Comparison between high transverse and low transverse Pfannenstiel skin incisions during cesarean delivery for morbidly obese patients.

OBJECTIVE: This study aimed to evaluate if placement of transverse cesarean skin incision above or below the overhanging pannus is associated with wound morbidity in morbidly obese patients. STUDY DESIGN: We identified a cohort of patients with body mass index (BMI) ≥40 kg/m2 undergoing cesarean delivery at a single center from 2017-2020 with complete postpartum records. Data was abstracted after institutional review board exemption, and patients were grouped by low transverse or high transverse skin incision. The primary outcome was a composite of wound infection, fascial dehiscence, incisional hernia, therapeutic wound vacuum, and reoperation. Secondary outcomes included the individual components of the composite, blood transfusion, operative time, and immediate neonatal outcome. T test and χ2 were used for continuous and categorical comparisons. Logistic regression was used to compute adjusted odds ratios for categorical outcomes and linear regression to compare operative times adjusting for factors associated with wound complications and surgical duration respectively. RESULTS: 328 patients met inclusion criteria: 65 with high transverse (infraumbilical and supraumbilical) and 263 with low transverse (Pfannenstiel) incision. 11% of patients had wound morbidity; high transverse incision was associated with 3.64-fold increased odds of composite wound morbidity (23.1% vs 8%, aOR 3.64, 95% CI 1.52-8.70) and 5.73-fold increased odds of wound infection (13.8% vs. 4.9%, aOR 5.73, 95% CI 1.83-17.96). Time from skin incision to delivery was 1.87 min longer (11.09 vs 14.98 min, ß = 1.87, 95% CI 0.17-4.61). There was no significant difference in neonatal outcomes, non-low transverse hysterotomy, or total operative time. CONCLUSION: High transverse skin incision for cesarean delivery was strongly associated with increased wound morbidity in morbidly obese patients.

Outcomes after cesarean delivery were assessed for 328 patients with morbid obesity.High transverse skin incision for cesarean delivery was associated with increased wound morbidity and wound infection.Prospective studies will be needed to determine if skin incision placement causes wound morbidity.

Biopolymeric Innovations in Ophthalmic Surgery: Enhancing Devices and Drug Delivery Systems.

The interface between material science and ophthalmic medicine is witnessing significant advances with the introduction of biopolymers in medical device fabrication. This review discusses the impact of biopolymers on the development of ophthalmic devices, such as intraocular lenses, stents, and various prosthetics. Biopolymers are emerging as superior alternatives due to their biocompatibility, mechanical robustness, and biodegradability, presenting an advance over traditional materials with respect to patient comfort and environmental considerations. We explore the spectrum of biopolymers used in ophthalmic devices and evaluate their physical properties, compatibility with biological tissues, and clinical performances. Specific applications in oculoplastic and orbital surgeries, hydrogel applications in ocular therapeutics, and polymeric drug delivery systems for a range of ophthalmic conditions were reviewed. We also anticipate future directions and identify challenges in the field, advocating for a collaborative approach between material science and ophthalmic practice to foster innovative, patient-focused treatments. This synthesis aims to reinforce the potential of biopolymers to improve ophthalmic device technology and enhance clinical outcomes.

Comparing students' performance in self-directed and directed self-learning in College of Medicine, University of Bisha.

Background: Student-centered learning strategy increases the likelihood of graduation of competent, self-dependent, and problem-solving physicians. The University of Bisha, College of Medicine (UBCOM) adopted self-directed learning (SDL) represented by problem-based learning (PBL), and directed self-learning (DSL) represented by team-based learning (TBL). Aim: To compare the students' performance in SDL and DSL among UBCOM students. Methodology: A total of 502 multiple choice questions (MCQs) from the mid-course and final exams were collected by the relevant subject experts from nine courses during the period from September 2020 till June 2023 that adopted PBL and TBL; 247 MCQs related to PBL and 255 related to TBL. Psychometric analysis was used to determine difficult, easy, and optimum questions (≤25%, ≥90%, and 26-89%, respectively). Point biserial as <0.19, 0.20-0.29, 0.30-0.39, and >0.40 which indicate poor, marginal, good, and excellent point biserial, respectively. Finally, the number of functional distractors was attempted by >5% of the candidates. Results: No significant differences were noted for the students' performance in MCQs related to PBL (representing self-directed, small group learning tool), and TBL (representing directed-self, large group learning tool) regarding difficulty index (DI), point biserial, and distractors functionality. Conclusion: It has been observed that there is no difference in students' performance whether PBL or TBL is used for learning Basic Medical Science courses. Small group learning such as PBL needs more resources in comparison to large group learning as in TBL, therefore any institute can decide on the adopted learning strategy depending on its resources and the number of students.

