Utilizing a Second Flap to Address the Effect of Postradiotherapy Soft Tissue Fibrosis in Head and Neck Malignancy.

Background Late effects of adjuvant radiation therapy (RT) on soft tissues can lead to hair loss, pigmentary changes, loss of tissue volume, and fibrosis, which appear months to years after the treatment. These changes are often progressive and are because of tissue hypoxia due to radiation-induced capillary endothelial damage. Tissue hypoxia may be compounded by subclinical infection following minor trauma, exposed hardware, or associated osteoradionecrosis. The combined effect of these factors causes significant deformities in soft tissue, affecting both function and appearance. Such changes are also seen in primarily transferred flaps, which have been radiated, resulting in severe, progressive soft tissue fibrosis, compromising function and aesthetics. In selected cases, a second flap may be needed to restore function and volume. Methods Data of patients who underwent secondary soft tissue transfers for postradiotherapy-related soft tissue changes were collected from the hospital electronic medical records, from January 2019 to 2023. Details regarding the primary surgery, dose, duration of adjuvant RT, time interval between adjuvant RT and secondary soft tissue transfer, indications, and the choice of the second flap were analyzed. Results Twenty-one patients had undergone secondary soft tissue transfer for extensive soft tissue fibrosis. In addition, associated compounding features like exposed implant and volume loss were observed. Two patients with osteoradionecrosis also had associated extensive soft tissue fibrosis necessitating replacement. Out of these 21 patients, 13 had undergone free tissue transfers, while 7 locoregional tissue transfers. Conclusion Late sequelae of adjuvant RT changes usually present from 6 months onwards. The radiated hypoxic tissue, due to capillary damage, leads to a chronic progressive fibrotic stage, causing loss of soft tissue volume and fibrosis. Replacing this tissue with a vascularized flap helps to restore volume and correct these secondary changes, improving overall quality of life.

Internal mammary artery perforator flap in the management of tracheoesophageal fistulae.

BACKGROUND: A pathological communication between the trachea and oesophagus - a tracheoesophageal fistula - may be congenital or acquired, benign or malignant, necessitating a multidisciplinary approach. Conservative attempts at closure of this abnormal connection are ineffective; the interposition of healthy vascular tissue offers the least chance of recurrence. METHODS: Outcomes of an islanded fasciocutaneous internal mammary artery perforator flap applied for tracheoesophageal fistula management were assessed in four radiated patients with laryngeal carcinoma using retrospective records. RESULTS: Four male patients, with an average age of 60.75 years, underwent tracheoesophageal fistula closure between September 2017 and February 2021. A left-sided second internal mammary artery perforator flap was used in all cases, with an average dimension of 10.5 × 4.5 cm. There were no complications of tracheoesophageal leak, flap issues or donor site morbidity on follow up. CONCLUSION: Recent advances in angiosomal territory mapping and microvascular dissection techniques, combined with an understanding of tracheoesophageal fistula pathology, have changed management perspectives in these difficult-to-treat patients.

Head-On Collision of Dissimilar Viscosity Drops.

The head-on collision of drops is governed by the interfacial tension, viscosity, and inertia of the impacting drops. Earlier studies show that depending on the relative magnitude of these forces, the outcome of a head-on collision of two identical drops of the same liquid is likely to culminate in coalescence or reflexive separation. In this study, the head-on collision of drops of miscible liquids having dissimilar viscosity has been investigated numerically. As the two drop liquids are miscible, it is anticipated that the average viscosity of the two liquids will replicate the transition boundaries of coalescence and reflexive separation for a single fluid. However, numerical simulations reveal that this is true only for low-viscosity ratios. A high-viscosity ratio creates asymmetric flow; hence, the average viscosity does not accurately represent the local viscous effect. The asymmetric flow also facilitates the pinch-off of a thread without the separation of a satellite. The present investigation reveals that viscosity contrast leads to two additional outcomes of the head-on collision of drops: encapsulation and crossing separation. We have built a phase diagram identifying the outcome of a head-on collision of dissimilar viscosity drops on the viscosity ratio (µr)-Weber number (We) plane based on the results of approximately 450 simulations.

