For these reasons, we made several changes. The detailed information can be found at By implementing these changes, we hope Part B will meet the ever-increasing needs of our authors to have their high-quality work rapidly disseminated.


The presence of donor-specific antibodies (DSAs) against HLA before kidney transplantation has been variably associated with decreased long-term graft survival. Data on the relation of pretransplant DSA with rejection and cause of graft failure in recipients of donor kidneys are scarce.  Patients transplanted between 1995 and 2005 were included and followed until 2016. Donor-specific antibodies before transplantation were determined retrospectively. For cause, renal transplant biopsies were reviewed. p < 0.01). One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years . One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years . One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years . In 80.5% of graft failures, a diagnostic renal biopsy was performed. The presence of pretransplant DSA (DSApos) increased the risk of graft failure within the first 3 months after transplantation (5.2% vs. 9.4%) because of rejection with intragraft thrombosis ( Pretransplant DSAs are a risk factor for early graft loss and increase the incidence for humoral rejection and graft loss but do not affect the risk for T cell-mediated rejection. The presence of donor-specific antibodies (DSAs) against HLA molecules is a risk factor for humoral rejection after kidney transplantation. The introduction of the complement-dependent cytotoxicity (CDC) test has been a major step forward in excluding high-risk donor-acceptor combinations . The CDCIn recent years, a number of other assays has become available which are able to recognize antibodies against HLA with a much greater level of sensitivity . The floThe presence of pretransplant DSA identifies patients which are sensitized to allogeneic HLA, e.g., by pregnancy, blood transfusions, or a previous transplantation. Therefore, pretransplant DSA may identify patients with both an increased risk for antibody-mediated rejection as well as T cell-mediated rejection . To dateWithin the Dutch National Profiling Consortium of Antibody Repertoire and Effector functions (PROCARE), pretransplant DSAs were measured retrospectively in all recipients of a kidney transplant in the period 1995–2005 in the Netherlands , 15. ThiIn this study, the pretransplant DSA data were combined with the clinical and renal histopathological data of our transplantation center and the impact of pretransplant DSA on the type of graft rejection and cause of graft loss was analyzed.This study included all 734 kidney transplantations performed between January 1995 and December 2005 at the Erasmus Medical Center in the Netherlands. The last follow-up date was January 1, 2017.The pretransplantation protocol used PRA assessment and CDC testing. A positive CDC crossmatch of the recipient with the potential donor, but not the percentage of PRA, was an absolute contraindication for transplantation. In every case of transplantation, the CDC crossmatch was negative with current and historic peak sera. PRA did not influence the medical policy regarding the type of induction therapy or subsequent immune suppressive medication used. All transplantations were ABO compatible.Bead assay defined DSA was not taken into consideration in the matching procedure within the period of patient inclusion. Informed consent for data collection and use of leftover sera was obtained from all subjects. Sera used for DSA determination were assessed within the larger cohort of the PROCARE study comprising all Dutch kidney transplant centers . RecipieThe baseline and clinical follow-up transplantation data were retrieved from the Netherlands Organ Transplant Registry (NOTR), which was over 99% complete for our center at time of this study. Graft failure is defined as loss of kidney function when the patient returns to dialysis or receives a retransplant. For the analysis of rejection-free survival and rejection-related graft failure, the recipients who died with a functioning graft (141 patients) were censored at the time of death and patients lost to follow-up censored at the time of the visit to the outpatient clinic . Primary nonfunction of the graft is defined as the persistent need for dialysis after transplantation or the absence of graft function in preemptively transplanted end-stage renal disease patients.Time from transplantation to the first renal biopsy showing rejection was taken to calculate rejection-free survival.n = 10), and for statistical analysis, these cases were combined with the humoral rejections.The renal biopsies were performed because of progressive loss of graft function and scored in accordance with the Banff criteria 2015. Rejection episodes were classified as cellular (T cell-mediated rejection), humoral (antibody-mediated rejection), or mixed-type rejection. The latter type of rejection presented a small group . Plasmapheresis was rarely performed, and in case of rapid declining graft function without sufficient response to therapy, antithymocyte immunoglobulin was given.The presence of HLA antibodies (HLA-Abs) in the pretransplant sera was assessed as described previously . In brieThe number of DSAs per individual, the maximum MFI of DSA, and the cumulative MFI of DSA were calculated and used for the relation with transplant outcome.U test for continuous variables. All p values were 2-tailed.Differences in patient, donor, and transplant characteristics between the DSA-positive and -negative group were assessed by Fisher's exact test for categorical variables and Mann–Whitney Death-censored graft loss and incidence of rejection were assessed by Kaplan–Meier analysis with log-rank statistics for difference between strata. All data were analyzed for the first 3 months, the first year after transplantation, and after the first year of transplantation, given the clear differences in clinical events early and late after transplantation.p value of <0.1 were considered for further analysis by stepwise forward regression to calculate hazard ratios and corresponding confidence intervals. pH assumption of variables was tested by visual inspection of log-minus log graphs and further tested by assessment of time-dependency using the Cox regression with time-dependent covariate module in SPSS. All variables met the demands of pH unless stated otherwise. Interaction terms that met statistical significance (p < 0.05) were included in the multivariate model. Normal probability plots were made, and presence of significant correlations was assessed. Absence of collinearity in the model covariates was formally assessed by calculating the variance inflation factor. Statistical analysis was performed with software IBM SPSS statistics 21.Univariate Cox proportional hazards analysis was used to identify clinical and demographic variables associated with rejection and graft survival. Variables with a p=0.04). Death with functioning graft occurred in 141 patients, and in 195 cases out