Increased Mortality Rate Research Articles

Redesigning a Stopped Clinical Trial as an Emulated Trial Using Real-World Data to Explore the Effectiveness of Slow-Release Oral Morphine as a Treatment for Opioid Use Disorder.

Canada is currently experiencing a problematic opioid crisis with increasing mortality rates. Traditional randomized controlled trials (RCTs) that examine the effectiveness of pharmacological treatment options for people with opioid use disorder (OUD) are challenging to conduct. An increasingly popular methodology is through the implementation of emulated clinical trials, a methodology in which key elements of a "target" RCT are replicated using previously collected healthcare-based data. They can possibly address some of the common challenges found in the conduct of RCTs, such as prolonged timelines, high cost, and poor participant recruitment. In effect, emulated trials accelerate knowledge generation by producing real-world evidence that can be akin to phase 3 effectiveness trials, without any need to recruit live participants or administer investigational products. During the COVID-19 pandemic, several trials were stopped due to increased pandemic-related research restrictions, leaving important questions about OUD treatment unanswered. In this commentary, we describe the transition of a traditional RCT to an emulated trial spurred by challenges posed by the COVID-19 pandemic. We describe our transition using a notable published framework with regards to the population sample, interventions, outcomes, and proposed analyses. This commentary aims to help other researchers and trialists apply emulated trials in substance use research and beyond, emphasizing the role of this methodology in clinical research and advancing scientific knowledge that could be otherwise lost or unattainable.

Bacteremias in Hemato-Oncological Pediatric Patients: Clinical and Microbiological Characteristics

Abstract Background In haemato-oncologic patients bacteremia is frequent increasing mortality rates, therefore surveillance and close follow up is essential to optimize treatment. The use of invasive devices used frequently in this population increases the incidence of infections by gram-positive microorganisms (currently gram-negative bacilli have been added). Therefore, we propose the characterization the microorganisms to identify the epidemiologic conditions, and the areas of improvement to establish improvement care strategies for this population. Methods We conducted a retrospective study at the haemato-oncologic diseases service at the National Medical Center “20 de Noviembre”. Prevalence of bacteremia in pediatric patients with cancer and neutropenia in Mexican population, which ranges from 8% to 36%, assuming that our results could be similar to higher percentage, employing a proportion formula with a study population of 65 patients. Results It was demonstrated in our population studied that in all cases of bacteremia, patients were in depth neutropenia at diagnosis. The most prevalence phase of chemotherapy was Induction phase (69.2%), with Total XV ST Jude protocol. The clinical data revealed the following frequencies in 100% of the patients: Fever (92%), Tachycardia (72%), Shivering and piloerection (65%), Elevated acute-phase reactants PCT (51%), CPR (32%), and Tachypnea (28%). Cases of Central Line-associated Bloodstream Infection (CLABSI) was reported in 86.2%, affecting individuals with vascular devices. The predominant microbiological isolate in our patients was Escherichia coli ESBL (31%), followed by Klebsiella pneumoniae (18%), and Pseudomonas aeruginosa (13.8%), Staphylococcus epidermidis (11%). Other bacteria were identified at even lower frequencies, such as Stenotrophomonas maltophilia (5%), Klebsiella oxytoca (5%), Staphylococcus aureus (3%), Serratia marcescens (3%), Enterococcus faecalis (3%), and Enterobacter cloacae (3%). The least observed in our population was the identification of Acinetobacter baumannii (2%). The different outcomes recorded in our sample were highly consistent, with a resolution rate of infection in 97% of cases and 3% of cases resulting in death attributable to bacteremia (Table 1). Conclusion The low mortality found in this study may be due to the early initiation of empirical antibiotic treatment in “golden hour”, a protocol carried out in our Center, as well as the identification of severity scales.