Using the DiCoT framework for integrated multimodal analysis in mixed-reality training environments.

Simulation-based training (SBT) programs are commonly employed by organizations to train individuals and teams for effective workplace cognitive and psychomotor skills in a broad range of applications. Distributed cognition has become a popular cognitive framework for the design and evaluation of these SBT environments, with structured methodologies such as Distributed Cognition for Teamwork (DiCoT) used for analysis. However, the analysis and evaluations generated by such distributed cognition frameworks require extensive domain-knowledge and manual coding and interpretation, and the analysis is primarily qualitative. In this work, we propose and develop the application of multimodal learning analysis techniques to SBT scenarios. Using these analysis methods, we can use the rich multimodal data collected in SBT environments to generate more automated interpretations of trainee performance that supplement and extend traditional DiCoT analysis. To demonstrate the use of these methods, we present a case study of nurses training in a mixed-reality manikin-based (MRMB) training environment. We show how the combined analysis of the video, speech, and eye-tracking data collected as the nurses train in the MRMB environment supports and enhances traditional qualitative DiCoT analysis. By applying such quantitative data-driven analysis methods, we can better analyze trainee activities online in SBT and MRMB environments. With continued development, these analysis methods could be used to provide targeted feedback to learners, a detailed review of training performance to the instructors, and data-driven evidence for improving the environment to simulation designers.

Identifying and describing subtypes of spontaneous empathic facial expression production in autistic adults.

BACKGROUND: It is unclear whether atypical patterns of facial expression production metrics in autism reflect the dynamic and nuanced nature of facial expressions across people or a true diagnostic difference. Furthermore, the heterogeneity observed across autism symptomatology suggests a need for more adaptive and personalized social skills programs. Towards this goal, it would be useful to have a more concrete and empirical understanding of the different expressiveness profiles within the autistic population and how they differ from neurotypicals. METHODS: We used automated facial coding and an unsupervised clustering approach to limit inter-individual variability in facial expression production that may have otherwise obscured group differences in previous studies, allowing an "apples-to-apples" comparison between autistic and neurotypical adults. Specifically, we applied k-means clustering to identify subtypes of facial expressiveness in an autism group (N = 27) and a neurotypical control group (N = 57) separately. The two most stable clusters from these analyses were then further characterized and compared based on their expressiveness and emotive congruence to emotionally charged stimuli. RESULTS: Our main finding was that a subset of autistic adults in our sample show heightened spontaneous facial expressions irrespective of image valence. We did not find evidence for greater incongruous (i.e., inappropriate) facial expressions in autism. Finally, we found a negative trend between expressiveness and emotion recognition within the autism group. CONCLUSION: The results from our previous study on self-reported empathy and current expressivity findings point to a higher degree of facial expressions recruited for emotional resonance in autism that may not always be adaptive (e.g., experiencing similar emotional resonance regardless of valence). These findings also build on previous work indicating that facial expression intensity is not diminished in autism and suggest the need for intervention programs to focus on emotion recognition and social skills in the context of both negative and positive emotions.

Transport Behavior of Commercial Anticancer Drug Protein-Bound Paclitaxel (Paclicad) in a Micron-Sized Channel.