of the 242 death-censored graft failures (80.5%), a diagnostic renal biopsy was performed. Graft failure because of rejection was diagnosed in more than half of these cases, with a significantly higher frequency of ABMR-related graft failure in the DSApos group .The clinical and transplant characteristics of recipients and kidney stratified according to the presence of pretransplant DSA (DSApos versus DSAneg recipients) are given in p=0.03). This was caused by a significant higher incidence of primary nonfunctioning grafts in which the majority could be attributed to acute rejection with severe arteritis. In 7 out of 10 cases from the DSAneg group, but none of the cases of the DSApos group, this was accompanied by tubulointerstitial rejection (p=0.02). Instead, renal biopsies in the DSApos group frequently showed intra-arterial thrombi or thrombotic microangiopathy . The type of DSA  was not related to the incidence of ABMR (data not shown). In addition, the average number of DSA's per individual, the maximum MFI of DSA, and the cumulative MFI of DSA were not related to late rejection.The presence of preexistent DSA significantly increased the incidence of ABMR after kidney transplantation  with a cUnivariate and multivariate analyses showed that the presence of pretransplant DSA was significantly associated with ABMR, with a significant interaction between DSA presence and receiving a deceased donor kidney .In contrast, the long-term incidence of TCMR (patients more than 12 months after transplantation) became close to zero 5 years after transplantation. The cumulative hazard of TCMR in the patient groups with or without pretransplant DSA was overlapping .p=0.02). The graft loss because of ABMR was significantly increased in den DSApos recipients (p=0.01, The group of patients with pretransplant DSA had a significantly decreased death-censored graft survival . Graft s p=0.01, . After fMultivariable analysis showed that age of donor, recipient age, and the interaction term for pretransplant DSA and donor type were significantly associated with the long-term risk of graft failure . The typIn contrast, graft failure because of TCMR was most frequent in the first years after transplantation but became increasingly rare thereafter and was not influenced by the presence of pretransplant DSA .The results of this study show that pretransplant DSA significantly increase the incidence of ABMR and ABMR-related graft failure but not of TCMR.The short-term consequences of pretransplant DSA after kidney transplantation are an increase in severe vasculitis with thrombosis leading to graft loss, in particular in recipients of a deceased donor kidney. Our data also indicate that pretransplant DSA can result in intrarenal thrombosis without vasculitis. However, we cannot exclude the possibility of the sampling error, and isolated vasculitis lesions may have been present. Nevertheless, pretransplant DSA are clearly associated with intragraft thrombosis early after transplantation, which obviously contributes to graft loss. Three months after transplantation, the combination of vasculitis with multiple thrombi was not observed anymore. Graft loss associated with pretransplant DSA was predominantly observed in recipients of a deceased donor kidney. This may be caused by increased immunogenicity of the deceased donor kidney expressing more HLA and adhesion molecules on endothelial and tubular cells in combination with an increased vulnerability for severe vascular damage –21. In lPretransplant DSAs were predominantly found in patients, which were sensitized by a previous transplantation and therefore more frequently found in recipients of a deceased donor kidney. It is to be expected that allosensitization of T cells is also increased in the DSApos patients resulting in patients more prone to TCMR after transplantation. However, the incidence of TCMR was not affected by the presence of pretransplant DSA in this study and was previously even reported to be decreased . This maSome publications have reported on the outcome of routine kidney allograft biopsies in patients with preexistent DSA and described histopathological signs of antibody-mediated rejection, specifically microvascular inflammation, in over 50% of all kidney allograft biopsies at 12 months . In addiAfter the first year of transplantation, pretransplant DSA significantly increased the risk for ABMR and was associated with decreased overall graft survival. The latter was largely due to an increase in ABMR-related graft failure with a significant interaction between pretransplant DSA and deceased donor kidney. This is in accordance with a previous publication of the PROCARE study which showed a stronger negative effect of pretransplant DSA on deceased donor graft survival . The sigOf note, this specific interaction was not confirmed in a recent publication from Germany reporting about a large number of kidney transplantations with or without pretransplant DSA . HoweverIn this study, we were unable to identify a relation between the MFI value of the DSA and the risk for ABMR or graft loss. Other groups did find a significant relation between a high MFI value and the risk for ABMR in recipients receiving a deceased donor kidney , 29. HowThe relative contribution of TCMR to graft loss was almost absent beyond 5 years after transplantation. These findings are in line with several reports identifying ABMR as a major cause of late graft loss –32.A limitation of our study is the lack of information on newly formed DSA after transplantation. Also, within the period of transplantation, few patients received induction therapy and the data are therefore difficult to extrapolate to the current practice. However, this also offers an advantage as our findings are not obscured or biased by the use of different regimes of induction therapy. Clearly, within the current era of transplantation, the potential deleterious effect of DSA is recognized, and a recipient preferably does not receive a kidney in the presence of DSA or receives an intensified induction therapy with at least T cell depletion. However, our data also indicate that the majority of patients with pretransplant DSA do not have an increased risk for ABMR-related graft loss.Nevertheless, kidney transplantation in the presence of DSA should be avoided if possible. The increased risk for early graft loss, particularly in case of a deceased donor kidney, should be balanced against a possible substantial increase in waiting time.Another limitation is that, during the study period, the clinical practice of taking a diagnostic renal biopsy, the definition of humoral rejection, and treatment schedules all have changed. These changes could not be adequately accounted for, and therefore, their effect on the results of our study is essentially unknown.The presence of pretransplant DSA increases the risk for ABMR and graft loss but is not associated with a changed incidence of TCMR. These findings are important for risk stratification of patients awaiting a donor kidney and the use of desensitization protocols.


