A study comparing the cost-effectiveness of conventional and drug-eluting transarterial chemoembolisation (cTACE and DEB-TACE) for the treatment of hepatocellular carcinoma in an Australian public hospital.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and transarterial chemoembolisation (TACE) is an established technique to treat patients with intermediate-stage HCC. The aim of this study was to generate accurate costing data on cTACE and DEB-TACE in an Australian setting and assess whether one of the procedures offers favourable cost-effectiveness. METHODS: Costing study using data from all TACE procedures performed at a single centre between January 2018 and December 2022. Data were included from all direct and indirect costs including operative costs, wages, overheads, ward costs, transfusion, pathology, pharmacy and ward support. Cost-effectiveness was assessed by dividing local costs by existing high-quality data on quality-adjusted life years (QALYs). RESULTS: 64 TACE treatments were performed on 44 patients. Mean age was 66.5 years and 91% were male. Overall median total cost per patient for the entire TACE treatment regime was AUD$7380 (range AUD$3719-$20,258). However, 39% of patients received more than one treatment, and the median cost per individual treatment was AUD$5270 (range AUD$3533-$15,818). The difference in median cost between cTACE (AUD$4978) and DEB-TACE (AUD$9202) was significant, P < 0.001. In calculating cost-effectiveness, each cTACE treatment cost AUD$2489 per QALY gained, while each DEB-TACE cost AUD$3834 per QALY gained. The incremental cost-effectiveness ratio (ICER) for DEB-TACE over cTACE was AUD$10,560 per QALY gained. CONCLUSION: Both cTACE and DEB-TACE are low-cost treatments in Australia. However, DEB-TACE offers a solution with an ICER of AUD$10,560 per QALY gained which is below the Australian government willingness to pay threshold and thus is a more cost-effective treatment.

Reconstructive techniques for radiation-induced hemifacial sequelae: A hemangioma case study.

INTRODUCTION AND IMPORTANCE: The use of radiation therapy for infantile hemangiomas 30 years ago has led to severe consequences in adulthood. CASE PRESENTATION: This article shares the experience of using multiple reconstructive procedures to treat radiation-induced hemifacial sequelae for capillary malformations. Based on the damaged anatomical surgical units, appropriate reconstructive materials are used for the surgery. Thin antero-lateral thigh (ALT) flaps cover lesions on the forehead and cheeks, while a skin expander covers the temporal scalp lesion. Autologous grafting covers damage in both eyelids. CLINICAL DISCUSSION: Choosing a suitable reconstructive material will provide aesthetic outcomes such as facial symmetry, skin color compatibility, and textural similarity in the constructive areas for the patient. The patients were highly satisfied with the surgical results. CONCLUSION: Using appropriate surgical techniques and materials, along with meticulous attention to facial integrity, can achieve optimal aesthetic and functional outcomes in patients with severe facial disfigurement from radiation therapy. A thorough understanding of pathophysiology and anatomy, along with skillful execution, can result in a successful outcome and improved quality of life.

Serial Tissue Expansion and Skin Grafts in the Management of a Giant Congenital Nevus of the Face: Review of Literature and Case Report.

Giant congenital nevi, especially on the head and neck, pose a challenge for plastic surgeons. This requires extensive experience in detailed planning, combining different techniques, and selecting appropriate materials for reconstruction. There have been reports of using a tissue expander, serial resection method, and full-thickness skin grafts for this type of nevus. However, the best way to completely remove a giant congenital nevus is endless. In this article, we would like to present a case of a left hemifacial giant congenital nevus in which we used multiple tissue expansion to fully replace the nevus, along with some of our modification techniques.

Mathematical model for IL-2-based cancer immunotherapy.