Etiological Agents of Superficial Surgical Site Infections among Post Operative Patients Attending a Teaching Hospital in Southeastern Nigeria

Surgical site infections (SSI) are infections at or around the site of incision where surgical procedure is conducted. It is a major cause of hospital morbidity, resulting in prolonged hospital stay, increased treatment costs, higher rates of re-operation, and even increased mortality rates. The etiological agents of superficial surgical site infections among post-operative patients attending a Teaching Hospital in Southeastern Nigeria were evaluated using standard microbiological methods. Seventy superficial surgical wound swab specimens were properly and aseptically obtained from post-operative patients after ethical clearance was duly obtained from the hospital’s ethical committee. Pure microbial cultures were obtained after 24 - 48 hours incubation, aerobically at 25oC, on blood, nutrient and Sabouraud’ Dextrose agar plates. The isolates were identified based on their morphological, physiological, biochemical and molecular characteristics. Out of the 70 surgical swab specimens collected, 81% were bacterial isolates which included Staphylococcus aureus 41%, Escherichia coli 16%, Pseudomonas aeruginosa 14% and Staphylococcus xylosus 10%. The fungi isolates (19%) were Candida tropicalis 8% and Trichosporon asahii 11%. These isolates were probably endogenous and exogenous flora from the patients’ and hospital’ environments respectively; thereby necessitating the need for adequate patient care before, during and after surgical procedures.

Linking hearts and minds: understanding the cardiovascular impact of bipolar disorder.

Bipolar disorder is a severe and recurring condition that has become a significant public health issue globally. Studies indicate a heightened risk and earlier onset of cardiovascular diseases among individuals with bipolar disorder, potentially increasing mortality rates. The chronic nature of bipolar disorder leads to disturbances across multiple systems, including autonomic dysfunction, over-activation of the hypothalamic-pituitary-adrenal axis and increased levels of peripheral inflammatory markers. These disruptions cause endothelial damage, the formation of plaques and blood clots, in addition to the medications used to treat bipolar disorder and genetic associations contributing to cardiovascular disease development. Understanding the complex interplay between bipolar disorder and cardiovascular events is essential for the prevention and effective management of cardiovascular conditions in individuals with bipolar disorder.

Adaptation and carry over effects of extreme sporadic heat stress in Culex mosquitoes

Mosquitoes, as temperature-sensitive ectothermic vectors, exhibit temperature-dependence. This study investigates Culex pipiens pallens (Cx. pallens) responses to abrupt temperature increases and their implications on mosquito physiology.First instar larvae (24hr post hatching) and newly enclosed adults (24hr post emergence) were separately exposed to heat shock regimes of 33 °C, 37 °C, and 42 °C for 3 days alongside a control temperature of 27 °C. Results showed that mortality was triggered at 42 °C within a day. Adult male mosquitoes were less tolerant to all temperatures than larvae and adult females (p < 0.05). Exposing larvae to constant temperatures for 3 days significantly decreased larvae's development time, growth rate and adult emergence (p < 0.05). Reproductive fitness was significantly reduced (p < 0.05) in males emerging from larvae exposed to 37 °C. Life table parameters showed significant increased mortality rate, kill power and decreased life expectancy at the embryonic stage (p < 0.05). Furthermore, heatwaves deactivated the Transient receptor protein ankyrin 1 at 37 °C (p < 0.05) in larvae but not adults. Calmodium, Heat shock protein 90, and small heat shock protein expression were significantly decreased in larvae at 37 °C (p < 0.05) as compared to larvae raised at 33 °C and 27 °C.In conclusion, we classified the heat waves into three categories: adaptable (33 °C), critical (37 °C), and fatal (42 °C). Prolonged exposure of Culex pallens larvae to extreme heat affects the male reproductive output. These findings may serve as an important reference for forecasting vector and pest dynamics and used to tailor mosquito prevention and control measures.

Detection of a stress related acoustic signature by passive acoustic monitoring in Atlantic salmon farming

Crowding is a necessary operation for moving fish out of or between sea cages in Atlantic salmon farming. These operations consist of gradually reducing available volume in the nets to increase the biomass density. This is known to stress the fish, increase risk of injury, and can in extreme cases increase mortality rates. To reduce the negative impacts of crowding, the operation must be adjusted based on real-time monitoring of fish welfare. Today, this is mainly done by manually monitoring surface activity, as the high fish density limits the use of available tools. In this paper a new approach for monitoring was applied to crowding of meso-scale cages containing 40 fish each, using automatic detection of passive acoustic signatures. Four synchronised hydrophones were deployed and the acoustic signature was defined from the recordings. The automatic detection algorithm recorded an extreme increase in registered acoustic events during crowding, as high as 1000 events per 10 min period, compared to only 20 events per 10 min period on the day following crowding. Correlating the number of acoustic events to recorded heart rate and activity measures from implants in the salmon indicate that automatically registering acoustic events is a promising method for monitoring farmed fish.