Assessment of extremely premature lambs supported by the Extrauterine Environment for Neonatal Development (EXTEND).

BACKGROUND: Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. METHODS: Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. RESULTS: The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. CONCLUSION: EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. IMPACT: Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.

Burns in South Asia: Outcomes from South Asian Burn Registry (SABR).

BACKGROUND: South Asian region contributes 59 % to the global mortality due to burns. However, we find a paucity of literature on the outcomes of burns from low- and middle-income countries (LMICs). South Asian Burn Registry (SABR) is a facility-based burns registry that collected data on in-patient burn care. This study assesses factors associated with mortality, length of hospital stay at the burns center, and functional status of burn patients. METHODS: Prospective data was collected from two specialized public sector burn centers between September 2014 - January 2015 from Bangladesh and Pakistan. Multivariable logistic, linear, and ordinal logistic regression was conducted to assess factors associated with inpatient-mortality, length of hospital stay, and functional status at discharge, respectively. RESULTS: Data on 883 patients was analyzed. Increased association with mortality was observed with administration of blood product (OR:3, 95 % CI:1.18-7.58) and nutritional support (OR:4.32, 95 % CI:1.55-12.02). Conversely, antibiotic regimens greater than 8 days was associated with decreased mortality (OR:0.1, 95 % CI:0.03-0.41). Associated increase in length of hospital stay was observed in patients with trauma associated with their burn injury, history of seizures (CE:47.93, 95 % CI 12.05-83.80), blood product (CE:22.09, 95 % CI:0.83-43.35) and oxygen administration (CE:23.7, 95 % CI:7.34-40.06). Patients who developed sepsis (OR:6.89, 95 % CI:1.92-24.73) and received blood products during hospitalization (OR:2.55, 95 % CI:1.38- 4.73) were more likely to have poor functional status at discharge. CONCLUSION: This study identified multiple factors associated with worse clinical outcomes for burn patients in South Asia. Understanding these parameters can guide targeted efforts to improve the process and quality of burn care in LMICs.

Investigating the characteristics of biomass wastes via particle feeder in downdraft gasifier.

Particle feeding plays a crucial role in the gasifier due to its effects on the efficiency and performance metrics of the thermochemical process. Investigating particle size distribution's impact on downdraft gasification reactor performance, this study delves into the significance of feedstock characteristics (moisture, volatile matter, fixed carbon, and ash contents) during the particle feeding stage. Various biomass wastes (date palm waste, olive pomace and sewage sludge) at diverse compositions and sizes are subjected to empirical determination of mass flow rates (MFR), power ratings, and storage times for each feedstock. The preheating process in the gasifier is considered, employing both an approximation and analytical solution. In addition, the influence of the equivalence ratio (ER) on the syngas yield is analyzed. The collected data reveals that for average particle size of 200 µm, the highest MFR (in g/min) are 0.518 ± 0.033, 7.691 ± 0.415, and 16.111 ± 1.050, for palm wood biomass, olive pomace and sewage sludge, respectively. Smaller particles (80 µm) led to extended storage times. Moreover, the lumped capacitance approximation method consistently underestimates preheating time, with a percentage error of 6.26%-17.08%. Response surface methodology (RSM) optimization analysis provides optimal gasification conditions for palm wood biomass, olive pomace, and sewage sludge with maximum cold gas efficiencies (CGEs) of 58.01%, 63.29%, and 52.27%. The peak conversion was attained at gasification temperatures of 1089.83 °C, 1151.93 °C, and 1102.91 °C for palm wood biomass, olive pomace, and sewage sludge, respectively. In addition, gasification equilibrium model determined optimal gasification temperatures as 1150 °C for palm biomass, 1200 °C for olive pomace, and 1150 °C for sewage sludge with respective syngas efficiencies of 59.62%, 64.13%, and 53.66%. Consequently, the examination of the dosing procedure, preheating dynamics, particle dimensions, ER, storage time, and their combined impacts offer practical insights to effectively control downdraft gasifiers in handling a variety of feedstocks.

