Bilateral Superior Gluteal Artery Perforator (SGAP) Flap: Modified Concept in Perineal Reconstruction.

Background/Objectives: Perineal reconstruction after abdominoperineal excision often requires complex closures and is fraught with wound healing complications. Flap-based approaches introduce non-irradiated vascularized tissue to the area of resection to fill a large soft-tissue defect and dead space, reduce the risk of infection, and facilitate wound healing. Employing perforator flaps with their beneficial donor site properties, the authors have developed a concept of bilateral superior gluteal artery perforator (SGAP) flaps to restore extensive perineal defects. Methods: This retrospective case series was conducted between September 2015 and December 2019. We included three patients who received bilateral SGAP flap reconstruction after oncological resection. One deepithelialized SGAP flap was used for obliteration of dead space, combined with the contralateral SGAP flap for superficial defect reconstruction and wound closure. Results: Within this patient population, two male and one female patient, with a median age of 62 years (range, 52-76 years), were included. Six pedicled SGAP flaps were performed with average flap dimensions of 9 × 20 cm (range 7-9 × 19 × 21). No flap loss or no local recurrence were documented. In one case, partial tip necrosis with prolonged serous drainage was observed, which was managed by surgical debridement. No further complications were detected. Conclusions: The combination of two SGAP flaps provides maximal soft tissue for defect reconstruction and obliteration of dead space, while maintaining a very inconspicuous donor site, even with bilateral harvesting. Given these advantages, the authors recommend this promising approach for successful reconstruction of perineal defects.

Influence of Tranexamic Acid in Body Contouring Surgery: Significant Changes on Complication Rates after Abdominoplasty.

BACKGROUND: Complications after abdominoplasty remain an unsolved issue in body contouring surgery. The antifibrinolytic drug tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery. The aim of this study was to investigate the influence of intravenously administered TXA on complications and patient safety after abdominoplasty. METHODS: Within this retrospective single-center study, patients who underwent abdominoplasty and received intravenous TXA were selected and compared to randomly selected patients who underwent abdominoplasty without administration of TXA. The patient population was divided into two study groups (TXA vs no TXA). Demographic and surgical data as well as complications were evaluated and compared. Appropriate statistical analysis was performed. RESULTS: Fifty-seven female and 3 male patients with a median age of 38 years and a mean BMI of 25.6 ± 3.3 kg/m2 were included in the study. Except smoking history, demographic data showed no statistically significant differences between both groups. The most common complication was seroma formation (n = 16; 23.9%), and its occurrence was statistically significantly lower in the TXA group (p = 0.023). Furthermore, postoperative seroma aspiration was performed in statistically significant lower numbers in the TXA group (p < 0.05). No thromboembolic events or seizures were observed. DISCUSSION: The outcomes of this study showed that the intravenous administration of TXA leads to a significant reduction of seroma formation and postoperative seroma aspiration after abdominoplasty. Simultaneously, no adverse thromboembolic events were detected. Hence we would recommend administration of TXA in body contouring surgery to decrease the incidence of seroma formation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.

Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment. The patient underwent chemotherapy and haploidentical transplantation and is currently in remission. Blast cells contain a single vector insertion activating the LIM-only protein 2 (LMO2) proto-oncogene, confirmed by physical interaction, and low Adenosine Deaminase (ADA) activity resulting from methylation of viral promoter. The insertion is detected years before T-ALL in multiple lineages, suggesting that further hits occurred in a thymic progenitor. Blast cells contain known and novel somatic mutations as well as germline mutations which may have contributed to transformation. Before T-ALL onset, the insertion profile is similar to those of other ADA-deficient patients. The limited incidence of vector-related adverse events in ADA-deficiency compared to other γ-RV GT trials could be explained by differences in transgenes, background disease and patient's specific factors.

Implementation and validation of 2-D-array based tests in routine linac quality assurance.

