Machine Perfusion Deters Ischemia-Related Derangement of a Rodent Free Flap: Development of a Model.

INTRODUCTION: Machine perfusion can enable isolated support of composite tissues, such as free flaps. The goal of perfusion in this setting is to preserve tissues prior to transplantation or provide transient support at the wound bed. This study aimed to establish a rodent model of machine perfusion in a fasciocutaneous-free flap to serve as an affordable testbed and determine the potential of the developed support protocol to deter ischemia-related metabolic derangement. METHODS: Rat epigastric-free flaps were harvested and transferred to a closed circuit that provides circulatory and respiratory support. Whole rat blood was recirculated for 8 h, while adjusting the flow rate to maintain arterial-like perfusion pressures. Blood samples were collected during support. Extracellular tissue lactate and glucose levels were characterized with a microdialysis probe and compared with warm ischemic, cold ischemic, and anastomosed-free flap controls. RESULTS: Maintenance of physiologic arterial pressures (85-100 mmHg) resulted in average pump flow rates of 360-430 µL/min. Blood-based measurements showed maintained glucose and oxygen consumption throughout machine perfusion. Average normalized lactate to glucose ratio for the perfused flaps was 5-32-fold lower than that for the warm ischemic flap controls during hours 2-8 (P < 0.05). CONCLUSIONS: We developed a rat model of ex vivo machine perfusion of a fasciocutaneous-free flap with maintained stable flow and tissue metabolic activity for 8 h. This model can be used to assess critical elements of support in this setting as well as explore other novel therapies and technologies to improve free tissue transfer.

Early Return of Motion in Patients With Intramedullary Screw Placement for Metacarpal and Phalangeal Fracture Fixation.

INTRODUCTION: Hand fractures are associated with significant morbidity. Current management standards often result in prolonged immobilization, stiffness, and delayed return to functional use. Intramedullary (IM) compression screws offer minimal soft tissue disruption and early postoperative active motion. In this study, we describe our outcomes after intraosseous fracture fixation using IM cannulated headless screws for a multitude of fracture patterns. METHODS: This study is a retrospective review of patients who underwent IM screw placement for fixation of metacarpal and phalangeal fractures by a single surgeon from 2017 to 2022. Data were collected to include patient demographics, fracture details, postoperative complications, and follow-up. Time to range of motion and return to unrestricted motion was recorded. RESULTS: There were 69 patients with 92 fractures (n = 54 metacarpal, n = 38 phalanx). The median patient age was 45 years (range, 18-89 years) with 75.4% males. Majority presented with a single fracture (n = 50, 72.5%), and 38 patients (55.1%) had open fractures. Small finger was the most affected digit (n = 35, 37.6%). The median time to allow range of motion from surgery was 8.7 days (interquartile range, 0-32) with 32 days (interquartile range, 10-62) for unrestricted use of the hand. Thirty-five patients (50.7%) were allowed controlled motion from the first postoperative day. One patient had loss of reduction requiring reintervention for hardware removal, and 1 patient had superficial skin infection managed with oral antibiotics. CONCLUSIONS: Our findings indicate that the IM screw provides reliable fixation for a wide variety of fracture patterns with a low complication rate and offers early return to functional use.

A Model to Study Wound Healing Over Exposed Avascular Structures in Rodents With a 3D-Printed Wound Frame.

BACKGROUND: Soft tissue defects with exposed avascular structures require reconstruction with well-vascularized tissues. Extensive research is ongoing to explore tissue engineered products that provide durable coverage. However, there is a lack of controlled and affordable testbeds in the preclinical setting to reflect this challenging clinical scenario. We aimed to address this gap in the literature and develop a feasible and easily reproducible model in rodents that reflects an avascular structure in the wound bed. METHODS: We created 20 × 20 mm full thickness wounds on the dorsal skin of Lewis rats and secured 0.5-mm-thick silicone sheets of varying sizes to the wound bed. A 3D-printed wound frame was designed to isolate the wound environment. Skin graft and free flap survival along with exposure of the underlying silicone was assessed. Rats were followed for 4 weeks with weekly dressing changes and photography. Samples were retrieved at the endpoint for tissue viability and histologic analysis. RESULTS: The total wound surface area was constant throughout the duration of the experiment in all groups and the wound frames were well tolerated. The portion of the skin graft without underlying silicone demonstrated integration with the underlying fascia and a histologically intact epidermis. Gradual necrosis of the portion of the skin graft overlying the silicone sheet was observed with varying sizes of the silicone sheet. When the size of the silicone sheet was reduced from 50% of the wound surface area, the portion surviving over the silicone sheet increased at the 4-week timepoint. The free flap provided complete coverage over the silicone sheet. CONCLUSION: We developed a novel model of rodent wound healing to maintain the same wound size and isolate the wound environment for up to 4 weeks. This model is clinically relevant to a complex wound with an avascular structure in the wound bed. Skin grafts failed to completely cover increasing sizes of the avascular structure, whereas the free flap was able to provide viable coverage. This cost-effective model will establish an easily reproducible platform to evaluate more complex bioengineered wound coverage solutions.