Somatostatin Receptor Imaging with [18F]FET-ßAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study.

There is a clinical need for 18F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [68Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [18F]fluoroethyl-triazole-[Tyr3]-octreotate ([18F]FET-ßAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [18F]FET-ßAG-TOCA PET/CT compared with [68Ga]Ga-DOTA- peptide PET/CT in patients with NET. Methods: Forty-five patients with histologically confirmed NET, grades 1 and 2, underwent PET/CT imaging with both [18F]FET-ßAG-TOCA and [68Ga]Ga-peptide performed within a 6-mo window (median, 77 d; range, 6-180 d). Whole-body PET/CT was conducted 50 min after injection of 165 MBq of [18F]FET-ßAG-TOCA. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios at both lesion and regional levels by 2 unblinded, experienced readers. A randomized, blinded reading of both scans was also then undertaken by 3 experienced readers, and consensus was assessed at a regional level. The ability of both tracers to visualize liver metastases was also assessed. Results: A total of 285 lesions were detected on both imaging modalities. An additional 13 tumor deposits were seen in 8 patients on [18F]FET-ßAG-TOCA PET/CT, and [68Ga]Ga-DOTA-peptide PET/CT detected an additional 7 lesions in 5 patients. Excellent correlation in SUVmax was observed between both tracers (r = 0.91; P < 0.001). No difference was observed between median SUVmax across regions, except in the liver, where the median tumor-to-background ratio of [18F]FET-ßAG-TOCA was significantly lower than that of [68Ga]Ga-DOTA-peptide (2.5 ± 1.9 vs. 3.5 ± 2.3; P < 0.001). Conclusion: [18F]FET-ßAG-TOCA was not inferior to [68Ga]Ga-DOTA-peptide in visualizing NET and may be considered in routine clinical practice given the longer half-life and availability of the cyclotron-produced fluorine radioisotope.

Unveiling the mechanisms and challenges of cancer drug resistance.

Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer treatment strategies are evolving due to innate and acquired resistance capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells to survive and progress under unfavorable conditions. Although the mechanism of drug resistance is being widely studied to generate new target-based drugs with better potency than existing ones. However, due to the broader flexibility in acquired drug resistance, advanced therapeutic options with better efficacy need to be explored. Combination therapy is an alternative with a better success rate though the risk of amplified side effects is commonplace. Moreover, recent groundbreaking precision immune therapy is one of the ways to overcome drug resistance and has revolutionized anticancer therapy to a greater extent with the only limitation of being individual-specific and needs further attention. This review will focus on the challenges and strategies opted by cancer cells to withstand the current therapies at the molecular level and also highlights the emerging therapeutic options -like immunological, and stem cell-based options that may prove to have better potential to challenge the existing problem of therapy resistance. Video Abstract.

Cancer metastasis: Molecular mechanisms and clinical perspectives.

Metastatic progression combined with non-responsiveness towards systemic therapy often shapes the course of disease for cancer patients and commonly determines its lethal outcome. The complex molecular events that promote metastasis are a combination of both, the acquired pro-metastatic properties of cancer cells and a metastasis-permissive or -supportive tumor micro-environment (TME). Yet, dissemination is a challenging process for cancer cells that requires a series of events to enable cancer cell survival and growth. Metastatic cancer cells have to initially detach themselves from primary tumors, overcome the challenges of their intravasal journey and colonize distant sites that are suited for their metastases. The implicated obstacles including anoikis and immune surveillance, can be overcome by intricate intra- and extracellular signaling pathways, which we will summarize and discuss in this review. Further, emerging modulators of metastasis, like the immune-microenvironment, microbiome, sublethal cell death engagement, or the nervous system will be integrated into the existing working model of metastasis.

Outcomes in elderly patients undergoing hepatic resection compared to liver transplant for hepatocellular carcinoma.

