The robotic-assisted free jejunal flap for neovaginal canal creation in gender-affirming vaginoplasties.

INTRODUCTION: One of the biggest challenges with gender-affirming vaginoplasty was the creation of a long-lasting, durable, patent, and self-lubricating neovaginal canal that allowed for spontaneous, pain-free sexual intercourse. The jejunum was a durable, physiologic, and intestinal option to create the neovaginal canal that minimizes the adverse effects of skin graft, peritoneal, and colonic vaginoplasties. Free jejunal vaginoplasties had been performed in cis females for congenital genitourinary anomalies like Mullerian agenesis or after gynecologic-oncologic surgery but had yet to be reported for gender-affirming vaginoplasties. The purpose of this report was to present a technique for a physiologic, intestinal, gender-affirming vaginoplasty without the disadvantages of colonic vaginoplasties. PATIENTS AND METHODS: This report presented six patients, all natal males who identified as female, undergoing robotic-assisted free jejunal flap gender-affirming vaginoplasty. Mean age was 35.8 years (range: 21-66). Mean body mass index was 33.2 kg/m2 (range: 28.0-41.0). The proximal aspect of the neovaginal canal was created intra-abdominally by elevating peritoneal flaps from the posterior bladder wall to be reflected downward into the external neovaginal canal. The jejunal flap was harvested. The greater saphenous vein was harvested to create an arteriovenous loop between the flap vessels and the recipient femoral artery in an end-to-side fashion and a branch of the femoral vein. The jejunal flap was passed intra-abdominally through the groin incision and then trans-peritoneally into the neovaginal canal. The jejunal segment was inset to the proximal peritoneal flaps and the distal inverted penoscrotal skin of the neovaginal introitus. RESULTS: Mean length of the harvest jejunal segment was 19.2 cm (range: 15-20). Mean time to ambulation, foley removal, and first vaginal dilation were 3.3 (range: 3-4), 4.0 (range: 3-5), and 4.5 days (range: 4-6), respectively. By a mean follow-up duration of 8.0 months (range: 1-14), mean vaginal depth and diameter were 7.0 and 1.3 cm (range: 1.0-1.5), respectively. Two (33.3%) patients experienced postoperative complications, including groin hematoma (n = 1, 16.7%) and reoperation for correction of dehiscence of the jejunal flap to the vaginal introitus (n = 1, 16.7%). CONCLUSION: Gender-affirming surgeons should consider a free vascularized segment of jejunum as an option to line the neovaginal canal in the correct patients.

Prognostic Significance of Immune Cell Infiltration in Muscle-invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and RTOG 0712.

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation.

Long-term Outcomes of Chemoradiation for Muscle-invasive Bladder Cancer in Noncystectomy Candidates. Final Results of NRG Oncology RTOG 0524-A Phase 1/2 Trial of Paclitaxel + Trastuzumab with Daily Radiation or Paclitaxel Alone with Daily Irradiation.

BACKGROUND: Chemo-radiation is a well-established alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Many patients due to age or medical comorbidity are unfit for either radical cystectomy, or standard cisplatin- or 5-fluorouracil-based chemoradiation, and do not receive appropriate treatment with curative intent. We treated patients with a less aggressive protocol employing seven weekly doses of paclitaxel and daily irradiation. In those whose tumors showed overexpression of her2/neu, seven weekly doses of trastuzumab were also administered. OBJECTIVE: To report the long-term survival outcomes and toxicity results of the of NRG Oncology RTOG 0524 study. DESIGN, SETTING, AND PARTICIPANTS: Seventy patients were enrolled and 65 (median age: 76 yr) were deemed eligible. Patients were assigned to daily radiation and weekly paclitaxel + trastuzumab (group 1, 20 patients) or to daily radiation plus weekly paclitaxel (group 2, 45 patients) based on tumor her2/neu overexpression. Radiation was delivered in 1.8 Gy fractions to a total dose of 64.8 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was unresolved treatment-related toxicity. The secondary endpoints were complete response rate, protocol completion rate, and disease-free and overall survival. RESULTS AND LIMITATIONS: Protocol therapy was completed by 60% (group 1) and 76% (group 2); complete response rates at 12 wk were 62% in each group. Acute treatment-related adverse events (AEs) of grade ≥3 were observed in 80% in group 1 and 58% in group 2. There was one treatment-related grade 5 AE in group 1. Unresolved acute treatment-related toxicity was 35% in group 1 and 31% in group 2. The median follow-up was 2.3 yr in all patients and 7.2 yr in surviving patients. Overall survival at 5 yr was 25.0% in group 1 and 37.8% in group 2 (33.8% overall). At 5 yr, disease-free survival was 15.0% in group 1 and 31.1% in group 2. CONCLUSIONS: In a cohort of patients with muscle-invasive bladder cancer who are not candidates for cystectomy or cisplatin chemotherapy, chemoradiation therapy offers a treatment with a significant response rate and 34% 5-yr overall survival. While there were many AEs in this medically fragile group, there were few grade 4 events and one grade 5 event attributable to therapy. PATIENT SUMMARY: Patients with invasive bladder cancer who cannot tolerate surgery were treated with radiation and systemic therapy without surgically removing their bladders. Most patients tolerated the treatment, were able to keep their bladders, and showed a significant treatment response rate.