The use of buccal mucosa grafts in urethral reconstruction for complex anterior urethral strictures has gained popularity over the years with very good outcomes reported in literature. We report on the successful repair of a complex anterior urethral stricture in a 14-year-old boy following catheterization using this method at the Komfo Anokye Teaching Hospital. The aim is to describe the method of dorsal onlay oral mucosa graft urethroplasty and to review the literature. Urethral strictures in children are uncommon. They may present as lower urinary tract symptoms or acute urine retention . The cauRetrograde urethrography (RUG) with or without micturating cystourethrogram (MCUG) is the gold standard confirmatory test. In some situations, urethroscopy may be required for confirmation and treatment. Penile and long bulbar urethral strictures are generally regarded as complex strictures. This is because they do not lend themselves to simple excision and primary anastomosis .They require tissue transfer in the form of grafts, flaps, or staged repair. Since the 1990s, the use of the buccal mucosal grafts to repair such complex anterior strictures has gained enormous popularity and acceptance due to its reproducibility and durable long term success rates of 85% and beyond –8.Of significant debate is whether to place the graft ventrally or dorsally on the urethra. The dorsal approach seems cumbersome but the outcome is definitely better due to the mechanical support offered to the graft by the ventral aspect of the corporeal bodies –11.We report on the successful application of the use of the oral mucosa graft dorsal onlay urethroplasty technique as described by Guido Barbagli  in a 14-A 14-year-old boy had laparotomy for a mesenteric cyst 7 years ago during which he had a transurethral bladder catheter passed. Few weeks after discharge from the hospital, he began to experience difficulty in passing urine. It started as straining at urination with a poor stream which worsened over time. Over the cause of the past 7 years, he has had multiple dilatations which did not resolve the problem until a suprapubic catheter was passed for him a year ago and referred to see the urologist at KATH.On examination, he had normal growth for his age. He had a two-way suprapubic catheter in situ with indurations along the penile and bulbar urethra.A retrograde urethrogram demonstrated a partial narrowing of the penile and bulbar urethra .A routine urine examination was done which revealed leukocytosis for which reason a urine culture was requested that isolated Klebsiella species sensitive to only amikacin.A one-week course of parenteral amikacin was given after which a repeat urine culture was negative.Other tests done included a full blood count and kidney function tests which were all within normal ranges. Thus, patient was scheduled for urethroplasty.Patient positioning was the standard lithotomy with padding of the pressure points with administration of general anaesthesia with oropharyngeal intubation.A 7 cm × 2 cm lower lip oral mucosa graft starting from the right lateral angle of the mouth extending to the left cheek Figures  was harvA midline perineal incision was made through the skin, subcutaneous tissues, and fascia. The perineal muscles were divided in the midline and carefully dissected away from the urethra. The urethra was then circumferentially mobilized off the corporeal bodies from the bulbar to the penile urethra going beyond the strictured segments as defined by a catheter passed per the urethral meatus and a bougie dilator proximally from the cystostomy wound by sharp dissection with fine scissors.The urethra was then rotated 180° bringing the dorsal aspect ventrally with the aid of sutures placed proximally and distally on the dorsal aspect of the urethra . A dorsaThe oral mucosa graft was quilted to the ventral aspect of the corporeal bodies, and the left edge of the urethral plate was sutured to the left lateral aspect of the graft in interrupted fashion using vicryl 4/0 Figures  and 7.A size of 16Fr urethral catheter was advanced into the bladder, and the contralateral edge of the urethral plate was then sutured to the right edge of the oral mucosa graft over it .Postoperatively, a size of 16Fr catheter wound drain was left in situ and closed wound dressing done . A spigoThe donor site healed within 7 days without any complications with no special dressing .Both the suprapubic and urethral catheters were removed 4 weeks postoperatively when RUG showed no urinary extravasation . PatientPoor quality latex catheters are known to cause extensive anterior urethral strictures mainly from allergic reactions and urethritis –15.Repeated minimally invasive treatment options like dilatation and direct vision internal urethrotomy (DVIU) have not been found useful in the management of complex anterior strictures  as happeThe management of such complex strictures relies on tissue transfer techniques or staged urethroplasty , 18.Staged urethroplasty beyond the high revision rates has the tendency to increase morbidity and financial burden and has challenges with psychosocial adjustment , 19. In The use of genital fasciocutaneous flaps is a viable option for managing such complex anterior urethral strictures in a single stage . It alsoBuccal mucosa has become the graft material of choice in the management of complex anterior urethral strictures. This is because it is readily available and easily harvested from the cheek or lip, allowing for the scar to be hidden with low oral morbidity. It is also hairless, with a thick elastin-rich epithelium, which makes it tough yet easy to handle and a thin and highly vascular lamina propria, which facilitates graft take and survival . We chosThe use of skin, bladder, lingual, and rectal mucosa for onlay urethroplasty has also been reported in literature when certain conditions preclude the use of buccal mucosa .Buccal mucosa grafts for dorsal onlay urethroplasty as first described by Barbagli is a versatile technique as it obviates a lot of the challenges associated with the ventral onlay approach such as sacculations, diverticulum formation, and troublesome postvoid dribbling due to inadequacy of the graft support . This isHowever, the abundant corpus spongiosum of the proximal bulbar urethra lends adequate support to a ventrally placed graft as opposed to strictures involving the distal bulbar and penile urethra, in which the dorsal approach is preferable due to the paucity of the corpus spongiosum , 28.The success rate of buccal mucosa graft urethroplasty has been estimated in literature to range from 80 to 95% with the dorsal onlay approach having a slight advantage over the ventral approach –31.We chose the oral mucosa graft dorsal onlay urethroplasty technique for this patient because it is fairly simple to harvest the graft with little morbidity at the donor site and has excellent cosmesis with durable long-term success rate.This patient had no major complications following the surgery and has a good stream of urine with a peak flow rate of 24mls/s after one year of follow-up.The oral mucosa graft dorsal onlay urethroplasty for complex anterior urethral strictures is applicable to complex anterior urethral strictures in children. The technique is simple to perform with minimal morbidities and has good outcomes.


