Cohort Of Patients Research Articles

Hyperactivation of the PI3K Pathway in Inborn Errors of Immunity: current understanding and therapeutic perspectives

Abstract Phosphoinositide-3-kinase (PI3K) pathway function is crucial to normal development, differentiation and function of immune cells including B, T and NK cells. Following the description of two cohorts of patients with a primary immunodeficiency with gain-of-function variants in the PIK3CD gene a decade ago, the disease entity activated PI3K delta syndrome (APDS) was named. Since then, many more patients with PIK3CD variants have been described, and loss-of-functions variants in PIK3R1 and PTEN have also been linked to APDS. Importantly, the availability of small molecules that inhibit the PI3K pathway have enabled targeted treatment of APDS patients. In this review, we define (1) the PI3K pathway and its role in inborn errors of immunity; (2) the clinical and immunological presentation of APDS1 (PIK3CD GOF), APDS2 (PIK3R1 LOF) and related disorders; (3) Diagnostic approaches to identify and functionally validate the genetic causes of disease; (4) therapeutic interventions to target PI3K hyperactivation; and finally (5) current challenges and future perspectives that require attention for the optimal treatment of patients with APDS and APDS-L diseases.

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults

ABSTRACTBackgroundPatients with PAX3/7‐FOXO1 fusion‐negative rhabdomyosarcomas (fnRMS) harbouring the rare L122R MYOD1 mutation have significantly poorer prognosis than other fnRMS. We undertook a detailed clinicopathological evaluation of a cohort of patients with MYOD1 mutated fnRMS in order to improve risk stratification and treatment options.ProcedureHistological, mutational and clinical data from a cohort of patients with MYOD1 mutant RMS treated in Europe were analysed.ResultsThirty‐two cases with mutant MYOD1 RMS were identified from patients enrolled in sequential European rhabdomyosarcoma clinical trials from 1992 to 2022 (n = 22) and non‐trial cohorts (n = 10). Thirty cases had the recurrent L122R missense mutation, one case harboured a K124E mutation and one case had a truncating mutation (S63X). Increased MyoD1 and reduced MYF4 immunostaining were consistent features of MYOD1L122R‐mutated RMS. Applying the risk stratification of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 trial, among 20 localised RMS cases that could be assigned a risk category, one was Very High Risk, 13 were High Risk and six were Standard Risk. Eight patients had distant metastases at diagnosis. Of the 25 patients with adequate clinical follow‐up data, 15/25 (60%) patients had an event at a median time of 9 months (12/15 included failure of local control) and 13/25 (52%) died of disease.ConclusionThis MYOD1 mutant cohort demonstrates increased MYOD and reduced MYF4 immunostaining, high risk of local failure and poor survival in agreement with other studies. Increased treatment intensity and improved local control should be considered for these patients.

Targeting LLT1 as a potential immunotherapy option for cancer patients non-responsive to existing checkpoint therapies in multiple solid tumors

