Survival Benefit Research Articles

Is pancreatic adenosquamous carcinoma (PASC) a surgical disease? A large healthcare system review

IntroductionPancreatic cancer represents an increasing cause of cancer-related deaths. Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreas cancer. Optimal treatment is not well-defined. This review aims to provide a detailed analysis of the natural history, management, and outcomes of the patients with PASC within a single large healthcare system. Materials and methodsA large healthcare database was used to retrospectively identify all patients with histological diagnosis of PASC from 2010 to 2020. The cohort was evaluated as a whole and according to the following management modalities: operative, non-metastatic non-operative, and patients with metastatic disease. Abstracted data included patient characteristics, oncologic characteristics at presentation, and details of surgical and non-surgical treatment. ResultsIn total, 60 patients with PASC were identified. All patients had confirmed histopathological diagnosis of PASC. Mean age at the time of diagnosis was 70.9 years, and 28 patients were male (46.7 %). Most patients presented with pancreas head tumors (60 %). Thirty-four patients presented with non-metastatic disease (56.6 %). The operative group consisted of 17 patients (28.3 %). Most patients received adjuvant systemic therapy (70.6 %). Majority of patients experienced recurrence (76.5 %), with median time to recurrence at 6.5 months. Median overall survival in the operative group was 19.1 months. Seventeen patients with non-metastatic disease (28.3 %) did not undergo resection. Median overall survival of this cohort was 3.3 months. Systemic chemotherapy was used in 8 patients. Approximately half of patients with non-metastatic disease (9/17) did not receive any treatment due to rapid physical deterioration or poor functional status at baseline. Median survival for the non-treatment group was 1.7 months. At presentation, 26 patients (43.3 %) had metastatic disease. Most common site of metastasis was the liver. Median survival for patients with metastatic disease was 3.1 months. DiscussionPASC is a distinct entity from glandular PDAC, and it appears to be a more aggressive disease process. Complete resection confers survival benefit but is not curative. Furthermore, few patients undergo surgery, even with seemingly resectable disease. Systemic therapy administration is limited in many patients due to physiologic decline. Dismal clinical course and poor survival is universal among all patients who do not undergo any treatment modality, regardless of metastatic status. Globally grim prognosis appears to be due early systemic effects, disease progression and lack of effective systemic therapy. ConclusionsPASC remains a poorly understood cancer and portends particularly poor prognosis. It is associated with a rapid clinical decline, poor response to systemic therapy, early recurrence, and poor overall survival. However, ability to treat with surgery and chemotherapy may best prolong survival. SynopsisPancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer. In this study, we evaluated 60 patients with PASC. PASC is a systemic disease characterized by rapid clinical decline, poor response to systemic therapy, early recurrence, and poor survival. Despite resection or systemic therapy, patients succumb rapidly.

Survival Analysis of Conversion Surgery in Borderline Resectable and Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma Addressing Selection and Immortal Time Bias: A Retrospective Single-Center Study.

The purpose of this study was to provide a detailed evaluation of the oncological advantages of surgery following neoadjuvant chemotherapy (NAC) for patients with borderline resectable (BR) or unresectable (UR) pancreatic ductal adenocarcinoma (PDAC), with a focus on minimizing biases. Recently, NAC has become the standard care for BR or UR locally advanced (UR-LA) PDAC, however, many studies have assessed survival benefits and favorable variables without consideration for biases, particularly immortal time bias. This study included patients diagnosed with BR or UR-LA PDAC at Juntendo University Hospital from 2019 to 2022. To mitigate bias, we applied methods such as propensity score matching (PSM), time-dependent covariate Cox proportional hazard regression analysis (TDC), landmark analysis, and multivariable Cox proportional hazards regression model. The study analyzed 124 patients, dividing them into a surgery group (n = 57) and a chemotherapy-only group (n = 67). After PSM, there were 21 matched pairs. Survival analysis using TDC analysis showed that the surgery group had significantly better overall survival compared with the chemotherapy-only group in both the entire cohort and the matched pairs. Cox regression analysis of the entire cohort also revealed a similar superiority of surgery, while the landmark analysis showed varying results depending on the landmark setting. After careful adjustment for selection and immortal time biases, surgery following NAC appears to significantly extend survival in patients with BR or UR PDAC.

Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) for Pancreatic Adenocarcinoma: A Review.