CNS Oncology. 2020 promises to be an exciting year and we look forward to growing the reach and audience of the journal as we enter the new decade. However, before we start this new period, I would like to look back over the past year and our highlights from 2019.To all of our readers, Happy New Year and welcome to the first issue of Volume 9 of CNS Oncology.Our most-read article of the year comes from Ugonma Chukwueke and Patrick Wen, both of the Dana-Farber Cancer Institute , and reviews the recommendations of the Response Assessment in Neuro-Oncology (RANO) working groups . Distincet al. , describing their study evaluating whether circulating tumor DNA could facilitate genomic interrogation in patients with primary brain tumors [Next up, we have a preliminary communication written by David E Piccioni n tumors . ContrarAnother 2019 article that has hit our most-read list is an editorial that evaluates the benefits of whole-brain radiation therapy versus stereotactic radiosurgery for the treatment of brain metastases . Written®, an investigational therapeutic medical device that is being developed for the treatment of both pediatric and adult glioblastoma. With feasibility studies in both American [Finally, we have a set of three articles each discussing the Nativis VoyagerAmerican  and AustAmerican  populatiAmerican .To our editorial board, we thank you for your continued input, be it in an ambassadorial, advisory or authorship role. Led by our senior editors Alba Brandes  and Henry Friedman , our international board provides valuable assistance and advice that facilitate the publication process; we look forward to working together in the coming year.On this note, if you are interested in joining our editorial board or wish to provide feedback or suggestions for the journal, please do not hesitate to get in touch; we value any and all input that can contribute to the growth and development of the journal.To help further spread the work we publish, we continue to utilize the power of social media and share new work through platforms such as Twitter and LinkedIn to ensure articles can be shared with the largest possible audience; if you do not already, we welcome you to follow us on Twitter (@fsg_cns) or join our oncology group on LinkedIn, Future Science Group Oncology. In using social media, it is our aim to reach all relevant stakeholders in the field of CNS oncology – including researchers, clinicians, charities, patients, academics/educators and patient advocates, just to name a few.Our partnerships with the sites Oncology Central  and NeurVideo Journal of Biomedicine [I am also excited to announce our partnership with the medicine . Now, oumedicine . Follow Our readers remain central to the success of our journal and we welcome any feedback. Please do not hesitate to contact us with any suggestions for what you would like to see featured or any article proposals of your own. We welcome a wide range of unsolicited article proposals so please do get in touch for more information.I would like to finish by once again thanking all of the authors and reviewers who helped to make Volume 8 possible; we hope to continue to build on this success and look forward to another great year.


Composite graft as a reconstructive therapy option has limitations in size so that it is easily necrotic. Deferoxamine administration has been associated with increased neo-vascularity in wounds. We aimed to compare the administration of deferoxamine and Platelet-Rich Plasma (PRP) injection in a composite graft in rabbits.Thirty New Zealand rabbits were divided into three groups; the control group, the deferoxamine group, and the PRP group. The composite graft with a diameter of 2 cm was taken and replanted after rotating it 180°. The mean graft viability and the mean number of capillaries were evaluated on day 7 (POD 7) by macroscopic and histological evaluation using Hematoxylin-Eosin staining.p = 0.21), the mean survival rate in the control, deferoxamine, and PRP groups reached a significant level with p-value of 0.006 .While the mean number of capillaries was not significantly different in control, deferoxamine, and PRP groups (Deferoxamine group had the highest number of capillaries, but had the lowest survival rate. In the PRP group, it had the lowest number of capillaries, but had the highest survival rate. •Composite grafts yield better results than skin grafts in plastic and reconstructive surgery.•The failure rate of composite graft is quite high due to limitations of re-vasculature.•The usage of deferoxamine might have a beneficial effect on increasing the graft survival. Composite grafts yield better results than skin grafts in discrepancies in color and texture at the donor site, causing less scar contracture, because more tissue structure is provided by transferring 2 or more different tissue types. However, the composite graft has limited graft viability when the recipient defect is more than 1.5 cm in diameter [With the limitation of re-vasculature, the failure rate of composite graft is quite high . AngiogeHowever, the availability of PRP in local health services is an obstacle. Therefore, the use of alternative drugs needs to be considered. Deferoxamine as an iron chelating agent has been shown to have a wound healing effect ,7. We ai22.1Thirty male New Zealand rabbits, aged 9–12 months, weighing 