BackgroundHigh levels of LLT1 expression have been found in several cancers, where it interacts with CD161 on NK cells to facilitate tumor immune escape. Targeting LLT1 could potentially relieve this inhibitory signal and enhance anti-tumor responses mediated through NK cells. Using the ‘The Cancer Genome Atlas’ (TCGA) database, we investigated the role of LLT1 in the tumor microenvironment (TME) across various cancers. Identifying such biomarkers could create new therapeutic options for patients in addition to complementing existing immunotherapies.MethodsLLT1 expression was evaluated in 33 cancers using TCGA transcriptome data. Univariate Cox regression analysis was employed to assess the correlation of LLT1 expression with patient survival. The relationship between LLT1 expression with immune infiltrates, immune gene signatures, and cancer genomic biomarkers (TMB, MSI, and MMR) was also investigated. Immunofluorescence studies were conducted to validate LLT1 expression in tumors. Furthermore, using the CRI iAtlas data, we evaluated LLT1 distribution and its correlation with other immune checkpoint genes in patients non-responsive to existing immune checkpoint therapies across multiple solid cancers.ResultsHigh expression of LLT1 was observed in 12 cancers, including BRCA, CHOL, ESCA, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, STAD, SARC, and PCPG. In certain cancers like COAD, KICH, and KIRC, high LLT1 expression was associated with poor prognosis. Further analysis revealed that upregulated LLT1 was associated with an abundance of NK and T cell infiltrates in the TME, as well as exhaustive immune biomarkers, and inversely associated with pro-inflammatory and tumor suppressor signatures. High LLT1 expression is also positively correlated with genomic biomarkers in certain cancers. Immunofluorescence studies confirmed moderate to high LLT1 expression in immune-resistant prostate cancer, glioma, ovarian cancer, and immune-sensitive liver cancer cell lines. An independent assessment of clinical cohorts from CRI iAtlas showed a correlation of upregulated LLT1 with multiple immunosuppressive genes in patients non-responsive to current ICIs.ConclusionsThe biomarker analysis revealed a clear association between elevated LLT1 expression and an immunosuppressive TME in patient cohorts from TCGA and clinical databases. Therefore, this study provides a foundation for utilizing LLT1 as a potential target to improve clinical responses in ICI non-responsive patients with upregulated LLT1.

Looks Can Be Deceiving: Diagnostic Power of Exome Sequencing in Debunking 15q11.2 Copy Number Variations

Background/Objectives: The pathogenetic role of 15q11.2 Copy Number Variations (CNVs) remains contentious in the scientific community, as microdeletions and microduplications in this region are linked to neurodevelopmental disorders with variable expressivity. This study aims to explore the diagnostic utility of Exome Sequencing (ES) in a cohort of pediatric patients with 15q11.2 CNVs. Methods: We enrolled 35 probands with 15q11.2 microdeletions or microduplications from two genetic centers between January 2021 and January 2023. Chromosomal Microarray Analysis (CMA) and ES were performed with written consent obtained from all parents. Pathogenic variants were classified according to ACMG guidelines. Results: CMA identified additional pathogenic CNVs in 3 of 35 children (9%). Subsequent ES revealed likely pathogenic or pathogenic variants in 11 of 32 children (34%). Notably, a higher percentage of isolated autism spectrum disorder (ASD) diagnoses was observed in patients without other CNVs or point mutations (p = 0.019). Conclusions: The ES analysis provided a diagnostic yield of 34% in this pediatric cohort with 15q11.2 CNVs. While the study does not dismiss the contribution of the CNV to the clinical phenotype, the findings suggest that ES may uncover the underlying causes of neurodevelopmental disorders. Continuous monitoring and further genetic testing are recommended for all 15q11.2 CNV carriers to optimize clinical management and familial counseling.

Body mass index and type 2 diabetes mellitus as metabolic determinants of immune checkpoint inhibitors response in melanoma

BackgroundImmune checkpoint inhibitors (ICIs) have improved survival outcomes in melanoma. Studies exploring the correlations between body mass index (BMI), type 2 diabetes (T2DM) and the outcomes of ICI treatment have...

Associations of Microvascular Risk Factors with Sporadic Vestibular Schwannoma Outcomes Following Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) is increasingly used for small-to-medium-sized sporadic vestibular schwannoma (VS) and is associated with good tumor control and low-risk of adverse radiation-associated events. The exact mechanism of VS tumor control is unknown but may relate to microvascular hyalinization and resultant tumoral ischemia. This study examined associations of microvascular risk factors with outcomes following SRS. Historical cohort of patients who underwent SRS for sporadic VS from 2000 to 2022. Tertiary academic center. Associations of microvascular risk factors with tumor control and complications were evaluated using Cox proportional hazards regression. In total 749 patients were studied, 31% with a history of smoking, 38% obesity, 19% hypertension, 8% diabetes, 3% peripheral vascular disease, and 2% history of coronary bypass. Regarding tumor control, no factor was associated with salvage treatment following SRS (n = 42). Hypertension (hazard ratio [HR] 2.81; P = .02) and coronary bypass (HR 6.91; P = .002) were significantly associated with developing facial nerve paresis (n = 22). No significant associations with new facial spasms (n = 53) were identified. Lastly, 191 of 294 patients with serviceable hearing at SRS progressed to nonserviceable hearing at a median 2.0 years (interquartile range: 1.0-5.0). After multivariable adjustment for age and ipsilateral hearing status, the HR for the association of smoking history with time to nonserviceable hearing was 1.46 (95% confidence interval 1.04-2.04; P = .03). We demonstrate that hypertension and history of coronary bypass may be associated with development of facial nerve weakness, while smoking may be associated with accelerated hearing loss in patients undergoing SRS for sporadic VS. These data may help guide patient counseling and inform decision-making regarding treatment.