Use of wound edge inversion (epibole) to generate recalcitrant and inflamed diabetic wounds.

Robust and predictive pre-clinical models of recalcitrant diabetic wounds are critical for advancing research efforts toward improving healing. Murine models have logistic and genetic benefits versus larger animals; however, native murine healing inadequately represents clinically recalcitrant wounds in humans. Furthermore, current humanization techniques employing devices, deleterious mutations or chemical agents each carry model-specific limitations. To better replicate human wounds in a mouse, we developed a novel wound-edge inversion (WEI) technique that mimics the architecture of epibole and mitigates contracture, epithelialization, and consequently wound closure. In this study, we evaluated the reliability and durability of the WEI model in wild-type and obese diabetic mice and compared to healing after (i) punch biopsy, (ii) mechanical/silicone stenting or (iii) exogenous oxidative stressors. In wild-type mice, WEI demonstrated favourable closure characteristics compared to both control and stented wounds, however, wounds progressed to closure by 4 weeks. In contrast, diabetic WEI wounds persisted for 6-10 weeks with reduced contracture and epithelialization. In both diabetic and wild-type mice, WEI sites demonstrated persistence of inflammatory populations, absence of epithelialization, and histologic presence of alpha-SMA positive granulation tissue when compared to controls. We conclude that the WEI technique is particularly valuable for modelling recalcitrant diabetic wounds with sustained inflammation and dysfunctional healing.

Venous Thromboembolism Rates After Free Flap Reconstruction of the Head and Neck Region.

BACKGROUND: Venous thromboembolism (VTE) is a major concern for the postoperative hospitalized patient, especially after long and complex procedures. Cancer itself also contributes to the hypercoagulable state, further complicating the management of patients. Despite prophylaxis, breakthrough events can occur. We aimed to assess our institutional VTE and bleeding rates after free flap reconstruction of the head and neck (H&N) region and the factors associated with VTE events. METHODS: A retrospective review of the patients who underwent H&N free flap reconstruction at an academic center from 2012 to 2021 was performed from a prospectively maintained database. Data regarding patient demographics, medical history, surgical details, and overall outcomes were collected. Outcomes studied included postoperative 30-day VTE rates and major bleeding events. Patients who had a VTE event were compared with the rest of the cohort to identify factors associated with VTE. RESULTS: Free flap reconstruction of the H&N region was performed in 949 patients. Reconstruction after cancer extirpation for squamous cell carcinoma was the most common etiology (79%). The most common flap was thigh based (50%), followed by the fibula (29%). The most common postoperative VTE chemoprophylaxis regimen was enoxaparin 30 mg twice daily (83%). The VTE and bleeding rates over the 10-year period were 4.6% (n = 44) and 8.7% (n = 83), respectively. Body mass index (28.7 ± 5.8 vs 26.2 ± 6.6, P = 0.013) and pulmonary comorbidities were found to be significantly higher in patients who had a VTE event (43% vs 27%, P = 0.017). Patients with a VTE event had a prolonged hospital stay of 8 more days (19.2 ± 17.4 vs 11 ± 7, P = 0.003) and a higher incidence of bleeding events (27% vs 8%, P < 0.001). CONCLUSIONS: Postoperative VTE is a significant complication associated with increased length of hospitalization in patients undergoing free flap reconstruction of the H&N region. Institutional measures should be implemented on an individualized basis based on patient comorbidities to improve the postoperative VTE rates, while balancing the bleeding events.

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region.

BACKGROUND: Venous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population. METHODS: A cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups. RESULTS: Out of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087-6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339-2.838). CONCLUSIONS: Enoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

Automated Decellularization of the Rodent Epigastric Free Flap: A Comparison of Sodium Dodecyl Sulfate-Based Protocols.