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest neoplasms in the world. Although various advancements in the treatment and management of this disease have been made, no significant overall survival benefit has been achieved. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been proposed as a treatment for patients who are unfit for surgery or with inoperable PDAC. We conducted a literature review of the PubMed and Embase databases to identify and analyze studies on the use of EUS-RFA in inoperable PDAC. Eleven studies with a total of 122 patients were analyzed to assess the population characteristics, feasibility and safety of the procedure, and overall survival of the population. Technical success was achieved in 95.1% of cases, and no intraoperative complications were reported. The most common early complication reported was abdominal pain (21 out of 122 patients) with a total early complication rate of 29.6%, and none of these complications affected hospital stays or post-procedure recovery. Late complications were reported in four patients (3.2%). Post-procedure cytoreduction was achieved in all patients, although disease progression was reported in 119 of 122 patients. The overall survival rate did not differ from that reported in the literature. We found that EUS-RFA could be a valid palliative option for inoperable patients,a bridge for surgeryreducing the size of the tumor and its vascular relationship, or a first-line therapy in a subset of selected patients. Larger cohort and prospective studies should be conducted to establish guidelines for this procedure.

Prehospital blood transfusion : Opportunities and challenges for the German emergency medical services

Exsanguination is the leading cause of preventable death in severe trauma. Immediate hemorrhage control and transfusion of blood products are critical to maintain oxygen delivery and address trauma-induced coagulopathy. While prehospital blood product transfusion (PHBT) is established in neighboring countries, the fragmented configuration of Germany's emergency medical service (EMS) infrastructure has delayed the adoption of widespread PHBT programmes. This review aims to provide an updated perspective on the evolution, international practices and research needs of PHBT within the German context. This narrative review is based on aPubMed search using the search terms "prehospital" and "blood*". From an initial 4738 articles, 333 were directly related to PHBT and were subjected to further detailed examination. The literature, including referenced studies, was categorized into areas such as history, rationale, international practices, and evidence, and analyzed for quality. The benefit of early blood transfusion in major trauma has been established since WW1, explaining the efforts to initiate this lifesaving intervention as early as possible in the care pathway, including the prehospital field. Recent randomized trials have faced design and recruitment challenges, reflecting the complexity of the research question. These trials have yielded inconclusive results regarding the survival benefits of PHBT in civilian settings. This scenario raises doubts about the capability of randomized trials to resolve questions concerning survival advantages. Despite these difficulties, there is adiscernible trend indicating potential improvements in patient outcomes. In Germany, the incidence of trauma-associated shock stands at 38per 100,000 individuals per year. It is estimated that between 300 and 1800 patients annually possibly benefit from PHBT. Prehospital Blood Transfusion appears to be promising but identifying patient groups most likely to benefit as well as the most suitable blood products remain unresolved issues. In Germany PHBT programs are not yet widely established. Paradoxically, this situation, paired with the extensive German Trauma Registry, provides aprime opportunity for comprehensive prospective cohort studies, addressing the balance between PHBT benefits, logistical feasibility, and implementation strategies. Such studies are essential for establishing guidelines and integrating PHBT efficiently into German trauma care protocols.

The Relationship Between 10-year Changes in Cognitive Ability and Subsequent Mortality: Findings from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Trial.

Cognitive ability and cognitive decline are related to mortality in older adults. Cognitive interventions have been found to improve cognitive performance and slow cognitive decline in later life. However, the longitudinal effects of cognitive interventions on mortality in older adults remain unclear. Using twenty-year follow-up data from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, we examined the association between cognitive trajectory (i.e., intercept, slope, and retest effect) and mortality, using shared growth-survival models. We evaluated the effect of ACTIVE cognitive training (memory, reasoning, and speed of processing) on mortality risk. Among the 2,802 participants, 2,021 died on or before the year 2019 (72.1%). Higher baseline, slower decline, and greater retest effects in general cognitive performance were associated with lower mortality risk after adjusting for covariates. Associations with mortality were similar contrasting general and domain-specific cognitive abilities. We did not observe any significant effects of ACTIVE cognitive training in memory, reasoning, or speed of processing on all-cause mortality. Our findings suggest cognitive training interventions do not have a significant effect on cognitive trajectory and mortality among older adults; rather, older adults with higher education tend to incur greater survival benefits from memory training.

