Advanced Disease Research Articles

Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer.

Background: Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care. More recently, targeted therapies have proven beneficial in a molecularly selected subgroup of patients with cholangiocarcinoma who have progressed on previous lines of systemic treatment. However, only a minority of patients with BTCs whose tumours harbour specific molecular alterations can access these therapies. Methods: In relation to ADCs, studies regarding use of antibody-drug conjugates in cancer, particularly in BTCs, were searched in Embase (1974 to 2024) and Ovid MEDLINE(R) (1946 to 2024) to obtain relevant articles. Examples of current clinical trials utilising ADC treatment in BTCs were extracted from the ClinicalTrials.gov trial registry. Conclusions: Overall, this review has highlighted that ADCs have shown encouraging outcomes in cancer therapy, and this should lead to further research including in BTCs, where treatment options are often limited. The promising results observed with ADCs in various cancers underscore their potential as a transformative approach in oncology, warranting continued exploration and development and the need for education on the management of their specific toxicities. By addressing current challenges and optimising ADC design and application, future studies could potentially improve treatment outcomes for patients with BTCs and beyond, potentially in both early and advanced stage settings.

Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.

The spectinamides are novel, narrow-spectrum semisynthetic analogs of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis. Spectinamides, including lead MBX-4888A (Lee-1810), exhibit promising therapeutic profiles in mice, as single drugs and as partner agents with other anti-tuberculosis antibiotics including rifampin and/or pyrazinamide. Here, we show that MBX-4888A, given by injection with the front-line standard of care regimen, is treatment shortening in multiple murine tuberculosis infection models. The positive treatment responses to MBX-4888A combination therapy in multiple mouse models, including mice exhibiting advanced pulmonary disease, can be attributed to favorable distribution in tissues and lesions, retention in caseum, along with favorable effects with rifampin and pyrazinamide under conditions achieved in necrotic lesions. This study also provides an additional data point regarding the safety and tolerability of spectinamide MBX-4888A in long-term murine efficacy studies.

Therapeutic targeting of senescent cells in the CNS.

Senescent cells accumulate throughout the body with advanced age, diseases and chronic conditions. They negatively impact health and function of multiple systems, including the central nervous system (CNS). Therapies that target senescent cells, broadly referred to as senotherapeutics, recently emerged as potentially important treatment strategies for the CNS. Promising therapeutic approaches involve clearing senescent cells by disarming their pro-survival pathways with 'senolytics'; or dampening their toxic senescence-associated secretory phenotype (SASP) using 'senomorphics'. Following the pioneering discovery of first-generation senolytics dasatinib and quercetin, dozens of additional therapies have been identified, and several promising targets are under investigation. Although potentially transformative, senotherapies are still in early stages and require thorough testing to ensure reliable target engagement, specificity, safety and efficacy. The limited brain penetrance and potential toxic side effects of CNS-acting senotherapeutics pose challenges for drug development and translation to the clinic. This Review assesses the potential impact of senotherapeutics for neurological conditions by summarizing preclinical evidence, innovative methods for target and biomarker identification, academic and industry drug development pipelines and progress in clinical trials.

Advances in AI-based combination therapies versus standard treatments for heart failure in patients with advanced kidney injury

Background: Recent advancements in AI and Machine Learning (ML) can help manage kidney disease and heart failure by providing predictive analytics and personalized treatment plans, improving diagnostic accuracy, and assisting clinicians in controlling chronic disease symptoms like acute kidney injury (AKI) and Managing Heart Failure (HF). We evaluated AI and ML role in predicting AKI and managing HF patients and it involved analyzing various predictive models and technologies to improve early detection provide personalized treatment, and enhance overall patient outcomes in complex renal and cardiac conditions. Methodology: We conducted our search on databases Scopus, PubMed, and Web of Science. Empirical evidence and state of the art of cutting-edge literature and real-time field research was analyzed. Results: AI advancements in HF management for advanced kidney disease AKI include unsupervised machine learning for risk stratification, reinforcement learning for predictive modeling and dynamic management, and LLMs and chatbots for diagnostic support and patient education. New developments in AI and medical technology are predictive analytics for AKI, automated ultrasound interpretation, AI-enhanced dialysis monitoring, HF risk prediction, remote monitoring, and telehealth integration, and making personal treatment strategies according to patient needs. Innovations like wearable dialysis devices, bioengineered kidney tissues, ECMO, LVADs, TAVR, SGLT2 inhibitors, CRT, and nephroprotective drugs have also improved patient outcomes as these have enabled personalized care and early intervention strategies. Conclusion: It is possible to conclude that AI has revolutionized AKI and HF management. Novel technologies offer precise and adaptive care that strictly addresses individual patient needs.

