Microsurgical Practice with Use of Smartphone Camera as the Microscopic Field.

Accessibility of microsurgical equipment is a major barrier to proper training of surgeons before live patient free flap surgery. A technique is presented that uses a smartphone camera as the microscopic field, eliminating the need for an expensive operative microscope for surgical practice. A convenient and cost-effective simulation protocol could reduce the time frame of the microsurgery learning curve. Furthermore, the use of the smartphone video function may allow improved feedback by mentors, improving access and communication between microsurgical teachers and learners. The PocketSuture smartphone stand is a commercially available device that allows the smartphone camera to be used as magnification. The proposed education protocol included suture practice, vessel dissection, and free tissue transfer in nonliving animal models, with vessel anastomosis and patency confirmation performed with a smartphone camera for field magnification. Video of the suturing technique allowed feedback from the mentor. A progressive suturing protocol leading to the ability to perform microsurgical anastomosis on nonliving animal models was developed. The basic costs for the stand, instrument set and suture were less than $500. The PocketSuture smartphone stand can be used for microsurgical training with real-time video for plastic surgery learners with limited access to microscopes and local mentors.

CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Fetal surgery for open neural tube defect with severe ventriculomegaly.

OBJECTIVE: Prenatal open neural tube defect (ONTD) repair is performed to decrease the risk of needing treatment for hydrocephalus after birth and to preserve motor function. Some centers may not consider patients to be candidates for surgery if severe ventriculomegaly is present and there is no expected benefit in risk for hydrocephalus treatment. This study sought to compare the postnatal outcome of fetuses with ONTD and severe ventriculomegaly (ventricular width ≥ 15 mm) that underwent prenatal repair with the outcome of fetuses with severe ventriculomegaly that underwent postnatal repair and fetuses without severe ventriculomegaly (< 15 mm) that underwent prenatal repair. METHODS: This was a retrospective study of fetuses with ONTD that underwent prenatal or postnatal repair between 2012 and 2021 at a single institution. The cohort was divided into two groups based on preoperative fetal ventricular size: those with severe ventriculomegaly (ventricular width ≥ 15 mm) and those without severe ventriculomegaly (< 15 mm). Fetal ventricular size was measured by magnetic resonance imaging before surgery using the standardized approach and the mean size of the left and right ventricles was used for analysis. Motor function of the lower extremities was assessed at the time of referral by ultrasound and if flexion-extension movements of the ankle were seen it was considered as preserved S1 motor function. Postnatal outcomes, including motor function of the lower extremities at birth and the need for a diversion procedure for hydrocephalus treatment during the first year after birth, were collected and compared between groups. Multivariate regression analysis was used to adjust for potential confounders. RESULTS: In this study, 154 patients were included: 145 underwent fetal surgery (101 fetoscopic and 44 open hysterotomy) and nine with severe ventriculomegaly underwent postnatal repair. Among the 145 patients who underwent fetal surgery, 22 presented with severe ventriculomegaly. Fetuses with severe ventriculomegaly at referral that underwent prenatal repair were significantly more likely to need hydrocephalus treatment by 12 months after birth than those without severe ventriculomegaly (61.9% vs 28.9%, P < 0.01). However, motor function assessment at birth was similar between both prenatal repair groups (odds ratio, 0.92 (95% CI, 0.33-2.59), P = 0.88), adjusted for the anatomical level of the lesion. The prenatal repair group with severe ventriculomegaly had better preserved motor function at birth compared to the postnatal repair group with severe ventriculomegaly (median level, S1 vs L3, P < 0.01; proportion with S1 motor function, 68.2% vs 11.1%, P < 0.01). Fetuses with severe ventriculomegaly that underwent prenatal repair had an 18.9 (95% CI, 1.2-290.1)-times higher chance of having intact motor function at birth, adjusted for ethnicity, presence of club foot at referral and gestational age at delivery, compared with the postnatal repair group. There was no significant difference in the need for hydrocephalus treatment in the first year after birth between prenatal and postnatal repair groups with severe ventriculomegaly (61.9% vs 87.5%, P = 0.18). CONCLUSIONS: Although fetuses with ONTD and severe ventriculomegaly do not seem to benefit from fetal surgery in terms of postnatal hydrocephalus treatment, there is an increased chance of preserved motor function at birth. Results from this study highlight the benefit of prenatal ONTD repair for cases with severe ventriculomegaly at referral to preserve motor function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

A conserved but structurally divergent loop in acyl protein thioesterase 1 regulates its catalytic activity, ligand binding, and folded stability.