Targeted dynamic phospho-proteogenomic analysis of gastric cancer cells suggests host immunity provides survival benefit

Despite of massive emergence of molecular targeting drugs, the mainstay of advanced gastric cancer (GC) therapy is DNA-damaging drugs. Using a reverse-phase protein array-based proteogenomic analysis of a panel of eight GC cell lines, we identified genetic alterations and signaling pathways, potentially associated with resistance to DNA-damaging drugs, including 5-fluorouracil (5FU), cisplatin, and etoposide. Resistance to cisplatin and etoposide, but not 5FU, was negatively associated with global copy number loss, vimentin expression, and caspase activity, which are considered hallmarks of previously established EMT subtype. The segregation of 19,392 protein expression time courses by sensitive and resistant cell lines for the drugs tested revealed that 5FU-resistant cell lines had lower changes in global protein dynamics, suggesting their robust protein level regulation, compared to their sensitive counterparts, whereas the cell lines that are resistant to other drugs showed increased protein dynamics in response to each drug. Despite faint global protein dynamics, 5FU-resistant cell lines showed increased STAT1 phosphorylation and PD-L1 expression in response to 5FU. In publicly available cohort data, expression of STAT1 and NFκB target genes induced by proinflammatory cytokines was associated with prolonged survival in GC. In our validation cohort, total lymphocyte count (TLC), rather than PD-L1 positivity, predicted a better relapse-free survival rate in GC patients with 5FU-based adjuvant chemotherapy than those with surgery alone. Moreover, TLC+ patients who had no survival benefit from adjuvant chemotherapy were discriminated by expression of IκBα, a potent negative regulator of NFκB. Collectively, our results suggest that 5FU resistance observed in cell lines may be overcome by host immunity or by combination therapy with immune checkpoint blockade.

Long-term effects of left atrial appendage isolation in surgical ablation of atrial fibrillation based on lesion set: a multi-centre propensity-score weighted study

BackgroundThis present study aimed to investigate the impact of left atrial appendage (LAA) isolation on adverse clinical outcomes, with a further stratified analysis by biatrial (BA) and left atrial lesion...

127 (PB115): Survival benefit and tumor regression with a dual RAS/β-catenin inhibitor, ADT-030, in murine models of pancreatic and lung cancer

127 (PB115): Survival benefit and tumor regression with a dual RAS/β-catenin inhibitor, ADT-030, in murine models of pancreatic and lung cancer

Clinical research progress of fruquintinib in the treatment of malignant tumors.

Malignant tumors represent an important cause of mortality within the global population. Tumor angiogenesis, recognized as one of the key hallmarks of malignant tumors, is crucial for supplying essential nutrients and oxygen for tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are key drivers of tumor angiogenesis. Targeted therapeutic interventions not only effectively inhibit tumor growth by specifically blocking tumor angiogenesis but have also made breakthroughs in the treatment of malignant tumors. Fruquintinib, an anti-angiogenic small molecule drug developed independently in China, functions as a potent tyrosine kinase inhibitor with high selectivity. It effectively curtails tumor growth by binding to and inhibiting VEGFR-1, VEGFR-2, and VEGFR-3. Additionally, fruquintinib offers several advantages including minimal off-target toxicity, robust resistance profiles, and commendable efficacy. This agent can be used alone or in combination with other treatments. It has shown high effectiveness and survival benefits across various malignant tumors such as colorectal cancer, gastric cancer, non-small cell lung cancer, breast cancer, and other malignant tumors. Therefore, this article conducts a systematic review encompassing the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of fruquintinib. Through this review, we aimed to offer a reference for the clinical application and subsequent development of fruquintinib.

Immune checkpoint inhibitor combinations for patients with advanced endometrial cancer: a network meta-analysis and cost-utility analysis

BackgroundImmune checkpoint inhibitor combinations show significant survival advantages compared with chemotherapy for patients with advanced endometrial cancer.ObjectiveTo compare the efficacy, safety, and cost-effectiveness of different immunotherapy combinations for clinician and...