Carbon monoxide-releasing molecule-3 ameliorates traumatic brain injury-induced cardiac dysfunctions via inhibition of pyroptosis and apoptosis.

Traumatic brain injury (TBI) frequently results in cardiac dysfunction and impacts the quality of survivors' life. It has been reported that carbon monoxide-releasing molecule-3 (CORM-3) administration immediately after hemorrhagic shock and resuscitation (HSR) ameliorated the HSR‑induced cardiac dysfunctions. The purpose of this study was to determine whether the application of CORM-3 on TBI exerted therapeutic effects against TBI-induced cardiac dysfunctions. Rats were randomly divided into four groups (n = 12) including Sham, TBI, TBI/CORM-3 and TBI/inactive CORM-3 (iCORM-3) groups. TBI was established by a weight-drop model. The rats in the TBI/CORM-3 group and TBI/iCORM-3 group were intravenously injected with CORM-3 and iCORM-3 (4mg/kg) following TBI, respectively. The time of death in the rats that did not survive within 24h was recorded. 24h post-trauma, the cardiac function, pathological change, serum troponin T and creatine kinase-MB (CK-MB) levels, pyroptosis, apoptosis and expressions of TUNEL staining, Gasdermin D (GSDMD), IL-1β, IL-18, ratio Bax/Bcl-2 were assessed by echocardiography, hematoxylin-eosin staining, chemiluminescence, immunofluorescence, and western blot assays, respectively. TBI-treated rats exhibited dramatically decreased ejection fraction and aggravated myocardial injury, increased mortality rate, elevated levels of serum troponin T and CK-MB, promoted cardiac pyroptosis and apoptosis, and upregulated expressions of cleaved caspase-3, GSDMD N-terminal fragments, IL-1β, IL-18, and ratio of Bax/Bcl-2, whereas CORM-3 partially reversed these changes. CORM-3 ameliorated TBI-induced cardiac injury and dysfunction. This mechanism may be responsible for the inhibition of pyroptosis and apoptosis in cardiomyocyte.

Epidemiology of Morbidity and Mortality of COVID-19 Patients During the Period of June 2020-September 2021 in Sulianti Saroso Infectious Disease Hospital, Indonesia.

The increasing mortality rate of COVID-19 has remained an international public health concern. Limited studies on clinical treatment and morbidity in hospital settings are available in Indonesia. This present study aims to analyse demographic characteristics, clinical signs and treatment in COVID-19 patients and their association to the mortality case in Sulianti Saroso Infectious Disease Hospital. The study applied a retrospective cohort approach to all COVID-19 inpatients confirmed by polymerase chain reaction (PCR) testing in Sulianti Saroso Infectious Disease Hospital from 1 June 2020 to 30 September 2021. Overall survival rates until the end of the study were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox regression model was used to evaluate the crude and adjusted hazard ratios for associated factors. We collected 1,970 inpatient data that met our inclusion and exclusion criteria. Most of them were 19 years old-59 years old (73.2%) and male (52.6%), and 966 (49%) patients had comorbidities. Approximately 63.9%, 89.2%, 89.8%, 82%, and 14.1% of the patients had ferritin levels ≤ 800, received antiviral treatment, were treated in non-intensive wards, had a moderate or mild clinical stage and did not survive, respectively. In the adjusted analysis, mortality was associated with sex (hazard ratio [HR]: 1.12; 95% CI: 1.02, 1.23), presence of comorbidity (HR: 1.19; 95% CI: 1.08, 1.30) and favipiravir (FPV) plus azithromycin treatment (HR: 1.21; 95% CI: 1.06,1.39). FPV treatment (HR: 1.35; 95% CI: 1.04, 1.75) was associated with higher mortality. Tailored approaches to treatment, considering individual risk factors and comorbidities, are crucial in improving patient outcomes.