Human acyl protein thioesterases (APTs) catalyze the depalmitoylation of S-acylated proteins attached to the plasma membrane, facilitating reversible cycles of membrane anchoring and detachment. We previously showed that a bacterial APT homologue, FTT258 from the gram-negative pathogen Francisella tularensis, exists in equilibrium between a closed and open state based on the structural dynamics of a flexible loop overlapping its active site. Although the structural dynamics of this loop are not conserved in human APTs, the amino acid sequence of this loop is highly conserved, indicating essential but divergent functions for this loop in human APTs. Herein, we investigated the role of this loop in regulating the catalytic activity, ligand binding, and protein folding of human APT1, a depalmitoylase connected with cancer, immune, and neurological signaling. Using a combination of substitutional analysis with kinetic, structural, and biophysical characterization, we show that even in its divergent structural location in human APT1 that this loop still regulates the catalytic activity of APT1 through contributions to ligand binding and substrate positioning. We confirmed previously known roles for multiple residues (Phe72 and Ile74) in substrate binding and catalysis while adding new roles in substrate selectivity (Pro69), in catalytic stabilization (Asp73 and Ile75), and in transitioning between the membrane binding ß-tongue and substrate-binding loops (Trp71). Even conservative substitution of this tryptophan (Trp71) fulcrum led to complete loss of catalytic activity, a 13°C decrease in total protein stability, and drastic drops in ligand affinity, indicating that the combination of the size, shape, and aromaticity of Trp71 are essential to the proper structure of APT1. Mixing buried hydrophobic surface area with contributions to an exposed secondary surface pocket, Trp71 represents a previously unidentified class of essential tryptophans within α/ß hydrolase structure and a potential allosteric binding site within human APTs.

Ambulation after in-utero fetoscopic or open neural tube defect repair: predictors for ambulation at 30 months.

OBJECTIVES: To compare the ambulatory status of a cohort of children who had undergone prenatal repair of an open neural tube defect (ONTD) using one of two different methods (fetoscopic or open hysterotomy) with that of a cohort who had undergone postnatal repair, and to identify the best predictors of ambulation at 30 months of age. METHODS: This was a retrospective review of a cohort of children who underwent ONTD repair either prenatally (n = 110), by fetoscopic surgery (n = 73) or open hysterotomy surgery (n = 37), or postnatally (n = 51), in a single tertiary hospital between November 2011 and May 2023. The cohort comprised a consecutive sample of cases who had undergone ONTD repair in-utero following Management of Myelomeningocele Study (MOMS) trial criteria and cases who had undergone postnatal repair, meeting the same criteria, which were also followed up after birth at the same institution. Motor function assessment by ultrasound was recorded at referral, 6 weeks after prenatal repair, or after referral in postnatally repaired cases, and at the last ultrasound scan before delivery. Clinical examinations to assess motor function at birth and at 12 months were retrieved from records. Intact motor function was defined as first sacral myotome (S1) motor function. Ambulatory status data at each follow-up visit were collected. The proportion of children who were able to walk independently after 30 months of age was compared between those who had undergone fetoscopic vs open prenatal surgery and between prenatal (by either fetoscopic or open surgery) and postnatal ONTD repair. Logistic regression analyses were performed to identify predictors for independent ambulation. RESULTS: After 30 months, the proportion of infants who were able to walk independently was higher in prenatally vs postnatally repaired cases (51.8% vs 15.7%, P < 0.01), and there was no difference between those with fetoscopic (52.1%) vs open (51.4%) prenatal repair (P = 0.66). In the prenatally repaired group, having intact motor function at 12 months (adjusted odds ratio (aOR), 9.14 (95% CI, 2.64-31.63), P < 0.01) and at birth (aOR, 4.50 (95% CI, 1.21-16.80), P = 0.02) were significant predictors of independent walking at 30 months; an anatomical level of lesion below L2 at referral (aOR, 1.83 (95% CI, 1.30-2.58), P = 0.01) and female gender (aOR, 3.51 (95% CI, 1.43-8.61), P < 0.01) were also predictive for this outcome. CONCLUSIONS: Prenatally repaired cases of ONTD have a better chance of being able to walk independently at 30 months than do those who undergo postnatal repair. In patients with prenatally repaired ONTD, ambulatory status at 30 months can be predicted by observing a low lesion level at referral (below L2) and intact motor function postnatally. These results have implications for parental counseling and planning for supportive therapy in pregnancies affected by ONTD. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Perforation of cavum septi pellucidi in open spina bifida and need for hydrocephalus treatment by 1 year of age.