Survey of spinal tuberculosis in Basrah

Background. Tuberculous spondylitis (TS) or spinal tuberculosis is secondary either to pulmonary or intestinal tuberculosis and may be the initial manifestation of tuberculosis (TB). Spinal TB also called Pott’s disease is by definition, an advanced severe disease, requiring accurate evaluation and aggressive systemic therapy. Objective. This study was conducted to demonstrate the prevalence and clinical, laboratory, and management characteristics of patients with spinal tuberculosis in Basrah governorate. Methods. A cross-sectional descriptive retrospective and prospective study was conducted during the period of March 2020 to December 2021. All cases either registered at the tuberculous center / Basrah Health Director were viewed by phone calling or recall or newly diagnosed with spinal tuberculous which attended to Basrah Teaching Hospital. Those patients were followed after diagnosis and treatment initiation for any clinical improvement, worsening or no improvement after diagnosis. Results. Among 51 enrolled patients with spinal tuberculosis in this study, the age distribution was 20-39 years old 23 (45.09%). Most of the patients were males (32) with rates 62.74%. The most common site of vertebral involvement is dorsal segment 29 (56.86%). The most common presenting complaints were: back pain in 49 patients (96.07%). Regarding the examination findings, 2(13.33%) with deformity either kyphotic or gibbous deformity. Most of the examined patients had a power grade 1-3/5 (93.33%) in the lower limbs. Out of the 4 cases of cervical tuberculosis, all of them had been managed conservatively, while 6 out of 16 cases (37.5%) diagnosed with lumber lesions were managed conservatively, and 10 cases (62.5%) were managed surgically. Conclusion. The prevalence and characteristics of patients with spinal TB follow the global trend, although some differences were recorded, but it was not that significant. The surgical approach is still superior to the conservative one in the improvement of neurological deficits.

EFFICACY OF INDUCTION CHEMOTHERAPY WITH PACLITAXEL AND CARBOPLATIN IN LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HYPOPHARYNX: A DESCRIPTIVE CASE SERIES

Introduction: Head and neck cancer including hypopharyngeal carcinoma is one of commonest malignancies in Pakistan. According to the Pakistan Medical Research Council (PMRC) reports, it was found to be the commonest malignancy in males and was second highest to breast cancer in females. The patients for the management of hypopharyngeal cancer present with locally advanced disease. Induction chemotherapy with paclitaxel and carboplatin is being used for few years but the results have not been documented yet. The aim of this study is to design a protocol in future with improved outcome and acceptable morbidity. Objective:To determine the efficacy of induction chemotherapy with paclitaxel & carboplatin in locally advanced squamous cell carcinoma of hypopharynx in terms of frequency of complete and partial response. Settings:This study was conducted at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad. Study Design: Descriptive case series. Duration of study: 6 months from 01/08/2017 to 31/01/2018 Material and methods:In this study a total of 59 patients were observed by using World Health Organization sample size calculator where confidence level: 95%, anticipated population proportion: 67%, relative precision: 12%. Moreover, nonprobability consecutive sampling technique was used for sample collection. Results:Mean age was 60 ± 11.87 years. 40(68%) patients were males while 19(32%) were females. 22(38%) patients had carcinoma of stage III, 32(54%) patients had carcinoma of stage IVA while 5(8%) patients had carcinoma of stage IVB. Moreover, induction chemotherapy was effective in 42(72%) patients and was not effective in 17(28%) patients. Conclusion:Our study concludes that induction chemotherapy with paclitaxel & carboplatin was 72% effective in locally advanced squamous cell carcinoma of hypopharynx in terms of frequency of complete and partial response.