Non-invasive Anemia Detection and Prediagnosis

Background Anemia is a significant global health concern, often stemming from iron deficiency or deficiencies in folate, vitamins B12, and A. Anemia disproportionately impacts vulnerable populations like children, adolescent girls, and pregnant or postpartum women. Purpose Anemia is a serious public health issue, impairing productivity, cognitive development, and increasing mortality rates. Anemia is usually detected through blood tests measuring hemoglobin levels, but non-invasive solutions are rquired to lower discomfort, enhance accessibility, and allow for regular monitoring. These methods are essential for early detection in vulnerable populations. Methodology The research methodology involves extracting valuable information from nail images using data mining algorithms. The focus is on calculating the percentage of blue- and red-stained cells within specific regions of interest in the nail images. Machine-learning algorithms are employed to transform these data into actionable insights for disease diagnosis. Results The system demonstrates effectiveness in accurately detecting anemia and providing prediagnosis reports to healthcare providers. The reports include comprehensive information such as patient symptoms, health history, test results, and the doctor’s preliminary assessment. This aids in timely and accurate treatment decisions. Conclusion This research showcases the potential of image processing and machine learning in improving anemia diagnosis and facilitating personalized healthcare interventions.

Outcomes and Management of Dislocated Hip Hemiarthroplasty.

Purpose and aims Hip hemiarthroplasty (HHA) is a common procedure undertaken to manage intracapsular neck of femur fractures. Dislocation of HHA is one of the most dreadful complications. There is a paucity of clinical evidence to guide decision-making for managing these patients. The aim of this study was to describe the operative management and outcomes of patients with dislocated hemiarthroplasties of the hip and outline a treatment strategy for their management. Methods We conducted a retrospective analysis of all the patients presenting to University Hospitals of Derby and Burton, UK with hip fractures between 2016-2022. We included all the patients who underwent a hemiarthroplasty for their fracture. We excluded patients who had malignancy and if clinical data was missing. Each operative intervention and subsequent dislocationswere recorded. We recorded the following outcome measures: dislocation, surgical interventions, mortality, revision surgery, cognition status, residential status, and mobility. We also compare these outcomes with the patients who had HHA and did not sustain any dislocation. Results Of the 1134 patients treated with HHA during this period, 33 patients sustained dislocation. Of the 33 patients, 29 were female and 4 were male with mean ages of87.4±7.4 and89.25±9.54,​ respectively. Following the first dislocation, 25 patients were treated with closed reduction, six patients had excision arthroplasty (EA), and two patients were treated non-operatively. About 21 patients went on to have second and third dislocations, none of these had EA and others had conversion to total hip replacement (THR). Nearly 80% of dislocations occurred within two months of the initial procedure. The mean mental test score was 7.91±2.01 (p=0.001) and was significantly higher in patients who underwent conversion to THR. The average ASA grade was significantly higher in patients who had closed reduction (2.93±0.25, p=0.001)and EA (3.28±0.46, p=0.002)compared to the patients who had no dislocation. Patients who underwent EA had significantly higher acute length of hospital stay23.5±13.5(p=0.02) and mortality (p=0.001)compared to other groups. We found no significant difference in dislocation rates where the initial procedure was carried out by registrars or consultants (p=0.567). Conclusion We concluded that the dislocation risk is higher in females and within the first two months of the index procedure. More than 80% of patients had a second dislocation following a successful closed reduction. In our cohort, 45% of patients had EA (Girdlestone procedure) and 36% had a conversion to THR. EA was associated with increased mortality rates, acute length of hospital stays, and significant change to premorbid mobility status. Amultidisciplinary team (MDT) approachis necessary following the second dislocation to prevent further morbidity associated with recurrent dislocations.

Early clinical predictors of infected pancreatic necrosis: a multicentre cohort study

BackgroundInfected pancreatic necrosis (IPN) exacerbates complications in patients with acute pancreatitis (AP), increasing mortality rates if not treated promptly. We aimed to evaluate the predictive value of clinical characteristics within...

Development of venous thromboembolic event risk calculator for metabolic and bariatric surgery patients to reduce mortality