Plasma exchange does not improve overall survival in patients with acute liver failure in a real world cohort

Background and AimsTherapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF. MethodsThis multicentre retrospective cohort study included consecutive patients with ALF admitted to all 7 tertiary liver transplant centres in the United Kingdom (UK) between June 2013 and December 2021. Changes in clinical variables following PEX treatment was assessed and overall survival and transplant free survival (TFS) to hospital discharge of patients receiving PEX were compared to those receiving standard medical therapy (SMT). Propensity score matching was performed to control for intergroup covariates and selection bias. ResultsWe included 378 patients with ALF (median (IQR) age 36 (28-48), 64% (n=242) female) of which 120 received PEX. There was a significant improvement in most clinical variables following PEX, including median dose of noradrenaline (reduction from 0.35 μg/kg/min (0.19 - 0.70 μg/kg/min) to 0.16 μg/kg/min (0.08 - 0.49) (p = 0.001). There was no significant difference between PEX and SMT groups in overall survival (51.4 % v 62.6 % respectively, p = 0.12) or TFS (42.6 % v 53.1 %, p = 0.24). ConclusionPEX is now frequently used in the management of ALF patients in the UK. It is associated with significant improvement in haemodynamic parameters but there is no survival benefit. Impact and implicationsPEX is frequently used in the management of patients with ALF in the UK. This real-world study demonstrates significant improvement in haemodynamic status but has not confirmed the survival benefit seen in previous published literature. These results should help inform future use of PEX.

Stroke Prevention With Prophylactic Left Atrial Appendage Occlusion in Cardiac Surgery Patients Without Atrial Fibrillation: A Meta-Analysis of Randomized and Propensity-Score Studies.

The role of left atrial appendage occlusion (LAAO) in patients without previous atrial fibrillation (AF) is not established. This meta-analysis was conducted on patients with normal sinus rhythm who underwent cardiac surgery, with and without concomitant LAAO, to evaluate its effect on the incidence of cerebrovascular accidents (CVAs). A systematic review was conducted from inception until December 2023 for randomized and propensity-score studies comparing CVA in patients without AF undergoing cardiac surgery with or without LAAO. Six studies met our inclusion criteria with a total of 4130 patients: 2146 in the LAAO group and 1984 in the no-LAAO group. The risk ratio of postoperative AF was 1.05 (95% CI, 0.86-1.28); P=0.628. The CVA rates at 5 years were 6.8±1.0% in the no-LAAO group and 4.3±0.8% in the LAAO group (log-rank P=0.021). The Cox regression analysis for CVA in patients undergoing LAAO reported a hazard ratio of 0.65 (95% CI, 0.45-0.94); P=0.022. Landmark analysis at 4 years highlighted a significant difference in overall survival between no-LAAO and LAAO groups, 86±12.2% versus 89.6±11.0%; P=0.041. In this meta-analysis of patients without previous AF undergoing cardiac surgery, LAAO was associated with a decreased risk of CVA, no difference in the incidence of postoperative atrial fibrillation, and a significant overall survival benefit at a 4-year landmark analysis. Although these findings support LAAO, the randomized LeAAPS trial (Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction Trial), LAA-CLOSURE trial (A Randomized Prospective Multicenter Trial for Stroke Prevention by Prophylactic Surgical Closure of the Left Atrial Appendage in Patients Undergoing Bioprosthetic Aortic Valve Surgery), and LAACS-2 trial (Left Atrial Appendage Closure by Surgery-2) will help define the effectiveness of LAAO in patients undergoing cardiac surgery who have risk factors for AF and CVA. URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42024496366.

Aberrant activation of a miR-101–UBE2D1 axis contributes to the advanced progression and chemotherapy sensitivity in human hepatocellular carcinoma

AbstractChemotherapeutic drugs, such as cisplatin (cis-dichlorodiamineplatinum [II], cDDP) and 5-fluorouracil (5Fu), are widely used in transarterial chemoembolization (TACE), which is a standard therapy for patients with hepatocellular carcinoma (HCC). Chemoresistance is a major cause of TACE treatment failure in HCC patients. Our previous studies have identified the expression levels of miR-101 responsive genes, such as EED, EZH2, STMN1 and JUNB, exhibit significant correlation with the occurrence and progression of HCC, while the role of miR-101 responsive gene signatures in the chemoresistance of HCC treatment remains unclear. In this study, we identified ubiquitin-coupled enzyme E2D1 (UBE2D1) as a crucial regulatory factor in the chemoresistance of HCC, which is a direct target of miR-101 and exhibits significant correlation with miR-101-responsive gene signatures. The bioinformatics analysis showed the expression of UBE2D1 was significantly increased in HCC tissues and was closely correlated with the poor prognosis. In addition, we analyzed the role of miR-101/UBE2D1 axis in regulating chemo-sensitive of HCC cells. Our results showed that miR-101 increases the DNA damage and apoptosis of HCC cells by inhibiting the expression of UBE2D1, which in turn increases the sensitivity of HCC cells to cDDP and 5Fu both in vitro and in vivo. Therefore, simultaneous assessment of miR-101 and UBE2D1 expression levels might provide an effective approach in preselecting HCC patients with survival benefit from TACE treatment. Moreover, further elucidation of the underlying molecular mechanisms of the miR-101/UBE2D1 axis could provide novel insight for targeted therapy of HCC.