Development of a nomogram for predicting pancreatic portal hypertension in patients with acute pancreatitis: a retrospective study

IntroductionPancreatic portal hypertension (PPH) is a rare complication of acute pancreatitis (AP) that can lead to severe gastrointestinal bleeding. The risk factors associated with PPH, as well as the overall...

A 5‐year natural history cohort of patients with facioscapulohumeral muscular dystrophy determining disease progression and feasibility of clinical outcome assessments for clinical trials

A 5‐year natural history cohort of patients with facioscapulohumeral muscular dystrophy determining disease progression and feasibility of clinical outcome assessments for clinical trials

Penile inversion vulvo-vaginoplasty with scrotal graft for trans women: surgical technique and results of initial experience.

A significant proportion of trans women is demanding for a genital gender-affirming surgery, with vulvo-vaginoplasty being the most frequently requested procedure. The gold standard for primary vaginoplasty in trans women is the penile skin inversion technique with scrotal skin graft, which allows for increased depth of the vaginal cavity. The assessment of vulvo-vaginoplasty outcomes utilizing penile skin inversion and scrotal skin graft in individuals assigned male at birth in the surgeon's learning curve involves evaluating aesthetics, functionality, and sexual aspects. A total of 76 individuals assigned male at birth were included in 2 French university hospitals from 2020 to 2022. They underwent vulvo-vaginoplasty following 8 key steps: scrotal skin excision; bilateral orchiectomy; dissection between the rectum, bladder, and prostate; penile dissection; clitoroplasty; urethroplasty; penile skin inversion with scrotal skin graft; labioplasty. The average follow-up period was 12.4months, with participants averaging 35.7years of age. Each patient was invited to complete a questionnaire during follow-up. The study's outcomes encompassed the assessment of both early and late surgical complications, postoperative sexuality, aesthetic results, and voiding satisfaction. Of the total patients, 15.8% experienced major early postoperative complications, while 3% encountered major late postoperative complications. No complication was classified 4 or 5 in Clavien-Dindo scale. Most early complications were related to issues in vulvar healing, which did not compromise long-term aesthetic results. Patients-reported satisfaction was 82% after the procedure. Vulvo-vaginoplasty utilizing penile skin inversion and scrotal skin graft for individuals assigned male at birth is a reproductive surgery procedure that can be successfully performed by experienced urologist. It achieves high patient-reported satisfaction even during the learning curve. The surgical procedures were consistent, and the sizable cohort of patients accurately reflects the learning curve of both surgeons. However, extrapolating long-term complications is challenging due to the relatively brief follow-up period. Additionally, there is a lack of self-reported sexual function data, and the scales used to assess patient-reported quality of life and urinary satisfaction are not specifically validated for transgender patients. Vulvo-vaginoplasty utilizing penile skin inversion and scrotal skin graft for individuals assigned male at birth is a complex surgical procedure. It appears to be achievable by experienced urologists during their learning curve, resulting in similar functional and surgical outcomes, along with high patient satisfaction.