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [177Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results. METHODS: This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [177Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([177Lu]Lu-PSMA-617 group) or standard of care alone (control group) using permuted blocks. Randomisation was stratified by baseline lactate dehydrogenase concentration, liver metastases, ECOG performance status, and androgen receptor pathway inhibitor inclusion in standard of care. Patients in the [177Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [177Lu]Lu-PSMA-617 every 6 weeks for four cycles plus two optional additional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy. The alternate primary endpoints were radiographic progression-free survival and overall survival, which have been reported. Here we report the key secondary endpoint of time to first symptomatic skeletal event, and other secondary endpoints of HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF). Patient-reported outcomes and symptomatic skeletal events were analysed in all patients who were randomly assigned after implementation of measures designed to reduce the dropout rate in the control group (on or after March 5, 2019), and safety was analysed according to treatment received in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, NCT03511664, and is active but not recruiting. FINDINGS: Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [177Lu]Lu-PSMA-617 group (n=385) or control group (n=196) on or after March 5, 2019, and were included in analyses of HRQOL, pain, and time to first symptomatic skeletal event. The median age of patients was 71 years (IQR 65-75) in the [177Lu]Lu-PSMA-617 group and 72·0 years (66-76) in the control group. Median time to first symptomatic skeletal event or death was 11·5 months (95% CI 10·3-13·2) in the [177Lu]Lu-PSMA-617 group and 6·8 months (5·2-8·5) in the control group (hazard ratio [HR] 0·50, 95% CI 0·40-0·62). Time to worsening was delayed in the [177Lu]Lu-PSMA-617 group versus the control group for FACT-P score (HR 0·54, 0·45-0·66) and subdomains, BPI-SF pain intensity score (0·52, 0·42-0·63), and EQ-5D-5L utility score (0·65, 0·54-0·78). Grade 3 or 4 haematological adverse events included decreased haemoglobin (80 [15%] of 529 assessable patients who received [177Lu]Lu-PSMA-617 plus standard of care vs 13 [6%] of 205 who received standard of care only), lymphocyte concentrations (269 [51%] vs 39 [19%]), and platelet counts (49 [9%] vs five [2%]). Treatment-related adverse events leading to death occurred in five (1%) patients who received [177Lu]Lu-PSMA-617 plus standard of care (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received standard of care only. INTERPRETATION: [177Lu]Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to skeletal events compared with standard of care alone. These findings support the use of [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment. FUNDING: Advanced Accelerator Applications (Novartis).

Below-the-knee Amputation with Targeted Muscle Reinnervation: Operative Technique and Technical Pearls.

Postamputation pain from symptomatic neuromas and/or phantom limb pain can have a significant detrimental impact on patients' quality of life following a major lower extremity amputation. Various methods of physiologic nerve stabilization, such as targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface, have been proposed as the best current techniques to prevent that pathologic neuropathic pain. Methods: This article details our institution's technique that has been performed safely and effectively on over 100 patients. Our approach and rationale for each of the major nerves of the lower extremity are presented. Results: In contrast to other described techniques for TMR for below-the-knee amputations, this current protocol does not involve performing transfers on all five major nerves, as one must balance rates of symptomatic neuroma formation and nerve-specific phantom limb pain with needed operative time and surgical morbidity from removing proximal sensory function and denervation of the donor motor nerve branches. This technique also differs significantly from others by performing a transposition of the superficial peroneal nerve to place the neurorrhaphy away from the weight-bearing stump. Conclusion: This article details our institution's approach to physiologic nerve stabilization via TMR at time of below-the-knee amputation.