BACKGROUND: Free tissue transfer to cover complex wounds with exposed critical structures results in donor-site morbidity. Perfusion decellularization and recellularization of vascularized composite tissues is an active area of research to fabricate complex constructs without a donor site. Sodium dodecyl sulfate (SDS)-based protocols remain the predominant choice for decellularization despite the deleterious effects on tissue ultrastructure and capillary networks. We aimed to develop an automated decellularization process and compare different SDS perfusion times to optimize the protocol. METHODS: A three-dimensional-printed closed-system bioreactor capable of continuously perfusing fluid through the vasculature was used for decellularization. The artery and vein of rat epigastric fasciocutaneous free flaps were cannulated and connected to the bioreactor. Protocols had varying durations of 1% SDS solution (3, 5, and 10 days) followed by 1 day of 1% Triton X-100 and 1 day of 1x phosphate-buffered saline. The residual DNA was quantified. Microarchitecture of the constructs was assessed with histology, and the vascular network was visualized for qualitative assessment. RESULTS: The structural integrity and the microarchitecture of the extracellular matrix was preserved in the 3- and 5-day SDS perfusion groups; however, the subcutaneous tissue of the 10-day protocol lost its structure. Collagen and elastin structures of the pedicle vessels were not compromised by the decellularization process. Five-day SDS exposure group had the least residual DNA content (p < 0.001). Across all protocols, skin consistently had twice as much residual DNA over the subcutaneous tissues. CONCLUSION: A compact and integrated bioreactor can automate decellularization of free flaps to bioengineer regenerative constructs for future use in reconstruction of complex defects. A decellularization protocol with 5 days of 1% SDS exposure was the most successful to keep the residual DNA content at a minimum while preserving the structural integrity of the tissues.

ChatGPT Is Equivalent to First-Year Plastic Surgery Residents: Evaluation of ChatGPT on the Plastic Surgery In-Service Examination.

BACKGROUND: ChatGPT is an artificial intelligence language model developed and released by OpenAI (San Francisco, CA) in late 2022. OBJECTIVES: The aim of this study was to evaluate the performance of ChatGPT on the Plastic Surgery In-Service Examination and to compare it to residents' performance nationally. METHODS: The Plastic Surgery In-Service Examinations from 2018 to 2022 were used as a question source. For each question, the stem and all multiple-choice options were imported into ChatGPT. The 2022 examination was used to compare the performance of ChatGPT to plastic surgery residents nationally. RESULTS: In total, 1129 questions were included in the final analysis and ChatGPT answered 630 (55.8%) of these correctly. ChatGPT scored the highest on the 2021 exam (60.1%) and on the comprehensive section (58.7%). There were no significant differences regarding questions answered correctly among exam years or among the different exam sections. ChatGPT answered 57% of questions correctly on the 2022 exam. When compared to the performance of plastic surgery residents in 2022, ChatGPT would rank in the 49th percentile for first-year integrated plastic surgery residents, 13th percentile for second-year residents, 5th percentile for third- and fourth-year residents, and 0th percentile for fifth- and sixth-year residents. CONCLUSIONS: ChatGPT performs at the level of a first-year resident on the Plastic Surgery In-Service Examination. However, it performed poorly when compared with residents in more advanced years of training. Although ChatGPT has many undeniable benefits and potential uses in the field of healthcare and medical education, it will require additional research to assess its efficacy.

A Single Superior Gluteal Artery Perforator Flap in Reconstruction of Large Midline Sacral Defects: A Method for Practical Harvest and Safe Closure.

BACKGROUND: Large midline sacral defects are reconstructive challenges. Superior gluteal artery perforator (SGAP) flap provides enough tissue and versatility to cover large defects; however, a single flap may be insufficient. We present a technique to cover large defects using single SGAP flaps. METHODS: Large sacral defects (>100 cm2) reconstructed with single SGAP flaps were included. Angle of transposition (45°-60°) was determined based on the tissue laxity and mobility of gluteal area. Perforator identification, intramuscular dissection, or skeletonization was not performed. Outcomes were measured as achieving durable reconstruction, flap viability, and complications. RESULTS: There were 17 patients (12 male, 5 females; aged 25-72 years) with different etiologies. The mean flap surface area (136.1 ± 45.6 cm2, between 9 × 8 and 26 × 10 cm) was smaller than the mean defect surface area (211.1 ± 87.2 cm2, between 10 × 10 and 28 × 14 cm) (P < 0.001). All flaps survived with no partial or complete flap loss. Minor dehiscence in 4 patients (2 at donor site and 2 at recipient site) healed with dressing changes or using negative-pressure vacuum therapy. All patients had durable outcomes without any recurrence. CONCLUSION: Single unilateral SGAP flaps can be used to completely cover midline large sacral defects. It is important to design the flaps to have a joint side with the defect in the proximal part and use the intrinsic mobility of gluteal soft tissues for the closure. Flaps can be (1) planned to be smaller than the defects, (2) harvested with no intramuscular perforator dissection or pedicle skeletonization, and (3) transposed with an angle less than 60°.