BACKGROUND: Hepatic resection (HR) is an excellent option for patients with hepatocellular carcinoma (HCC). For patients meeting the Milan criteria, a liver transplant (LT) is also a viable option for patients with HCC, especially those with end-stage liver disease. With increasing rates of LTs amongst the elderly, we sought to determine long-term outcomes in patients who underwent HR compared to LTs in this patient population. METHODS: We queried the national cancer database for elderly patients (≥70 years) diagnosed with HCC between 2004 and 2020. The primary outcome was overall survival (OS) computed using the Kaplan-Meier method and Cox proportional hazard regression. One-to-one propensity score matching was conducted on the basis of clinicodemographic features to account for baseline differences between patients undergoing each procedure. RESULTS: Of the 5090 patients included, 4674 (91.8%) and 416 (8.2%) patients underwent HR and LT, respectively. Compared with HR patients, patients receiving LT had better OS (p < 0.001) and greater median survival time (65.6 months HR vs. 97.9 months LT, p < 0.001). On multivariable analysis, a LT was independently associated with improved survival (adjusted hazard ratio: 0.61, 95% confidence interval: 0.50-0.76, p < 0.001). CONCLUSIONS: LT is associated with improved survival for well-selected elderly patients with HCC. Age alone should not be used as the sole parameter for the candidacy of LT in elderly patients.

Outcomes in elderly patients undergoing hepatic resection compared to ablative therapy for hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatic resection is an excellent option in the care of patients with hepatocellular carcinoma (HCC). Elderly patients often forego hepatic resection in favor of liver-directed ablative therapies due to the increased likelihood of adverse postoperative outcomes due to age. We sought to determine long-term outcomes in patients who underwent hepatic resection compared to liver-directed ablative therapy in this patient population. METHODS: We queried the National Cancer Database for elderly patients (≥70 years) diagnosed with HCC between 2004 and 2018. The primary outcome was overall survival (OS) computed using the Kaplan-Meier method and Cox proportional hazard regression. RESULTS: A total of 10 032 patients were included in this analysis. On unadjusted analysis (p < 0.001) as well as multivariable analysis (hazard ratio: 0.65, 95% confidence interval: 0.57-0.73), hepatic resection was associated with improved OS. The protective association between hepatic resection and OS persisted after 1:1 propensity score matching. CONCLUSIONS: Hepatic resection is associated with improved survival for well-selected elderly patients with HCC. While age is often thought of as influencing the decision to offer surgery, our study, in combination with others, demonstrates that it should not. Instead, other objective indicators of performance and functional status may be considered.

Lavender plant: Farming and Health benefits.

Natural remedies from a range of sources, including plants, animals, microorganisms, and marine life, have made a significant contribution to the treatment of many ailments. Lavender is a Mediterranean shrub from the Lamiaceae family. Lavender flowers (Lavandula flores) include active ingredients (3%), anthocyanins, sugars, phytosterols, minerals, and tannins and are majorly used for herbal applications. Lavender essential oil's descriptive and analytical composition varies depending on genotype, growing region, climatic circumstances, propagation, and morphological characteristics. There are around 300 chemical components in essential oil. Linalool, terpinen-4-ol, linalyl acetate, ocimene, acetate lavandulol, and cineole are the most prominent constituents. Lavender oil has antibacterial and antioxidant properties. The lavender extract helps to prevent dementia and may slow cancer cell growth, while lavender oil is used to treat skin problems. This review will cover the recent medical, economic and regional advancements in levander propagation and how the Council of Scientific & Industrial Research Indian Institute of Integrative (CSIR IIIM) aroma mission is actively acting as a bridge between farmers and their economic improvement by attracting them to the field of medicinal plant cultivation.

Impact of Medicaid Expansion on the Treatment and Outcomes of Intrahepatic Cholangiocarcinoma.