Perioperative misgendering experiences in patients undergoing gender-affirming surgery: a call for a gender-inclusive healthcare environment.

Background: Transgender individuals have long experienced discrimination and exclusion from medicine. Misgendering occurs when an individual is referred to using a gender or address incongruent with their identity. We evaluated the incidence of misgendering throughout the perioperative experience for patients undergoing gender-affirming surgery (GAS). Methods: Patients diagnosed with gender dysphoria who previously received GAS by the senior author were contacted to complete an IRB-approved survey to evaluate instances of misgendering while in the hospital for GAS. Study results were summarized using descriptive statistics. Results: Of 471 patients contacted, 182 completed the survey (38.6%). The most cited gender identity was transfemale (28.0%). Most patients reported respect for their gender identity (60.4%) and name (76.8%) during their perioperative experience. Twenty-two percent cited triggering experiences, and 15.4% reported interactions with healthcare employees causing them to reach out to a support system. Misgendering most commonly included incorrect use of patients' preferred names and/or pronouns (n = 50, 86.2%), most commonly at surgical check-in (n = 10, 45.5%). Recommendations to improve feelings of gender congruence during patients' stay included updated names and gender identities in electronic medical records (80.8%), and names and pronouns listed on curtains and doors (52.3%) and name tags (51.5%). Conclusions: Until now, the exact incidence of misgendering among patients seeking GAS have not been well established. Despite high levels of satisfaction, a large proportion still reported serious instances of misgendering. Improvements must be made to the perioperative experience to reduce misgendering and provide support and comfort during the sensitive period surrounding patients' gender transition.Level of evidence: Not gradable. Supplementary Information: The online version contains supplementary material available at 10.1007/s00238-022-02040-2.

Selecting a chest masculinization plastic surgeon: a survey of transgender patients.

Background: Chest masculinization is a commonly performed gender-affirming procedure in transmasculine and non-binary patients and has increased in prevalence in recent years despite continued barriers to surgical care. With the expansion of insurance coverage and trained surgeons, patients at times have the opportunity to be selective in choosing their gender-affirming surgeon. This study aimed to investigate factors that transmasculine individuals consider important when selecting their chest masculinization plastic surgeon. Methods: All patients who underwent chest masculinization with a single surgeon between January 2018 and December 2021 were surveyed via an online questionnaire to rate 21 factors associated with surgeon selection. Multiple-choice questions and free text space were included to further clarify patient preferences. Results were analyzed to rate factors in order of importance. Results: One hundred three individuals completed the survey, generating a response rate of 49.5%. Average patient age at time of surgery was 27.0 years, and 2.0% of patients had prior gender affirmation surgery (GAS). The top five most important factors were surgeon specialization in GAS, insurance coverage, board certification, number of times surgeon has performed procedure, and availability of Before and After photographs. The five least important factors were age of surgeon, medical publications, availability of YouTube videos, location of training, and surgeon presence on social media. Conclusions: Transmasculine patients employ distinct criteria when selecting a chest masculinization gender-affirming plastic surgeon. An improved understanding of these factors informs providers of ways to enhance patient access to information and gender-affirming care.Level of evidence: Not gradable.

A Pilot Investigation into Targeted Muscle Reinnervation for Complex Regional Pain Syndrome, Type II.

Complex regional pain syndrome (CRPS) is a debilitating condition, characterized by severe pain with vascular, motor, or trophic changes. Varied presentations make this a diagnostic and therapeutic challenge. There is a lack of high-quality evidence demonstrating efficacy for most existing therapies, particularly with surgical intervention for type II CRPS (CRPS-II). Targeted muscle reinnervation (TMR) is a surgical technique to transfer the terminal end of a divided nerve to a recipient motor nerve, shown to limit phantom limb pain, residual limb pain, and postamputation neuroma pain. Methods: Herein, we describe a series of 13 patients undergoing TMR for CRPS-II by a single surgeon from 2018 to 2021 in the upper (38%) and lower extremities (62%). All patients had a diagnosis of CRPS-II with either traumatic or postsurgical etiology, each seeking TMR with or without concomitant treatment to control their pain after previous therapies had failed. Three patients had previous lower extremity amputation, whereas three others received lower extremity amputation at the time of TMR, each indicated for control of CRPS pain. Results: Of the patients receiving TMR within 1 year of CRPS diagnosis, all three reported improved function, and two patients were able to tolerate a prosthetic for ambulation after previous pain prevented prosthetic use. Of the entire cohort, all but one patient reported reduced pain interference or improved function. Conclusions: These outcomes suggest that TMR may provide some benefit to reducing pain severity patients with CRPS, even after a more chronic disease course. Further prospective trials are warranted.

