[Effects of bilobated superficial peroneal artery perforator flap in repairing two adjacent wounds of the fingers].

Objective: To investigate the therapeutic efficacy of bilobated superficial peroneal artery perforator flap in repairing two adjacent wounds of the fingers. Methods: A retrospective observational study was conducted. From January 2021 to January 2022, 15 patients with two adjacent wounds of the fingers who met the inclusion criteria were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 10 males and 5 females, aged 25 to 51 years. The area of single wound after debridement was from 2.5 cm×2.0 cm to 7.5 cm×2.5 cm. All the wounds were repaired by the bilobated superficial peroneal artery perforator flap from the lower leg. The single lobe area of bilobated flap was from 3.0 cm×2.0 cm to 8.0 cm×3.0 cm. The wounds in all the donor sites were sutured directly. During the operation, the number of resected flaps, the number and type of carried perforators were recorded, and the calibers of perforator and superficial peroneal artery and the length of vascular pedicle were measured. The survival of flap and the wound healing in the donor and recipient sites were recorded after operation. The recovery of donor and recipient sites were recorded during follow-up. At the last follow-up, the repair effect of flap was evaluated by the comprehensive evaluation scale, and the sensory function of flap was evaluated by the sensory function evaluation standard of British Medical Research Association. Results: During the operation, 15 bilobated flaps were successfully resected, carrying 36 superficial peroneal artery perforators, all of which were septocutaneous perforators with the caliber of 0.2-0.8 mm. The caliber of superficial peroneal artery was 0.4-1.1 mm and the length of vascular pedicle was 3-8 cm. After operation, all the flaps survived with no vascular crisis occurred, and the wounds in donor and recipient sites healed well. During the follow-up of 6 to 12 months, the color and texture of flaps were similar to those of normal tissue in the hand and the appearance of flap was good in 10 cases; the other 5 cases underwent the stage Ⅱ flap thinning and plastic surgery 6 months after operation due to the bloated appearance of flaps. There was only linear scar in the donor site of lower leg, with no obvious scar hyperplasia or pigmentation, and there was no obvious adverse effect on the sensation or motor function of the distal limbs in the donor area. At the last follow-up, the repair effect of flap of 15 patients was excellent in 11 cases and good in 4 cases, and the sensory function of the flap was evaluated as grade S2 in all cases. Conclusions: The bilobated superficial peroneal artery perforator flap has high proportion of septocutaneous perforator, and the blood supply is sufficient and reliable. Using this flap to repair two adjacent wounds of the fingers causes minimal damage to the donor area, only one group of blood vessels is needed to be anastomosed to repair two wounds, the difficulty of microoperation is reduced, and good flap repair effect and sensory function can be obtained.

[Curative effects of the superficial peroneal artery perforator flap carrying multiple perforators in repairing hand and foot wounds].