Implementing a drug interaction protocol for oral systemic anti-cancer therapy with focus on CDK4/6 inhibitors.

302 Background: Oral anti-cancer therapies (OACTs) are being increasingly used. Despite their convenience, OACTs introduce challenges with adherence, prescribing errors, and high incidence of drug-drug interactions (DDIs). Currently, there are limited guidelines for DDI checking. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the management of metastatic ER+/HER2- breast cancer. While an overall survival benefit has been demonstrated with Ribociclib, its use can be problematic due to frequent DDIs and the risk of QTc prolongation. DDIs are routinely checked in our center with two interaction checkers, but they are not always documented due to a lack of a standardized protocol. This study aims to evaluate current DDI checking practices, identify common DDIs, and implement a systematic DDI protocol. Methods: A retrospective review was conducted on patients (pts) prescribed CDK4/6i in our center from Jan 2023 to Apr 2024. Data on pt demographics, treatment, DDI documentation, toxicity, and survival were collected. Retrospective DDI checks using Lexi-Interact and Drugs.com were performed. Results: A total of 65 pts were included, with 38 on Ribociclib and 27 on Palbociclib. The median follow-up was 11.6 months (range: 1-71). The median age of pts on Ribociclib was 54 (range: 35-77), compared to 61 (range: 44-82) on Palbociclib. The median number of medications was three with Ribociclib and five with Palbociclib. Seven pts (26%) were prescribed Palbociclib due to contraindications to Ribociclib, including cardiac disease (n=2), QTc-prolonging medications (n=4), and advanced age (n=1). DDI checks were documented in 46% of Ribociclib and 14% of Palbociclib pts (p=0.0063). There was a weak negative correlation between DDI documentation and toxicity, stronger in the Palbociclib arm (-0.079 for Ribociclib vs. -0.335 for Palbociclib). Retrospective checks revealed DDIs in 50% of Ribociclib and 52% of Palbociclib pts. Major DDIs were identified in 21% of Ribociclib and 7% of Palbociclib pts (p=0.133). Common major DDIs involved opioids and QTc-prolonging medications, most frequently antidepressants. Grade ≥3 toxicity occurred in 49% of Ribociclib vs. 64% of Palbociclib pts (p=0.21). Ribociclib caused more rash, liver toxicity, and diarrhea, while Palbociclib had significantly more grade ≥3 neutropenia (48% vs. 21%, p=0.042). No QTc prolongation was observed. Dose reductions were more common with Palbociclib (48% vs. 32%, p=0.27). There was no significant difference in survival data. Conclusions: Our findings highlight the importance of systematic DDI checks in pts receiving OACTs. Implementing a standardized protocol could reduce adverse interactions and improve pt outcomes. Further studies are needed to validate these findings and develop DDI guidelines. A standardized DDI protocol has now been developed for our center, with plans to re-audit after implementation.

Efficacy Analysis of PTCD + TACE vs PTCD + Apatinib in the Treatment of HCC with Obstructive Jaundice: A Retrospective Study.