Prevalence of Comorbid Psychiatric Conditions and Chronic Pain in Patients Seeking Peripheral Nerve Surgery.

Background: In peripheral nerve surgery, the presence of psychiatric diagnoses and medications may affect outcomes and perioperative neuropathic pain management. The purpose of this study was to determine the prevalence of psychiatric diagnoses and chronic pain in patients referred to a peripheral nerve surgery clinic. Methods: This is a retrospective review of patients seen at a peripheral nerve clinic from July 1, 2017 to June 30, 2021. Medical records were reviewed for demographics; peripheral nerve diagnosis; psychiatric diagnoses; psychotropic prescriptions; use of nonneuroleptic/nonnarcotic, neuroleptic, and narcotic medications; and peripheral nerve surgical candidacy and outcome. Results: Six hundred twenty-two patients were included in this study. The most common reasons for referral were 24.8% lower extremity neuroma, 23.2% lower extremity compressive neuropathy, and 14.0% upper extremity compressive neuropathy. Of the included patients' 37.1% had a psychiatric diagnosis, and 36.3% were taking a psychotropic medication. The percentage of patients taking chronic nonneuroleptic/nonnarcotic pain medications was 34.3%' with 42.8% taking neuroleptic, and 24.9% narcotic medications. Patients with a psychiatric diagnosis were more likely to be taking neuroleptic (48.9% versus 38.9%, P < 0.001) and narcotic pain medications (27.3% versus 17.4%, P = 0.004) and less likely to have a positive surgical outcome (65.7% versus 83.0%, P = 0.001). Conclusions: Patients referred to a peripheral nerve surgery clinic frequently have psychiatric diagnoses and take chronic psychotropic and chronic pain medications. Knowledge of this will best help the peripheral nerve surgeon evaluate a patient for surgery, optimize perioperative care, and safely and effectively manage expectations.

Potential application of dental stem cells in regenerative reconstruction of oral and maxillofacial tissues: a narrative review.

Background and Objective: Oral and maxillofacial (OMF) defects caused by congenital conditions, injuries, ablative surgery for benign and malignant head & neck tumor, can often lead to OMF deformities and malfunctions in speech, mastication/chewing, and swallowing as well as have deleterious psychological effects and socioeconomic burdens to patients. Due to the unique complex 3D geometry of the head and neck region, reconstruction and rehabilitation of OMF defects remain a major challenge for OMF surgeons.The purpose of this narrative review is to update the information on the biological properties and functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their potential application in tissue engineering (TE) and regenerative reconstruction of OMF tissues. Methods: A data-based search was performed by using PubMed database whereby articles published between 2000 and 2021 in English were included in the search with the following key words: dental stem cells, OMF reconstruction, OMF TE and regeneration. Key Content and Findings: Currently, the advancement in stem cell biology, biomaterial science, and TE technology has demonstrated the significant potential application of stem cell-based therapy in regenerative reconstruction and rehabilitation of OMF defects. However, no stem cell-based product or device has been translated into clinical application to replace microsurgical free tissue transfer, the current mainstay of care in the reconstruction of OMF defects. Conclusions: Currently, microsurgical free tissue transfer remains the gold standard mainstay of care for the reconstruction of OMF defects due to their abundant blood supply and flexibility for transplantation. However, several major challenges, such as the limited availability, the requirement of a second surgery, donor site morbidity, and the risk of free flap failure, have promoted the development of novel approaches. Due to the advancement in stem cell biology, biomaterial science, and TE technology, stem cell-based regenerative therapy is emerging as a promising therapeutic approach for a variety of diseases, including regenerative reconstruction and rehabilitation of OMF defects. In this narrative review, we update on the characteristics and biological functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their released cell-free products, extracellular vesicles (EVs). We also highlighted their potential application in TE and regenerative reconstruction of OMF defects in animal models and clinical studies and the potential challenges in this field.