TMS-evoked potentials unveil occipital network involvement in patients diagnosed with Parkinson’s disease within 5 years of inclusion

Distinguishing Parkinson’s disease (PD) subgroups may be achieved by observing network responses to external stimuli. We compared TMS-evoked potential (TEP) measures from stimulation of bilateral motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and visual cortex (V1) between 62 PD patients (age: 69.9 ± 7.5) and 76 healthy controls (age: 69.2 ± 4.3) using a TMS–EEG protocol. TEP measures were analyzed using two-way ANCOVA adjusted for MOCA. PD patients were divided into tremor dominant (TD), non-tremor dominant (NTD) and rapid disease progression (RDP) subgroups. PD patients showed lower wide-waveform adherence (wWFA) (p = 0.025) and interhemispheric connectivity (IHCCONN) (p < 0.001) compared to healthy controls. Lower occipital IHCCONN correlated with advanced disease stage (r = −0.37, p = 0.0039). The RDP and NTD groups showed lower wWFA in response to occipital stimulation than the TD group (p = 0.005). Occipital TEP measures identified RDP patients with 85% accuracy. These findings demonstrate occipital network involvement in early PD stages, suggesting that TEP measures offer insights into altered networks in PD subgroups.

Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth

Exploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth.

Locoregional Therapies for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.

Neoadjuvant Immunotherapy and De-Escalation of Surgery in Locally Advanced Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T cell lymphoma diagnosed in patients with a history of breast implants. Most patients develop a periprosthetic effusion at early stages of disease while less common presentations include a palpable mass, severe capsular contracture, lymphadenopathy, or cutaneous erythema. Due to the complex nature of this disease, a multidisciplinary approach is necessary for optimal management, particularly in locally advanced disease or inoperable patients. We present the successful use of neoadjuvant therapeutic protocols in two cases of locally advanced BIA-ALCL. The first case, a 52-year-old patient with a left breast mass-like stage III disease who underwent combined targeted immunotherapy and chemotherapy (BV-CHP). Following a complete radiological and metabolic response, the patient underwent bilateral implant removal, right total intact capsulectomy, left en bloc capsulectomy and skin resection from the left inframammary fold in continuity with the capsule. The second case, a 65-year-old patient with a right breast swelling and mass-like stage IIA disease who received targeted immunotherapy, Brentuximab vedotin (BV). Following a complete metabolic response, she underwent bilateral implant removal and en bloc capsulectomy. A literature review and the reported cases suggest the effectiveness of targeted immunotherapy as monotherapy or in combination with chemotherapy in locally advanced BIA-ALCL in disease downstaging, surgical de-escalation, reduction of significant post-operative complications and an acceptable tolerance profile. Although surgery is an essential part of treatment, timing and type of intervention should be carefully planned, especially when primary, radical resection is uncertain.

Audit from a Hemodialysis Facility in a small town in Punjab

Patients with advanced Chronic Kidney Disease ultimately require Renal Replacement Therapy. In the absence of widespread availability of renal transplant, dialytic therapies remain the last court of appeal for most of the patients with CKD V. Hemodialysis remains the most common form of dialytic therapy utilized by the patients. Since the governmental support for dialysis has increased in the recent years, now the therapy is also available in smaller cities and towns. This is commendable since it reduces the financial burden of patients associated with travelling to larger cities twice a week to receive dialysis therapy. These centers in smaller towns have their own profile of problems to deal with. Here we present our data collected from hemodialysis centre in a small city of Pakistan.

Muscle-Invasive Bladder Cancer in Non-Curative Patients: A Study on Survival and Palliative Care Needs.