A basic mathematical model for IL-2-based cancer immunotherapy is proposed and studied. Our analysis shows that the outcome of therapy is mainly determined by three parameters, the relative death rate of CD4+ T cells, the relative death rate of CD8+ T cells, and the dose of IL-2 treatment. Minimal equilibrium tumor size can be reached with a large dose of IL-2 in the case that CD4+ T cells die out. However, in cases where CD4+ and CD8+ T cells persist, the final tumor size is independent of the IL-2 dose and is given by the relative death rate of CD4+ T cells. Two groups of in silico clinical trials show some short-term behaviors of IL-2 treatment. IL-2 administration can slow the proliferation of CD4+ T cells, while high doses for a short period of time over several days transiently increase the population of CD8+ T cells during treatment before it recedes to its equilibrium. IL-2 administration for a short period of time over many days suppresses the tumor population for a longer time before approaching its steady-state levels. This implies that intermittent administration of IL-2 may be a good strategy for controlling tumor size.

Laparoscopic treatment for median arcuate ligament syndrome in children: A case report.

In median arcuate ligament syndrome (MALS), the median arcuate ligament compresses the celiac trunk and surrounding nerves leading to chronic functional abdominal pain and vague gastrointestinal symptoms. MALS can be effectively treated by dividing the arcuate ligament through open surgery or laparoscopy. This is a rare vascular condition and mostly encountered in adult patients. We hereby report a case of a pediatric patient diagnosed with MALS and treated successfully by laparoscopic approach. An 11-year-old girl presented with severe abdominal cramps for 3 months, accompanied by nonbilious vomiting. Computed tomography (CT) angiography demonstrated clear images of celiac trunk compression suggesting MALS. Laparoscopic surgery to cut the ligament and decompress the celiac artery was performed. The patient was discharged on day 7 postoperative with no recurrence of symptoms after 12 months of follow-up. This report suggested the diagnostic value of CT scan, and the safety and the feasibility of laparoscopic surgical techniques to treat MALS in children.

The free anterolateral thigh flap substituted for a pedicled biparietal flap in reconstructing complex frontal defect.

Complex scalp defects involving soft and hard tissues pose challenges for plastic surgeons. The solution for each defect must depend on various factors and even the technical development of the infrastructure. We present a case study in which the patient had a significant total frontal defect. The first surgery was a bi-parietal flap as a salvage option to cover the defect. However, aesthetic satisfaction was not achieved. The second surgery used the anterolateral thigh flap to enhance the aesthetic result, and the placement of titanium mesh was an appropriate choice. This case may be an example of how different solutions can lead to variable results and what needs to be considered when dealing with complex scalp defects.

A cost outcome study of varicocoele embolisation and future pregnancy in an Australian public hospital setting.

INTRODUCTION: Varicocoele is commonly encountered in males with infertility. Studies have shown that varicocoele repair (surgery or embolisation) can improve the rate of subsequent pregnancy. In Australia, there have been no studies assessing the cost of varicocoele embolisation and current practice is based on international data. This study aimed to assess the cost of varicocoele embolisation and estimate the treatment cost per pregnancy. METHODS: Retrospective cost-outcome study of patients treated by embolisation between January 2018 and 2023. A bottom-up approach was used to calculate procedure costs whereas a top-down approach was used to calculate costs for all other patient services, including direct and indirect costs. To calculate cost per pregnancy, costs were adjusted according to existing published data on the rate of pregnancy after embolisation. RESULTS: Costing data from 18 patients were included, of median age 33.5 years (range 26-60) and median varicocoele grade 2.5 (range 1-3). All patients had unilateral treatment, most commonly via right internal jugular (16 patients, 89%) and using a 0.035″ system (17 patients, 94%). The median cost for the entire treatment including procedural, non-procedural, ward and peri-procedural costs was AUD$2208.10 (USD$1405 or EUR€1314), range AUD$1691-7051. The projected cost to the healthcare system per pregnancy was AUD$5387 (USD$3429 or EUR€3207). CONCLUSION: Total varicocoele embolisation cost and the cost per-pregnancy were lower than for both embolisation and surgical repair in existing international studies. Patients undergoing varicocoele treatment should have the option to access an interventional radiologist to realise the benefits of this low-cost pinhole procedure.