Patient outcome following selective serotonin reuptake inhibitor prescribing in primary care in Wales (UK)

AbstractObjectiveThis study investigated prescribing patterns of two cohorts of patients treated with selective serotonin reuptake inhibitors (SSRI) in primary care in Wales (UK), to better understand drivers for increased usage.MethodsThis e‐cohort study included patients receiving a first READ‐coded SSRI prescription in SAIL in either 2005 or 2015. Patients were followed up for 3 years from date of SSRI prescription. Influence of age and other demographic data on prescribing patterns, and details of mental health or medication reviews that took place were identified.ResultsIn total 67,006 patients were included across the two cohorts; 29,534 in 2005, and 37,472 in 2015. Citalopram was the most commonly prescribed SSRI in both cohorts. A READ‐coded diagnosis relating to SSRI treatment could not be identified in 24,797 patients. The percentage of patients continuing treatment for 3 years was 6.9% and 11.3% in 2005 and 2015, respectively. In total, 21,150 (72%) patients in the 2005 cohort and 23,947 (64%) in the 2015 cohort received at least one medication review during follow‐up.ConclusionsThe proportion of patients continuing longer term treatment was small, whilst the number of recorded mental health and medication reviews offers some reassurance that prescribing remained appropriate.

Standardizing Nutritional Care for Cancer Patients: Implementation and Evaluation of a Malnutrition Risk Screening

Introduction Cancer-related malnutrition is a highly prevalent, yet often overlooked concern in clinical practice. Although cancer-related management guidelines recommend standardized nutritional care, its implementation is scarce. The aim of this study was to investigate the prevalence of malnutrition and the medical need for nutrition counseling in cancer patients employing a novel standardized nutritional management program (containing malnutrition risk screening, nutritional assessment and counseling). Furthermore, differences of malnutrition parameters in different cancer patient cohorts were examined. Methods Cancer patients were screened for malnutrition using the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) on the first day of their inpatient admission to the internal oncology or hematology wards. PG-SGA total score and classification into the three PG-SGA nutrition stages (A, B, C) were used to determine nutritional status. In case of a positive screening, nutritional assessment and individualized counseling by a nutritionist followed. For group comparisons, patients were divided into different groups (e.g., age, gender, tumor entity) and were evaluated accordingly. Results A total of 1,100 inpatients were included. 56.8 % of the patients had suspected or already existing malnutrition. The most common nutrition impact symptom was loss of appetite (26.7 %), followed by fatigue (16.5 %) and pain (16.0 %). Female (p < 0.001), elderly (p < 0.001) and patients with upper gastrointestinal tract tumors (p < 0.001) showed an unfavorable nutritional status and higher need for counseling. Despite suffering from malnutrition, patients had Body Mass Indices within the upper end of the normal range. Conclusion This study shows a high prevalence of malnutrition in hospitalized cancer patients and highlights the need for a standardized nutritional management in the clinical setting. Therefore, it is recommended to provide a malnutrition risk screening for all cancer patients and a following adequate assessment and personalized nutritional care if needed.

The effects of dexmedetomidine on thiol/disulphide homeostasis in coronary artery bypass surgery: a randomized controlled trial

BackgroundThiol-disulfide homeostasis (TDH) plays a pivotal role in various physiological mechanisms, including antioxidant defence, detoxification, apoptosis, regulation of enzyme activities and cellular signal transduction. TDH can be used as a biomarker to detect oxidative stress (OS) levels and ischemia status in the tissues. Coronary artery bypass grafting (CABG) surgery is a procedure associated with high oxidative stress. Dexmedetomidine, an alpha-2 agonist anaesthetic agent, has antioxidant effects. In this study, the effects of dexmedetomidine on oxidative stress in CABG surgery were investigated.MethodsPatients who underwent on-pump CABG surgery were divided into two groups: those receiving dexmedetomidine (Group D) and those not receiving dexmedetomidine (Group C). From anesthesia induction to the end of surgery, patients in Group D received intravenous infusions of 0.05–0.2 mcg/kg/min remifentanil and 0.2–0.7 mcg/kg/h dexmedetomidine. Patients in Group C received intravenous infusion of 0.05–0.2 mcg/kg/min remifentanil. Blood samples were collected from the patients 30 min before induction of anesthesia (T1), 30 min after removal of the aortic cross-clamp (T2), and at the end of the surgery (T3). Thiol-disulfide homeostasis (TDH) was assessed using a novel method. A novel automated method enables the determination of native thiols, total thiols and disulfides levels in plasma, allowing the calculation of their respective ratios.ResultsIn patients receiving dexmedetomidine, lower postoperative levels of disulfide, disulfide/native thiol, and disulfide/total thiol, along with higher native thiol/total thiol, were observed compared to the control group. (p < 0.05) Postoperative native thiol and total thiol levels were similar for both groups. (p > 0.05)ConclusionsIn our study, through dynamic thiol-disulfide measurements, we found that levels of oxidative stress (OS) were lower in patients who received dexmedetomidine. We believe that the positive effects of dexmedetomidine on OS could be beneficial in CABG surgery. Furthermore, we anticipate that with further studies conducted in larger patient cohorts, the clinical utilization of dexmedetomidine will become more widespread.Trial registration numberNCT05895331 / 06.07.2023.