Protein-bound paclitaxel has been developed clinically as one of the most successful chemotherapy drugs for the treatment of a wide variety of cancers. However, these medications, due to their nanoscale properties, may often induce capillary blocking while migrating through minute blood vessels. Considering the detrimental impact of this restriction, we investigated the transport of protein-bound paclitaxel, Paclicad, in a 7 µm microchannel mimicking the identical mechanical confinement of the blood capillaries. The drug was reported to migrate through a constricted microchannel without obstruction at a solution flow rate of 20-50 µL/h. The onset of an agglomeration site was observed at higher flow rates of 70-90 µL/h, while complete capillary obstruction was observed at 100 µL/h. The mobility of the particles was also calculated, and the results suggested that the presence of varying cross-sections affects the mobility of the drug particles. The trajectory of the particle migration was observed to be less tortuous at the higher flow rate, but the tortuous nature appeared to increase with the presence of agglomeration sites in the flow field. The experimental results were also compared with the computational model of the drug particle. The drug particle was modeled both as Newtonian and as an FENE-P viscoelastic drop. The drop interface tracking was done by the VOF method using the open source software Basilisk. The particle displacement was better estimated by both the FENE-P and Newtonian model at a flow rate of 30 µL/h, while deviation was observed at a flow rate of 50 µL/h. The FENE-P model was observed to show higher deformation than the Newtonian model at both flow rates. The experimental results provided better insight into the agglomeration tendency of Paclicad, migrating through a constricted microchannel at higher flow rates. The numerical model could be further employed to understand the more complex intravenous transport of drugs.

Opportunities and Challenges in Developing Technology-Based Social Skills Interventions for Adolescents with Autism Spectrum Disorder: A Qualitative Analysis of Parent Perspectives.

Interest continues to be high in technology-based interventions for individuals with autism spectrum disorder (ASD). Understanding the preferences and challenges of technology use among individuals with ASD can inform the design of such interventions. Through 18 interviews with parents, we used an iterative inductive-deductive approach to qualitative analysis and explored uses of technology for social skills development among adolescents with ASD. Our findings include parents' observations about their adolescent's preferences in types of technology devices and digital content, as well as both positive and negative effects of technology use on mood and behavior. Parents highlighted several avenues of technological preferences and risks that may inform intervention design, enhance user engagement, and capitalize on users' strengths while buttressing areas for growth.

Early Experience with Dabrafenib-Trametinib Combination in Patients with BRAF-Mutated Malignant Melanoma-A Single-Center Experience.

Background Combination of dabrafenib-trametinib is one of the standard treatments in patients with BRAF-mutated advanced malignant melanoma (MM). Real-world data on the usage of this combination is scarce, especially from India. Here, we are reporting our early experience with the usage of this combination therapy. Materials and Methods This is a single institutional data assessment of patients with BRAF-mutated MM registered and treated with BRAF-MEK inhibitors in our hospital. Clinico-pathological features and treatment details were reviewed for all patients. Results A total of seven patients with BRAF-mutated MM treated with this combination therapy with a median age of 66.5 years (range: 49-72 years) and a male:female ratio of 3:4. Six (85.7%) patients had metastatic disease at presentation. In total, 80% of our patient population had two or less than two sites of metastasis at presentation. The initial response rate of the study population was 71%. The drug was well tolerated with fever being the most common side effect which was seen in two (28.5%) of the patients. Conclusion Combination of dabrafenib-trametinib is effective in patients with BRAF-mutated MM with good tolerability. Further studies are required to look for improvement in outcome in this group of patients.

A framework for scabies control.

Scabies is a neglected tropical disease (NTD) that causes a significant health burden, particularly in disadvantaged communities and where there is overcrowding. There is emerging evidence that ivermectin-based mass drug administration (MDA) can reduce the prevalence of scabies in some settings, but evidence remains limited, and there are no formal guidelines to inform control efforts. An informal World Health Organization (WHO) consultation was organized to find agreement on strategies for global control. The consultation resulted in a framework for scabies control and recommendations for mapping of disease burden, delivery of interventions, and establishing monitoring and evaluation. Key operational research priorities were identified. This framework will allow countries to set control targets for scabies as part of national NTD strategic plans and develop control strategies using MDA for high-prevalence regions and outbreak situations. As further evidence and experience are collected and strategies are refined over time, formal guidelines can be developed. The control of scabies and the reduction of the health burden of scabies and associated conditions will be vital to achieving the targets set in WHO Roadmap for NTDs for 2021 to 2030 and the Sustainable Development Goals.