IntroductionVenous thromboembolic events (VTEs) after Metabolic and Bariatric Surgery (MBS) result in significant morbidity and are the leading cause of mortality. The objective of this study was to identify patients who are at a high risk for developing VTE and who may benefit from extended chemoprophylaxis following MBS. MethodsUsing the 2015-2019 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) participant user file (PUF), we identified 696,069 patients who completed 30-day follow-up data and met the inclusion criteria. Using logistic regression analysis, we identified preoperative and postoperative risk factors associated with VTE and validated our model externally using the MBSAQIP 2020-2021 datasets (N = 273,692). The Hosmer–Lemeshow test was used for goodness of fit and calibration. We also compared our model’s discriminatory capability with that of other VTE risk assessment tools. We then used these risk factors to create an online open source application. ResultsThe overall incidence of VTE after MBS in the 696,069 (MBSAQIP 2015-2019 database) patients included in our analysis was .40% (2759 patients). Our model had a good predictive capability, with a C-statistic of .66. Our model also demonstrated good fit with a Hosmer–Lemeshow chi-square of 11.06 (P = .198). A cut-off point of .4% resulted in a sensitivity of 48.28%, with 24% of patients having a VTE risk greater than .4% within the 2015-2019 MBSAQIP dataset. Among all the perioperative factors selected in the PUF, high risk for VTE included African American race (AOR 1.625, P < .0001), operation length in minutes (AOR: 1.003, P < .0001), preop functional status (AOR 1.012, P = .007), procedure type (RYGB; AOR .768, P < .0001 and RBS; AOR .758, P = .019 with respect to sleeve), preop body mass index (BMI) (AOR 1.012, P < .001), history of pre-op vein thrombosis requiring therapy (AOR 5.041, P < .0001), post-op superficial or organ space surgical site infection (AOR 2.713, P < .0001), preop venous stasis (AOR 1.425, P = .019),at least one readmission within 30 days(AOR 1.583, P < .0001), or at least one reoperation within 30 days (AOR 4.399, P < .0001). ConclusionVTE after MBS can result in increased mortality rates. High-risk patients might benefit from extended chemoprophylaxis. Our model suggests that patients with a VTE risk ≥ .4% in the first 30 days following surgery may benefit from extended chemoprophylaxis.

Determining What Proportion of Helicopter Emergency Medical Services–Transported Patients Are Urban Versus Rurally Based: A Retrospective 36-Year Geospatial Analysis of a Critical Care Helicopter Emergency Medical Services Organization's Patient Transports

ObjectiveThere is an increased mortality rate of patients residing in rural compared with urban communities. Helicopter emergency medical services (HEMS) decrease both the time to hospital arrival and trauma mortality in patients originating from rural areas. An unreported number of urban residents are served by HEMS. Our objective was to quantify the fraction of urban residents who live in the adjoining city of a HEMS base and are transferred by helicopter while they are in rural areas. MethodsThis was a retrospective analysis of HEMS charts between 1985 and 2022. Records were assessed for patients’ city and postal code. A secondary database was searched to assess mission location. ResultsThirty-five thousand nine hundred seventy-one cases were analyzed; 3,871 (10.76%) cases involved patients residing within the urban area of an open HEMS base, and 32,100 (89.24%) did not. This contrasts with 2.04% of all missions conducted in urban areas. Cases flown with patients from outside of the 3 provinces were as follows: British Columbia (1,233/21,941; 5.3% of Alberta cases), international (988/35,971; 2.7% of total cases), Ontario (177/4,691; 3.6% of Manitoba cases), and other provinces combined (158/3,5971; 0.4% of total cases). ConclusionWe highlight the impact of HEMS, where it serves both rural residents and all people who work in, travel through, visit, or recreate across the areas that our HEMS supports.

Propofol Ameliorates Sepsis-Induced Myocardial Dysfunction via Anti-Apoptotic, Anti-Oxidative Properties, and mTOR Signaling.

Sepsis often leads to cardiomyopathy, contributing to increased mortality rates. 2,6-Diisopropylphenol (propofol), an anesthetic, has demonstrated efficacy in protecting cardiomyocytes from cell death caused by hypoxia and reoxygenation. This study examined the effects of propofol on sepsis-associated myocardial dysfunction and explored the underlying mechanism of action. Mice and rat cardiomyocytes (H9C2 cell line) were used to establish a sepsis-induced myocardial dysfunction model. Lipopolysaccharides (LPS)-treated mice and H9C2 cells were treated with propofol, with rapamycin used for mechanistic studies in H9C2 cells. Cardiac function was evaluated by echocardiographic measurements. Heart tissues were stained with hematoxylin and eosin, and heart weight/body weight ratio along with the levels of cardiac biomarkers were measured using Enzyme Linked Immunosorbent Assay (ELISA). Activation of the mammalian target of rapamycin (mTOR) pathway was assessed by western blotting. Apoptosis in heart tissues and H9C2 cells was evaluated using Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay, and cell viability was quantified using Cell Counting Kit (CCK)-8 assay. Oxidative stress in H9C2 cells was assessed by measuring reactive oxygen species (ROS) levels through immunofluorescence staining and malondialdehyde (MDA) and superoxide dismutase (SOD) levels using ELISA. Propofol reversed LPS-induced myocardial changes and cardiac dysfunction (p < 0.05). In mouse tissues and H9C2 cells, propofol reversed LPS-induced mTOR pathway inhibition and apoptosis (p < 0.001). Moreover, propofol alleviated oxidative stress in LPS-treated cells. The activation of the mTOR pathway by propofol, along with its inhibitory effects on oxidative stress and apoptosis in cardiomyocytes, was negated by rapamycin (p < 0.001). Propofol ameliorates sepsis-induced myocardial dysfunction triggered by LPS through the mTOR pathway, thereby promoting antioxidative stress and reducing cell apoptosis.