OBJECTIVE: In-utero repair of an open neural tube defect (ONTD) reduces the risk of developing severe hydrocephalus postnatally. Perforation of the cavum septi pellucidi (CSP) may reflect increased intraventricular pressure in the fetal brain. We sought to evaluate the association of perforated CSP visualized on fetal imaging before and/or after in-utero ONTD repair with the eventual need for hydrocephalus treatment by 1 year of age. METHODS: This was a retrospective cohort study of consecutive patients who underwent laparotomy-assisted fetoscopic ONTD repair between 2014 and 2021 at a single center. Eligibility criteria for surgery were based on those of the Management of Myelomeningocele Study (MOMS), although a maternal prepregnancy body mass index of up to 40 kg/m2 was allowed. Fetal brain imaging was performed with ultrasound and magnetic resonance imaging (MRI) at referral and 6 weeks postoperatively. Stored ultrasound and MRI scans were reviewed retrospectively to assess CSP integrity. Medical records were reviewed to determine whether hydrocephalus treatment was needed within 1 year of age. Parametric and non-parametric tests were used as appropriate to compare outcomes between cases with perforated CSP and those with intact CSP as determined on ultrasound at referral. Logistic regression analysis was performed to assess the predictive performance of various imaging markers for the need for hydrocephalus treatment. RESULTS: A total of 110 patients were included. Perforated CSP was identified in 20.6% and 22.6% of cases on preoperative ultrasound and MRI, respectively, and in 26.6% and 24.2% on postoperative ultrasound and MRI, respectively. Ventricular size increased between referral and after surgery (median, 11.00 (range, 5.89-21.45) mm vs 16.00 (range, 7.00-43.5) mm; P < 0.01), as did the proportion of cases with severe ventriculomegaly (ventricular width ≥ 15 mm) (12.7% vs 57.8%; P < 0.01). Complete CSP evaluation was achieved on preoperative ultrasound in 107 cases, of which 22 had a perforated CSP and 85 had an intact CSP. The perforated-CSP group presented with larger ventricles (mean, 14.32 ± 3.45 mm vs 10.37 ± 2.37 mm; P < 0.01) and a higher rate of severe ventriculomegaly (40.9% vs 5.9%; P < 0.01) compared to those with an intact CSP. The same trends were observed at 6 weeks postoperatively for mean ventricular size (median, 21.0 (range, 13.0-43.5) mm vs 14.3 (range, 7.0-29.0) mm; P < 0.01) and severe ventriculomegaly (95.0% vs 46.8%; P < 0.01). Cases with a perforated CSP at referral had a lower rate of hindbrain herniation (HBH) reversal postoperatively (65.0% vs 88.6%; P = 0.01) and were more likely to require treatment for hydrocephalus (89.5% vs 22.7%; P < 0.01). The strongest predictor of the need for hydrocephalus treatment within 1 year of age was lack of HBH reversal on MRI (odds ratio (OR), 36.20 (95% CI, 5.96-219.12); P < 0.01) followed by perforated CSP on ultrasound at referral (OR, 23.40 (95% CI, 5.42-100.98); P < 0.01) and by perforated CSP at 6-week postoperative ultrasound (OR, 19.48 (95% CI, 5.68-66.68); P < 0.01). CONCLUSIONS: The detection of a perforated CSP in fetuses with ONTD can reliably identify those cases at highest risk for needing hydrocephalus treatment by 1 year of age. Evaluation of this brain structure can improve counseling of families considering fetal surgery for ONTD, in order to set appropriate expectations about postnatal outcome. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Delayed skin grafting protocol following Integra™ application for non-radiated scalp reconstruction for decreased wound depth and improved contour.