To assess the survival outcomes of patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not candidates for curative treatment and to identify the factors influencing these outcomes. We conducted an analysis of patients diagnosed with MIBC who were either unable or unwilling to undergo curative therapy. We evaluated overall survival (OS) and cancer-specific survival (CSS) and examined their associations with various clinical variables. Additionally, we assessed emergency department visits and palliative procedures. The study included 142 patients with a median age of 79.4 years and a Charlson Comorbidity Index of 9.8. At diagnosis, 59.2% of the patients had localized disease, 23.2% had metastatic disease, and 49.3% presented with hydronephrosis. Curative treatment was excluded due to comorbidities in 40.1% of cases and advanced disease stage in 36.6%. The 1-year and 2-year OS rates were 42.8% and 23.6%, respectively, with a median survival of 10.6 months. The 1-year and 2-year CSS rates were 49.6% and 30.2%, respectively, with a median survival of 11.9 months. Worse survival outcomes were associated with advanced disease stage and the presence of hydronephrosis. Patients excluded from curative treatment solely due to age had a relatively better prognosis. On average, patients visited the emergency department three times: 19% underwent palliative transurethral resection of the bladder tumor, 14.8% received radiotherapy to control hematuria, and nephrostomy tubes were placed in 26.1% of cases. Patients with MIBC who are unable or unwilling to undergo curative treatment have a median overall survival of less than one year, with worse outcomes observed in those with advanced disease stage and hydronephrosis.

Safety of Sofosbuvir-Based Direct-Acting Antivirals for Hepatitis C Virus Infection and Direct Oral Anticoagulant Co-Administration.

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit.

Extracorporeal membrane oxygenation as a bridge to lung transplantation: 5-year outcomes and bridge to decision in a large, older cohort

BackgroundExtracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has expanded considerably, though evidence-based selection criteria and long-term outcome data are lacking. The purpose of this study was to evaluate whether risk factors often used to exclude patients from ECMO BTT—specifically older age and not yet being listed for transplant—are validated by long-term outcomes.MethodsTo ensure minimum 5-year follow-up, a retrospective cohort study was performed of adult patients actively listed for lung transplantation at a high-volume center and bridged on ECMO between January 2012 and December 2017. Data was collected through January 1, 2023.ResultsAmong 50 patients bridged on ECMO, 25 survived to transplant. Median age at listing was 58 (interquartile range [IQR], 42–65) in the transplanted group and 65 (IQR, 56.5–69) in the deceased group (P = 0.051). One-year, 3-year, and 5-year survival were 88% (22/25), 60% (15/25), and 44% (11/25), respectively, with eight patients still living at the time of review. Median time spent at home during the year post-transplant was 340 days (IQR, 314–355). Older age at listing was a negative predictor of survival on ECMO to transplant (odds ratio 0.92 [95% confidence interval, 0.86–0.99], P = 0.01). Thirteen patients were placed on ECMO prior to being listed and three were listed the same day as ECMO cannulation, with 10/16 transplanted. No significant difference in post-transplant survival was found between patients placed on ECMO prior to listing (n = 10) and those already listed (n = 15) (P = 0.93, log-rank). Serial post-transplant spirometry up to 5 years and surveillance transbronchial biopsy demonstrated good allograft function and low rates of cellular rejection.ConclusionsIn one of the oldest cohorts of ECMO BTT patients described, favorable survival outcomes and allograft function were observed up to 5 years irrespective of whether patients were previously listed or bridged to decision. Despite inherent limitations to this retrospective, single-center study, the data presented support the feasibility of ECMO BTT in older and not previously listed advanced lung disease patients.

Merkel Cell Carcinoma: A Case Report and Literature Review

Merkel cell carcinoma (MCC) is a rare but very aggressive cutaneous malignant tumor of neuroendocrine origin with an increasing incidence rate. Its pathogenesis is linked to Merkel cell polyomavirus, and advanced age, white skin exposed to UV and immunodeficiency are among these risk factors. Its treatment is based on surgery in localized disease and immunotherapy in locally advanced or metastatic disease. We report here the case of a 79-year-old patient, followed at the Oncology-Radiotherapy Department of the Mohammed VI University Hospital in Marrakech, for treatment of a MCC of the lower lip. He benefited from primary surgery followed by adjuvant radiotherapy with an encouraging response. Currently he is under surveillance. Knowledge of this rare malignant tumor will allow health professionals to improve its management by establishing the diagnosis early and indicating adequate treatment, because therapeutic advances in recent years have significantly improved survival.

