Atmospheric undular bores.

We show that a recently-derived model for the propagation of nonlinear waves in the atmosphere admits undular bores as travelling-wave solutions. These solutions represent waves consisting of a damped oscillation behind a front that is preceded by a uniform breeze-type flow. The generation of such wave profiles requires a jump in the heat source across the leading front of the wave, a feature that is consistent with observations.

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.

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.

Prenatal surgery in fetal myelomeningocele with severe ventriculomegaly.

OBJECTIVES: Prenatal myelomeningocele (MMC) repair is performed to decrease risk for treatment of hydrocephalus after birth and to preserve motor function. Some centers may not consider patients candidates for surgery if severe ventriculomegaly is present and there is no expected benefit in decreased risk for hydrocephalus treatment. This study sought to compare postnatal outcomes of fetuses with MMC and severe ventriculomegaly (>15mm) who underwent prenatal repair, with fetuses with severe ventriculomegaly who underwent postnatal repair and fetuses with ventriculomegaly (<15mm) who underwent prenatal repair. METHODS: This was a retrospective study of fetuses with MMC that underwent prenatal or postnatal repair between 2012 and 2021 at a single institution. The cohort was divided based on preoperative fetal ventricular size into two groups, those with severe ventriculomegaly (≥15 mm) and those without severe ventriculomegaly (<15 mm). Fetal ventricular size was measured by MRI prior to surgery using the standardized approach and the mean of the left and right ventricle was used for analysis. Motor function of 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 lower extremities assessed at birth and need for diversion procedure for hydrocephalus treatment during the first year of life were collected and compared between groups. Data was presented as median and range or number and percentages as appropriate. P value >0.05 was considered statistically significant. Multivariate regression analysis was used to adjust for potential confounders. RESULTS: 154 patients were included in this study: 145 patients underwent fetal surgery (101 fetoscopic and 44 open hysterotomy) and 9 patients with severe ventriculomegaly underwent postnatal repair. Among the 145 patients who underwent fetal surgery, 22 presented with severe ventriculomegaly. Prenatally repaired fetuses with severe ventriculomegaly at referral were at a significantly higher need for hydrocephalus treatment by 12 months than those without severe ventriculomegaly (62% vs. 29%, p<0.01). However, motor function assessment at birth was similar between both prenatally repaired groups (OR=0.92, 95% CI [0.33-2.59], p=0.88) adjusted for the anatomical level of the lesion. The prenatally repaired group with severe ventriculomegaly had better preserved motor function levels at birth compared to the postnatal repair group with severe ventriculomegaly (L3 with 11.1% S1 motor function; p=<0.01 and p=<0.01). Prenatally repaired patients with severe ventriculomegaly had an 18.9 times chance of having an intact motor function at birth [95% CI (1.2 - 290.1)] adjusted for ethnicity, presence of clubfeet at referral, and gestational age at delivery compared to postnatal repair. There was not a significant difference in the need for hydrocephalus treatment in the first year of life between prenatal and postnatal repair of patients with severe ventriculomegaly (61.9% vs 87.5%, p=0.18). CONCLUSIONS: Although fetuses with MMC and severe ventriculomegaly do not seem to benefit from fetal surgery in terms of postnatal hydrocephalus treatment, they benefit from increased chance of preserved motor function at birth. Results from this study highlight the benefits of having prenatal MMC repair for cases with severe ventriculomegaly at referral to preserve motor function. This article is protected by copyright. All rights reserved.

Ambulation after in-utero fetoscopic and open spina bifida repair: predictors for ambulation at 30 months.

OBJECTIVE: Ambulatory outcomes from children who underwent a new minimally invasive fetal spina bifida surgery approach are included in this study for the first time. Identifying cases with better chances of independent ambulation from fetal life can have an important impact on patient counseling. The objectives of this study were: (1) To compare the ambulatory status of a cohort of children who had a prenatal spina bifida repair using two different methods (fetoscopic and open) with a cohort who underwent postnatal repair; and (2) to identify the best predictors for ambulation. METHODS: Retrospective review of a cohort of children who had spina bifida repair from 2011-2023 using prenatal fetoscopic surgery (N=73), prenatal open-hysterotomy surgery (N=37) or postnatal repair (N=51) in a single tertiary hospital. Consecutive sample of cases who underwent a spina bifida repair in utero following MoMs trial criteria and cases who underwent postnatal repair, meeting same criteria, also followed up after birth at the same institution. Motor function (MF) assessment by ultrasound was recorded at initial evaluation (MF1), 6 postoperative weeks or equivalent (MF2) and prior to delivery (MF3). Clinical exams to assess MF at birth and at 12 months were recorded. First sacral myotome (S1) MF was classified as "intact MF". Ambulatory status data at each follow-up visit was collected. The proportion of cases who were able to walk independently were compared between fetoscopic and open prenatal surgeries and between prenatal (by fetoscopic or open surgery) and postnatal spina bifida repair. Logistic regression analyses were performed to identify predictors for independent ambulation. RESULTS: At 30 months, the proportion of independent ambulators was higher in prenatally vs. postnatally repaired cases (51.8% vs.15.7%; p<0.01). No differences in ambulatory outcomes were seen in the comparison between fetoscopic (52%) vs. open (51.3%; p=0.95) prenatal repair. In the prenatal repair group, having an "intact MF" at 12 months [Odds ratio 7.71 (95%CI: 2.77-21.47), p<0.01] and at birth [4.38 (1.53-12.56), p<0.01], predicted significantly being an independent ambulator by 30 months; the anatomical level of lesion below L2 was also predictive for this outcome [3.68(1.33-9.88), p=0.01]. CONCLUSION: Ambulatory status by 30 months can be predicted by observing S1 MF postnatally. Results from this study have implications for parental counseling and planning for supportive therapies. This article is protected by copyright. All rights reserved.