Anesthetic Management of an Adult With Hyperekplexia Undergoing a Laparoscopic Colectomy: A Case Report.

Hyperekplexia is a rare genetic disorder characterized by an exaggerated startle response to innocuous stimuli. There are several case reports documenting the administration of general anesthesia to infants and children with hyperekplexia and 1 case report documenting the use of a labor epidural in a parturient. These cases suggest a possible resistance to depolarizing neuromuscular blocking agents and increased risk of malignant hyperthermia. There are no case reports of adults with hyperekplexia receiving general anesthesia. We report the case of a 20-year-old woman with hyperekplexia who safely received general anesthesia without neuromuscular blockade for a laparoscopic colectomy.

Facial Feminization Surgery: A Systematic Review of Perioperative Surgical Planning and Outcomes.

Background: Facial feminization is a critical step in a transfeminine patient's surgical transition. However, the existing literature on the various types of feminization surgeries suffers from inadequate reporting on perioperative aspects of care, such as preoperative evaluation and postoperative outcomes. The aim of this study is to evaluate facial feminization surgery (FFS), preoperative planning, and patient reported outcomes after various types of procedures. Methods: An electronic database search of Ovid MEDLINE was completed according to PRISMA guidelines for articles pertaining to FFS. Study characteristics, operative information, and patient demographics were collected. Data concerning preoperative imaging, virtual simulation, postoperative complications, and patient-reported outcome measures (PROMs) were collected and analyzed for patterns. Results: A total of 22 papers representing 1302 patients were included for analysis. The most commonly discussed operations included upper face procedures, particularly of the forehead (17 studies, 77%). When discussed, preoperative planning for FFS included standard photography in 19 (86%) studies, advanced imaging, such as cephalometry or computed tomography, in 12 (55%) studies, and virtual simulation of surgical outcomes in four (18%) studies. Patient-centered outcomes, such as postoperative satisfaction, were described in 17 (77%) studies. Standardized PROMs were heterogenous across included studies with only 11 (50%) including at least one PROM. Conclusions: FFS is common, safe, and highly satisfying for transfeminine patients seeking surgical intervention for identity actualization. Future research concerning transgender care must evaluate advanced surgical planning and 3D simulation combined with more standardized assessment of PROMs to ensure high-quality analysis of patient satisfaction.

Incidence and Nerve Distribution of Symptomatic Neuromas and Phantom Limb Pain after Below-Knee Amputation.

BACKGROUND: Patients with major lower limb amputations suffer from symptomatic neuromas and phantom-limb pain due to their transected nerves. Peripheral nerve surgery techniques, such as targeted muscle reinnervation and regenerative peripheral nerve interface, aim to physiologically prevent this nerve-specific pain. No studies have specifically reported on which nerves most frequently cause chronic pain. The authors studied the nerve-specific incidence of symptomatic neuroma formation and phantom limb pain in patients undergoing a below-knee amputation, to better tailor use of targeted muscle reinnervation and regenerative peripheral nerve interface. METHODS: This was a retrospective review of all patients undergoing a below-knee amputation from January 1, 2013, to December 31, 2018, at MedStar Georgetown University Hospital. All below-knee amputations were performed with a posterior skin flap, myotenodesis, and traction neurectomies of all nerves. Postoperative notes were reviewed for the presence of a symptomatic neuroma, defined as localized pain and a Tinel sign over a known sensory nerve, and nerve-specific phantom limb pain, defined as pain of the missing limb corresponding to a known dermatome. RESULTS: One hundred ninety-eight patients were included in this study. The rate of symptomatic neuroma formation was 14.6 percent (29 of 198), with the superficial peroneal and saphenous nerves most often involved. Diabetes and obesity were protective against symptomatic neuroma formation. The rate of nerve-specific phantom limb pain was 12.6 percent (25 of 198) and highly correlated with the presence of a symptomatic neuroma. CONCLUSION: To optimize outcomes for amputees, it is critical that surgeons best understand what nerves are more likely to form symptomatic neuromas and lead to nerve-specific phantom limb pain, so that surgeons can best tailor primary or secondary management of the major sensory nerves. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Targeted Muscle Reinnervation Improves Pain and Ambulation Outcomes in Highly Comorbid Amputees.

