Holger J. Klein

Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation.

Sensitization describes the acquired ability of the immune system to react to foreign human leukocyte antigens (HLA) by producing antibodies and developing memory cells. In the field of transplantation, recipient preformed HLA antibodies due to previous sensitization have been identified - beneath ABO incompatibility - as a major factor for acute graft rejection. Several reasons for sensitization have largely been studied, such as previous blood transfusions, pregnancies or former transplants. Recent studies indicate that the use of assist devices (e.g. ECMO) or cadaveric skin allotransplantation providing temporary coverage in burn patients may lead to additional sensitization. As vascularized composite allotransplantation (VCA) has become a rapidly advancing therapeutic option for reconstruction of complex tissue defects in burns, it seems even more important to become familiar with immunological principles and to be cautiously aware of both sources of sensitization and therapeutic concepts in burns avoiding sensitization. This may also include emergency VCAs in burn patients as potential strategy for early definitive reconstruction avoiding procedures triggering HLA antibody formation. We hereby provide an overview on current evidence in the field of pre- and peritransplant sensitization, followed by posttransplant strategies of desensitization and their potential impact on future treatments of burn patients.

Primary functional and aesthetic restoration of the fingernail in distal fingertip amputations with the eponychial flap

Fingertip injuries often result in fingernail defects. Reconstruction of this structure is important for adequate functional and aesthetic results. This study evaluates the eponychial flap reconstruction technique in 45 fingertip amputations with loss of more than half the fingernail. In 33 cases the procedure was performed in combination with a palmar island flap for pulp reconstruction. Average follow up was 5 months. All eponychial flaps healed uneventfully. In 44 cases, the pulp volume was restored without nail growth disturbance. Five complications (9%) were observed (pain, soft nail, and nail deformity). Only one hook nail deformity required reoperation. All patients were satisfied with the aesthetic and functional outcome. We found eponychial flap fingernail reconstruction effective even for injuries proximal to the lunula and have extended the indication for this technique to very proximal fingernail defects. Eponychial flap reconstruction is a simple, safe, and time-effective technique without donor site morbidity. Simultaneous reconstruction of dorsal and palmar injuries should both be performed primarily resulting in the restoration of a satisfying fingertip.

Long-term clinical outcome after epineural coaptation of digital nerves

This study evaluates the long-term clinical outcome and complication rate after digital nerve repair in adults and aims to identify possible prognostic factors of sensory recovery. End-to-end epineural coaptation was performed under magnification. A total of 93 coapted digital nerves were clinically evaluated with a mean follow-up of 3.5 years (range 1–6 years). The mean two-point discrimination was 10.6 mm (versus 4.4 mm for the contralateral side). Cutaneous pressure threshold tested with Semmes–Weinstein monofilaments showed a mean value of 2.7 (versus 2.2 for the contralateral side). Only 2% of our patients developed painful neuromas. None of our patients recovered normal functional sensibility, however, recovery of protective sensation contributed to a high reported level of satisfaction. No correlation was observed between the sensory outcome and age, smoking, mechanism of injury, lesion to or anastomosis of a digital artery, or time of immobilization. The only identified predictor of the result was the surgeon’s level of experience. This highlights the importance of adequate training and practice in the surgical repair of smaller peripheral nerves. Level of evidence: IV

Impact of a femoral snare approach as a bailout procedure on success rates in lead extractions

OBJECTIVES In cases of challenging transvenous lead extraction procedures, limitations exist for the subclavian approach (SCA). In case of absent alternative approaches, the procedure may end with failure. Therefore, we investigated the femoral snare approach (FSA) as bailout procedure. METHODS From December 2010 to August 2013, 114 patients with 190 leads were scheduled for transvenous lead extraction procedures [mean implant duration (MID): 74.7 (1-384) months]. In 28 leads [MID: 133.8 (36-384) months] the FSA was used. In 20 leads [MID: 127.5 (52-258) months] the FSA was performed as bailout approach and in 8 leads [MID: 149.6 (36-384) months] as first-line approach due to complete intravascular lead position. RESULTS In all FSA procedures (n = 28), clinical success was 85.7% and complete procedural success 64.3%. In FSA procedures as bailout approach (n = 20), clinical success was 80.0% and complete procedural success 55.0%. In first-line FSA procedures (n = 8), clinical success was 100.0% and complete procedural success 87.5%. Overall (n = 190) clinical success was 96.3%, complete procedural success 91.1%. By adding the FSA in cases of insufficient or impossible SCA, clinical success was increased by 12.6% (from 83.7 to 96.3%) and complete procedural success by 9.5% (from 81.6 to 91.1%). Comparison of leads extracted by SCA with leads extracted by FSA revealed that MID [133.8 (36-384) vs 64.4 (1-300) months; P < 0.0001] and the rate of passive fixation leads (67.9 vs 28.4%; P < 0.0001) were significantly higher in the FSA group. CONCLUSIONS In cases of failed or impossible subclavian approach, the femoral snare approach may improve overall success rates without relevantly increasing operative risk.