2500–3000 g were isolated under standard conditions for 7 days. Rabbits that were sick, had an infection during the procedures, or died during the procedures were excluded from this study. The work has been reported in line with the ARRIVE guideline .2.2All experiments were performed in the Faculty of Veterinary Medicine of Universitas Airlangga. These experimental procedures were performed with the prior approval of the Medical and Health Research Ethics Committee of the Faculty of Medicine, Universitas Airlangga (2. KE.131.07.2018). Each rabbit was injured in the ear with a diameter of 2 cm, full thickness through and through. Then the composite graft on the rabbit ears consisting of skin tissue, sub cutis, and rabbit auricula cartilage in the form of a circle 1 cm in diameter was excised from the rabbit auricula, rotated 180°, and sewn back .Fig. 1CoIn group I, no subcutaneous injection was given. Group II was given subcutaneous 100 mg/kg deferoxamine injection , in all four quadrants outside the composite graft using a 1 cc injection syringe one day before the composite graft, post graft treatment procedure, and within the first 3 days. Group III was given PRP injection of 0.5 ml subcutaneous, post graft, and within the first 3 days. The viability of the graft was checked every day and the 7th day was assessed with Visitrak . On the 7th day, the skin was harvested for examination of vascular density.Composite graft was assessed for its viability based on macroscopic observations, the non-viable tissue was described by the presence of necrotic, darker color accompanied by dry tissue, such as tanning in the red marker areas in 2.3t-test was used to evaluate the capillary count between groups. For statistical analyses, a p-value of less than 0.05 was considered to be significant and 95% confidence interval was used in this study.Kruskal-Wallis and Mann-Whitney test were used to evaluate the graft survival between groups. Independent 3vs. deferoxamine vs. PRP reached a significant level . Further analysis showed that control vs. PRP, and deferoxamine vs. PRP differ significantly with p-value of 0.003 and 0.004, respectively , and deferoxamine vs. PRP . But, in contrast, control vs. PRP showed a significant difference   .Table 2C4Deferoxamine group has the lowest graft viability rate with only 63.8%, this is in contrary to the results obtained by Wang's  study, nThe viability of a composite graft depends on several factors, such as skin grafts. The viability of the composite graft comes from serum inhibition, re-anastomosis of blood vessels, and neovascularization . HoweverSeveral conditions that can reduce the viability of the composite graft, such as the pressure on the composite graft can damage the recanalization and neovascularization process, this is because the pressure makes the ischemic tissue, ischemic tissue releases inflammatory mediators that cause edema, moreover will cause vascular thrombosis . On the The high viability results were in the PRP group, which had a mean graft viability of 99.6%. This is in line with Choi's  study coPlatelet-rich plasma (PRP) contains various growth factors such as platelet derived growth factor (PDGF), transforming growth factor - β (TGF-β), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF), insulin-like growth factor (IGF1), endothelial cell growth factor (ECGF) . The groDespite having a low mean graft viability in the deferoxamine treatment group, the histological findings in the form of capillary count were the highest of the other groups, although statistically there was no significant difference. Thangarajah  states tThe results differed in the PRP group, the number of capillaries in the PRP group was the least, this could be due to the wound healing process running very well. Li  found a Our study is not without limitation. First, we did not measure level of the growth factor to see the effect of injection of deferoxamine and PRP on the composite graft. Second, we did not perform histological examination on the 3rd day after the graft as a comparison to prove that the PRP administration also increase the number of capillaries before experiencing a decrease in the number on the 7th day. Therefore, further study with larger sample is necessary to confirm our findings.5Administration of deferoxamine three days before grafting can significantly increase the viability of composite graft. Our study implies that the usage of deferoxamine might have beneficial effect on composite graft viability.Not commissioned, externally peer-reviewed.Not applicable.The authors declare that this study had no funding source.Rianto Noviady Ramli conceived the study and approved the final draft. Aditya Rifqi Fauzi drafted the manuscript. Agus Santoso Budi and Sitti Rizaliyana critically revised the manuscript for important intellectual content. All authors read and approved the final draft. All authors facilitated all project-related tasks.Not applicable.Rianto Noviady Ramli.Not applicable.No potential conflict of interest relevant to this article was reported.


The affiliation for the fourth author is incorrect. The correct affiliations are not indicated. Miguel D. Mahecha is not affiliated with #1 but with: Remote Sensing Centre for Earth System Research, Leipzig University, Germany and Helmholtz Centre for Environmental Research, UFZ, Leipzig Germany.