Objective: To investigate the curative effects of the superficial peroneal artery perforator flap carrying two and more homologous perforators in repairing hand and foot wounds. Methods: A retrospective observational study was conducted. From January to September 2021, 23 patients with hand and foot wounds combined with bone or tendon exposure who met the inclusion criteria were admitted to Suzhou Ruihua Orthopaedic Hospital, including 16 males and 7 females, aged 23 to 68 years. After expansion of the wound, the wound area was 3.0 cm×2.0 cm to 11.0 cm×4.0 cm. All the wounds were repaired with the superficial peroneal artery perforator flap carrying two and more homologous perforators. The area of the resected flap was 4.0 cm×2.0 cm to 12.0 cm×5.0 cm. All the wounds in donor areas were sutured directly. During the operation, the resection of the flap, the number and caliber of carried perforators, the caliber of superficial peroneal artery, the length of vascular pedicle, and the number of accompanying veins of the superficial peroneal artery were recorded. The survival of the flap, the occurrence of complications, and the wound healing in the donor area were observed after operation. The recovery of the donor and recipient areas was followed up. At the last follow-up, the comprehensive evaluation scale was used to evaluate the curative effect of flap repair, and the sensory grading scale was used to evaluate the sensory function of the recipient area. Results: Totally 24 flaps were successfully resected in surgical operations, carrying 56 superficial peroneal artery perforators in total, with the caliber of perforators of 0.20-0.70 mm. The calibers of all perforators carried by 7 flaps were smaller than 0.40 mm. Nineteen flaps carried 2 perforators each, 3 flaps carried 3 perforators each, 1 flap carried 4 perforators, and 1 flap carried 5 perforators. During the operation, the superficial peroneal artery was resected with a caliber of 0.40-1.50 mm, the vascular pedicle was 2-6 cm in length, and each superficial peroneal artery had two accompanying veins. After operation, all the flaps survived smoothly, no vascular crisis or distal necrosis occurred, and the wounds healed well in the donor area. During the follow-up of 6 to 10 months after operation, the color, texture, and elasticity of the recipient area were good. Among them, 6 recipient areas were thinned and reshaped because of bloating. There was only linear scar and no obvious scar hyperplasia or pigmentation in the donor area, without significant change in sensory or motor function. At the last follow-up, the curative effect evaluation of flap repair was excellent in 22 flaps and good in 2 flaps, and the sensory function evaluation of the recipient area was grade S3 in 1 area and grade S2 in 23 areas. Conclusions: The superficial peroneal artery perforator flap with two and more homologous perforators has sufficient and reliable blood supply and is effective in repairing hand and foot wounds. It provides an ideal solution for the clinical problem in which the original operation scheme is abandoned due to the existence of only multiple slender perforators of caliber smaller than 0.40 mm, and only a single perforator in the operative field that cannot satisfy the needs of the flap blood supply and recipient area.

[Morphological study on the transverse branch of lateral femoral circumflex artery based on digital subtraction angiography].

Objective: To summarize the morphological characteristics of the transverse branch of lateral femoral circumflex artery (LFCA) using digital subtraction angiography (DSA) and explore its clinical significance. Methods: A retrospective observational study was conducted. From October 2020 to May 2021, 62 patients with soft tissue injuries in the extremities were hospitalized in Suzhou Ruihua Orthopedic Hospital, including 40 males and 22 females, aged from 20 to 72 years. DSA was performed in the lateral femoral region of patients before the anterolateral thigh flap transplantation, and in combination with imaging scale to observe and measure the general condition of the blood vessels and the occurrence (with the occurrence rate being calculated), source artery, location of the origin point, direction of course, and the location of the perforating point of the cutaneous perforator of the transverse branch of LFCA, and in addition to classify the morphological characteristics of the transverse branch. Results: DSA detection showed that the femoral artery, the deep femoral artery, and the branches of LFCA were clearly distinguishable in 62 patients. Transverse branches of LFCA were observed in 59 patients, including 52 cases with a single transverse branch, and 7 cases with double transverse branches. The occurrence rate of transverse branches was 95.2% (59/62). A total of 66 transverse branches of LFCA were observed, of which 3 originated from the deep femoral artery, and 63 originated from the LFCA. The origin point of the transverse branch was 6.5-12.7 cm away from the anterior superior iliac spine. The transverse branch which was approximately perpendicular to the long axis of the body, originated outwards, ran between the ascending branch of LFCA and the oblique branch of LFCA, and branched along the way, with the trunk running under the greater trochanter. The perforating point of the cutaneous perforator of the transverse branch was 8.0-18.0 cm away from the anterior superior iliac spine. In the classification of morphological characteristics of the transverse branch of LFCA, the most common type was the one that originated from the same trunk with other branches of LFCA, accounting for 50.0% (31/62), followed by the one that originated from the singular trunk of LFCA (12 cases) or deep femoral artery (3 cases), accounting for 24.2% (15/62); the special type accounted for 21.0% (13/62), including 7 cases of double transverse branches and 6 cases of the transverse branch originated from the same trunk with multiple other branches of LFCA; those with small/absent transverse branch only accounted for 4.8% (3/62). Among the above-mentioned common trunk relationship of two branches, those with shared trunk of ascending and transverse branches were most frequently observed, accounting for 77.4% (24/31); those with shared trunks of the transverse and oblique branches (5 cases) and the transverse and descending branches (2 cases) accounted for 22.6% (7/31) altogether. Conclusions: A high incidence rate of the transverse branch of LFCA is observed through DSA. The transverse branch originates from the lateral femoral artery approximately perpendicular to the long axis of the body, mainly from the same trunk with another main branch of LFCA, especially the ascending branch. This positioning analysis can provide an important reference for the design and resection of anterolateral femoral flaps.