The aim was to evaluate the safety and effectiveness of PTCD combined with TACE in the treatment of hepatocellular carcinoma with obstructive jaundice and to compare the efficacy of TACE in patients with different levels of bilirubin after PTCD. The clinical data of 141 patients with HCC complicated with obstructive jaundice were analyzed retrospectively. The patients underwent PTCD first. When the total bilirubin decreased, the patients received TACE or Apatinib treatment. They were divided into two groups: (1) PTCD+TACE group, N=68; (2) PTCD+Apatinib group, N=73. The PTCD+TACE group had higher ORR and DCR than the PTCD+Apatinib group (57.4% vs 12.3%, p < 0.001;80.9% vs 60.3%, p = 0.010). The mPFS of the PTCD+TACE group was longer than that of the PTCD+Apatinib group (7.1 months vs 3.8 months, p < 0.001). The mOS of the PTCD+TACE group was longer than that of the PTCD+Apatinib group(11.5 months vs 7.7 months, p < 0.001). In the subgroup analysis of the PTCD+TACE group, the results showed that the survival benefits of the groups with total bilirubin <2 times and 2-3 times were greater. In patients with HCC and obstructive jaundice, superselective TACE(lipiodol+epirubicin emulsion) significantly prolonged OS and PFS compared with Apatinib after using PTCD to reduce total bilirubin to <100umol/L. Patients whose total bilirubin dropped to ≤3 times of the upper limit of normal value after PTCD had longer OS and PFS than patients >3 times.

Surgical resection and overall survival in cT4b sinonasal non-squamous cell carcinoma.

Surgical resection is associated with higher overall survival (OS) than definitive radiotherapy (RT) or chemoradiotherapy (CRT) in cT4b sinonasal squamous cell carcinoma (SCC). Our study investigates the survival benefit of surgical resection in cT4b sinonasal non-SCC. The 2004 to 2019 National Cancer Database was queried for patients with cT4b sinonasal non-SCC undergoing definitive treatment with (1) surgical resection + additional therapy (RT, chemotherapy, or both), (2) RT alone, or (3) CRT. Surgical resection + additional therapy and definitive RT/CRT were compared with Kaplan-Meier and multivariable Cox regression models. Of 629 patients satisfying inclusion criteria, 513 (81.6%) underwent surgical resection + additional therapy and 116 (18.4%) underwent definitive RT/CRT. The most frequent histologic types were undifferentiated carcinoma (23.7%), adenoid cystic carcinoma (22.6%), and adenocarcinoma (20.7%). Few patients presented with clinical nodal metastasis (15.7%). There were 4 (0.8%) mortalities within 90 days of surgical resection. Patients undergoing surgical resection with positive surgical margins had higher 5-year OS than those undergoing definitive RT/CRT (56.3% vs. 39.4%, p = .039) and similar 5-year OS as those with negative margins (56.3% vs. 63.9%, p = .059). Patients undergoing neoadjuvant chemotherapy had similar 5-year OS as those undergoing definitive RT/CRT (60.9% vs. 39.5%, p = .053). Age at diagnosis, tumor diameter, and surgical resection + additional therapy (aHR 0.64, 95% CI 0.45-0.91) were associated with OS (p < .05). Surgical resection + additional therapy was associated with higher OS than definitive RT/CRT in cT4b sinonasal non-SCC. Surgical resection may benefit select patient with cT4b sinonasal non-SCC. 4.

Targeted orbital intervention in the management of sino-orbital mucormycosis cases.

Many countries from South-East Asia reported an epidemic of sino-orbital mucormycosis (SOM), otherwise a rare disease, during the coronavirus disease 2019 pandemic. SOM, a potentially fatal disease, is typically treated with orbital exenteration and systemic antifungals after metabolic stabilization. There is no clear evidence of survival benefit of exenteration in the literature, and thus, there have been attempts at globe conserving treatments like orbital infusion after limited debridement and intraorbital injections with Amphotericin B (IOAB). We conducted a prospective comparative interventional study at a tertiary eye care hospital to evaluate treatment outcomes with the use of adjunctive IOAB in cases of SOM with mild to moderate orbital disease. Thirty-six patients of SOM with mild to moderate orbital disease were recruited in the study. In the intervention group, 23/26 (885%) eyes had stable orbital disease at the end of treatment (4-6 weeks). No deterioration in visual acuity was noted as a result of treatment. In 8/26 (30.77%) patients, inflammation was noted as a side effect of IOAB requiring temporary discontinuation of injections. The mean follow-up for cases was 14.2 months (range 12-15 months). 1/23 (4.35%) patients had relapse of orbital disease at 3 months. Twenty-one patients are alive on last follow-up. Of the patients who refused treatment (controls), 2/9 (22.22%) patients relapsed. One of these patients with relapse underwent exenteration, while the other was managed with IOAB. At a follow-up of 14 months (range 12-15 months), eight patients are alive. On evaluating the ocular parameters in salvaged eyes, improvement in extraocular movements was noted in 75-80% cases. The degree of proptosis and resistance to retropulsion did not change significantly. In the current study, an improvement in the globe salvage rates was noted in cases of SOM with mild to moderate orbital disease treated with adjunctive IOAB as compared to controls at a mean follow-up of 14 months, although it did not achieve statistical significance. The study supports the inclusion of IOAB in routine management of mild to moderate orbital disease.