PURPOSE: In medical linac quality assurance (QA), to replace film dosimetry with low-resolution 2-D ionization chamber array measurements, to validate the procedures, and to perform a comprehensive sensitivity analysis. METHODS: A 2-D ionization chamber array with a spatial resolution of 7.62 mm was deployed to perform the following tests: Junction tests, MLC transmission test, beam profile constancy vs. gantry angle test, beam profile constancy vs. low dose delivery test, and beam energy constancy vs. low dose delivery test. Test validation and sensitivity analyses based on short- and long-term statistics of the test results were performed. RESULTS: All selected mechanical and dosimetry tests could be successfully performed with a 2-D array. Considering the tolerance limits recommended by the AAPM Task Group 142 report (2009), sensitivities of 99.0% or better and specificities ranging from 99.5% to 99.9% could be achieved in all tests when the proper metrics were chosen. CONCLUSIONS: The results showed that a low-resolution 2-D ionization chamber array could replace film dosimetry without having to sacrifice high test sensitivity. Its implementation in the routine clinical linac QA program may involve considerable QA time savings.

Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control.

INTRODUCTION: Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. MATERIALS AND METHODS: A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called 'whoops procedure', (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. RESULTS: All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). CONCLUSIONS: Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.

Undiagnosed Patent Foramen Ovale and Thrombophilic Gene Mutations Resulting in Pulmonary Embolism with Cryptogenic Stroke after Cosmetic Breast Surgery.

Undiagnosed disorders or gene mutations can lead to life-threatening events even in cosmetic surgery. Herein, the authors present a case of a young and supposedly healthy 36-year-old woman who survived an episode of bilateral pulmonary embolism and cryptogenic stroke after cosmetic breast augmentation-mastopexy. Two days after cosmetic surgery, the patient presented at the emergency stroke unit after she collapsed at home, following frequent generalized seizures. After she was transferred to the intensive care unit, it was revealed that the patient had an undiagnosed patent foramen ovale and several thrombophilic gene mutations. During the stay, two episodes of active bleeding and beginning nipple-areola complex hypoperfusion led to bilateral implant removal. As a final result, the patient lost her breast implants and experienced persistent hypoesthesia of the entire left hemi body. However, this case might highlight deficits in current venous thromboembolism risk assessment and prophylaxis due to the missing considerations of undiagnosed disorders or gene mutations. Further, recommendations on dealing with implants or aesthetic outcome in crucial episodes should be introduced.

Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study.

lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified ß-globin gene (ßA-T87Q ) to produce anti-sickling hemoglobin (HbAT87Q ). The efficacy and safety of lovo-cel for SCD are being evaluated in the ongoing phase 1/2 HGB-206 study (ClinicalTrials.gov: NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo-cel's benefit-risk profile. Following modest expression of HbAT87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B (n = 2, patients B1 and B2), including improvements to cell collection and lovo-cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbAT87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo-cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo-cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.

Liparthroplasty for Thumb Carpometacarpal Joint Osteoarthritis: A Case Series with Median 5 Years of Follow-Up.

Liparthroplasty has recently been discussed as a promising bridging therapy after failed conservative treatment options to postpone arthroplasty surgery of the thumb carpometacarpal joint as long as possible. The current study investigates the sustainability of this method in seven stage II and twenty-four stage III osteoarthritis patients (twenty-seven female and four male cases). Data were evaluated preinterventionally, six months postinterventionally, and two years postinterventionally, as well as a final follow-up assessment after median 5.1 years. We found a significant reduction of all postinterventional disabilities of the arm, shoulder, and hand (dash) scores and pain levels compared to the ones prior to liparthroplasty. Moreover, we even detected a reduction in both parameters within the postinterventional course, so that the DASH scores of our final investigation were significantly lower than the values after six months. Furthermore, 12 of our 31 cases demanded a surgical conversion due to recurrence of symptoms. A binary regression analysis found smokers to have 11 times higher odds for therapy failure, leading to surgical conversion. Seventeen out of nineteen patients in our final assessment stated that they were pleased with liparthroplasty. Due to favorable mid-term outcomes of 61% of the 31 initially treated patients, we recommend liparthroplasty as a reliable bridging therapy for preserving joint integrity as long as possible, especially in non-smoking patients.

HIV- 1 lentivirus tethering to the genome is associated with transcription factor binding sites found in genes that favour virus survival.