[Clinical effects of anterolateral thigh flap with blood supply source of medial femoral perforator in repairing the wounds on extremities].

Objective: To investigate clinical effects of anterolateral thigh flap with blood supply source of medial femoral perforator in repairing the wounds on extremities. Methods: A retrospective observational study was conducted. From October 2018 to June 2021, Suzhou Ruihua Orthopedic Hospital admitted 12 patients (11 males and 1 female, aged 24-64 years) who met the inclusion criteria, and did not have the lateral circumflex femoral artery during anterolateral thigh flap resection, or changed to medial femoral perforator as a source of blood supply due to small perforator to repair the wound with flap transplantation. The wounds were on the upper limbs in 7 cases and on the lower limbs in 5 cases. The wound area after debridement was 8.0 cm×5.0 cm-24.0 cm×6.5 cm, and the applied flap area was 9 cm×6 cm-25 cm×7 cm. During transplantation, the perforating branch or source artery of the flap was anastomosed end to end with the vascular pedicle of the recipient area. Subcutaneous beauty suture was performed on all the donor wounds. After operation, the survival of the flap and vascular crisis were observed; and the wound healing at the donor site was observed. During follow-up, the texture of the flap and complications at the donor site were observed. At the last follow-up, the effect of flap repair was evaluated by using the modified self-made comprehensive efficacy rating table. Results: After operation, all the flaps of patients survived without vascular crisis; the wounds in the donor site healed smoothly. During follow-up of 6 to 26 months, the flaps had good texture; only linear scars remained in the donor area without scar contracture, pain or other discomfort. At the last follow-up, the total score of flap repair effect of 12 patients was 75-95, with an average of 87, of which 5 cases were rated as excellent, 6 cases as good, and 1 case as fair, and the proportion of excellent and good patients was 11/12. Conclusions: The application of anterolateral thigh flap with blood supply from the medial femoral perforator to repair wounds on extremities is an alternative method for the vascular variations such as no descending branch, oblique branch, or small perforator of the lateral circumflex femoral artery during the resection of the anterolateral thigh flap. This operation has the advantages of simple operation, small trauma, and others, which effectively ensures the smooth operation.

[Anatomical characteristics and clinical application of anterolateral thigh perforator flap pedicled with oblique branch trunk of lateral circumflex femoral artery in the muscular septum].