A stochastic framework for evaluating CAR T cell therapy efficacy and variability.

Based on a deterministic and stochastic process hybrid model, we use white noises to account for patient variabilities in treatment outcomes, use a hyperparameter to represent patient heterogeneity in a cohort, and construct a stochastic model in terms of Ito stochastic differential equations for testing the efficacy of three different treatment protocols in CAR T cell therapy. The stochastic model has three ergodic invariant measures which correspond to three unstable equilibrium solutions of the deterministic system, while the ergodic invariant measures are attractors under some conditions for tumor growth. As the stable dynamics of the stochastic system reflects long-term outcomes of the therapy, the transient dynamics provide chances of cure in short-term. Two stopping times, the time to cure and time to progress, allow us to conduct numerical simulations with three different protocols of CAR T cell treatment through the transient dynamics of the stochastic model. The probability distributions of the time to cure and time to progress present outcome details of different protocols, which are significant for current clinical study of CAR T cell therapy.

Using Free Chimeric Anterolateral Thigh Flap For Reconstruction Of Composite Dorsal Hand Defect.

Background: Simultaneous repair of the extensor tendons and soft tissues in hand injuries remains challenging. The free chimeric anterolateral thigh (ALT) flap with fascia lata (FL) flap represents an alternative for hand reconstruction. This report describes the reconstruction of the extensor tendon and skin defects using free chimeric ALT flaps with FL. Methods: Eight patients (one female and seven male) underwent reconstruction of complex hand defects with free chimeric ALT and FL flaps. The defects were caused by crushing injuries, burns, snakebite scars, and animal bite wounds. The average skin defect was 116 cm2. Perforators were selected for the skin paddle and the FL flap. The thinning procedure was performed microsurgically. Results: The skin paddle size ranged from 12 to 23 cm in length and 6 to 11 cm in width, and the FL flaps ranged from 3 × 5 to 12 × 5 cm. The mean pedicle length was 7.88 cm. Nine extensor tendons were repaired with FL flaps. The flap thickness after thinning was only 3-6 mm. The donor site was closed primarily in six patients, and skin grafts were used in two cases. All flaps survived without complications. The follow-up period lasted from 17 to 80 months. Range of motion was achieved with satisfaction. Conclusion: The chimeric-thinned ALT and FL flap is a valuable material, and it should be considered a reconstructive option for hand soft tissue and extensor tendon reconstruction. This technique allows us to achieve a good appearance and extensor function without donor-site morbidity.

Viability Profiles of Normal and Cancer Bladder Cells With Metformin, Nitrate and Adenosine Monophosphate-Activated Protein Kinase Inhibitor.

Background: There is no literature report on how metformin and adenosine monophosphate-activated protein kinase (AMPK) inhibitor affect normal and cancer bladder cells under the presence of nitrate. Methods: Various treatment concentrations and methods were used to study the effects of nitrate, metformin, and/or AMPK inhibitor on normal and/or cancer bladder cells. Normal bladder cells were exposed to nitrate or metformin alone or in combination. The effects of AMPK on normal bladder cells were investigated with nitrate and metformin pretreatment. The effects of varying metformin concentrations on cancer bladder cells were examined as well. Results: Metformin has produced almost no changes in cell viability of normal cells with various concentrations. Addition of both nitrate and metformin at the same time resulted in less than 17% cell viability as compared to the controlled values; however, this value is about 10% better than nitrate alone for 24 h and approximate 27% better for 48 h. Pre-treatment of normal cells with AMPK inhibitor for 6 h prior to addition of metformin and nitrate reduced the cell viability greatly. The treatment of cancer bladder cells with metformin indicated an inverse relationship between metformin concentration and cancer bladder cell viability. Conclusion: Metformin assisted normal bladder cells in surviving in the presence of nitrate, but its total survival was greatly reduced by AMPK inhibitors. Metformin inhibited the growth of bladder cancer cells.