Preoperative anemia is associated with increased length of stay in adult spinal deformity surgery: evaluation of a large single-center patient cohort and future suggestions for patient optimization

Preoperative anemia is associated with increased length of stay in adult spinal deformity surgery: evaluation of a large single-center patient cohort and future suggestions for patient optimization

Association of the Revised Trauma Score with Mortality and Prehospital LSI Among Trauma and Non-Trauma Patients

ABSTRACT OBJECTIVES The combination of broad conditional applicability and ease of data collection make some general risk scores an attractive tool for clinical decision making under acute care conditions. To date, general risk scores have demonstrated moderate levels of accuracy for key outcomes, but there are no definitive general scores integrated universally into prehospital care. The objective of our study was to demonstrate a relationship between the revised trauma score (RTS) and prehospital lifesaving interventions (LSI) and downstream hospital mortality among a large, diverse, multi-year cohort of critical care transport patients. We hypothesized that the RTS is associated with mortality and prehospital LSI generally across all conditions, including non-trauma. METHODS We conducted a retrospective observational study using a pre-established cohort of sequentially enrolled patients from a regional air medical service between the years 2012 and 2021. Pediatric patients, non-transports, and those transported to hospitals outside the regional health system were excluded from the study. Both trauma and non-trauma patients were included in this study. We performed logistic regressions to evaluate the association between RTS and the outcomes of LSI and hospital mortality, while controlling for age, sex, and medical category. Graphs were constructed to plot RTS against prehospital LSI and survival percentage. RESULTS Our final patient cohort was 62,424 patients. 58.4% of all patients required a prehospital LSI. Non-trauma cases made up 69.7% of the patient population. The Revised Trauma Score was inversely proportional with both prehospital LSI and mortality. The logistic regression model yielded an odds ratio (OR) of 0.55 (95% CI 0.54 - 0.56) for the association between RTS and death. Additionally, when the components of RTS were associated with mortality, they each showed a statistically significant OR. The Revised Trauma Score was also associated with prehospital LSI (OR 0.10; 95% CI 0.03 - 0.33). CONCLUSIONS In a large helicopter EMS cohort of both trauma and non-trauma patients, the RTS was inversely associated with prehospital LSI and hospital mortality. The generalized utility of RTS demonstrated in our study warrants further investigation of this measure as a broader triage tool.

Revalidation of Proactive Gastrostomy Tube Placement Guidelines for Head and Neck Cancer Patients Receiving Helical Intensity-Modulated Radiotherapy

The Royal Brisbane and Women’s Hospital (RBWH) Swallowing and Nutrition Management Guidelines for Patients with Head and Neck Cancer were developed to enable evidence-based decision-making by the Head and Neck Multidisciplinary Team (H&amp;N MDT) regarding enteral nutrition support options. The purpose of this study was to revalidate these guidelines in a cohort of patients receiving helical intensity-modulated radiotherapy (H-IMRT) compared to a historical cohort who received primarily 3D-conformal radiotherapy. Eligible patients attending the RBWH H&amp;N MDT between 2013 and 2014 (n = 315) were assessed by the guidelines, with high-risk patients being recommended proactive gastrostomy tube placement. Data were collected on guideline adherence, gastrostomy tube insertions, the duration of enteral tube use and weight change. Sensitivity, specificity and positive predictive and negative predictive values were calculated and compared with the historical cohort. Overall guideline adherence was 84%, with 60% and 96% adherence to the high-risk and low-risk pathways, respectively. Seventy patients underwent proactive gastrostomy tube placement (n = 62 high-risk; n = 8 low-risk). Validation outcomes were sensitivity 73% (compared to 72%) and specificity 86% (compared to 96%). The guidelines yielded a high sensitivity and specificity, remaining valid in a cohort of patients treated with H-IMRT. Further studies are recommended to improve the sensitivity and understand the decrease in specificity in order to make ongoing guideline improvements.