Evaluation of Cutaneous Spatial Resolution and Pressure Threshold Secondary to Digital Nerve Repair.

Background: As the sophistication of functional reconstruction procedures continues to increase, so does the need for valid, precise, and reliable instruments to assess their clinical results. The authors compare two tests for spatial resolution and two for cutaneous pressure threshold in an adult patient cohort having undergone microsurgical digital nerve repair after traumatic transection. Methods: Patients who underwent epineural coaptation after digital nerve transection at the authors’ institution between June of 2006 and December of 2011 were asked to participate in a follow-up examination assessing spatial resolution (two-point discrimination and grating orientation test) and cutaneous pressure threshold (Semmes-Weinstein monofilament test and pressure-specifying sensory device). Interinstrument correlations were conducted and critically elucidated. Results: Eighty-one patients (26 female and 55 male patients; median age, 42 years; interquartile range, 23 years) were examined with a mean follow-up period of 3.5 ± 1.4 years. Although all tests could differentiate between the healthy and operated fingers, poor to moderate correlations were found between two-point discrimination and grating orientation test (&rgr;operated = 0.483, p < 0.0001; &rgr;healthy = 0.350, p < 0.0001), and between Semmes-Weinstein monofilament test and Pressure-Specified Sensory Device testing (&rgr;operated = 0.287, p = 0.01; &;healthy = 0.382, p < 0.001), indicating that they measure different properties. Altogether, the grating orientation test proved superior to two-point discrimination, whereas Pressure-Specified Sensory Device testing was superior to Semmes-Weinstein monofilament testing. Conclusions: Thoughtful use of test instruments is advisable when assessing sensibility of the hand. This study suggests including Pressure-Specified Sensory Device testing to assess cutaneous pressure threshold and the grating orientation test to assess spatial resolution in clinical, routine test batteries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, III.

Pancreatic Stone Protein Predicts Postoperative Infection in Cardiac Surgery Patients Irrespective of Cardiopulmonary Bypass or Surgical Technique

Introduction We investigated the role of pancreatic stone protein (PSP) in predicting the occurrence of infection in the postoperative course of cardiac surgery patients. Several biomarkers indicating the presence of inflammation and infection are available in the clinical routine; yet, their utility in the postoperative course of patients following cardiac surgery remains uncertain. Moreover, cardiopulmonary bypass, also referred to as “on-pump surgery”, increases the susceptibility to an exaggerated inflammatory state. However, the impact of such extracorporeal circulation on circulating PSP levels remains poorly understood. Methods In a prospective cohort of unselected patients undergoing cardiac surgery, we set out to elucidate the diagnostic accuracy of serum PSP levels as opposed to canonical biomarkers (CRP, WBC) of inflammation to discriminate between the presence of infection and surgical trauma,. In addition, we investigated whether the biomarkers were influenced by the surgical technique employed, i.e. on-pump vs. off-pump and minimally invasive surgery vs. sternotomy. Levels of circulating PSP and routine inflammatory biomarkers (CRP, WBC) were measured in samples taken from 120 patients at baseline as well as at postoperative day 1–3. Results Univariate analysis showed that among the biomarkers investigated, only PSP levels had discriminatory power to differentiate infection from surgical trauma in the postoperative course of the entire cohort of patients following cardiac surgery. With regard to cardiac surgical interventions, there was no significant association between the absence or presence of extracorporeal circulation and PSP levels. However, there was a significant difference in the slope of the rise of postoperative PSP between minimally invasive surgery as opposed to patients subjected to sternotomy. Conclusion In an unselected population of cardiac surgery patients, post-operative serum PSP levels were significantly associated with the presence of infection in both the on-pump and off-pump setting. Of note, the surgical technique employed (sternotomy vs. minimally invasive approach) had a significant impact on postoperative PSP levels.

Diagnosis and perioperative management of ruptured AAA mimicking symptomatic groin hernia

Highlights • RAAA presenting as symptomatic groin hernia has poor survival.• CTA for diagnosis and preoperative planning is strongly recommended.• Hypotensive haemostasis lowers mortality.• Coinciding inguinal hernias should not be repaired at the same time.