Objective: To explore the anatomical characteristics of the anterolateral thigh perforator flap pedicled with oblique branch trunk of lateral circumflex femoral artery in the muscular septum and the clinical effect of this flap in repairing skin and soft tissue defects in the extremities. Methods: A retrospective observational study was conducted. From December 2020 to April 2021, 59 patients with skin and soft tissue defects in the extremities admitted to the Department of Hand Surgery of Suzhou Ruihua Orthopaedic Hospital met the inclusion criteria, including 46 males and 13 females, aged 20 to 81 years. The wound area after debridement ranged from 8 cm×5 cm to 38 cm×20 cm. According to the condition of the wound, the perforators in the anterolateral femoral region on the unaffected side were located by color Doppler ultrasound. The anterolateral thigh perforator flap with the oblique branch of lateral circumflex femoral artery as the source artery was designed, and the wound was repaired by unilateral flap or series combination of bilateral flaps (with the area of unilateral flap ranging from 7 cm×5 cm to 37 cm×11 cm). The wound of the donor site was sutured directly. The following items were recorded, including the number of perforators in the anterolateral femoral region marked before operation, the course characteristics of oblique branch trunk of lateral circumflex femoral artery and its perforators, and the number, origin, and type of perforators observed during operation, the flap repair mode and the flap harvest time. After operation, the survival condition of the flap, the wound healing time in the recipient site, and the suture healing in the donor area were observed, and the recovery of the donor and recipient areas was followed up. At the last follow-up, the sensation function evaluated by sensory rating scale of British Medical Research Association and two-point discrimination of the area transplanted with flap were recorded, and the improved comprehensive curative effect evaluation scale of flap was used to evaluate the repair effect of the flap. Results: A total of 156 perforators were marked in the anterolateral femoral region before operation, and 144 perforators were observed during the operation, of which 98 came from the oblique branch of the lateral circumflex femoral artery, and the first perforator of the oblique branch was the intermuscular septal perforator. Once formed, most oblique branch trunk of lateral circumflex femoral artery in the muscular septum could be divided into the deep branch and the superficial branch at the middle and upper 1/3 junction of the line between the anterior superior iliac spine and the lateral edge of the patella, the deep branch mainly ran in the muscle of vastus intermedius and vastus lateralis, and rarely developed the skin perforators, while the superficial branch mainly ran in the muscular septum between the rectus femoris and the vastus lateralis, and grew out the perforators to the proximal skin of the anterolateral femoral region. Fifty-six patients were repaired with unilateral flap and 3 patients with bilateral flap in series combination, with the harvesting time of the unilateral flap ranged from 9 to 99 min. Three patients developed arterial crisis within 48 hours after operation and survived after timely exploration; the flap of 1 patient developed necrosis 11 days after operation and was repaired by abdominal split-thickness skin graft; the other flaps survived smoothly. The wound healing time in the recipient area was 10 to 42 days after operation, and the sutures in the donor area healed well. During the follow-up of 6 to 10 months, 8 patients underwent thinning and plastic surgery 6 months after operation because of bloating in the flap transplantation area, while the other patients had a good shape of the flap transplantation area, with no deep tissue infection such as osteomyelitis, with soft texture, good elasticity, no pain, and good blood circulation; all the donor areas were left with linear scars, normal blood circulation in the distal extremities, no limitation of knee joint motion or quadriceps muscle strength. At the last follow-up, the sensation function was restored in the flap transplantation area of the affected limb, including 14 cases of S1 grade and 45 cases of S2 grade; there was only one point of two-point discrimination; the curative effect evaluation of flap repair included excellent in 24 cases, good in 35 cases, and general in 3 cases. Conclusions: The anterolateral thigh perforator flap pedicled with oblique branch trunk of lateral circumflex femoral artery in the muscular septum has the advantages of relatively concealed donor area, large cutting width, and simple operation during surgery. It protects the donor area to the greatest extent while repairing skin and soft tissue defects in the extremities, and is a useful supplement to the classic anterolateral thigh perforator flap.

NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia.

A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m-2, 30.7 mg m-2 and 44.1 mg m-2, respectively. The outcomes did not differ significantly among the different genotypes.

Unrelated cord blood transplantation for thalassaemia: a single-institution experience of 35 patients.

Our study was designed to prospectively determine whether or not unrelated cord blood transplantation (CBT) can produce outcomes comparable to related donor transplantation for children with ß-thalassaemia. In 35 patients, 40 transplants were performed between October 2003 and September 2009. HLA matching at enrolment was 6/6 (n=8), 5/6 (n=16), 4/6 (n=27), or 3/6 (n=1) by low-resolution HLA-A, -B, and high-resolution DRB1. These patients received non-manipulated grafts without ex vivo expansion or T-cell depletion. The median number of nucleated and CD34+ cells infused was 7.8 × 10(7)/kg (range, 2.8-14.7 × 10(7)/kg) and 4.0 × 10(5)/kg (range, 1.7-19.9 × 10(5)/kg), respectively. The 5-year OS and thalassaemia-free survival after the first transplant were 88.3 and 73.9%, respectively. The cumulative incidence of TRM at 2 years was 11.7%. Fourteen patients developed chronic skin GVHD. Thirty patients were alive and transfusion-independent with a Lansky performance score ≥80% achieved between 6 and 76 months post transplant (median, 36 months). These data compare acceptably with the survival rates of related-donor BMT for thalassaemia and suggest that patients without an available HLA-compatible sibling but who have well-matched unrelated donors should also be considered for CBT.

Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma.

We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27-64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504-2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6-4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4-12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87-12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC.

Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia.

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

The experience of cancer-related fatigue in Taiwanese children.