Adopting prospective antimicrobial stewardship (AMS) practice in high-risk immunosuppressed groups: an urgent call to action in the era of antimicrobial resistance (AMR).

Life-saving immunosuppressive treatments including intensive chemotherapy and bone marrow transplantation expose patients to a considerable risk of death from infection globally. With evolving AMR and transmission, this could spell disaster for patients across the world and society at large. Antimicrobial stewardship (AMS) and prompt appropriate management of potentially fatal, emergent infections are essential. It is now apparent that antibacterial prophylaxis in patients with haematological cancer may not provide survival benefit while simultaneously increasing risks for AMR carriage. With evolving AMR and increasing immunosuppressed populations across the world, we must institute robust AMS practices. Significant resources are used to combat the impact of AMR on immunosuppressed patients. For lower-middle income countries (LMICs) these resources may not be available and as such the impact caused by AMR is greater. By considering the patient journey holistically we consider risk of infection presented to patients temporally and geographically. A short-term and easy to implement approach of multi-disciplinary team (MDT)-style advance care planning for infection is advocated. Antimicrobials, when used appropriately, enable healthcare procedures to occur and exist. Indeed, the very future of clinical medicine will rely on this yet to be realized value of enablement. Proactive effort and change must occur across all sectors with holism; hence our impetus for convening a joint industry and clinical working group. With at-risk immunosuppressed groups being a sentinel for change, awareness and implementation of patient-centric actions for infection are essential and our recommendations serve as an urgent call to action.

Concurrent Chemoradiotherapy versus Radiotherapy Alone in the Treatment of Stage II and T3N0M0 Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis

AimsThe efficacy of concurrent chemoradiotherapy (CCRT) for Stage II and T3N0 nasopharyngeal carcinoma (NPC), particularly during the shift from two-dimensional conventional radiotherapy (2DCRT) to intensity-modulated radiotherapy (IMRT) is debated.Therefore this study aims to systematically evaluate and meta-analyze survival benefits of CCRT versus radiotherapy alone for Stage II and T3N0 NPC, stratified by radiotherapy techniques. Materials and methodsAs of April 1, 2024, we conducted an exhaustive literature search across databases such as PubMed, Embase, Cochrane Library, and Web of Science, with the aim of identifying and screening studies that compare the efficacy of CCRT versus radiotherapy alone in the treatment of Stage II and T3N0 NPC. ResultsA total of 10 studies encompassing 5015 patients were included in this comprehensive analysis. The findings indicate that, apart from progression-free survival (PFS), CCRT did not improve survival outcomes, including overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRRFS), and failure-free survival (FFS), with all P values exceeding 0.05. Concurrently, the incidence of grade ≥3 adverse events associated with CCRT was significantly elevated (odds ratio [OR] = 3.77, 95% confidence interval [CI] = 2.75–5.15, P < 0.0001). Subgroup analysis revealed that, compared with RT, the combination of 2DCRT with concurrent chemotherapy significantly improved OS (hazard ratio [HR] = 0.57, 95% CI = 0.46–0.71, P < 0.00001), PFS (HR = 0.65, 95% CI=0.53–0.78, P < 0.00001), DMFS (HR = 0.54, 95% CI = 0.37–0.79, P = 0.002), and LRRFS (HR = 0.63, 95% CI = 0.49–0.82, P = 0.0005). In contrast, the combination of IMRT with concurrent chemotherapy failed to demonstrate improvements in OS, PFS, DMFS, or LRRFS, with all P values exceeding 0.05. ConclusionIn contrast with RT, CCRT did not enhance survival in stage II and T3N0 NPC patients, yet caused more adverse reactions. 2DCRT combined with concurrent chemotherapy significantly improved OS, PFS, DMFS, and LRRFS, while IMRT with concurrent chemotherapy showed no clinical benefits.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation

BackgroundAn association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with...