As the availability of kidneys for transplantation continues to be outpaced by its growing demand, there has been an increasing utilization of older deceased donors in the last decades. Considering that definition of factors that influence deceased donor kidney transplant outcomes is important for allocation policies, as well as for individualization of post-transplant care, the purpose of this study was determine the risks for death censored graft survival and for patient survival conferred by older age of the donor in the context of the age of the recipient and of risk factors for graft and/or patient survival. The investigation was conducted in a single-center cohort of 5,359 consecutive first kidney transplants with adult deceased donors performed on non-prioritized adult recipients from January 1, 2002, to December 31, 2017. Death censored graft survival and patient survival were lower in older donors, whereas graft survival was higher and patient survival was lower in old recipients. The analyses of combinations of donor and recipient ages showed that death censored graft survival was lower in younger recipients in transplants from 18 to 59-year old donors, with standard or extended criteria, but no difference in graft survival was observed between younger and older recipients when the donor was ≥ 60-year old. Patient survival was higher in younger recipients in transplants with younger or older donors. Two to six HLA-A,B,DR mismatches, when compared to 0-1 MM, conferred risk for death-censored graft survival only in transplants from younger donors to younger recipients. Pre-transplant diabetes conferred risk for patient survival only in 50–59-year old recipients, irrespectively, of the age of the donor. Time on dialysis ≥ 10 years was a risk factor for patient survival in transplants with all donor-recipient age combinations, except in recipients with ≥ 60 years that received a kidney from an 18–49-year old donor. In conclusion, the results obtained in this study underline the importance of analyzing the impact of the age of the donor taking into consideration different scenarios. Transplantation is considered the preferred treatment option for patients with end stage renal disease offering survival advantage over long-term dialysis, independently of patient age. As the availability of kidneys for transplantation continues to be outpaced by its growing demand, there has been an increasing utilization of older deceased donors in the last decades –6. The pWith the aim of reducing waiting time for older patients, the Eurotransplant Senior Program or “old for old” was implemented within the Eurotransplant kidney allocation algorithm. This program is based on regional allocation of kidneys from ≥ 65-year old deceased donors to ≥ 65-year old recipients and has been very successful in increasing the number of transplants in elderly recipients , 10–12.The negative impact on kidney graft outcomes of older age of donors and of recipients has been repeatedly reported in the literature , 13–15, Considering that definition of factors that influence deceased donor kidney transplant outcomes is important for allocation policies, as well as for individualization of post-transplant care, the purpose of this study is to investigate the risk for death censored graft survival and patient survival conferred by the combination of the age of the donor and the age of the recipient, along with other factors that may interfere with graft and/or patients survival, such as recipient sex, donor-recipient sex mismatch, pre-transplant diabetes, time on dialysis, cold ischemia time and HLA mismatches , 18–38.This is a retrospective single center study on data from 5,359 consecutive first kidney transplants with adult deceased donors performed in non-prioritized adult recipients, from January 1, 2002, to December 31, 2017.The kidney allocation was performed following the Brazilian national criteria, which is based on HLA-A, B, DR, with emphasis on HLA-DR, compatibility. Kidneys from donors under 18 years of age (not part of this study) are allocated to <18 year-old recipients. In addition, <18 year-old recipients also compete for adult donor kidneys . PatientN = 2,783), (2) 50–59 years with standard criteria (SCD) (N = 567), (3) 50–59 years with extended criteria (ECD), (N = 980), and (4) with 60 or more years . ECD was defined according to the United Network for Organ Sharing, i.e., donors with 60 or more years or with 50–59 years with at least two of these three criteria: history of hypertension, serum creatinine ≥1.5 mg/dL, or death by cerebrovascular accident. For two donors with 50–59 years it was not possible to determine whether they belonged to standard or extended criteria categories and they were excluded from any analysis concerning donor age.Among the donors, there were 3,066 (57.2%) males and 2,293 (42.8%) females. Four donor age groups were considered: (1) 18–49 years , 50–59 years  and ≥ 60 years .Among the recipients, there were 3,298 (61.5%) males and 2,061 (38.5%) females, 932 (17.4%) had pre-transplant diabetes, and 3,027 (57.1%) were on dialysis for ≥ 10 years. Three age categories were considered: 18–49 years  transplants. Concerning HLA compatibility, 1,226 (22.9%) transplants were performed with 0-1 HLA-A,B,DR mismatches.P-value < 0.10 in the log rank test. Cases with any missing value were excluded. A two-sided P-value ≤ 0.05 was considered statistically significant.The endpoints analyzed were death censored graft survival and patient survival, during the first 5 post-transplant years. Analyses were performed with the GraphPad Prism® 5.0  and SPSS  . Graft and patient survival curves were constructed with the Kaplan-Meier method and compared with log rank test or Cox regression analysis. In the Cox regression analyses were included variables with p < 0.001) and patient (p < 0.001) survival, whereas no impact was observed regarding donor sex. Recipient's older age positively impacted death-censored graft survival (p < 0.001) and negatively impacted patient survival (p < 0.001). No significant differences were observed regarding recipient sex, although a tendency (p = 0.062) was observed toward a higher patient survival in female recipients. Donor-recipient sex mismatch had no influence on death-censored graft or patient survival. Cold ischemia time > 24 h and 2–6 HLA-A,B,DR mismatches impacted negatively on death-censored graft survival  whereas pre-transplant diabetes and time on dialysis ≥ 10 years had a negative impact on patient survival (p < 0.001 for both variables).The univariate analyses results are presented in p < 0.10 in the univariate analyses and the results are presented in p < 0.05 in the univariate analysis remained significant, whereas sex of the recipient and HLA-A,B,DR mismatches that presented borderline (0.05 > p < 0.10) significance in the univariate analysis were not significant in the multivariate analysis.The multivariate analysis included all variables with p = 0.78). Considering transplants from 18–49-year old donors as reference, graft survival was lower in