Adipose-derived Stromal Cells attenuate Acute Rejection and Graft Vasculopathy in Rodent Vascularized Composite Allotransplantation

Introduction Vascularized composite allotransplantation (VCA) is successfully used for reconstruction of major defects of the upper extremity and face. Both rejection and graft vasculopathy (GV) seriously endanger long-term outcomes, eventually leading to graft failure. GV remains widely unexplored in VCA, and so does the role of adipose-derived stromal cells (ASCs) in acute rejection. Methods ASCs were isolated from donors, characterized and their immunomodulatory capacity investigated. Systemic (SASC) versus local intragraft (LASC) ASC administration was evaluated for therapy of acute rejection and GV in fully mismatched rat hind-limb transplants after discontinuation of immunosuppression (FK-506). Tissues (skin/muscle/vessels) and blood samples were taken prior and after therapy for histopathology (H&E; Elastin van Gieson; von Willebrand factor [vWF]) and cytokine analysis (Multiplex). Results ASCs (CD45-CD29+CD90+) suppressed alloresponse in vitro and reduced pro-inflammatory cytokine levels in mixed lymphocyte reactions (IL-&agr;, IL-&bgr;, IL-2, GM-CSF). In vivo, ASC administration at grade II rejection significantly delayed progression to grade III (7.57±1.13 days SASC, 7.29±1.11 days LASC vs 2.75±0.7 days Controls; n=23 animals). Significant GV was detected during acute rejection in controls, whereas ASC administration reduced intima/media ratio (IMR) in arterioles of allograft skin and muscle. However, GV did not affect the greater (femoral) vessels. vWF analysis revealed increased expression in femoral vessels of controls, compared to significantly reduced expression after both local and systemic cell therapy, similar to naïve vessels. Discussion and Conclusion Systemic or local ASC therapy significantly reduces progression of onset acute rejection in VCA through attenuation of alloresponse and suppression of pro-inflammatory cytokines. GV was observed during acute rejection in small arterioles, but not in femoral vessels, and was significantly reduced after cytotherapy. vWF was increased in femoral vessels, despite no manifest GV, suggesting early endothelial damage. If vWF is a potential early marker for GV development in VCA needs to be investigated. This study was supported by the Swiss National Science Foundation.

Sonographic study of repair, gapping and tendon bowstringing after primary flexor digitorum profundus repair in zone 2

We report sonographic findings with clinical outcomes after zone 2 flexor digitorum profundus tendon repairs in ten fingers. The tendons underwent a six-strand M-Tang core repair, no circumferential suture, and partial or complete division of the pulleys. Over 12 months after surgery and using ultrasound, we found no gapping at the repair site during finger motion. When the pulleys were divided, there was sonographic evidence of tendon bowstringing, but the bowstringing was minimal. Clinically, we did not find any fingers that displayed tendon bowstringing or had functional loss. With ultrasound examination, the repaired tendons remained enlarged over 12 months. Two patients developed heterotopic ossifications at the repair site without tendon gliding, and these required tenolysis. We conclude that the tendon repair site does not gap when a strong core suture is used in the repair without adding peripheral sutures. There is no notable tendon bowstringing clinically, though the repaired tendons have sonographic evidence of minor bowstringing. Level of evidence: III

Occurrence of Occult Malignancies in Reduction Mammoplasties

Objectives Patients undergoing reduction mammoplasty (RM) bear the risk of having occult breast cancer nests. The detection rate of malignant neoplasms in the resected specimens, varies greatly in the literature. The aim of our present study was to analyze risk factors and evaluate histopathological findings in our cohort of patients who underwent RM towards our center. Material and methods In this retrospective single center study we analyzed 559 female patients [median age 35.99 (±13.34)] who underwent RM between 2000 and 2010. The presence of carcinoma and ductal- (DCIS) or lobular carcinoma in situ (LCIS) were considered as pathological findings. Body mass index (BMI), age, surgical technique and mass of resected tissue were included into the analysis. Results There were 6 cases of occult neoplasia (1.08 %) including 2 cases of breast cancer, one multicentric DCIS and 3 cases of LCIS (0.54 %) in 559 patients. Patients with breast cancer showed a significant increased median age: 49y median (IQR ± 18) vs. 35y (IQR ± 21) (p = 0.004) and a trend towards increased BMI: 25.88 median (IQR ± 7.3) vs. 24.50 (IQR ± 4.09) (p = 0.219), compared to patients without pathological results. One patient with occult carcinoma had a negative preoperative mammography, a patient with LCIS a negative preoperative breast ultrasound. Conclusions In our study the occurrence of occult neoplasia was associated with increased age and showed a trend towards increased BMI when compared to patients without pathological findings. The study demonstrates the necessity of thorough medical history, preoperative diagnostic screening and histopathological analysis of all resected specimens.