DDB2 expression lights the way for precision radiotherapy response in PDAC cells, with or without olaparib

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Therapeutic options for PDAC are primarily restricted to surgery in the early stages of the disease or chemotherapy in advanced disease. Only a subset of patients with germline defects in BRCA1/2 genes can potentially benefit from personalized therapy, with the PARP inhibitor olaparib serving as a maintenance treatment for metastatic disease. Although the role of radiotherapy in PDAC remains controversial, the use of radiosensitizers offers hope for improving cancer management. Previously, we have shown that damage-specific DNA binding protein 2 (DDB2) is a potential prognostic and predictive biomarker for chemotherapy response in PDAC. In this study, we investigated the function of DDB2 in radiotherapy response, with and without radiosensitization by olaparib in PDAC cells. Our findings demonstrated DDB2 resistance to radiation effects, thereby improving cell survival and enhancing the repair of ionizing radiation-induced DNA double-strand breaks. We observed that DDB2 expression enhances the cell cycle arrest in the G2 phase by phosphorylating Chk1 and Chk2 cell cycle checkpoints. Additionally, we identified a novel link between DDB2 and PARP1 in the context of radiotherapy, which enhances the expression and activity of PARP1. Our findings highlight the potential of low-DDB2 expression to potentiate the radiosensitization effect of olaparib in PDAC cells. Collectively, this study provides novel insights into the impacts of DDB2 in the radiotherapy response in PDAC, enabling its employment as a potential biomarker to predict resistance to radiation. Furthermore, DDB2 represents a significant step forward in precision radiotherapy by widening the scope of patients who can be benefiting from olaparib as a radiosensitizer. Hence, this research has the potential to enrich the limited use of radiotherapy in the care of patients with PDAC.

Significant kidney disease in pregnancy: Feasibility and outcomes of a national population-based study using the Australasian Maternity Outcomes Surveillance System.

Current understanding of clinical practice and care for maternal kidney disease in pregnancy in Australia is hampered by limitations in available renal-specific datasets. To capture the epidemiology, management, and outcomes of women with significant kidney disease in pregnancy and demonstrate feasibility of a national cohort study approach. An Australian prospective study (2017-2018) using a new kidney disease-specific survey within the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with acute kidney injury (AKI), advanced chronic kidney disease (CKD), dialysis dependence or a kidney transplant were included. Demographic data, renal and obstetric management, and perinatal outcomes were collected. Among 58 case notifications from 12 hospitals in five states, we included 23 cases with kidney transplant (n = 12), pre-existing CKD (n = 8), newly diagnosed CKD (n = 2) and dialysis (n = 1). No cases of AKI were reported. Reporting rates were better in states with study investigators and, overall, cases were likely under-reported. Nearly 35% of women had a non-delivery-related antenatal admission. Nephrology involvement was 78.3% during pregnancy and 91% post-partum. Adverse events were increased, including pre-eclampsia (21.7%), and preterm birth (60.9%). Women had high rates of aspirin (82.6%) and antihypertensive (73.9%) use, indwelling catheter for labour/delivery (65.2%), caesarean delivery (60.9%), and blood transfusion (21.7%). This first-ever Australian prospective study of significant kidney diseases in pregnancy provided novel insights into renal-specific clinical patterns and practices. However, under-reporting was likely. Future studies need to overcome the challenges of case identification and data collection burden.

Identification of immune patterns in idiopathic pulmonary fibrosis patients driven by PLA2G7-positive macrophages using an integrated machine learning survival framework

Patients with advanced idiopathic pulmonary fibrosis (IPF), a complex and incurable lung disease with an elusive pathology, are nearly exclusive candidates for lung transplantation. Improved identification of patient subtypes can enhance early diagnosis and intervention, ultimately leading to better prognostic outcomes for patients. The goal of this study is to identify new immune patterns and biomarkers in patients. Immune subtypes in IPF patients were identified using single-sample gene set enrichment analysis, and immune subtype-related genes were explored using the weighted correlation network analysis algorithm. A machine learning integration framework was used to establish the optimal prognostic model, known as the immune-related risk score (IRS). Single-cell sequencing was conducted to investigate the major role of macrophage-derived PLA2G7 in the immune microenvironment. We assessed the stability of celecoxib in targeting PLA2G7 through molecular docking and surface plasmon resonance. IPF patients present two distinct immune subtypes, one characterized by immune activation and inflammation, and the other by immune suppression. IRS can predict the immune status and prognosis of IPF patients. Furthermore, multi-cohort analysis and single-cell sequencing analysis demonstrated the diagnostic and prognostic value of PLA2G7 derived from macrophages and its role in shaping the inflammatory immune microenvironment in IPF patients. Celecoxib could effectively and stably bind with PLA2G7. PLA2G7, as identified through IRS, demonstrates marked stability in diagnosing and predicting the prognosis of IPF patients as well as predicting their immune status. It can serve as a novel biomarker for IPF patients.