BACKGROUND: Approximately 200,000 people undergo a lower extremity amputation each year. Following amputation, patients suffer from chronic pain, inability to ambulate, and high mortality rates. Targeted muscle reinnervation is a nerve transfer procedure that redirects transected sensory and mixed nerves into motor nerves to treat neuroma and phantom limb pain. This study evaluates outcomes with prophylactic targeted muscle reinnervation at the time of below-knee amputation. METHODS: This is a cohort study comparing 100 patients undergoing below-knee amputation with primary targeted muscle reinnervation and 100 patients undergoing below-knee amputation with standard traction neurectomy and muscle implantation. Outcome metrics included the presence of residual and phantom limb pain, pain severity, opioid use, ambulation ability, and mortality rates. RESULTS: The targeted muscle reinnervation group was on average 60 years old with a body mass index of 29 kg/m2. Eighty-four percent had diabetes, 55 percent had peripheral vascular disease, and 43 percent had end-stage renal disease. Average follow-up was 9.6 months for the targeted muscle reinnervation group and 18.5 months for the nontargeted muscle reinnervation group. Seventy-one percent of targeted muscle reinnervation patients were pain free, compared with 36 percent (p < 0.01). Fourteen percent of targeted muscle reinnervation patients had residual limb pain, compared with 57 percent (p < 0.01). Nineteen percent of targeted muscle reinnervation patients had phantom limb pain, compared with 47 percent (p < 0.01). Six percent of targeted muscle reinnervation patients were on opioids, compared with 26 percent (p < 0.01); and 90.9 percent of targeted muscle reinnervation patients were ambulatory, compared with 70.5 percent (p < 0.01). CONCLUSION: Targeted muscle reinnervation reduces pain and improves ambulation in patients undergoing below-knee amputation, which may be critical in improving morbidity and mortality rates in this comorbid patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

High-Dose-Rate Brachytherapy for Primary Treatment of Refractory Proliferative Verrucous Leukoplakia of the Hard Palate.

Oral proliferative verrucous leukoplakia (PVL) is a rare, progressive form of leukoplakia with a high rate of malignant transformation. No therapies are known to lower the rate of malignant transformation and prevent a recurrence. An 84-year-old patient with a years-long history of symptomatic PVL of the hard palate refractory to CO2 laser ablation presented to the radiation oncology clinic for consideration of non-surgical management. High dose rate brachytherapy was used to deliver 36 Gy in 12 fractions to the hard palate using an Ir-192 source with a custom-molded applicator. By three months of follow-up, the patient had complete regression of the PVL and resolution of acute mucositis. With 18 months of follow-up, the patient remains disease- and symptom-free without toxicities of treatment. High dose rate surface applicator brachytherapy is a feasible and potentially effective treatment for oral PVL, yielding durable control with low long-term toxicity.

Retention Sutures and Negative Pressure Wound Therapy for Delayed Primary Closure of Fasciotomy Wounds.

Achieving primary closure of lower extremity fasciotomy wounds is difficult. Surgeons are faced with the option of waiting potentially long periods of time for edema to reside, in order to attempt delayed primary closure (DPC) versus closing at an earlier time with a split thickness skin graft. DPC offers superior aesthetic outcomes than split thickness skin grafts but traditionally cannot occur until later in the clinical course once excessive edema has subsided. We present a case of a young athlete with compartment syndrome, which was managed with an alternative technique for achieving DPC: serial partial closure under tension with retention sutures and negative pressure wound therapy. The successful outcome in this single case should prompt further studies investigating the objective benefits of this novel method to achieve DPC following fasciotomy.

Targeted Muscle Reinnervation to Expendable Motor Nerves for the Treatment of Refractory Symptomatic Neuromas in Nonamputees.