Improved expression and purification of highly-active 3 chymotrypsin-like protease from SARS-CoV-2.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease-19 (COVID-19). The COVID-19 pandemic has resulted in millions of deaths and widespread socio-economic damage worldwide. Therefore, numerous studies have been conducted to identify effective measures to control the spreading of the virus. Among various potential targets, the 3 chymotrypsin-like protease (3CLpro), also known as Mpro, stands out as the key protease of SARS-CoV-2, playing an essential role in virus replication and assembly, is the most prospective. In this study, we modified the commercial vector, pETM33-Nsp5-Mpro (plasmid # 156475, Addgene, USA), by inserting an autocleavage site (AVLQ) of 3CLpro and 6 × His-tag encoding sequences before and after the Nsp5-Mpro sequence, respectively. This modification enabled the expression of 3CLpro as an authentic N terminal protease (au3CLpro), which was purified to electrophoretic homogeneity by a single-step chromatography using two tandem Glutathione- and Ni-Sepharose columns. The enzyme au3CLpro demonstrated significantly higher activity (3169 RFU/min/µg protein) and catalytic efficiency (Kcat/Km of 0.007 µM-1.s-1) than that of the 3CLpro (com3CLpro) expressed from the commercial vector (pETM33-Nsp5-Mpro) with specific activity 889 RFU/min/µg and Kcat/Km of 0.0015 µM-1.s-1, respectively. Optimal conditions for au3CLpro activity included a 50 mM Tris-HCl buffer at pH 7, containing 150 mM NaCl and 0.1 mg/ml BSA at 37 °C.

Stabilization of Luminescent Mononuclear Three-Coordinate CuI Complexes by Two Distinct Cavity-Shaped Diphosphanes Obtained from a Single α-Cyclodextrin Precursor.

Slightly different reaction conditions afforded two distinct cavity-shaped cis-chelating diphosphanes from the same starting materials, namely diphenyl(2-phosphanylphenyl)phosphane and an α-cyclodextrin-derived dimesylate. Thanks to their metal-confining properties, the two diphosphanes form only mononuclear [CuX(PP)] complexes (X=Cl, Br, or I) with the tricoordinated metal ion located just above the center of the cavity. The two series of CuI complexes display markedly different luminescence properties that are both influenced by the electronic properties of the ligand and the unique steric environment provided by the cyclodextrin (CD) cavity. The excited state lifetimes of all complexes are significantly longer than those of the cavity-free analogues suggesting peculiar electronic effects that affect radiative deactivation constants. The overall picture stemming from absorption and emission data suggests close-lying charge-transfer (MLCT, XLCT) and triplet ligand-centered (LC) excited states.

Stochastic dynamics of human papillomavirus delineates cervical cancer progression.

Starting from a deterministic model, we propose and study a stochastic model for human papillomavirus infection and cervical cancer progression. Our analysis shows that the chronic infection state as random variables which have the ergodic invariant probability measure is necessary for progression from infected cell population to cervical cancer cells. It is shown that small progression rate from infected cells to precancerous cells and small microenvironmental noises associated with the progression rate and viral infection help to establish such chronic infection states. It implicates that large environmental noises associated with viral infection and the progression rate in vivo can reduce chronic infection. We further show that there will be a cervical cancer if the noise associated with precancerous cell growth is large enough. In addition, comparable numerical studies for the deterministic model and stochastic model, together with Hopf bifurcations in both deterministic and stochastic systems, highlight our analytical results.

Gallbladder perforation following trauma in an 18-month-old child with a common bile duct cyst.