The purpose of this study was to describe the experience of cancer-related fatigue in children of different ages in Taiwan. A total of 17 children with different stages of cancer were interviewed. The methods of data collection included interviews, participants' observations, medical chart reviews and the researcher's reflexive journals. Data were progressively analysed by using qualitative data analysis method throughout the process of data collection. The results indicated that children in all age groups used the word 'tiredness' or 'weary' instead of 'fatigue'. Patients in different age groups described the fatigue differently. Younger children (<9 years) reported that fatigue affected their ability to participate in physical activities. Children aged 10-12 years described fatigue as extreme tiredness that affected their daily lives both physically and psychosocially by altering their daily routine and school attendance and performance. Adolescents described fatigue as unrelievable tiredness that differed from normal tiredness and had a great impact on physical and psychosocial aspect, particularly altering their future life plans and self-performance. This study shows that the definition and impact of fatigue differs among children by age group. Defining and understanding the effects of fatigue can help clinicians assess fatigue and implement effective strategies to alleviate it.

Evaluation of readmission in children receiving allogeneic hematopoietic stem cell transplantation: an institutional experience.

BACKGROUND: Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased potential of graft-versus-host disease. We sought to ascertain whether the use of UCB transplantation for pediatric patients changed the rates of unscheduled readmission. METHODS: We analyzed the rate, causes, and evolution of hospitalization among patients receiving UCB versus matched sibling bone marrow. A retrospective analysis of the data from 54 patients who received a matched sibling hematopoietic stem cell transplantation (HSCT; n = 25; 46.3%) versus an unrelated cord blood transplantation (CBT; n = 29; 53.7%) was performed on subjects treated between 1998 and 2006. Patients who died before discharge (n = 4) were excluded from the readmission analysis. RESULTS: A total of 50 patients were recruited for the analyses. Their median age was 6.7 years (range = 0.2-17 years). The median duration of hospitalization was 18 days shorter in the sibling HSCT group than in the unrelated CBT group. There were 89 readmissions in 25 patients (50%): 49 readmissions (55%) in the related HSCT and 40 (45%) in the unrelated CBT cohorts. Forty-two percent of readmissions were due to infections. Mortality following transplantation in 10 patients (19%) included sepsis (n = 3), intracranial hemorrhage (n = 1), pulmonary hemorrhage (n =1), and relapse (n = 5). Seven patients received HSCT from HLA-identical sibling donors and three from a cord blood donor. CONCLUSION: For both groups, infection was the most common reason for readmission followed by graft failure and extramedullary relapse. Although the median hospital stay was shorter in the sibling donor group, some uncertainty exists as to whether the increased risk for readmission was related to proportionally more malignancies or to the severity of the illness. After HSCT, there was a frequent use of hospital resources: 46% of patients were hospitalized for a median of 11 days. The resulting health expenses seem to be useful, since 81% of subjects survived at 36-month follow-up.

Clinical factors associated with fatigue over time in paediatric oncology patients receiving chemotherapy.

The purpose of this study was to investigate the relationships between clinical factors (including haemoglobin value, chemotherapeutic agents, and corticosteroid use) and changing patterns of fatigue before and for the next 10 days following the start of a new round of chemotherapy in children with cancer. A prospective longitudinal design was used to collect data from 48 paediatric oncology patients who were about to begin a new round of chemotherapy and their parents. Fatigue levels were assessed using multidomain questionnaires with three categories of patient self-report (including 'General Fatigue', 'Sleep/Rest Fatigue', and 'Cognitive Fatigue') and four categories of parent proxy-report (including 'Lack of Energy', 'Unable to Function', 'Altered Sleep', and 'Altered Mood'). The findings suggest that fatigue from both patient self-report and parent proxy-report changed significantly over time. The major findings from this study are that patients have more problems with fatigue in the first few days after the start of a cycle of chemotherapy. Corticosteroid use and haemoglobin value were associated with significant increases in fatigue that were sustained for several days and reached the highest level of fatigue at day 5 for those receiving concurrent steroids. The association of chemotherapeutic agents with fatigue varied between patient self-report and parent report, but the type of chemotherapeutic agents used was not associated with most changes in fatigue.

Laser assisted ultrasound guided aspiration improves procedure time and reduces number of withdrawals.