Cardiotoxicity following thoracic radiotherapy for lung cancer.

Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and endpoints. How baseline cardiovascular profile and cardiac substructure radiation dose distribution impact the risk of cardiotoxicity is incompletely understood. As Thoracic Oncology departments seek to expand the indications for radiotherapy, and as the patient cohort becomes older and more comorbid, there is a pressing need for cardiotoxicity to be comprehensively characterised with sophisticated oncology, physics and cardio-oncology evaluations. This review synthesises the evidence base for cardiotoxicity in conventional radiotherapy, focusing on lung cancer, including current data, unmet clinical needs, and future scientific directions.

Interconnected Pathways: Exploring Inflammation, Pain, and Cognitive Decline in Osteoarthritis

The relationship among inflammation, pain, and cognitive decline in osteoarthritis (OA) patients is complex and has not been sufficiently explored; therefore, we undertook this research to evaluate how OA-related inflammation and pain affect cognitive functions, as well as to examine the potential of urinary markers as indicators of these conditions. This study examined fifty OA patients through clinical and cognitive assessments, morphological analyses, urinary biomarkers, and bioinformatics. Morphologically, 24% of patients had moderate to high synovial inflammation, which was significantly correlated with depressive symptoms, pain intensity, and self-reported anxiety. The Montreal Cognitive Assessment indicated minimal decline in most patients but showed negative correlations with age and inflammation severity. Urinary TNF-α and TGF-β1 levels positively correlated with body mass index and pain and synovitis score and immune cell infiltration, respectively. In contrast, cartilage oligomeric matrix protein and C-telopeptides of type II collagen showed inverse correlations with pain duration and cognitive function, respectively. Distinct patient clusters with higher inflammation were identified and were associated with reported pain and depressive symptoms. Urinary TNF-α and TGF-β1 can serve as biomarkers reflecting inflammation and disease severity in OA. This study suggests that synovial inflammation may be linked to mental and cognitive health in some patient cohorts.

Diagnostic Accuracy of Automated Diabetic Retinopathy Image Assessment Software: IDx-DR and RetCAD.

Automated diabetic retinopathy (DR) screening using artificial intelligence has the potential to improve access to eye care by enabling large-scale screening. However, little is known about differences in real-world performance between available algorithms. This study compares the diagnostic accuracy of two AI screening platforms, IDx-DR and RetCAD, for detecting referable diabetic retinopathy (RDR). Retinal images from 758 patients with diabetes were collected during screening from various clinics in Poland. Each patient was graded by three graders with 320 patients graded by Polish and 438 patients graded by Indian graders, with the majority decision serving as the reference standard. The images were evaluated independently by the IDx-DR and RetCAD algorithms. Sensitivity, specificity, positive and negative predictive values, and agreement between algorithms and human graders were calculated and statistically compared. IDx-DR demonstrated higher sensitivity of 99.3% but lower specificity of 68.9% for RDR detection compared to RetCAD which had 89.4% sensitivity and 94.8% specificity. The positive predictive value was higher for RetCAD (96.4% vs 48.1% for IDx-DR) while the negative predictive value was higher for IDx-DR (99.5% vs 83.1% for RetCAD). Both algorithms achieved high sensitivity (> 95%) for sight-threatening diabetic retinopathy detection. In this direct comparison using the same patient cohort, the two algorithms showed differences in their operating parameters for RDR screening. IDx-DR prioritized avoiding false negatives over false positives while RetCAD maintained a more balanced trade-off. These results highlight the variable performance of current artificial intelligence screening solutions and suggest the importance of considering algorithm performance metrics when deploying automated diabetic retinopathy screening programs, based on available healthcare resources.