The clinical use of Integra™ has expanded to include scalp reconstruction since its FDA approval in 1996. Integra™, or dermal regeneration template, can be utilized in patients who are elderly with multiple medical comorbidities. Well-established Integra™ techniques utilize skin grafting 1-2 weeks following evidence of template vascularity. Most studies show the time to graft placement as <30 days, with almost all <52 days. No single article proposes a time frame for applying STSG after neodermis regeneration. Therefore, we aimed to describe our protocol to define a time frame for delaying scalp reconstruction with STSG following dermal regeneration. Over the last several years, the senior author has utilized a delayed reconstruction with skin grafting method where-in Integra™ is applied to either debrided bone or exposed pericranium in selected patients, and allowed to mature for ~6 weeks before performing skin grafting. The results have been predictable, reproducible, and have yielded high levels of patient and provider satisfaction due to the improved contour cosmesis. In this pictorial essay, the authors' novel protocol is detailed.

Implantable arterial doppler efficacy in free flap reconstruction: A systematic review and meta-analysis.

The implantable arterial doppler (IAD) is frequently used to postoperatively monitor free flaps with high accuracy, but there are no guidelines for its use. Bedside exam is used adjunctively to determine necessary intervention. This systematic review seeks to discover why the doppler is used adjunctively despite its established record of accuracy. Criteria for inclusion and exclusion were established. In total, 280 articles were found on PubMed and Web of Science, then screened accordingly. Data from 22 articles were analyzed using a bivariate hierarchical random effects model. Twenty-two studies yielded 2996 total patients undergoing 3127 free flap procedures. The meta-analysis found a high sensitivity of 0.809 (95% CI = 0.709, 0.880) and specificity of 0.966 (95% CI = 0.947, 0.979). False-positive rate was found to be 0.034 (95% CI = 0.021, 0.053). Positive and negative predictive values were 0.711 (95% CI = 0.581, 0.817) and 0.979 (95% CI = 0.966, 0.988). Positive and negative likelihood ratios were 24.7 (95% CI = 14.5, 39.5) and 0.20 (95% CI = 0.12, 0.30). The established efficacy of the IAD is supported by this study. Clinical exams may remain as the final adjunct due to the risks of inaccurate IAD signals. Further studies are warranted to optimize its use for future practice guidelines.

Examining Trends in Implantable Arterial Doppler Usage Among North American Head and Neck Microsurgeons: A Survey Study.

BACKGROUND: There are variations in implantable arterial Doppler usage for microvascular free tissue monitoring among North American surgeons. Identifying utilization trends among the microvascular community may elucidate practice patterns that may be useful in determining protocols. Furthermore, study of this information may yield novel and unique applications in other disciplines such as vascular surgery. METHODS: Electronically disseminated survey study shared with a large database of North American head and neck microsurgeons. RESULTS: Seventy four percent of respondents use the implantable arterial Doppler; 69% report use in all cases. Ninety five percent remove the Doppler by the seventh postoperative day. All respondents felt that the Doppler did not impede care progression. Any implication of flap compromise was followed with a clinical assessment in 100% of respondents. If viable, 89% would continue monitoring after clinical examination, while 11% would take the patient for exploration regardless of clinical examination. CONCLUSIONS: The efficacy of the implantable arterial Doppler has been established in the literature and is supported by the results of this study. Further investigation is required to establish a consensus on use guidelines. The implantable Doppler is more often used in conjunction with rather than substitution for clinical examination.

CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.

Impact of smoking on donor site following rectus flap harvest for head and neck reconstruction.

OBJECTIVES: The rectus abdominis myocutaneous free flap has been widely used as a reconstructive option in head and neck reconstruction with great success. Challenging the popular assumption, this study sought to examine the effects of smoking on donor site complications in this population. METHODS: Multi-institution retrospective study of 103 patients (50 active smokers, 28 former and 25 never smoked). RESULTS: Overall complication rate was 14.5 %. Hernia rate 4.8 %, evisceration 0 %, dehiscence 2.9 %, infection 6.7 %. Smoking history did not significantlly influence complication rates (chi square test, p = 0.33). Abdominal wall closure technique also did not influence the complication rate (chi square test, p = 0.58). CONCLUSIONS: The rectus abdomonis myocutaneous free flap has an acceptable complication rate that does not appear to be influenced by smoking history. While patients should be counseled regarding smoking cessation, smoking habits should not delay treatment nor obviate consideration of rectus flap utilization.