INTRODUCTION: The Affordable Care Act increased insurance coverage for patients residing in states that expanded Medicaid coverage, but its impact on the outcomes of intrahepatic cholangiocarcinoma (ICC) is not clear. Therefore, we examine the impact of Medicaid expansion (ME) on access to treatment and outcomes of ICC. METHODS: We queried the National Cancer Database (NCDB) data for patients with a diagnosis of ICC (2010-2018). Difference-in-difference (DID) analysis was performed to assess the impact of January 2014 ME on curative-intent surgical resection, multimodal therapy, neoadjuvant chemotherapy, 30-day mortality, and overall survival (OS). RESULTS: Of the 2150 patients included in the study,1574 (73.2%) and 576 (26.8%) patients lived in non-ME and ME states, respectively. On adjusted DID, ME was independently associated with receipt of curative-intent surgical resection (DID coefficient: 0.05, 95% confidence interval [95% CI]: 0.04-0.06, p = 0.002) and multimodal therapy (DID coefficient: 0.08, 95% CI: 0.06-0.10, p = 0.004). In addition, ME was associated with improved OS in ME states (hazard ratio [HR]: 0.73, 95% CI: 0.62-0.87, p = 0.001) but not in non-ME states (HR: 0.95, 95% CI: 0.80-1.12, p = 0.536). CONCLUSION: ME status consistently predicted increased utilization of care processes that improved ICC outcomes, including greater rates of curative-intent surgery and multimodal therapy.

Small molecule '4ab' induced autophagy and endoplasmic reticulum stress-mediated death of aggressive cancer cells grown under adherent and floating conditions.

Metastasis is the leading cause of death in cancer patients and a major challenging aspect of cancer biology. Various adaptive molecular signaling pathways play a crucial role in cancer metastasis and later in the formation of secondary tumors. Aggressive cancer cells like triple negative breast cancer (TNBCs) are more inclined to undergo metastasis hence having a high recurrence rate and potential of micro-metastasis. Tumor cells in circulation known as circulating tumor cells (CTCs) offer an attractive drug target to treat metastatic disease. Cell cycle regulation and stress response of CTCs in blood has a crucial role in their survival and progression and thus may be considered therapeutically active hotspots. The cyclin D/cyclin-dependent kinase (CDK) pathway regulates cell cycle checkpoints, a process that is frequently dysregulated in cancer cells. Selective CDK inhibitors can limit the phosphorylation of cell cycle regulatory proteins by inducing cell cycle phase arrest, and thus may be an effective therapeutic strategy for aggressive cancer cells in their dividing phase at the primary or secondary site. However, during the floating condition, cancer cells halt their multiplication process and proceed through the various steps of metastasis. Current study showed that a novel CDK inhibitor 4ab induced autophagy and endoplasmic reticulum (ER) stress in agressive cancer cells grown under adherent and floating conditions resulting in paraptosis. Further, our results showed that 4ab efficiently induced cell death in aggressive cancer cells through ER stress-mediated activation of JNK signaling. Additionally, was observed that treatment of 4ab in tumor-bearing mice displayed a significant reduction in tumor burden and micro-metastasis. The outcome of these studies showed that 4ab can be a potential anti-tumor and anti-metastatic agent. Graphical representation of 4ab: image representing the effect of 4ab on death-inducing pathways in aggressive cancer cells. 4ab induces ER stress and activates autophagy leading to vacuolation of there by causing apoptosis in aggressive cancer cells.

Targeting redox regulation and autophagy systems in cancer stem cells.

Cancer is a dysregulated cellular level pathological condition that results in tumor formation followed by metastasis. In the heterogeneous tumor architecture, cancer stem cells (CSCs) are essential to push forward the progression of tumors due to their strong pro-tumor properties such as stemness, self-renewal, plasticity, metastasis, and being poorly responsive to radiotherapy and chemotherapeutic agents. Cancer stem cells have the ability to withstand various stress pressures by modulating transcriptional and translational mechanisms, and adaptable metabolic changes. Owing to CSCs heterogeneity and plasticity, these cells display varied metabolic and redox profiles across different types of cancers. It has been established that there is a disparity in the levels of Reactive Oxygen Species (ROS) generated in CSCs vs Non-CSC and these differential levels are detected across different tumors. CSCs have unique metabolic demands and are known to change plasticity during metastasis by passing through the interchangeable epithelial and mesenchymal-like phenotypes. During the metastatic process, tumor cells undergo epithelial to mesenchymal transition (EMT) thus attaining invasive properties while leaving the primary tumor site, similarly during the course of circulation and extravasation at a distant organ, these cells regain their epithelial characteristics through Mesenchymal to Epithelial Transition (MET) to initiate micrometastasis. It has been evidenced that levels of Reactive Oxygen Species (ROS) and associated metabolic activities vary between the epithelial and mesenchymal states of CSCs. Similarly, the levels of oxidative and metabolic states were observed to get altered in CSCs post-drug treatments. As oxidative and metabolic changes guide the onset of autophagy in cells, its role in self-renewal, quiescence, proliferation and response to drug treatment is well established. This review will highlight the molecular mechanisms useful for expanding therapeutic strategies based on modulating redox regulation and autophagy activation to targets. Specifically, we will account for the mounting data that focus on the role of ROS generated by different metabolic pathways and autophagy regulation in eradicating stem-like cells hereafter referred to as cancer stem cells (CSCs).