Standard Fixed Enoxaparin Dosing for Venous Thromboembolism Prophylaxis Leads to Low Peak Anti-Factor Xa Levels in Both Head and Neck and Breast Free Flap Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. METHODS: Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. RESULTS: Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p < 0.0001). CONCLUSION: Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

Flap Closure of Spinal Defects in High-Risk Patients: A 10-Year Institutional Experience.

BACKGROUND: Complication rates after spinal surgery are high, in part because of surgical advancements that have made procedures available to a broader range of medically complicated patients. The high rates of infection, hematoma, and dehiscence resulting in open wounds after spinal surgery often warrant plastic surgery involvement. In this study, we aim to examine the effects of preoperative and operative risk factors on complication rates, reoperation rates, and hospital length of stay after flap reconstruction of spinal defects. METHODS: A retrospective review was performed of 373 patients who required flap reconstruction for spinal wound closure at our institution between 2003 and 2013. Data regarding demographics, comorbidities, operative variables, and postreconstructive course were collected. RESULTS: Of the 373 patients, 97.3% had at least 1 comorbid condition associated with poor wound healing, 91.2% had a significant wound condition at the time of reconstruction, and 81.8% had a history of 2 or more spinal surgeries. After reconstruction, average hospital stay was 14 days, with 35% of patients developing complications and 30% requiring reoperation. Risk factors including elevated body mass index, diabetes, tobacco use, steroid use, low prealbumin level, therapeutic anticoagulation, infection, history of spine surgery, multilevel spinal reconstruction, and spinal hardware were associated with complications, reoperations, and prolonged length of stay. CONCLUSIONS: Local muscle flap coverage is an effective strategy for the reconstruction of spinal defects in medically complex patients. To reduce the inherently high risks associated with paraspinous reconstruction in this challenging population, special consideration should be given to preoperative and operative variables associated with poor outcomes. Early coordination between spine and plastic surgeons should be considered in patients at high-risk of wound complications.

Nipple-Sparing Mastectomy and Immediate Implant-Based Reconstruction with or Without Skin Reduction in Patients with Large Ptotic Breasts: A Case-Matched Analysis.

BACKGROUND: Nipple-sparing mastectomy (NSM) and implant-based immediate breast reconstruction are becoming preferred options with improved outcomes. However, reconstruction in patients with large and ptotic breasts is challenging. When mastectomy and skin reduction are combined in a single-staged procedure, the vasculature of the skin is disturbed leading to increased complication rates. This paper aims to compare complication rates of NSM and immediate implant-based reconstruction with or without reduction to determine the safety of reduction in this patient group. METHODS: Breast cancer patients that underwent NSM and implant-based immediate breast reconstruction between November 2010 and 2018 were analyzed. All implants were placed submuscularly. Patients with skin reduction and nipple-areolar complex transposition were matched in a 1:1 fashion with patients without reduction. RESULTS: There were 50 patients (72 procedures) in each group. Demographics of the groups were similar as a part of matching process. Mean implant volume in the reduction group was higher (399.93 ± 97.54 vs. 360.21 ± 82.54, p = 0.009). Full thickness skin necrosis rate was higher in the reduction group [12/72 (%17) vs. 2/72 (3%), p = 0.009], and the most common site was over the suture line [6/12 (50%)]. Complications in the reduction group were more common in reconstructions with implant volumes greater than 500 cc (p = 0.008). CONCLUSIONS: When compared with no reduction, the skin necrosis rate of NSM and immediate implant-based reconstruction with skin reduction is higher. The described technique can only be considered in patients with moderate breast volumes, grade II-III ptosis, and when the planned implant volume is low (< 500 cc). 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 .

Total aesthetic reconstruction of postburn bilateral breast loss using transverse myocutaneous gracilis free flaps: A case report and literature review.