This study evaluated the performance of in-vitro freehand aspiration of a simulated cyst with ultrasound aspiration guided by a newly designed laser assisted (LA) device. The LA device was equipped with an adjustable light source generating a sector light plane. This laser light plane was parallel to and overlapped the ultrasound acoustical plane, to help with needle positioning. Five operators randomly performed 30 freehand or LA ultrasound guided aspirations of a simulated cyst. The frequency was set at 8 MHz and depth at 4 cm. Procedure time and number of syringe withdrawals were statistically compared before and after using the LA device. Both experienced and inexperienced operators required significantly less time to perform the aspiration and had fewer syringe withdrawals when using the LA device. The LA device provides a reference plane in space, allowing the operator to more accurately position and adjust needle direction. Additional in-vivo testing is required to test the clinical practicability.

Cooperating mutations of receptor tyrosine kinases and Ras genes in childhood core-binding factor acute myeloid leukemia and a comparative analysis on paired diagnosis and relapse samples.

c-KIT mutations have been described in core-binding factor (CBF) acute myeloid leukemia (AML) at diagnosis. The role of c-KIT mutations in the relapse of CBF-AML is not clear. The role of CSF1R mutation in the pathogenesis of AML remains to be determined. We analyzed receptor tyrosine kinases (RTKs) and Ras mutations on 154 children with AML. Also, we examined the paired diagnosis and relapse samples in CBF-AML. CBF-AML accounted for 27% (41/154). c-KIT mutations were detected in 41.5% of CBF-AML at diagnosis (6 in exon 8, 10 in exon 17 and 1 in both exons 8 and 17) , FLT3-TKD 2.7%, N-Ras mutations 7.3% and K-Ras mutations 4.9%. FLT3-LM and CSF1R mutations were not found in CBF-AML. The mutations of RTKs and Ras were mutually exclusive except for one patient who had both c-KIT and N-Ras mutations. Eight of the 41 CBF-AML patients relapsed; four patients retained the identical c-KIT mutation patterns as those at diagnosis, the remaining four without c-KIT mutations at diagnosis did not acquire c-KIT mutations at relapse. Our study showed that 54% of childhood CBF-AML had RTKs and/or Ras mutations; c-KIT but not CSF1R mutations play a role in the leukemogenesis of childhood CBF-AML.

Transplantation of unrelated donor umbilical cord blood utilizing double-unit grafts for five teenagers with transfusion-dependent thalassemia.

To augment graft cell dose, we evaluated the safety of the combined transplantation of two partially HLA-matched umbilical cord blood (UCB) units. Five patients with transfusion-dependent thalassemia, median age 11.1 years (range 10-13.1), received 2 UCB units after myeloablative conditioning. Cord blood units were a 4/6-HLA-match or better with the recipient, and contained a minimum combined pre-freeze CD34 cell dose of 3.0 x 10(5)/kg. All patients engrafted at a median of 15 days (range 12-19). Four patients with durable trilineage engraftment showed acute grade I-III GVHD; none developed extensive chronic GVHD until the date of last contact. The median times to red blood cell transfusion independence and platelet engraftment were 32 and 49 days after transplant, respectively. With a median follow-up of 18.5 months (range 11-32), four patients transplanted with UCB from two different partially HLA-matched donors were transfusion-independent. Therefore, transfusion of two partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in long-term recipients of multiple transfusions for thalassemia.

CEBPalpha mutations in childhood acute myeloid leukemia.

CEBPalpha: mutations have been described in adult acute myeloid leukemia (AML) and conferred a favorable prognosis. However, CEBPalpha mutation has not been reported in children. We investigated 117 children with de novo AML using DNA PCR assay followed by sequencing for each PCR product. CEBPalpha mutations were detected in seven patients, four had FAB M2, two M1 and one M4. CEBPalpha mutations only occurred in patients with intermediate cytogenetics and not in 56 children with AML1-ETO, CBFbeta-MYH11, PML-RARalpha or MLL rearrangements. Five patients had mutations occurred in both N-terminal part and basic-leucine zipper (bZIP) domain, one had an N-terminal frameshift mutation and the remaining one had an inframe insertion in the bZIP domain. Cloning analysis on five samples carrying more than one mutations demonstrated one homozygous combined mutations and four heterozygous biallelic mutations. Four of seven CEBPalpha mutation(+) patients had cooperating mutations with FLT3-ITD or N-ras mutations compared to 27 in 109 CEBPalpha mutation(-) patients. Our results showed that CEBPalpha mutations occurred in 6% of childhood AML and most exhibited combined mutations in both N-terminal part and bZIP domain.