Connecting thiamine availability to the microbial community composition in Chinook salmon spawning habitats of the Sacramento River basin.

Thiamine deficiency complex (TDC) is a major emerging threat to global populations of culturally and economically important populations of salmonids. Salmonid eggs and embryos can assimilate exogenous thiamine, and evidence suggests that microbial communities in benthic environments can produce substantial amounts of thiamine. We therefore hypothesize that natural dissolved pools of thiamine exist in the surface water and hyporheic zones of riverine habitats where salmonids with TDC migrate, spawn, and begin their lives. To examine the relationship between dissolved thiamine-related compounds (dTRCs) and their microbial source, we determined the concentrations of these metabolites and the compositions of microbial communities in surface and hyporheic waters of the Sacramento River, California and its tributaries. Here we determine that all dTRCs are present in femto-picomolar concentrations in a range of critically important salmon spawning habitats. We observed that thiamine concentrations in the Sacramento River system are orders of magnitude lower than those of marine waters, indicating substantial differences in thiamine cycling between these two environments. Our data suggest that the hyporheic zone is likely the source of thiamine to the overlying surface water. Temporal variations in dTRC concentrations were observed where the highest concentrations existed when Chinook salmon were actively spawning. Significant correlations were seen between the richness of microbial taxa and dTRC concentrations, particularly in the hyporheic zone, which would influence the conditions where embryonic salmon incubate. Together, these results indicate a connection between microbial communities in freshwater habitats and the availability of thiamine to spawning TDC-impacted California Central Valley Chinook salmon.IMPORTANCEPacific salmon are keystone species with considerable economic importance and immeasurable cultural significance to Pacific Northwest indigenous peoples. Thiamine deficiency complex has recently been diagnosed as an emerging threat to the health and stability of multiple populations of salmonids ranging from California to Alaska. Microbial biosynthesis is the major source of thiamine in marine and aquatic environments. Despite this importance, the concentrations of thiamine and the identities of the microbial communities that cycle it are largely unknown. Here we investigate microbial communities and their relationship to thiamine in Chinook salmon spawning habitats in California's Sacramento River system to gain an understanding of how thiamine availability impacts salmonids suffering from thiamine deficiency complex.

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.

Strain control of a bandwidth-driven spin reorientation in Ca3Ru2O7.

The layered-ruthenate family of materials possess an intricate interplay of structural, electronic and magnetic degrees of freedom that yields a plethora of delicately balanced ground states. This is exemplified by Ca3Ru2O7, which hosts a coupled transition in which the lattice parameters jump, the Fermi surface partially gaps and the spins undergo a 90∘ in-plane reorientation. Here, we show how the transition is driven by a lattice strain that tunes the electronic bandwidth. We apply uniaxial stress to single crystals of Ca3Ru2O7, using neutron and resonant x-ray scattering to simultaneously probe the structural and magnetic responses. These measurements demonstrate that the transition can be driven by externally induced strain, stimulating the development of a theoretical model in which an internal strain is generated self-consistently to lower the electronic energy. We understand the strain to act by modifying tilts and rotations of the RuO6 octahedra, which directly influences the nearest-neighbour hopping. Our results offer a blueprint for uncovering the driving force behind coupled phase transitions, as well as a route to controlling them.

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.

Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques.

Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. IFNmod treatment resulted in a potent reduction in SARS-CoV-2 viral loads both in vitro in Calu-3 cells and in vivo in bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes of RMs. Furthermore, in SARS-CoV-2-infected RMs, IFNmod treatment potently reduced inflammatory cytokines, chemokines, and CD163+ MRC1- inflammatory macrophages in BAL and expression of Siglec-1 on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. Using an intervention targeting both IFN-α and IFN-ß pathways, this study shows that, whereas early IFN-I restrains SARS-CoV-2 replication, uncontrolled IFN-I signaling critically contributes to SARS-CoV-2 inflammation and pathogenesis in the moderate disease model of RMs.