Forked Paramedian forehead flap combined with nasolabial flap for pre-radiation coverage of exposed maxilla in the Total Rhinectomy patient.

Total rhinectomy is ontologically necessary for large and locally invasive carcinomas of the nasal cavity owing to the complex three-dimensional structure of the nose. Reconstruction options include singular or combined options of local tissue rearrangement, free flap reconstruction, and prosthetic reconstruction which may be delayed in the setting of post-ablative radiation therapy. If significant bony exposure is present prior to radiation, there is a substantial risk of osteoradionecrosis and the ensuing sequalae. In these cases, coverage of the bony defect may be advantageous prior to radiation and final reconstructive treatment. We present a case of a total rhinectomy defect for squamous cell carcinoma in a patient who had significant bony exposure prior to radiation which was resurfaced with a combined forked paramedian flap and nasolabial flap. The patient went on to be treated with a full course of radiation and had planned for a post-treatment nasal prosthesis.

Flap Debulking and Secondary Revisions in Head and Neck Reconstruction: A Systematic Review with Clinical Applications.

Flap debulking and secondary revisions are an integral factor in providing optimum outcomes to reconstructive patients. This review article summarizes systematically the available literature on flap debulking in head and neck reconstruction. The clinical applications of debulking techniques are discussed, including fractional direct excision, liposuction, and single-stage excision or planning with skin grafting. New technologies are also discussed.

Implication of chromosomal microarray analysis prior to in-utero repair of fetal open neural tube defect.

OBJECTIVE: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair. METHODS: This was a retrospective cohort study of pregnancies complicated by ONTD that underwent laparotomy-assisted fetoscopic repair or open-hysterotomy fetal surgery at a single tertiary center between September 2011 and July 2021. All patients met the MOMS eligibility criteria and had a normal karyotype. In a subset of the pregnancies (n = 77), CMA testing was also conducted. We reviewed the CMA results and divided the cohort into two groups according to whether clinically reportable copy-number variants (CNV) were detected (reportable-CNV group) or not (normal-CMA group). Surgical characteristics, complications, and maternal and early neonatal outcomes were compared between the two groups. The primary outcomes were fetal or neonatal death, hydrocephalus, motor function at 12 months of age and walking status at 30 months of age. Standard parametric and non-parametric statistical tests were employed as appropriate. RESULTS: During the study period, 146 fetuses with ONTD were eligible for and underwent in-utero repair. CMA results were available for 77 (52.7%) patients. Of those, 65 (84%) had a normal CMA and 12 (16%) had a reportable CNV, two of which were classified as pathogenic. The first case with a pathogenic CNV was diagnosed with a 749-kb central 22q11.21 deletion spanning low-copy-repeat regions B-D of chromosome 22; the second case was diagnosed with a 1.3-Mb interstitial deletion at 1q21.1q21.2. Maternal demographics, clinical characteristics, operative data and postoperative complications were similar between those with normal CMA results and those with reportable CNVs. There were no significant differences in gestational age at delivery or any obstetric and early neonatal outcome between the study groups. Motor function at birth and at 12 months of age, and walking status at 30 months of age, were similar between the two groups. CONCLUSIONS: Standard diagnostic testing with CMA should be offered when an ONTD is detected prenatally, as this approach has implications for counseling regarding prognosis and recurrence risk. Our results indicate that the presence of a clinically reportable CNV should not a priori affect eligibility for in-utero repair, as overall pregnancy outcome is similar in these cases to that of cases with normal CMA. Nevertheless, significant CMA results will require a case-by-case multidisciplinary discussion to evaluate eligibility. To generalize the conclusion of this single-center series, a larger, multicenter long-term study should be considered. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A protracted outbreak of difficult-to-treat resistant Pseudomonas aeruginosa in a haematology unit: a matched case-control study demonstrating increased risk with use of fluoroquinolone.