Analgesic effects of preincisional administration of dextromethorphan and tenoxicam following laparoscopic cholecystectomy.

BACKGROUND: Pre-incisional treatment with either N-methyl-D-aspartate (NMDA) receptor antagonists or non-steroidal anti-inflammatory drugs (NSAIDs) improves postoperative pain relief. This study examines the effect on postlaparoscopic cholecystectomy (LC) pain of a combination of dextromethorphan (DM), a NMDA-receptor antagonist, and tenoxicam, a NSAID, given preoperatively. METHODS: Eighty-eight ASA I or II patients scheduled for LC were entered into a randomized, double-blind study and randomly allocated to one of four groups. Controls received 20 mg (4 ml) of chlorpheniramine maleate (CPM) IM and 4 ml of normal saline (N/S) IV. Group DM received 40 mg of DM (containing 20 mg of CPM) IM and 4 ml of N/S IV. Group T were given CPM 20 mg IM, and tenoxicam 40 mg (4 ml) IV. Group DM + T were given DM 40 mg (containing 20 mg of CPM) IM, and tenoxicam 40 mg IV. All treatments were given 30 min before skin incision. Analgesic effects were evaluated by Visual Analog Scale (VAS) pain scores at rest and during coughing, at 1, 2, 4, 12, 24 and 48 h after surgery. The time to the first request for meperidine for pain relief, and total meperidine consumption, were recorded for 48 h after surgery. RESULTS: Compared to controls, patients given DM and DM + T first requested meperidine significantly later, had lower meperidine consumption, made fewer requests for meperidine, and had lower pain scores. There were significant differences between the DM + T and T groups at 2 and 4 h in both resting and incident VAS pain scores, the incidence of meperidine requests and the time to first meperidine injection. There were significant differences between groups DM and T at 1 h for resting pain and at 2 and 4 h for incident pain. Except for a significant difference in the incident pain score 1 h after surgery, there were no other differences in pain scores between the DM and DM + T groups. Neither synergistic nor antagonistic interaction was observed between DM and tenoxicam. CONCLUSIONS: The results suggest that pretreatment with DM, but not tenoxicam, provides significant pre-emptive analgesia for postoperative pain management in patients after LC surgery. Combining DM and tenoxicam also gives good pain relief.

FLT3-TKD mutation in childhood acute myeloid leukemia.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.

Synergistic effects of corticosterone and kainic acid on neurite outgrowth in axotomized dorsal root ganglion.

Corticosterone is the main adrenal glucocorticoids induced by stress in rats. Therapeutic use of high concentration of synthetic glucocorticoids in clinical treatment of spinal cord injury suggests that pharmacological action of glucocorticoids might be beneficial for nerve repair. In this article we cultured axotomized rat dorsal root ganglion neurons to investigate the effects of corticosterone and a glutamate receptor agonist kainic acid on neurite outgrowth. Our results revealed a synergistic effect of corticosterone and kainic acid in promoting neurite outgrowth when applied as early as one and two days in vitro, but not effective at three and four days in vitro. In addition, applied corticosterone and kainic acid were neurotoxic at three and four days in vitro but not at one and two days in vitro. The minimal concentrations of corticosterone and kainic acid to be effective were 10 microM and 1 mM, respectively. The neurotrophic effect of corticosterone and kainic acid was attenuated by the receptor tyrosine kinase A (TrkA) inhibitor AG-879. Western blot analysis and immunocytochemical studies revealed an increase of expressions of both TrkA and growth-associated protein GAP-43 in dorsal root ganglion neurons with combined treatment of corticosterone and kainic acid. Immunocytochemistry showed that corticosterone+kainic acid increase nerve growth factor immunoreactivity in dorsal root ganglion neurites and enhance GAP-43 immunointensity in dorsal root ganglion neurons. These results suggest that the neurotrophic effect of glucocorticoids on axonal regeneration might require facilitation of excitatory stimulation at an early stage of nerve injury, and nerve growth factor may mediate a growth signaling to accomplish the effect.