transplants from 50–59-year old ECD (hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.23–1.86, p < 0.001) and from ≥ 60-year old donors  (p = 0.002). Considering these results, three age groups of donors  were considered in the remaining analyses.Death-censored graft survival did not differ between 18–49 and 50–59-year old SCD  . The difPatient survival was significantly lower in transplants from donors of any age group > 50 years, as compared to transplants from 18–49-year-old donors . The patp < 0.001) and ≥ 60 years , in comparison with recipients aged 18–49 years (p = 0.093), they were combined for the remaining analyses.Death-censored graft survival was higher in recipient aged 50–59 years  and ≥ 60 years , in comparison with recipients aged 18–49 years (p < 0.001), the three groups were maintained separately for further analyses.Patient survival was significantly lower in recipients with 50–59 years  and with 50–59-year old ECD . There was no difference, however, in the graft survival in younger and older recipients  when the donor was ≥ 60-year old.The results are presented in p = 0.40).The results are presented in p = 0.003)  .p = 0.003) and from ≥50-year old  donors  donors .Significantly lower 5-year patient survival in patients with ≥ 10 years on dialysis was observed in transplants with all donor-recipient ages combinations, except in the case of recipients with ≥ 60 years that received a kidney from a 18–49-year old donor. The survival curves and the risk conferred by ≥ 10 years on dialysis in each donor-recipient age combination are presented in In the current scenario of kidney donor shortage, the use of older donors is unavoidably and thus it is important define/quantify the risks conferred by the advanced donor age that could be useful for allocation matters and for individualization of post-transplant care.The purpose of this study was to assess the risks for death-censored graft survival and for patient survival conferred by older age of the donor in the context of the age of the recipient and of other possible or well-recognized risk factors for graft and/or patient survival. The investigation was conducted in a single-center cohort of 5,359 consecutive first kidney transplants with adult deceased donors performed on non-prioritized adult recipients from January 1, 2002, to December 31, 2017. The end-points were death-censored graft survival and patient survival in the first 5 years post-transplant.The univariate analysis showed that donor and recipient age influenced both graft and patient survival, cold ischemia time and HLA-A,B,DR mismatches had an impact on graft survival, and pre-transplant diabetes and time on dialysis influenced patient survival. All these associations, except for cold ischemia time, were confirmed in multivariate analyses.p = 0.062) in the univariate analysis, but this association was not significant in the multivariate analysis and thus was not further analyzed. We believe that our data do not allow a definitive conclusion about the influence of the sex of the recipient on patient survival. On the other hand, we did not find any indication for an impact of donor-recipient sex mismatch on transplant outcomes, corroborating the results of other studies  between 18–49-year old (77.5%) and 50–59-year old (75.4%) recipients, but was significantly lower (p = 0.002) in ≥ 60-year old recipients  in relation to 50–59-year old recipients.Considering the opposite effects of recipient age on graft and on patient survival, we also calculated the overall graft survival, i.e., graft failure defined as death of the patient or return to dialysis, in relation to recipient age (data not shown). The results showed that 5-year overall graft survival was not statistically different  recipients. The 5-year graft survival of 2–6 HLA mismatched transplants from these donors in younger recipients was 84.3%, in contrast with survivals of 90.2%, in 0-1 mismatched grafts in younger recipients, 93.7% in 0–1 mismatched grafts in ≥ 50-year old recipients, and 91.7% in 2–6 mismatched grafts in ≥ 50-year old recipients. The explanation for these results would be the more robust immune response of the younger recipient and the conclusion would be that mismatched grafts should be avoided in younger recipients. This subject deserves further analyses, not only to confirm these results but also to investigate which kind of HLA mismatch should be considered. For instance, would avoiding HLA-DR mismatches be sufficient?Pre-transplant diabetes conferred a significant risk for the survival of 50–59-year old recipients, both in transplants from 18–49-year old donors (HR 2.24) and from ≥ 50-year old donors (HR 2.43). In 18–49-year old recipients, the survival of patients with pre-transplant diabetes was slightly inferior but the difference did not reach statistical significance, probably because of the lower number of diabetic patients in this age group. On the other hand, among ≥ 60-year old recipients, no difference in patient survival was observed between cases with or without pre-transplant diabetes. The explanation for this finding could be that most patients with more severe diabetes-related comorbidities could not survive long enough to reach the transplant because of increased mortality in the waitlist.The association of longer time on dialysis and inferior patient survival has already been repeatedly reported in the literature –31. In tIn summary, the main results of our study were: (1) association of increased age of the donor with lower graft and patient survivals; (2) association of increased age of the recipient with higher graft survival and with lower patient survival; (3) no difference in graft survival between transplants in younger and older recipients when the donor was ≥ 60-year old; (4) impact of HLA mismatches on death-censored graft survival only in transplants from younger donors to younger recipients; (5) association of pre-transplant diabetes with lower patient survival only in 50–59-year old recipients; (6) association of time on dialysis ≥ 10 years with lower patient survival in transplants with all donor-recipient ages combinations, except in recipients with ≥ 60 years that received a kidney from a 18–49-year old donor.This study has the limitation of being a single-center retrospective study in a relatively small cohort of 5,359 kidney transplants and with a limited number of factors that could be analyzed. In addition, some important factors could not be included, as the PRA (panel reactive antibody) because different methodologies for antibody determination have been used during the period covered by this study, socioeconomic variables, which are especially relevant in developing countries , 44 and In conclusion, this study has disclosed interesting interactions between age of the donor, age of the recipient and other factors that influence the survival of the graft and of the patient. Future multicentric studies, with large number of transplants, are warranted to further explore the impact of combinations of donor age with other risk factors to