Calcium carbonate-based antibacterial coating for improved biocompatibility in endoprosthetic implants

This article addresses a critical challenge in modern endoprosthetics: enhancing the biocompatibility of implanted materials to prevent and manage periprosthetic infec-tions. Current literature identifies periprosthetic infection as a leading cause of revision surgeries, with material incompatibility contributing to postoperative complications and increased mortality rates. To tackle this issue, a specialized coating for implant surfaces based on inorganic calcium carbonate is proposed. This material is selected for its fa-vorable biochemical properties, including a highly developed specific surface area and biocompatibility with human tissues. To enhance antibacterial properties, zinc and the antibiotic vancomycin are incorporated as modifiers. Research efforts have led to the development of a 3D model of an elbow joint endoprosthesis, ensuring reliable fixation within the bone structure. The stress-strain characteristics of the endoprosthesis are examined, determining safety margins for its components. A biocompatible coating com-posed of calcium carbonate is synthesized and modified with antibacterial agents. Imag-es of the coating's microparticles are obtained, and a biochemical analysis is performed using common postoperative pathogens, revealing zones of microorganism suppres-sion. The findings confirm an improved biocompatibility level, demonstrating the effec-tive antibacterial properties of the developed coating, with promising implications for preventing periprosthetic infections.

Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.

The increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3's role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3's critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape.

Perioperative Management Of Diabetes Mellitus In Older Hip Fracture Patients

Abstract Background Hip fracture is one of the most serious injuries sustained by older adults worldwide, associated with increased morbidity and almost 25% mortality at one year. Pre-existing comorbidity worsens prognosis, e.g. hip fracture patients with Diabetes Mellitus (DM) have increased mortality rates, worse functional outcomes, and higher post-operative complications rates. Perioperative blood glucose optimisation may improve outcomes, however this can be challenging due to periods of fasting and reduced intake, as well as complications such as infection. Local guidelines for the peri-operative management of DM have been developed and are sign-posted in our hip fracture integrated admission document. This audit aimed to compare current practice with those recommended in local guidance. Methods Since 1st January 2024, 31 hip fracture patients aged ≥65 years with DM have been admitted. Charts were available on twenty patients, and hence reviewed. Results Of 20 patients, four were on insulin; 13 on metformin; four on sulphonylureas; five on SGLT2 inhibitors; and six on DPP4 inhibitors. No intraoperative hypoglycemic events nor episodes of Diabetic Ketoacidosis were documented; however, ketones were not checked in the majority of patients during admission. Eleven (55%) had HbA1C either done in the previous six months or during admission. Blood Sugar Levels were checked on admission in 9/20 (45%). The protocol was followed in only one patient on insulin; and 5/13 metformin patients. The protocol was followed in all Sulphonylurea prescriptions, and in 4/5 SGLT2 inhibitor prescriptions, however these medications were not held by the Orthopaedic team, rather by nursing staff while the patient was fasting pre-operatively. Conclusion This audit demonstrates poor adherence to local guidance on peri-operative management of diabetes, particularly perioperative insulin adjustments. We aim to develop an educational intervention (including group teaching, plus distribution of flashcards and posters) for Orthopaedic SHOs and interns and re-audit in the coming months.