Reconstruction of breast burns are challenging, as it includes both functional and aesthetic components. Transverse myocutaneous gracilis (TMG) flap has been used for postmastectomy breast reconstruction in the absence of abdominal donor site availability. Use of this flap for the breast burns is limited. A 32-year-old female sustained 54% second and third degree burns resulting with bilateral total breast loss. Anterior and posterior thorax, upper and mid abdomen, neck, shoulders, and bilateral upper extremities were also involved. Inner medial thighs had an ample amount of tissue and had never been used as donor sites. The left TMG (28 × 12 cm, 1,413 g) was used for right, and the right TMG (30 × 14 cm, 1,635 g) was used for the left breast, 3 months apart. The contracture on the chest wall was completely excised. Venous anastomosis to the venae commitantes was performed using a 2.5 mm coupler, followed by an end-to-end arterial anastomosis to the internal mammary artery. Flaps were inset in a fashion so that the inferior part became the inframammary fold, and the anterior and posterior wings were joined in the upper pole, creating a conical shape. Minimal wound dehiscence in the postoperative course healed with dressing changes and both flaps survived completely. Nipple reconstruction and areolar tattooing was performed. The patient was very happy with the outcome at seventh year follow-up. TMG may be a valuable option even in bilateral cases of microsurgical autologous free tissue transfer for total aesthetic reconstruction of postburn breast loss.

Factors Associated With Complications in Immediate Breast Reconstruction in 1 Stage With Completely Submuscular Implants.

BACKGROUND: Immediate breast reconstruction in 1 stage using permanent implants is gaining popularity and can be performed with or without the use of acellular dermal matrices. This study aimed to investigate the results of breast implants placed submuscularly without acellular dermal matrix and assess the factors affecting surgical complications. METHODS: From November 2009 to March 2018, 138 patients underwent immediate breast reconstruction with permanent submuscular implants after concomitant skin-sparing or nipple-sparing mastectomies in a single institution. All implants were covered with sufficient soft tissue under a submuscular pocket. RESULTS: One hundred thirty-eight patients were enrolled, and a total of 196 breasts were operated. The average age and body mass index (BMI) of the patients were 44.9 ± 8.8 years and 23.7 ± 3.6 kg/m, respectively. The majority of the mastectomies were therapeutic (81%). The average volume of implants was 389 ± 89 mL, and the mean follow-up was 33 months. The overall complication rate was 17% (n = 23), with skin necrosis being the most common complication followed by infections. Having a BMI equal to or greater than 25 kg/m was found to be a statistically significant predictor for overall complications (P = 0.002), whereas smoking history, age, and implant volume were not statistically significant. CONCLUSIONS: Immediate breast reconstruction in 1 stage using permanent implants can be performed with acceptable complication rates and cosmetic outcomes. Our study demonstrated that high BMI is a risk factor for overall complications. With proper patient selection and surgical technique, implants could be completely covered under a submuscular pocket.

Total aesthetic subunit reconstruction of the burned anterior abdomen using pre-expanded pedicled anterolateral thigh flap-A case report.

Combination of tissue expansion and perforator flaps broadened the reconstructive options in burn cases with wide scar contractures. We report a case of total aesthetic subunit reconstruction of the anterior abdominal skin using a pre-expanded pedicled anterolateral thigh (ALT) perforator flap in a patient with postburn contractures. Seventeen-year-old girl had a history of scalding burn to the anterior abdomen, resulting in tight contractures inhibiting her mobility. After an expansion period of 6 months, the flap of 27 × 30 cm was elevated at the suprafascial plane and tunneled to the anterior abdomen. The flap was used to resurface the defect from xyphoid process down to the mons pubis and bilaterally at linea semilunaris. Postoperative course was uneventful. A good quality aesthetic and functional reconstruction was achieved at the 10-year follow-up. Pre-expanded pedicled ALT flaps may be considered as an option in extensive scarring requiring large amounts of tissue.

Role of robotic approach for management of complicated jejunoileal diverticulosis - video vignette.

Jejunoileal diverticulosis (JID) is a rare condition with a reported incidence lower than 0.1% (1-3). Surgery is the definitive treatment for JID and can be considered to improve the patient's quality of life and to prevent further occurrence of severe symptoms (3, 4, 5). Minimally invasive approach facilitates postoperative recovery, lowers risks and improves outcomes in JID treatment (6). This article is protected by copyright. All rights reserved.

Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center.

Background: Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results. Methods: A retrospective cohort study was conducted at Acibadem University's Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0-18 years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings. Results: The cohort comprised 172 pediatric patients, aged 0-5 years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients. Discussion: Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5 years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist's expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield.

Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared with Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms.

Introduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs. Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(≥7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE. Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.