Effective factors on postoperative 30–90 and 360-day mortality in non-small cell lung cancer

PurposePostoperative mortality and morbidity are serious problems, and the identification of risky patient groups will reduce mortality and morbidity rates. The aim of our study was to determine the mortality at 30, 90, and 360 days in patients who underwent surgical resection for non-small cell lung cancer (NSCLC). MethodsIn this single-center retrospective study, 935 patients who were operated on for NSCLC were included. Demographic characteristics, laboratory data, tumor characteristics, surgical method used, type of resection, postoperative complications, and the relationship between 30, 90, and 360-day mortality were analyzed. ResultsIn-hospital mortality was observed in 21 (2.2 %) of the 935 patients; the 30-90-360-day mortality rate was respectively 3 %, 4.9 %, and 12.1 %. The 30- and 90-day mortality rates were close (3 %, 4.9 % respectively), and the only difference was the additional surgical procedure. The common factors that increased 30-, 90-, and 360-day mortality were advanced disease stage, additional surgical procedure, length of stay longer than 7 days, low % forced vital capacity (FVC), presence of comorbidities, presence of postoperative complications, and pneumonectomy. ConclusionIn this study, 30-, 90-, and 360-day mortality rates and common and independent risk factors affecting mortality were determined. Although 30-day mortality is the most often utilized time period for assessing postoperative mortality, 90-day mortality can be used to predict postoperative mortality following a major surgical procedure. Preoperative mortality and morbidity are expected to decrease with more detailed preoperative examination of high-risk patients and special follow-up programs in the postoperative period.

Anesthesiological Preoperative Interview with a Palliative Care Patient: A Simulation-Based Experiment Using Standardized Patients.

Background and Objectives: Anesthesiologists come into contact with patients under palliative care in different clinical settings. They also routinely encounter these patients in their primary field of work, the operating room. Patients receiving palliative care who are scheduled for surgery will pose unique challenges in perioperative management, often presenting with advanced disease and with different psychosocial and ethical issues. This study aims to evaluate whether anesthesiologists without specialty training in palliative medicine will spot perioperative challenges presented by patients under palliative care and address them adequately. Materials and Methods: In this study, we simulated a preoperative anesthesiological interview using standardized patients and anesthesiologists (specialists as well as trainees). The standardized patients were asked to represent a patient under palliative care in need of surgery because of a mechanical ileus. We conducted 32 interviews, dividing the anesthesiologists into two groups. In one group, the standardized patients were instructed to address four problems, i.e., use of a port catheter for anesthesia, nausea and vomiting, pain medication, and an advance directive including a limitation of treatment (DNR-order). In the other group, these problems were also present, but were not actively addressed by the standardized patients if not asked for. The interviews were recorded, transcribed, and then analyzed. Results: In most cases, the medical problems were spontaneously identified and discussed. In only a few cases, however, was a therapy recommendation made for improved symptom control. The advance directive was spontaneously discussed by only 3 of the 32 (9%) anesthesiologists. In another 16 cases, the advance directive was discussed at the request of the standardized patients. The limitation of treatment stayed in place in all cases, and the discussion of the advance directives remained short, with an average duration of just over 5 min. Conclusions: In this study, the complex problems of patients under palliative care are not sufficiently taken into account in a preoperative anesthesiological interview. To improve treatment of the medical problems, therapists who have palliative medicine expertise, should be involved in the perioperative medical care, ideally as a multi-professional team. The discussion about perioperative limitations of treatment should be held beforehand, for example, as part of a structured advanced care planning discussion.