Prognostic value of CURB-65 and pneumonia severity index (PSI) in COVID-19 pneumonia: A retrospective cohort study

Objective: To validate a better scoring system between CURB-65 and the pneumonia severity index (PSI) to predict the need for intensive care unit admission and 30-day mortality in patients with COVID-19 pneumonia. Methods: A retrospective cohort study was conducted on patients in a tertiary care hospital in Kota, Rajasthan. Relevant data about history, and general and systemic examination with laboratory investigations was collected. Patients were categorized into different risk groups for ICU admission and 30-day mortality according to CURB-65 and PSI. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were calculated. Continuous variables, means and percentages were compared using the t-test for numerical data and the Chi-square test for nominal data. Results: 100 patients who tested positive for SARS-CoV-2 by RT-PCR were included; 67 were male and 33 were female. 58 patients had severe disease (SpO2≤90%) and 30 patients died. CURB-65 had an area under the curve (AUC) of 0.81 for predicting ICU admission, with a sensitivity of 92% and a specificity of 54% for high risk patients. Meanwhile, PSI had an AUC of 0.88, with a sensitivity of 83% and a specificity of 73% in high risk patients. In addition, CURB-65 had an AUC of 0.79 for predicting 30-day mortality, with a sensitivity of 60% and a specificity of 89% in high risk patients. PSI had an AUC of 0.71 for predicting 30-day mortality, with a sensitivity of 90% and a specificity of 46% in high risk patients. Conclusions: This single-centre retrospective study involving a cohort of COVID-19 patients demonstrates that CURB-65 and PSI are powerful tools for predicting mortality. However, PSI appears to be slightly better at predicting the need for intensive care unit admission in high-risk patients.

An investigation into the contributing factors to survival of ARDS patients supported by veno-venous ECMO.

This study aimed to identify characteristics associated with survival during and post Extra Corporeal Membrane Oxygenation (ECMO) therapy, in patients with acute respiratory distress syndrome (ARDS) during the COVID-19 pandemic. A retrospective observational study on 94 consecutive patients with confirmed COVID-19 induced ARDS supported by ECMO was carried out 49/94 (52.7%) patients survived to hospital discharge. Non-survivors were found to have significantly (p < .05) higher: Pre-ECMO International normalized ratios (INR), carbon dioxide partial pressure (pCO2), Acute Kidney Injury (AKI) scores and blood urea levels. Also, lower pre-ECMO peak inspiratory pressures (PIP), mean arterial pressure, saturation of arterial oxygen (SaO2), blood bicarbonate levels (HCO3), blood Ph and fewer trials off ECMO with shorter combined trial off times. Patients that did not survive were more likely to have renal impairment and have received peri-ECMO haemofiltration. Poor prognosis was significantly associated with: receiving pre-ECMO nitric oxide (HR = 3.047, CI = 1.247-7.447, p = .015), renal impairment (HR = 3.023, CI = 1.586-5.763, p < .001), AKI of 2 (HR = 3.611, CI = 1.382-9.441, p = .009) or 3 (HR = 3.275, CI = 1.235-8.685, p = .017), peri-ECMO haemofiltration (HR = 2.412, CI = 1.310-4.442, p = .005) and the ABO blood group B (HR = 3.103, CI = 1.335-7.212, p = .008). pre-ECMO high CO2 (HR = 1.134, CI = 1.031-1.248, p = .010), blood lactate (HR = 1.350, CI = 1.156-1.576, p < .001), INR (HR = 2.571, CI = 1.438-4.598, p=<0.001) and lower blood Ph (HR = 0.023, CI = 0.002-0.210, p < .001). Commonly used mortality scores may not be of use in a COVID-19 cohort of ECMO patients. The initiation of ECMO needs to be implemented prior to metabolic derangements, renal and fulminant respiratory failure.