Fabricating Flaps in the Forearm Prior to Tracheal Reconstruction.

Background The process of reconstruction of tracheal defects is complex and still not optimum. Options range from using staged reconstructions, combining flaps with autologous or alloplastic implants, as well as use of tissue-engineered constructs combined with vascularized tissues which are lined with cell cultures. Staged reconstructions using prelaminated epithelium, and prefabricated flaps, help in reconstruction of this complex structure. Prefabricating the flap at a different site allows for integration of the tissues prior to its transfer. Method This article reports two patients planned for tracheal reconstruction for the purpose of advanced papillary carcinoma of the thyroid invading the trachea. Staged reconstruction using a prefabricated radial artery forearm flap (RAFF) and split rib cartilage was performed. In the second patient, a young girl, a similar construct of the RAFF, prelaminated with buccal mucosa, was performed. However, in the latter case, an intraoperative decision by the head and neck team to limit excision of the trachea sparing the mucosa was taken; the reconstruct in the forearm was redundant and needed to be discarded, replacing the defect with a free superficial circumflex iliac artery perforator (SCIP) flap. Result At 3 years follow-up, both the patients are free of disease, with the construct serving its purpose in the older female.

Resource tracking for neglected tropical disease programmes: the first step for developing a sustainable financing strategy.

The adequacy of resources for programme implementation is a premise for achieving the targets set in the road map for neglected tropical diseases (NTDs) 2021-2030. During the decade 2010-2020, international health aid and pharmaceutical donations have driven progress to control and eliminate NTDs. In the next decade, domestic financing will be critical to sustain NTD control and elimination programmes. Tracking domestic resources for NTD programmes through country health accounts, a relatively mature health system resource tracking platform, could be the first step in raising the visibility of NTDs in the discussion of national health resource allocation.

Not so 'rare'-an example of malignant melanoma in India: report from a tertiary cancer centre.

PURPOSE: Malignant melanoma (MM) is rare in India. Indian data on demography and treatment outcome on advanced MM is very limited in the literature. MATERIALS & METHODS: This is a retrospective study of advanced MM treated between January 2013 and December 2020. We evaluated the clinicopathologic features, mutational profiles, survival outcome and prognostic factors in advanced MM patients. RESULTS: Out of a total 460 patients, 185 (42%) had metastatic disease at presentation and were enrolled in this study with a median age of 63 years (range: 28-93) and male:female ratio of 94:91. The mucosal primary was predominant (n = 110, 59%) than cutaneous primary (38%) and anorectum was the most common site (n = 84, 45%). Tumour mutational analysis was performed in 65 (35%) patients. BRAF mutations were detected in 12 patients and KIT mutations in 7 patients. Thirteen patients didn't have any mutations and 22 patients had mutations other than KIT & BRAF. Only 59 (32%) patients took any systemic treatment - immune checkpoint inhibitors (ICIs) in 17, temozolomide in 18 and paclitaxel/carboplatin in 18, tyrosine kinase inhibitors in 6 patients. After a median follow-up of 26 months (95% confidence interval (CI): 11.6-not reached), median progression-free survival (PFS) was 7.1 months (95% CI: 4.4-9.1) and median overall survival was 14.8 months (95% CI: 7.7-18.2 months). The use of ICI emerged as an only significant good prognostic factor (p ≤ 0.001) for PFS, on multivariate analysis. CONCLUSION: Mucosal origin was more common than cutaneous primary with anorectum being the most common site. BRAF mutation was less as compared to published literature. Very few patients received systemic therapy and the use of ICI showed superior PFS.