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.

Sequence and Structural Motifs Controlling the Broad Substrate Specificity of the Mycobacterial Hormone-Sensitive Lipase LipN.

Mycobacterium tuberculosis has a complex life cycle transitioning between active and dormant growth states depending on environmental conditions. LipN (Rv2970c) is a conserved mycobacterial serine hydrolase with regulated catalytic activity at the interface between active and dormant growth conditions. LipN also catalyzes the xenobiotic degradation of a tertiary ester substrate and contains multiple conserved motifs connected with the ability to catalyze the hydrolysis of difficult tertiary ester substrates. Herein, we expanded a library of fluorogenic ester substrates to include more tertiary and constrained esters and screened 33 fluorogenic substrates for activation by LipN, identifying its unique substrate signature. LipN preferred short, unbranched ester substrates, but had its second highest activity against a heteroaromatic five-membered oxazole ester. Oxazole esters are present in multiple mycobacterial serine hydrolase inhibitors but have not been tested widely as ester substrates. Combined structural modeling, kinetic measurements, and substitutional analysis of LipN showcased a fairly rigid binding pocket preorganized for catalysis of short ester substrates. Substitution of diverse amino acids across the binding pocket significantly impacted the folded stability and catalytic activity of LipN with two conserved motifs (HGGGW and GDSAG) playing interconnected, multidimensional roles in regulating its substrate specificity. Together this detailed substrate specificity profile of LipN illustrates the complex interplay between structure and function in mycobacterial hormone-sensitive lipase homologues and indicates oxazole esters as promising inhibitor and substrate scaffolds for mycobacterial hydrolases.

Development and Implementation of an Interdisciplinary Model for the Management of Breastfeeding in Women With HIV in the United States: Experience From the Children's Hospital Colorado Immunodeficiency Program.

BACKGROUND: Women with HIV in high-income settings have increasingly expressed a desire to breastfeed their infants. Although national guidelines now acknowledge this choice, detailed recommendations are not available. We describe the approach to managing care for breastfeeding women with HIV at a single large-volume site in the United States. METHODS: We convened an interdisciplinary group of providers to establish a protocol intended to minimize the risk of vertical transmission during breastfeeding. Programmatic experience and challenges are described. A retrospective chart review was conducted to report the characteristics of women who desired to or who did breastfeed between 2015 and 2022 and their infants. RESULTS: Our approach stresses the importance of early conversations about infant feeding, documentation of feeding decisions and management plans, and communication among the health care team. Mothers are encouraged to maintain excellent adherence to antiretroviral treatment, maintain an undetectable viral load, and breastfeed exclusively. Infants receive continuous single-drug antiretroviral prophylaxis until 4 weeks after cessation of breastfeeding. From 2015 to 2022, we counseled 21 women interested in breastfeeding, of whom 10 women breastfed 13 infants for a median of 62 days (range, 1-309). Challenges included mastitis (N = 3), need for supplementation (N = 4), maternal plasma viral load elevation of 50-70 copies/mL (N = 2), and difficulty weaning (N = 3). Six infants experienced at least 1 adverse event, most of which were attributed to antiretroviral prophylaxis. DISCUSSION: Many knowledge gaps remain in the management of breastfeeding among women with HIV in high-income settings, including approaches to infant prophylaxis. An interdisciplinary approach to minimizing risk is needed.

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.

Exploring postgraduate epidemiology competencies: Preparing our students for a post-COVID world.

OBJECTIVE: This research sought consensus from both experts and graduates on postgraduate epidemiology competencies. METHODS: In 2021, a two-round online survey using a modified Delphi method was undertaken exploring competencies across six domains. Focus groups were conducted with recent postgraduate epidemiology graduates to assess their viewpoints on learning experiences and employability. RESULTS: Forty-one experts participated in the first Delphi round. Nineteen factors reached consensus (>70% agreement) for importance and feasibility after two survey rounds in the following domains: general epidemiologic methods/concepts (n=8/13), advanced analytic/statistical skills (n=2/7), applied epidemiology/specialised fields (n=1/4), professional/transferrable skills (n=5/14), general public health knowledge/skills (n=2/4), independent research and work-integrated learning (n=1/3). Nine graduates participated in focus groups. A main theme was the substantial value gained in undertaking a dissertation, acknowledging its benefit for applying research skills and for networking opportunities. CONCLUSIONS: To ensure that high-quality epidemiological research and practice continues, we need consensus on the set of essential skills required of graduating students. IMPLICATIONS FOR PUBLIC HEALTH: Competencies for postgraduate epidemiology students require periodic review to safeguard a workforce that can meet emerging challenges and work across academia, research, policy, and practice.

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.