Myrica esculenta Buch.-Ham. (ex D. Don): A Review on its Phytochemistry, Pharmacology and Nutritional Potential.

Myrica esculenta is an important ethnomedicinal plant used in the traditional system of medicine and as an important nutraceutical. Several studies on the plant justify its use in alternative systems of medicine and establish a scientific rationale for its possible therapeutic application. The plant contains a range of biologically active classes of compounds, particularly diarylheptanoids, flavonoids, terpenes, tannins, and glycosides. The nutraceutical potential of the plant can be particularly attributed to its fruit, and several studies have demonstrated the presence of carbohydrates, proteins, fats, fiber content, and minerals like sodium, potassium, calcium, manganese, iron, copper, and zinc, in it. The current review aims to provide complete insight into the phytochemistry, pharmacological potential, and nutritional potential of the plant, which would not only serve as a comprehensive source of information but also will highlight the scope of isolation and evaluation of these molecules for various disease conditions.

Redox balance and autophagy regulation in cancer progression and their therapeutic perspective.

Cellular ROS production participates in various cellular functions but its accumulation decides the cell fate. Malignant cells have higher levels of ROS and active antioxidant machinery, a characteristic hallmark of cancer with an outcome of activation of stress-induced pathways like autophagy. Autophagy is an intracellular catabolic process that produces alternative raw materials to meet the energy demand of cells and is influenced by the cellular redox state thus playing a definite role in cancer cell fate. Since damaged mitochondria are the main source of ROS in the cell, however, cancer cells remove them by upregulating the process of mitophagy which is known to play a decisive role in tumorigenesis and tumor progression. Chemotherapy exploits cell machinery which results in the accumulation of toxic levels of ROS in cells resulting in cell death by activating either of the pathways like apoptosis, necrosis, ferroptosis or autophagy in them. So understanding these redox and autophagy regulations offers a promising method to design and develop new cancer therapies that can be very effective and durable for years. This review will give a summary of the current therapeutic molecules targeting redox regulation and autophagy for the treatment of cancer. Further, it will highlight various challenges in developing anticancer agents due to autophagy and ROS regulation in the cell and insights into the development of future therapies.

The impact of COVID-19 on mortality after hip fracture : a population cohort study from England.

AIMS: Hip fracture commonly affects the frailest patients, of whom many are care-dependent, with a disproportionate risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England. METHODS: We conducted a cohort study of patients with hip fracture recorded in the National Hip Fracture Database between 1 February 2019 and 31 October 2020 in England. Data were linked to Hospital Episode Statistics to quantify patient characteristics and comorbidities, Office for National Statistics mortality data, and Public Health England's SARS-CoV-2 testing results. Multivariable Cox regression examined determinants of 90-day mortality. Excess mortality attributable to COVID-19 was quantified using Quasi-Poisson models. RESULTS: Analysis of 102,900 hip fractures (42,630 occurring during the pandemic) revealed that among those with COVID-19 infection at presentation (n = 1,120) there was a doubling of 90-day mortality; hazard ratio (HR) 2.09 (95% confidence interval (CI) 1.89 to 2.31), while the HR for infections arising between eight and 30 days after presentation (n = 1,644) the figure was greater at 2.51 (95% CI 2.31 to 2.73). Malnutrition (1.45 (95% CI 1.19 to 1.77)) and nonoperative treatment (2.94 (95% CI 2.18 to 3.95)) were the only modifiable risk factors for death in COVID-19-positive patients. Patients who had tested positive for COVID-19 more than two weeks prior to hip fracture initially had better survival compared to those who contracted COVID-19 around the time of their hip fracture; however, survival rapidly declined and by 365 days the combination of hip fracture and COVID-19 infection was associated with a 50% mortality rate. Between 1 January and 30 June 2020, 1,273 (99.7% CI 1,077 to 1,465) excess deaths occurred within 90 days of hip fracture, representing an excess mortality of 23% (99.7% CI 20% to 26%), with most deaths occurring within 30 days. CONCLUSION: COVID-19 infection more than doubles the rate of early hip fracture mortality. Those contracting infection between 8 and 30 days after initial presentation are at even higher mortality risk, signalling the potential for targeted interventions during this period to improve survival.Cite this article: Bone Joint J 2022;104-B(10):1156-1167.