Assessing the prognostic impact of KDIGO criteria on acute kidney injury in very low birth weight infants: a critical insight

Purpose: To evaluate the incidence and identify risk factors for acute kidney injury (AKI) within the first 15 days of life in very low birth weight (VLBW) infants in a neonatal intensive care unit. Additionally, this study will examine whether AKI correlates with increased mortality rate in this population.Methods: A prospective analysis was conducted on VLBW infants admitted to the neonatal intensive care unit from March 2017 to July 2021, diagnosing AKI based on the neonatal modified Kidney Disease: Improving Global Outcomes criteria. Neonates who died before obtaining consent, had complex malformation, or only one serum creatinine measurement were excluded.Results: Out of 121 admitted VLBW infants, 97 were analyzed, with 20 (20.6%; 95% confidence interval, 12.6–28.7) diagnosed with AKI. Among these, 50% had creatinine abnormalities, 30% had urinary output changes, and 20% had both. Severe AKI (stage 2 or 3) was observed in 30% of cases, none required dialysis. AKI was associated with higher SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal Extension-II) scores, more frequent severe intraventricular hemorrhage, and an increased mortality rate (35%). Multivariate analysis identified AKI as an independent risk factor for mortality, with a 9.72-fold increased risk (95% confidence interval, 2.53–37.4; &lt;i&gt;P&lt;/i&gt;&lt;0.01), and a shorter time to death.Conclusions: Our findings underscore a significant incidence of AKI among VLBW infants, along with its strong association with increased mortality. These results highlight the critical need for thorough assessment of both serum creatinine and urinary output when diagnosing AKI in this vulnerable population.

Understanding the Relationship Between Comorbidities, Medication Nonadherence, Activities of Daily Living, and Heart Condition Status Among Older Adults in the United States: A Regression Analysis and Machine Learning Approach.

Nonadherence to medication among patients with heart disease poses serious risks, including worsened heart failure and increased mortality rates. This study aims to explore the complex interplay between comorbidities, medication nonadherence, activities of daily living, and heart condition status in older American adults, using both traditional statistical methods and machine learning. Data from 326 older adults with heart conditions, drawn from the Health and Retirement Study, were analyzed. Descriptive statistics characterized demographic profiles and comorbidities, whereas logistic regression, multiple regression analyses, and decision tree models were used to address our research inquiries. In addition, a machine learning approach, specifically decision tree models, was integrated to enhance predictive accuracy. Our analysis showed that factors like age, gender, hypertension, and stroke history were significantly linked to worsening heart conditions. Notably, depression emerged as a robust predictor of medication nonadherence. Further adjusted analyses underscored significant correlations between stroke and challenges in basic activities such as dressing, bathing, and eating. Depression correlated significantly with difficulties in dressing, bed mobility, and toileting, whereas lung disease was associated with bathing hindrances. Intriguingly, our decision tree model revealed that patients experiencing dressing challenges, but not toileting difficulties, were more prone to report no improvement in heart condition status over the preceding 2 years. Blending traditional statistics with machine learning in this study reveals significant implications for crafting personalized interventions to improve patients' depression, leading to increased activities of daily living, medication adherence, reduced severity of comorbidities, and ultimately better management of heart conditions.

Mortality Impact of Severe COVID-19 in the ICU: A Study from the Târgu Mureș Support Unit.

(1) Background: Since the onset of the COVID-19 pandemic, it has been recognized that a considerable proportion of critically ill patients may die of this disease. The current study aims to assess the overall 1-year outcomes within the UMFST COVID-19 Unit, providing valuable insights into the efficacy of specialized care facilities in managing severe cases of COVID-19. (2) Methods: This is a retrospective monocentric observational study including 294 patients confirmed to have SARS-CoV-2 infection. Demographic data and clinical and paraclinical parameters were assessed. Survival probabilities were estimated using Kaplan-Meier curves. (3) Results: Overall, the 1-year mortality was 89.4%. All deaths occurred in-hospital, with two patients dying after 28 days. Diabetes mellitus, chronic kidney failure, cerebrovascular disease, and atrial fibrillation were more prevalent in deceased patients. Thirty percent of patients needed endotracheal intubation during the first 24 h. The incidence of hospital-acquired pneumonia was higher among deceased patients. The SOFA score was significantly different between deceased vs. survivors. The survival analysis showed that the use of noradrenaline increased the likelihood of surviving COVID-19. (4) Conclusions: The severe comorbidities of the patients were the primary factors contributing to the increased mortality rate in the COVID-19 unit.