BACKGROUND: Between September 2016 and November 2020, 17 cases of difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) were reported in haematology patients at a tertiary referral hospital in the North of England. AIM: A retrospective case-control study was conducted to investigate the association between DTR-PA infection and clinical interventions, patient movement, antimicrobial use and comorbidities. METHODS: Cases were patients colonized or infected with the outbreak strain of DTR-PA who had been admitted to hospital prior to their positive specimen. Exposures were extracted from medical records, and cases were compared with controls using conditional logistic regression. Environmental and microbiological investigations were also conducted. FINDINGS: Seventeen cases and 51 controls were included. The final model included age [>65 years, adjusted OR (aOR) 6.85, P=0.232], sex (aOR 0.60, P=0.688), admission under the transplant team (aOR 14.27, P=0.43) and use of ciprofloxacin (aOR 102.13, P=0.030). Investigations did not indicate case-to-case transmission or a point source, although a common environmental source was highly likely. CONCLUSION: This study found that the use of fluoroquinolones is an independent risk factor for DTR-PA in haematology patients. Antimicrobial stewardship and review of fluoroquinolone prophylaxis should be considered as part of PA outbreak investigations in addition to standard infection control interventions.

Intraoral nasolabial flap for lower lip augmentation following post-radiation contracture.

The nasolabial flap (NLF) has been reported extensively for reconstruction of various intraoral and extraoral defects resulting from trauma or ablative surgery. However, it has not been described for post-radiation lip augmentation. Herein, we present the case of a 74-year-old female who previously underwent a subtotal glossectomy and free flap reconstruction followed by radiotherapy. While oncologically the patient did well, she developed a significant lower lip contracture which compromised oral intake, denture placement, lip excursion, and psychosocial well-being. The patient underwent release of the scar contracture and a NLF was utilized intraorally to act as a spacer between the gingiva and inner lip mucosa to augment the soft tissue deficit. The patient went on to regain oral intake and placement of her dentures, while reporting significant satisfaction with the post-procedural benefits.

Topical application of gemcitabine generates microvesicle particles in human and murine skin.

Chemotherapy has remained the mainstay for the treatment of multiple types of cancers. In particular, topical use of chemotherapy has been used for skin cancers. Though effective, topical chemotherapy has been limited due to adverse effects such as local and even systemic toxicities. Our recent studies demonstrated that exposure to pro-oxidative stressors, including therapeutic agents induces the generation of extracellular vesicles known as microvesicle particles (MVP) which are dependent on activation of the Platelet-activating factor-receptor (PAFR), a G-protein coupled receptor present on various cell types, and acid sphingomyelinase (aSMase), an enzyme required for MVP biogenesis. Based upon this premise, we tested the hypothesis that topical application of gemcitabine will induce MVP generation in human and murine skin. Our ex vivo studies using human skin explants demonstrate that gemcitabine treatment results in MVP generation in a dose-dependent manner in a process blocked by PAFR antagonist and aSMase inhibitor. Importantly, gemcitabine-induced MVPs carry PAFR agonists. To confirm the mechanisms, we employed PAFR-expressing and deficient (Ptafr-/- ) mouse models as well as mice deficient in aSMase enzyme (Spmd1-/- ). Similar to the findings using pharmacologic tools, genetic-based approaches demonstrate that gemcitabine-induced MVP release in WT mice was blunted in Ptafr-/- and Spmd1-/- mice. These findings demonstrate a novel mechanism by which local chemotherapy can generate bioactive components as a bystander effect in a process that is dependent upon the PAFR-aSMase pathway.

"Learning from the experts" - a novel advanced cadaveric course for Gynaecological Oncology (GO) Cytoreductive Surgery.

Background: Ovarian cancer cytoreductive surgery necessitates the use of advanced Simulation-Based Learning (SBL) to optimise skill-based teaching and achieve technical proficiency. Objective: We describe and appraise the role of a novel postgraduate cadaveric course for cytoreductive surgery for advanced ovarian/fallopian tube or primary peritoneal cancer. Materials and Methods: Several consultant-level surgeons with expertise in upper gastrointestinal, colorectal, hepatobiliary and urological surgery, were invited to teach their counterpart gynaecological oncology (GO) surgeons. The 2-day course curriculum involved advanced dissections on thiel-embalmed cadavers. All dissections included applicable steps required during GO cytoreductive surgeries. Outcome measures: We used a feedback questionnaire and structured interviews to capture trainers and delegates views respectively. Results: All delegates reported a positive educational experience and improvement of knowledge in all course components. There was no difference in the perception of feedback across junior versus senior consultants. Trainers perceived this opportunity as a "2-way learning" whether they got to explore in depth the GO perspective in how and which of their skills are applicable during cytoreductive surgery. Conclusions: Collaborating with other surgical specialities promotes a "learning from the experts" concept and has potential to meet the rapidly increased demand for multi-viscera surgical excellence in GO surgery. What's new?: The concept of involving experts from other surgical disciplines in advanced cadaveric courses for cytoreductive surgery in ovarian cancer, will solidify the effort to achieve excellence in the GO training. Such courses can be essential educational adjunct for most GO fellowships.