Evolution of the monitoring and evaluation strategies to support the World Health Organization's Global Programme to Eliminate Lymphatic Filariasis.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established with the ambitious goal of eliminating LF as a public health problem. The remarkable success of the GPELF over the past 2 decades in carrying out its principal strategy of scaling up and scaling down mass drug administration has relied first on the development of a rigorous monitoring and evaluation (M&E) framework and then the willingness of the World Health Organization and its community of partners to modify this framework in response to the practical experiences of national programmes. This flexibility was facilitated by the strong partnership that developed among researchers, LF programme managers and donors willing to support the necessary research agenda. This brief review summarizes the historical evolution of the GPELF M&E strategies and highlights current research needed to achieve the elimination goal.

Ecology of domestic dogs Canis familiaris as an emerging reservoir of Guinea worm Dracunculus medinensis infection.

Global eradication of human Guinea worm disease (dracunculiasis) has been set back by the emergence of infections in animals, particularly domestic dogs Canis familiaris. The ecology and epidemiology of this reservoir is unknown. We tracked dogs using GPS, inferred diets using stable isotope analysis and analysed correlates of infection in Chad, where numbers of Guinea worm infections are greatest. Dogs had small ranges that varied markedly among villages. Diets consisted largely of human staples and human faeces. A minority of ponds, mostly <200 m from dog-owning households, accounted for most dog exposure to potentially unsafe water. The risk of a dog having had Guinea worm was reduced in dogs living in households providing water for animals but increased with increasing fish consumption by dogs. Provision of safe water might reduce dog exposure to unsafe water, while prioritisation of proactive temephos (Abate) application to the small number of ponds to which dogs have most access is recommended. Fish might have an additional role as transport hosts for Guinea worm, by concentrating copepods infected with worm larvae.

Presentation and Management of Dermatofibrosarcoma Protuberans: a Single Center Protocol.

Dermatofibrosarcoma protuberans (DFSP) is a slow growing dermal tumor with a very low metastatic potential but with significant subclinical extension and capacity for local destruction with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision. We reviewed the excision technique along with the recurrence rates at a tertiary care center in eastern India. This study is a retrospective review of patients with DFSP from June 2011 to September 2018. Patients had initial wide excision using 2-3 cm margins with primary closure or reconstructive procedure; re-excision was done for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of excisions, reconstruction methods, radiation, and outcomes. A total of 31 patients with DFSP (15 males, 16 females), median age 41 years (range 14-82), were treated. Locations were extremities (13), trunk (12), and head and neck (06). The median number of excisions to achieve negative margins was 1 (range 1-3). Closure techniques included primary closure (13; 42%), tissue flaps (13; 42%), and skin grafting (05; 16%). There were 11 patients who received postoperative radiation, 4 for positive margins after maximal surgical excision. At a median follow-up of 24 months (range 1-72), 2 patients (6.5%) recurred locally, and 1 patient (3.2%) had lung metastasis. Using a standardized surgical approach including meticulous pathologic evaluation of margins, low recurrence rate (10%) was achieved with adequate margins (2-3 cm).

Midface Reconstruction: Planning and Outcome.

Reconstruction of the complex anatomy and aesthetics of the midface is often a challenge. A careful understanding of this three-dimensional (3D) structure is necessary. Anticipating the extent of excision and its planning following oncological resections is critical. In the past over two decades, with the advances in microsurgical procedures, contributions toward the reconstruction of this area have generated interest. Planning using digital imaging, 3D printed models, osseointegrated implants, and low-profile plates, has favorably impacted the outcome. However, there are still controversies in the management: to use single composite tissues versus multiple tissues; implants versus autografts; vascularized versus nonvascularized bone; prosthesis versus reconstruction. This article explores the present available options in maxillary reconstruction and outlines the approach in the management garnered from past publications and experiences.

Factors Affecting Postoperative Complications After Reconstructive Surgery in Oral Carcinoma Patients: A Prospective Study of 100 Patients.