Gallbladder rupture caused by blunt abdominal trauma is an uncommon injury, particularly in children. This condition occurs even less frequently in children with common bile duct cysts. The history is difficult to obtain, the clinical symptoms are indistinct, and their assessment is obscured by a slew of other lesions. Radiography cannot produce clear images. Thus, the diagnosis is frequently delayed and confirmed only during surgery. Case reports of gallbladder injury after abdominal trauma are relatively rare and there are only 50 case reports in literature for 100 years. Herein, we present the case of an 18-month-old girl who had a ruptured gallbladder funnel due to blunt abdominal trauma caused by domestic violence, with an early clinical presentation of septic shock and chylous effusion. The patient underwent surgery after being diagnosed with chylous ascites that had not responded to medical treatment. Based on the findings, single-stage laparoscopic surgery is confirmed to aid in the diagnosis and treatment of gallbladder injury in the presence of a common bile duct cyst.

One-stage Reconstruction with the Composite Anterolateral Thigh Flap for Skin and Extensor Tendon Defects of the Thumb by Snakebite.

Venomous snakebites can cause severe injury. The loss of tendon and skin of the hand is incredibly challenging for the surgeon. A single-staged reconstruction with the free composite anterolateral thigh flap is an acceptable option for a complex thumb injury. In this case, reconstruction for a 23-year-old patient with a complex cobra-induced thumb injury had failed to cover the defect with a skin graft. There was a limitation in choice, and the patient was treated with the free composite anterolateral thigh (ALT) flap and fascia lata flap in one stage to reconstruct both the extensor tendon and the soft tissue coverage. The flap was well-vascularized, and no complications were reported. A single-stage reconstruction with a composite ALT flap with vascularized fascia was chosen as a suitable alternative. The result is satisfying both aesthetically and functionally. This technique can help shorten treatment time and restore function quickly, allowing patients to return to work in less time. The disadvantages of this technique are flap thickness, which can affect finger movement and aesthetics. The composite ALT flap with vascularized fascia lata shows that it is a reliable procedure for single-staged reconstruction, especially combined with the tendon preparation in the hand.

Cooperative mechanisms underlie differences in myocardial contractile dynamics between large and small mammals.

Ca2+ binding to troponin C (TnC) and myosin cross-bridge binding to actin act in a synergistic cooperative manner to modulate myocardial contraction and relaxation. The responsiveness of the myocardial thin filament to the activating effects of Ca2+ and myosin cross-bridge binding has been well-characterized in small mammals (e.g., mice). Given the nearly 10-fold difference in resting heart rates and twitch kinetics between small and large mammals, it is unlikely that the cooperative mechanisms underlying thin filament activation are identical in these two species. To test this idea, we measured the Ca2+ dependencies of steady-state force and the rate constant of force redevelopment (ktr) in murine and porcine permeabilized ventricular myocardium. While murine myocardium exhibited a steep activation-dependence of ktr, the activation-dependent profile of ktr was significantly reduced in porcine ventricular myocardium. Further insight was attained by examining force-pCa and ktr-pCa relationships. In the murine myocardium, the pCa50 for ktr was right-shifted compared with the pCa50 for force, meaning that increases in steady-state force occurred well before increases in the rate of force redevelopment were observed. In the porcine myocardium, we observed a tighter coupling of the force-pCa and ktr-pCa relationships, as evidenced by near-maximal rates of force redevelopment at low levels of Ca2+ activation. These results demonstrate that the molecular mechanisms underlying the cooperative activation of force are a dynamic property of the mammalian heart, involving, at least in part, the species- and tissue-specific expression of cardiac myosin heavy chain isoforms.

Facial acid postburn reconstruction with multiple contemporary procedures in a stepwise fashion.