Nonreplantable Total Scalp Avulsion Reconstruction with Acellular Biologic Matrix and Long-Term Outcome.

ABSTRACT: Total scalp avulsion is a significant injury typically occurring as a result of industrial accidents involving high-speed rotary machines. Although ideal, scalp replantation is uncommon secondary to the nature of the injury and lack of viable microvas-cular anastomosis targets. Therefore, these defects are often reconstructed with microvascular free tissue transfer, with or without skin grafting. We present a unique case of a patient with total scalp avulsion achieving complete, stable skin coverage over partially intact periosteum using only spare parts of the amputated scalp as a temporary full-thickness graft and porcine urinary bladder matrix, thus, avoiding significant donor site morbidity or extensive surgery. At 4 years postoperative, the scalp coverage remains stable.

Association between ambulatory skills and diffusion tensor imaging of corpus callosal white matter in infants with spina bifida.

OBJECTIVES: To assess brain white matter using diffusion tensor imaging (DTI) at 1 year of age in infants diagnosed with open neural tube defect (ONTD) and explore the association of DTI parameters with ambulatory skills at 30 months of age. METHODS: Magnetic resonance imaging (MRI) was performed at an average of 12 months of age and included an echo planar axial DTI sequence with diffusion gradients along 20 non-collinear directions. TORTOISE software was used to correct DTI raw data for motion artifacts, and DtiStudio, DiffeoMap and RoiEditor were used for further postprocessing. DTI data were analyzed in terms of fractional anisotropy (FA), trace, radial diffusivity and axial diffusivity. These parameters reflect the integrity and maturation of white-matter motor pathways. At 30 months of age, ambulation status was evaluated by a developmental pediatrician, and infants were classified as ambulatory if they were able to walk independently with or without orthoses or as non-ambulatory if they could not. Linear mixed-effects method was used to examine the association between study outcomes and study group. Possible confounders were sought, and analyses were adjusted for age at MRI scan and ventricular size by including them in the regression model as covariates. RESULTS: Twenty patients with ONTD were included in this study, including three cases that underwent postnatal repair and 17 cases that underwent prenatal repair. There were five ambulatory and 15 non-ambulatory infants evaluated at a mean age of 31.5 ± 5.7 months. MRI was performed at 50.3 (2-132.4) weeks postpartum. When DTI analysis results were compared between ambulatory and non-ambulatory infants, significant differences were observed in the corpus callosum (CC). Compared with non-ambulatory infants, ambulatory infants had increased FA in the splenium (0.62 (0.48-0.75) vs 0.41 (0.34-0.49); P = 0.01, adjusted P = 0.02), genu (0.64 (0.47-0.80) vs 0.47 (0.35-0.61); P = 0.03, adjusted P = 0.004) and body (0.55 (0.45-0.65) vs 0.40 (0.35-0.46), P = 0.01, adjusted P = 0.01). Reduced trace was observed in the CC of ambulatory children at the level of the splenium (0.0027 (0.0018-0.0037) vs 0.0039 (0.0034-0.0044) mm2 /s; P = 0.04, adjusted P = 0.03) and genu (0.0029 (0.0020-0.0038) vs 0.0039 (0.0033-0.0045) mm2 /s; P = 0.04, adjusted P = 0.01). In addition, radial diffusivity was reduced in the CC of the ambulatory children at the level of the splenium (0.00057 (0.00025-0.00089) vs 0.0010 (0.00084-0.00120) mm2 /s; P = 0.02, adjusted P = 0.02) and the genu (0.00058 (0.00028-0.00088) vs 0.0010 (0.00085-0.00118) mm2 /s; P = 0.02, adjusted P = 0.02). There were no differences in axial diffusivity between ambulatory and non-ambulatory children. CONCLUSION: This study demonstrates a significant association between white matter integrity of connecting fibers of the corpus callosum, as assessed by DTI, and ambulatory skills at 30 months of age in infants with ONTD. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.