Lentiviral vectors (LV) are attractive for permanent and effective gene therapy. However, integration into the host genome can cause insertional mutagenesis highlighting the importance of understanding of LV integration. Insertion site (IS) tethering is believed to involve cellular proteins such as PSIP1/LEDGF/p75, which binds to the virus pre-integration complexes (PICs) helping to target the virus genome. Transcription factors (TF) that bind both the vector LTR and host genome are also suspected influential to this. To determine the role of TF in the tethering process, we mapped predicted transcription factor binding sites (pTFBS) near to IS chosen by HIV-1 LV using a narrow 20 bp window in infected human induced pluripotent stem cells (iPSCs) and their hepatocyte-like cell (HLC) derivatives. We then aligned the pTFBS with these sequences found in the LTRs of native and self-inactivated LTRs. We found significant enrichment of these sequences for pTFBS essential to HIV-1 life cycle and virus survival. These same sites also appear in HIV-1 patient IS and in mice infected with HIV-1 based LV. This in silco data analysis suggests pTFBS present in the virus LTR and IS sites selected by HIV-1 LV are important to virus survival and propagation.

The Versatility of the Fasciocutaneous Infragluteal (FCI) Flaps for locoregional or free flap reconstruction.

BACKGROUND: The wide range of reconstructive purposes requires specific demands and considerations for appropriate flap selection. One versatile and reliable option, which is rarely reported in current literature, is the fasciocutaneous infragluteal (FCI) flap. In this study, we present our results of performing the FCI flap for different clinical indications. PATIENTS AND METHODS: This retrospectively study was conducted between September 2011 and September 2019. We included 30 patients (21 females and 9 males) who underwent reconstruction with either pedicled or free FCI flap. Indications for performing FCI flap were uni- or bilateral autologous breast reconstruction, perineal reconstruction, congenital thoracic deformity, lower extremity coverage, and vulva reconstruction. RESULTS: Forty-one FCI flaps were performed (34 free and 7 pedicled flaps). The average flap dimension was 7  ×  20 cm (range, 7-8  ×  19-21) and the mean length of the pedicle was 13.4 cm (range, 10.5-15.5). The mean diameter of the artery was 2.5 mm (range, 2.2-3.2), the mean diameter of the accompanying vein was 3 mm (range, 2.4-3.3). The flap survival rate was 97.6% (one flap loss). The most common minor complications were infragluteal wound healing disorders and hematoma. CONCLUSION: The FCI flap provides constant and reliable anatomy with a long vascular pedicle as well as enough soft tissue bulk and a well-hidden scar. In our clinical practice, this flap has emerged as a first choice in perineal/vulvar reconstruction and a reliable alternative in breast reconstruction if the gold standard procedure cannot be performed. LEVEL OF EVIDENCE: IV (Therapeutic).

Morphological Relation of Peripheral Nerve Sheath Tumors and Nerve Fascicles: Prospective Study and Classification.

Removal of benign peripheral nerve sheath tumors (bPNST) represents a surgical challenge. The morphological relation of bPNST and healthy nerve fascicles are of utmost importance for achieving both removal of the entire tumor and preservation of functional integrity of the peripheral nerve. Thus, we intraoperatively assessed the morphological patterns between bPNST and nerve fascicles using photo documentation obtained between January 2009 and September 2021. In 31 patients (20 women and 11 men) with a mean age of 48 ± 18 years a total of 34 bPNST were removed. Four constant morphological patterns between bPNST relatively to nerve fascicles were detected: (1) bPNST is located peripherally (n = 16), (2) it splits the nerve into two main fascicles (n = 5), (3) it totally splits up the nerve out of the nerve's center (n = 8) und (4) it encloses the nerve and its fascicles (n = 5) without any detectable boundary layer. Histology revealed 28 schwannomas, five neurofibromas, and one perineurioma. The proposed classification reflects the increasing complexity of tumor removal with a higher type number. This might be beneficial for preoperative diagnostics, i.e., high-resolution ultrasound or MRI-tractography, as well as for planning the bPNST's surgical resection and the possible need for nerve reconstruction.

De-epithelialized Dermal Flap to Reduce Sacral Wound Healing Complications After Lower Body Lift Procedure.