better understand and predict the impact of the age of the donor on kidney transplant outcomes.gerbase@igen.org.br.The datasets generated for this study will not be made publicly available as the data are from a governmental state registry of transplantation data. Requests to access these datasets should be directed to Maria Gerbase-DeLima, Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.MG-D, KM, RM, FM, HT-S, and JM-P conceived and designed the study. MG-D and KM analyzed the data. MG-D and KM wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Introduction: Preoperative estimation of graft parameters can be useful while using hamstring grafts in knee ligament surgeries. Anthropometric parameters may be an easy way to predict the length and diameter of hamstring tendons. A prospective study was conducted to find the correlation between different anthropometric parameters and activity level of the patient on the length and diameter of the graft. Separate regression equations for males and females were also derived for easy prediction. Methods: Data were obtained from 95 patients who underwent arthroscopic anterior cruciate ligament reconstruction with autologous hamstring tendon graft. Variables studied were age, sex, height, weight, body mass index (BMI), thigh circumference, thigh length, Tegner activity level, diameter (double and quadruple) and length of semitendinosus tendon graft. Results: Height of the patient had strong correlation with graft length , double diameter  and quadruple diameter . Weight of the patients had strong positive correlation with graft length  and quadruple diameter . Thigh length was found to be positively correlating with graft length , double diameter  and quadruple diameter of graft . BMI and thigh circumference of the patients were not found to correlate with graft size. Male patients were found to have longer semitendinosus graft and larger double and quadruple diameter of the graft. There was no association between the Tegner activity scale and graft size. Regression equations between graft length and quadruple diameter and the anthropometric parameters are also derived. Conclusion: Height, weight and thigh length are useful anthropometric parameters in the prediction of hamstring tendon size. However, the patient’s Tegner activity level was not found to be associated with size of the hamstring tendon. Multiple graft choices are available for reconstruction of anterior cruciate ligament (ACL) , 2. HamsA total of 95 patients  undergoing arthroscopic ACL reconstruction with ipsilateral autologous hamstring grafts, between January 2017 to October 2018 were included in the study. Patients with medial side knee injury or previous fractures around the knee were excluded. Patients with atrophy of contra-lateral thigh muscles due to any other pathology were also excluded. All patients were operated by the same surgeon. Preoperatively, variables studied were age, sex, height, weight, BMI, thigh circumference , thigh length , and Tegner activity level before the injury. Intra-operatively, semitendinosus graft was harvested through a standard longitudinal incision over pes anserinus after removing all of its extensions to gastrocnemius. The muscle tissue was then removed to skeletonise the tendon. Length of the tendon was recorded using scale over the graft preparation board between the point of its insertion and a point proximally where it starts to taper. The periosteum of anteromedial tibia harvested along with graft was not taken into account while recording graft length. The diameter of the double and quadruple looped tendon was measured using graft sizing block , considering the smallest diameter hole the graft could pass through.Statistical analysis was done using SPSS 24. BMI was calculated using the standard formula using height and weight. Descriptive statistics were obtained for all variables. Correlation between variables was studied using Spearman correlation. One-way ANOVA was used to study the association between sex, Tegner activity level and size of graft.Data were obtained from 95 patients with a mean age of 30.2 years . Demographic and anthropometric parameters are summarised in r = −0.06, p > 0.05, n = 74), double diameter  and quadruple diameter .Maximum patients (45%) had a Tegner activity level of 4 . There wr = 0.32, p = 0.004, n = 95).Correlation between graft size and height, weight and thigh length is summarised in Simple regression analysis revealed the following equations:Graft parameters of male patients and female patients were analysed separately. The correlation has been tabulated in Simple regression equations for male and female patients separately are as follows:For male patients:For female patients:r = 0.41, p < 0.001), double diameter  and quadruple diameter . A statistically significant correlation between weight and graft length  and quadruple diameter  was also noted, which has been reported in only a few studies [r = 0.44, p < 0.001), double  and quadruple diameter   . Thus, tCorrelation between Tegner activity scale and graft parameters was also evaluated, which has not been studied before. It is plausible that patients with higher activity levels may have larger tendon sizes. No significant correlation was found between the two.The study also highlights easy and reliable regression equations for pre-operatively determining the tendon lengths and quadruple diameter from these data.Separate simple regression equations for both male and female patients could also be formulated as stated below:The findings from this study suggest that to achieve a quadruple-diameter of 8 mm with isolated semitendinosus tendon, the patient should have 155 cm height, 58 kg weight and 40 cm thigh length. Thus considering gender-specific equations, a female patient should have 168 cm height and a male patient should have 60 kg weight and 38 cm thigh length to obtain a quadruple graft diameter of 8 mm. According to the dataset, thigh-length has proven to be a more useful predictor in case of males, whereas height was correlating more significantly in females. This can help to avoid the intraoperative complication of having a small hamstring tendon. The patient can be counseled well before surgery about the need for any other tendon as a graft option. This study is important because data on the correlation of anthropometric parameters from Indian population are limited , and no The ability to predict the graft parameters preoperatively is undeniably useful. Common anthropometric parameters like height have been proven useful in several studies. However, this study found the weight of the patient and thigh length also as good predicting parameters for quadruple diameter and length of the graft. Pre-injury Tegner activity level fails to prove a useful parameter. Male patients with height lesser than 155 cm, weight lesser than 58 kg and thigh length lesser than 40 cm are not only at risk of a thinner graft, but also the tendon length may be shorter needing alternative graft options.The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.