Postoperative complications may result in significant functional morbidity, poor cosmetic results, prolonged hospitalization, preclusion of optimal treatment for the cancer, or even be pose threat to life. We prospectively assessed postoperative complications in 100 patients who underwent surgical resection with free or pedicled flap reconstruction as a primary modality of treatment in patients with carcinoma of the oral cavity. One hundred consecutive patients who underwent reconstructive surgery for oral cancer were prospectively analyzed for age, gender, comorbidities, tumor stage, nodal stage, primary sub-site of tumour, reconstructive procedure (free or pedicled), duration of surgery, blood transfusions during surgery, preoperative weight and body mass index, patient generated subjective global assessment status and tracheostomy to determine their effect on postoperative complications as determined on the CD scale. The sample comprised 100 patients with a mean age of 52.12 years (range 24-80 years) and 74% men (M:F ratio 3:1). A total of 40 patients developed surgical complications (including two deaths) while medical complications were seen in 10 patients (including one death). Tracheostomy (52 vs. 7%, p = 0.002) and age (54 vs. 49 years, p = 0.031) were associated with higher complication rate. Higher age and tracheostomy is associated with higher complications in postoperative period.

Unusual loco-regional presentation in papillary carcinoma of thyroid: A case series.

BACKGROUND: Papillary carcinoma of thyroid (PTC) is usually indolent with good prognosis and excellent long-term survival. However, PTC sometimes presents itself in unusual situations, posing diagnostic and therapeutic challenges. Owing to paucity of data, there is lack of consensus as to what treatment should be prescribed in patients with loco-regional spread other than the usual sites. MATERIALS AND METHODS: Six patients of PTC presenting with involvement of the aero-digestive tract, retropharyngeal, and para-pharyngeal lymph nodes and great vessels of the neck are included in this case series. RESULTS AND CONCLUSION: Though rare, unusual loco-regional presentation of PTC poses challenges in diagnosis and treatment. A keen clinical sense is paramount in effectively diagnosing these cases. Aggressive surgical resection and reconstruction results in good functional and aesthetic outcomes. Further studies are required for establishing specific guidelines on the approach to the treatment of these cases.

Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary.

Epithelial to mesenchymal transition (EMT) induces cell migration, invasion, and drug resistance, and consequently, contributes to cancer metastasis and disease aggressiveness. This study attempted to address crucial biological parameters to correlate EMT and drug-treated cancer cells traversing through microcapillaries, reminiscent of metastatic conditions. MDA-MB-468 breast cancer cells induced to undergo EMT by treatment with 20 ng/mL of epidermal growth factor (EGF) were initially passed through several blockages and then through a constricted microchannel, mimicking the flow of invasive metastatic cells through constricted blood microcapillaries. EMT cells acquired enhanced migratory properties and retained 50% viability, even after migration through wells 10-15 µm in size and a constricted passage of 7 µm and 150 µm in length at a constant flow rate of 50 µL/h. The hydrodynamic properties revealed cellular deformation with a deformation index, average transit velocity, and entry time of 2.45, 12.3 mm/s, and 31,000 µs, respectively for a cell of average diameter 19 µm passing through one of the 7 µm constricted sections. Interestingly, cells collected at the channel outlet regained epithelial character, undergoing reverse transition (mesenchymal to epithelial transition, MET) in the absence of EGF. Remarkably, real-time polymerase chain reaction (PCR) analysis confirmed increases of 2- and 2.7-fold in the vimentin and fibronectin expression in EMT cells, respectively; however, their expression reduced to basal level in the MET cells. A scratch assay revealed the pronounced migratory nature of EMT cells compared with MET cells. Furthermore, the number of colonies formed from EMT cells and paclitaxel-treated EMT cells after passing through a constriction were found to be 95 ± 10 and 79 ± 4, respectively, confirming that the EMT cells were more drug resistant with a concomitant two-fold higher expression of the multi-drug resistance (MDR1) gene. Our results highlight the hydrodynamic and drug-evading properties of cells that have undergone an EMT, when passed through a constricted microcapillary that mimics their journey in blood circulation.