Symptomatic neuromas can cause debilitating pain, significantly impairing patients' quality of life. There are numerous medical and surgical options for management. Targeted muscle reinnervation (TMR) is a nerve transfer procedure that is now commonly used to prevent or treat symptomatic neuromas or phantom limb pain in amputees. There are a few reports in the current literature about performing TMR in the nonamputee, but no cohort studies to date that report pain outcomes. This study evaluates TMR to treat symptomatic neuromas in nonamputee patients. This is a retrospective cohort study of all patients with symptomatic neuromas treated with TMR over a 1-year period from January 1,2019, to January 1, 2020, at MedStar Georgetown University Hospital. The neuromas are excised to healthy nerve fascicles, and a redundant donor motor fascicle is selected for nerve transfer. Patients were asked in clinic or via telephone about their preoperative and postoperative pain, function, and quality of life, and postoperative clinic notes were reviewed for complications and motor deficits. Fifteen patients were included in this study. Patients had symptomatic neuromas involving the upper extremity, lower extremity, and trunk. Pain frequency decreased from 6.7 times per week to 3.9 (P < 0.01) and from 9.1 times per day to 5.1 (P < 0.01). Pain severity decreased from an average of 7.9/10 to 4.3/10 (P < 0.01). Overall physical function increased from 3.7/10 to 5.8/10 (P = 0.01), and overall quality of life increased from 4.9/10 to 7.0/10 (P < 0.01). No patients had demonstrable weakness of the motor function of the donor nerve. Targeted muscle reinnervation is a viable surgical option for the treatment of symptomatic neuromas, particularly in those patients who have previously failed prior neuroma excisions.

Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction.

Auricular reconstruction is a technically demanding procedure requiring significant surgical expertise, as the current gold standard involves hand carving of the costal cartilage into an auricular framework and re-implantation of the tissue. 3D-printing presents a powerful tool that can reduce technical demands associated with the procedure. Our group compared clinical, radiological, histological, and biomechanical outcomes in single- and two-stage 3D-printed auricular tissue scaffolds in an athymic rodent model. Briefly, an external anatomic envelope of a human auricle was created using DICOM computed tomography (CT) images and modified in design to create a two-stage, lock-in-key base and elevating platform. Single- and two-stage scaffolds were 3D-printed by laser sintering poly-L-caprolactone (PCL) then implanted subcutaneously in five athymic rats each. Rats were monitored for ulcer formation, site infection, and scaffold distortion weekly, and scaffolds were explanted at 8 weeks with analysis using microCT and histologic staining. Nonlinear finite element analysis was performed to determine areas of high strain in relation to ulcer formation. Scaffolds demonstrated precise anatomic appearance and maintenance of integrity of both anterior and posterior auricular surfaces and scaffold projection, with no statistically significant differences in complications noted between the single- and two-staged implantation. While minor superficial ulcers occurred most commonly at the lateral and superior helix coincident with finite element predictions of high skin strains, evidence of robust tissue ingrowth and angiogenesis was visible grossly and histologically. This promising preclinical small animal model supports future initiatives for making clinically viable options for an ear tissue scaffold.

Hybrid Three-Dimensional-Printed Ear Tissue Scaffold With Autologous Cartilage Mitigates Soft Tissue Complications.

OBJECTIVES/HYPOTHESIS: To analyze the use of highly translatable three-dimensional (3D)-printed auricular scaffolds with and without novel cartilage tissue inserts in a rodent model. STUDY DESIGN: Preclinical rodent animal model. METHODS: This prospective study assessed a single-stage 3D-printed auricular bioscaffold with or without porcine cartilage tissue inserts in an athymic rodent model. Digital Imaging and Communications in Medicine computed tomography images of a human auricle were segmented to create an external anatomic envelope filled with orthogonally interconnected spherical pores. Scaffolds with and without tissue inset sites were 3D printed by laser sintering bioresorbable polycaprolactone, then implanted subcutaneously in five rats for each group. RESULTS: Ten athymic rats were studied to a goal of 24 weeks postoperatively. Precise anatomic similarity and scaffold integrity were maintained in both scaffold conditions throughout experimentation with grossly visible tissue ingrowth and angiogenesis upon explantation. Cartilage-seeded scaffolds had relatively lower rates of nonsurgical site complications compared to unseeded scaffolds with relatively increased surgical site ulceration, though neither met statistical significance. Histology revealed robust soft tissue infiltration and vascularization in both seeded and unseeded scaffolds, and demonstrated impressive maintenance of viable cartilage in cartilage-seeded scaffolds. Radiology confirmed soft tissue infiltration in all scaffolds, and biomechanical modeling suggested amelioration of stress in scaffolds implanted with cartilage. CONCLUSIONS: A hybrid approach incorporating cartilage insets into 3D-printed bioscaffolds suggests enhanced clinical and histological outcomes. These data demonstrate the potential to integrate point-of-care tissue engineering techniques into 3D printing to generate alternatives to current reconstructive surgery techniques and avoid the demands of traditional tissue engineering. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1008-1015, 2021.