BACKGROUND: Lower or circumferential body lift procedures in the massive-weight-loss population have been associated with significant complication rates. Particularly, the sacral area is at risk of wound-healing problems due to high wound tension or shear forces. OBJECTIVES: The authors introduced a de-epithelialized dermal flap to reinforce the sacral area. METHODS: Within this retrospective study, outcomes of 40 consecutive patients who underwent lower body lift between 2017 and 2021 were analyzed. The patient population was divided into 2 study groups (sacral flap vs no flap) including 20 patients each. Demographic and surgical data as well as complications were evaluated and compared. Appropriate statistical analysis was performed. RESULTS: Thirty-seven female and 3 male patients with a median age of 36.5 years (range, 23-54 years) and a mean weight loss of 46.3 ±â€…12 kg participated in the study. The most common complication was sacral wound dehiscence (n = 7, 17.5%), and its occurrence was statistically significantly lower in the sacral flap group (P = 0.037). The odd ratios for complications when executing the sacral flap procedure were reduced to 0.306 (95% confidence interval = 0.075 to 1.246) and 0.261 (95% confidence interval = 0.055 to 1.250) for the uncorrected and corrected logistic regressions, respectively. In addition, findings showed a significantly shorter hospital stay as well as statistical trends towards a lower occurrence of overall complications in the sacral flap group. Concerning the remaining data, no statistically significant differences between study groups were detected. CONCLUSIONS: The presented de-epithelialized dermal flap leads to a significant reduction of sacral wound-healing complications and a shorter hospital stay for patients. This surgical technique is easily reproduceable, rapid, and effective; therefore, we would recommend it for each circumferential or lower body lift procedure.

Long-term outcomes of lentiviral gene therapy for the ß-hemoglobinopathies: the HGB-205 trial.

Sickle cell disease (SCD) and transfusion-dependent ß-thalassemia (TDT) are the most prevalent monogenic disorders worldwide. Trial HGB-205 ( NCT02151526 ) aimed at evaluating gene therapy by autologous CD34+ cells transduced ex vivo with lentiviral vector BB305 that encodes the anti-sickling ßA-T87Q-globin expressed in the erythroid lineage. HGB-205 is a phase 1/2, open-label, single-arm, non-randomized interventional study of 2-year duration at a single center, followed by observation in long-term follow-up studies LTF-303 ( NCT02633943 ) and LTF-307 ( NCT04628585 ) for TDT and SCD, respectively. Inclusion and exclusion criteria were similar to those for allogeneic transplantation but restricted to patients lacking geno-identical, histocompatible donors. Four patients with TDT and three patients with SCD, ages 13-21 years, were treated after busulfan myeloablation 4.6-7.9 years ago, with a median follow-up of 4.5 years. Key primary endpoints included mortality, engraftment, replication-competent lentivirus and clonal dominance. No adverse events related to the drug product were observed. Clinical remission and remediation of biological hallmarks of the disease have been sustained in two of the three patients with SCD, and frequency of transfusions was reduced in the third. The patients with TDT are all transfusion free with improvement of dyserythropoiesis and iron overload.

Metacarpal reconstruction with a medial femoral condyle flap based on a 3D-printed model: a case report.

Metacarpal bone reconstruction renders a surgical challenge. We describe a case using 3D printing assisted medial femoral condyle flap for extensive metacarpal reconstruction after wide resection of a large giant cell tumor recurrence. Thus, the length and stability of the entire third ray could be restored without any tumor recurrence. (50 w).

Longitudinal analyses of CLL in mice identify leukemia-related clonal changes including a Myc gain predicting poor outcome in patients.

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy mainly occurring at an advanced age with no single major genetic driver. Transgenic expression of TCL1 in B cells leads after a long latency to a CLL-like disease in aged Eµ-TCL1 mice suggesting that TCL1 overexpression is not sufficient for full leukemic transformation. In search for secondary genetic events and to elucidate the clonal evolution of CLL, we performed whole exome and B-cell receptor sequencing of longitudinal leukemia samples of Eµ-TCL1 mice. We observed a B-cell receptor stereotypy, as described in patients, confirming that CLL is an antigen-driven disease. Deep sequencing showed that leukemia in Eµ-TCL1 mice is mostly monoclonal. Rare oligoclonality was associated with inability of tumors to develop disease upon adoptive transfer in mice. In addition, we identified clonal changes and a sequential acquisition of mutations with known relevance in CLL, which highlights the genetic similarities and therefore, suitability of the Eµ-TCL1 mouse model for progressive CLL. Among them, a recurrent gain of chromosome 15, where Myc is located, was identified in almost all tumors in Eµ-TCL1 mice. Interestingly, amplification of 8q24, the chromosomal region containing MYC in humans, was associated with worse outcome of patients with CLL.