INTRODUCTION AND IMPORTANCE: Facial deformities caused by chemical burns are often complex, seriously affecting the patient's function and quality of life. Treating these injuries requires the incorporation of multi-staged procedures to achieve the desire appearance. CASE PRESENTATION: A 32-year-old male patient had a total face disfigurement after an acid burn injury. He had apparent front, cheek, and lips scarring and complete nose deformities. His eyebrows were lost. Bilateral upper and lower eyelids adhered to the eye socket. He went through 3 primary operations with many different procedures. The treatment time was shortened over 5 months thanks to the appropriate combination of many processes in the same stage and the proper sequence of surgeries. After 7 years of follow up, the patient was satisfied with the aesthetic results, with no functional limitations. CLINICAL DISCUSSION: Reconstruction of total facial burn sequelae is always a challenge for surgeons, as it requires much experience to schedule multi-staged procedures, which takes a long time, choose the appropriate material for different anatomical units, and achieve functional and simultaneous aesthetic improvement. The most important thing is to create a prioritized order, adhere to the principles of subunit reconstruction, pay attention to functional and simultaneous aesthetic improvement, and restore the contour and symmetry of the landmarks. CONCLUSION: By arranging surgeries properly, using suitable reconstructive materials, and paying attention to the integrity of the facial units, an excellent aesthetic and functional outcome can be achieved in a patient with severe facial disfiguration caused by acid burns.

Viral Encephalitis after Hematopoietic Cell Transplantation: A Systematic Review.

Viral encephalitis is a rare but serious complication after hematopoietic cell transplantation (HCT). The nonspecific early signs and symptoms and rapid progression can make it difficult to diagnose and treat in a timely fashion. To better inform clinical decision making in post-HCT viral encephalitis, a systematic review of prior studies of viral encephalitis was performed, with the goal of characterizing the frequency of various infectious etiologies and their clinical course, including treatments and outcomes. A systematic review of studies of viral encephalitis was performed. Studies were included if they described a cohort of HCT recipients who were tested for at least 1 pathogen. Of 1613 unique articles initially identified, 68 met the inclusion criteria, with a total of 72,423 patients studied. A total of 778 cases of encephalitis were reported (1.1%). Human herpesvirus 6 (HHV-6) (n = 596), Epstein-Barr virus (n = 76), and cytomegalovirus (n = 33) were the most commonly reported causes of encephalitis, and HHV-6 encephalitis tended to occur the earliest, accounting for most cases prior to day +100 post-transplantation. Of 29,671 patients with available transplantation data, encephalitis was diagnosed in 282 of 4707 (6.0%) cord blood transplantation (CBT) recipients, in 372 of 24,664 (1.5%) non-CBT allogeneic HCT recipients, and in 5 of 300 (1.7%) autologous HCT recipients. Of the 282 CBT encephalitis cases, 270 (95.7%) were caused by HHV-6. Overall, 288 (37.0%) of the 778 patients with encephalitis died, and 75 deaths were attributable to encephalitis, with the time between diagnosis and death ranging from 3 to 192 days. Viral encephalitis occurs in approximately 1% of HCT recipients, and HHV-6 is the most common cause. Mortality following encephalitis in HCT recipients is high, indicating an urgent need for advancement in preventive and therapeutic strategies.

Reconstruction of the thoracic radiation-induced ulcer with the pedicled internal mammary artery fasciocutaneous flap: Review of the literature and a case report.

Objective: The pedicled Internal Mammary Artery Perforator (IMAP) flap is not yet a well-known technique. However, it seems practical for use in thoracic radiation-induced ulcer, especially in recurrence after the failure of convenient reconstructive techniques. This technique is applied to patients with breast hypertrophy. In this article, we present our experience with the indications, surgery details, and advantages of this technique. Materials and methods: A 63-year-old woman had a right mastectomy 11 years ago. The patient's ulcers recurred after radiotherapy and were treated with a regional and local flap. The opposite breast was ptotic, and the patient was not eligible for microsurgery. The patient underwent reconstruction using the contralateral pedicle IMAP flap. Results: The IMAP flap was designed with a size of 14 × 22 cm, including the inferior half of the breast and the areolar. The flap could completely cover the chest wall defect, and the contralateral breast was reduced to match. The final results were evaluated after two years of follow-up. Conclusion: The contralateral breast pedicle IMAP flap is a reliable, versatile, and easy-to-perform technique. This flap is a useful technique for chest wall coverage after radiation-induced ulcers, particularly in elderly patients. The major limitation of this technique is the higher risk of second primary breast cancer as the transfer flap of the contralateral breast.