Reoperation and revision rates at ten years after 1,312 cemented Thompson's hemiarthroplasties : any need to change to a different implant?

AIMS: Despite multiple trials and case series on hip hemiarthroplasty designs, guidance is still lacking on which implant to use. One particularly deficient area is long-term outcomes. We present over 1,000 consecutive cemented Thompson's hemiarthroplasties over a ten-year period, recording all accessible patient and implant outcomes. METHODS: Patient identifiers for a consecutive cohort treated between 1 January 2003 and 31 December 2011 were linked to radiographs, surgical notes, clinic letters, and mortality data from a national dataset. This allowed charting of their postoperative course, complications, readmissions, returns to theatre, revisions, and deaths. We also identified all postoperative attendances at the Emergency and Outpatient Departments, and recorded any subsequent skeletal injuries. RESULTS: In total, 1,312 Thompson's hemiarthroplasties were analyzed (mean age at surgery 82.8 years); 125 complications were recorded, necessitating 82 returns to theatre. These included 14 patients undergoing aspiration or manipulation under anaesthesia, 68 reoperations (5.2%) for debridement and implant retention (n = 12), haematoma evacuation (n = 2), open reduction for dislocation (n = 1), fixation of periprosthetic fracture (n = 5), and 48 revised stems (3.7%), for infection (n = 13), dislocation (n = 12), aseptic loosening (n = 9), persistent pain (n = 6), periprosthetic fracture (n = 4), acetabular erosion (n = 3), and metastatic bone disease (n = 1). Their status at ten years is summarized as follows: 1,180 (89.9%) dead without revision, 34 (2.6%) dead having had revision, 84 (6.6%) alive with the stem unrevised, and 14 (1.1%) alive having had revision. Cumulative implant survivorship was 90.3% at ten years; patient survivorship was 7.4%. CONCLUSION: The Thompson's stem demonstrates very low rates of complications requiring reoperation and revision, up to ten years after the index procedure. Fewer than one in ten patients live for ten years after fracture. This study supports the use of a cemented Thompson's implant as a cost-effective option for frail hip fracture patients.Cite this article: Bone Jt Open 2022;3(9):710-715.

Prenatal treprostinil reduces the pulmonary hypertension phenotype in the rat model of congenital diaphragmatic hernia.

BACKGROUND: Persistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH. METHODS: In a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity. Next, an efficacy study was performed assessing the effects of treprostinil administration at 900 and 1500ng/kg/min from gestational day (GD) 16 until term (GD 21) in CDH and control pups. Pulmonary vascular and airway morphometry, lung mechanics, and expression patterns of genes implicated in the prostaglandin vasoactive pathway were studied. FINDINGS: In rats maternal administration of 1500ng/kg/min treprostinil reached target foetal concentrations, with no detrimental maternal or foetal side-effects. Prenatal exposure to 900 and 1500 ng/kg/min treprostinil reduced the medial wall thickness (%MWT) (CDH·900, 38.5± 8·4%; CDH.1500, 40·2±9·7%; CDH, 46·6±8·2%; both p < 0·0001) in rat pups with CDH, however increased the %MWT in normal foetuses (C.T.900, 36·6±11·1%; C.T.1500, 36·9±9·3%; C.P., 26·9±6·2%; both p < 0·001). Pulmonary airway development, lung hypoplasia and pulmonary function were unaffected by drug exposure. INTERPRETATION: In pregnant rats maternally administered treprostinil crosses the placenta, attains foetal target concentrations, and is well tolerated by both mother and foetuses. This report shows a significant reduction of pulmonary arteriole muscularization with prenatal treprostinil in a nitrofen rat model, supporting the promise of this treatment approach for PH of CDH. FUNDING: United Therapeutics Corporation provided treprostinil and financial support (ISS-2020-10879).