Implementation of a clinical breast exam and referral program in a rural district of Pakistan.

BACKGROUND: The role of clinical breast examination (CBE) for early detection of breast cancer is extremely important in lower-middle-income countries (LMICs) where access to breast imaging is limited. Our study aimed to describe the outcomes of a community outreach breast education, home CBE and referral program for early recognition of breast abnormalities and improvement of breast cancer awareness in a rural district of Pakistan. METHODS: Eight health care workers (HCW) and a gynecologist were educated on basic breast cancer knowledge and trained to create breast cancer awareness and conduct CBE in the community. They were then deployed in the Dadu district of Pakistan where they carried out home visits to perform CBE in the community. Breast cancer awareness was assessed in the community using a standardized questionnaire and standard educational intervention was performed. Clinically detectable breast lesions were identified during home CBE and women were referred to the study gynecologist to confirm the presence of clinical abnormalities. Those confirmed to have clinical abnormalities were referred for imaging. Follow-up home visits were carried out to assess reasons for non-compliance in patients who did not follow-through with the gynecologist appointment or prescribed imaging and re-enforce the need for follow-up. RESULTS: Basic breast cancer knowledge of HCWs and study gynecologist improved post-intervention. HCWs conducted home CBE in 8757 women. Of these, 149 were warranted a CBE by a physician (to avoid missing an abnormality), while 20 were found to have a definitive lump by HCWs, all were referred to the study gynecologist (CBE checkpoint). Only 50% (10/20) of those with a suspected lump complied with the referral to the gynecologist, where 90% concordance was found between their CBEs. Follow-up home visits were conducted in 119/169 non-compliant patients. Major reasons for non-compliance were a lack of understanding of the risks and financial constraints. A significant improvement was observed in the community's breast cancer knowledge at the follow-up visits using the standardized post-test. CONCLUSIONS: Basic and focused education of HCWs can increase their knowledge and dispel myths. Hand-on structured training can enable HCWs to perform CBE. Community awareness is essential for patient compliance and for early-detection, diagnosis, and treatment.

Development of palliative care clinical practice guidelines and referral care pathways for primary care practitioners in Pakistan.

BACKGROUND: Despite a large burden of life-limitingillness, there exists a dearth of services of palliative care in Pakistan. International guidelines have questionable applicability in Pakistan due to the socioeconomic differences. We generated a protocol describing the process of developing comprehensive palliative care guidelines and palliative care referral pathways for primary care practitioners to adopt in Pakistan. METHODS: A GRADE-ADOLOPMENT approach with modification has been employed to create guidelines for a Pakistani context. The "National Comprehensive Cancer Network Guidelines Insights: Palliative Care, Version 2.2021" was used as the source guideline. Recommendations from the source guideline were reviewed by two local palliative care specialists to either "Adopt," "Adapt" or "Exclude". The finalized recommendations were incorporated into the local palliative care guideline. Clinical diagnosis and referral pathways were made from the finalized guideline. Any gaps in management found in the pathways were filled by taking existing recommendations from other credible guidelines. RESULTS: Twenty-seven recommendations were adopted without modification. No recommendations were deemed to be adapted and 15 were excluded. The referral care pathways created were reflective of the local guideline and included elements of initial assessment, preliminary management, reassessment, and referral. 6 additional recommendations were made. CONCLUSION: The described clinical practice guidelines and primary care clinical referral pathways will aid to standardize palliative care provision in Pakistan. These can be used by other resource constrained settings to develop guidelines within their own local context.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism.

INTRODUCTION: Coronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles. METHODS: Adult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Two women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2). CONCLUSION: Gene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid's ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.

Predictors of clinical outcomes in patients with sepsis: A retrospective study from a tertiary care hospital in Pakistan.

OBJECTIVE: To assess associations between various clinic-demographic factors and clinical outcomes among patients treated for sepsis. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of all patients aged >18 years diagnosed with sepsis from January to December 2019. Multivariable logistic regression was used to evaluate independent associations between predictors and outcomes. Data was analysed using R packages. RESULTS: Of the 1,136 patients, 621(54.6%) were male and 515(45.3%) were female. The overall mean age was 59.05±16.91 years. Female gender (odds ratio: 1.029; 95% confidence interval: 1.03-1.64) was found to be an independent predictor of septic shock, while hypertension (odds ratio0.75; 95% confidence interval: 0.59-0.95) emerged as a protective factor. Chronic kidney disease (odds ratio: 1.539; 95% confidence interval: 1.14-2.07) was an independent predictor of prolonged length of stay, while older age appeared to be protective (odds ratio: 0.98; 95% confidence interval: 0.98-0.99). Mortality was associated with a significantly lower odds of Escherichia coli on culture (odds ratio: 0.26; 95% confidence interval: 0.12-0.54). CONCLUSIONS: Independent associations were found between specific patient characteristics and adverse clinical outcomes.

Quality of life after robotic versus conventional minimally invasive cancer surgery: a systematic review and meta-analysis.

Optimizing postoperative quality of life (QoL) is an essential aspect of surgical oncology. Minimally invasive surgery (MIS) decreases surgical morbidity and improves QoL outcomes. This meta-analysis aimed to compare post-operative QoL after oncologic resections using different MIS modalities. The PubMed, Embase, Scopus, and CENTRAL databases were searched for articles that compared post-operative QoL in patients undergoing video-assisted thoracoscopic (VATS) or laparoscopic surgery (LS) versus robotic surgery (RS) for malignancy. Quality assessment was performed using the ROBINS-I and Cochrane Risk of Bias 2 (RoB-2) tools. Meta-analysis was performed using an inverse-variance random effects model. 27 studies met the inclusion criteria, including 5 randomized controlled trials (RCTs). 15 studies had a low risk of bias, while 11 had a moderate risk of bias and 1 had serious risk of bias. 8330 patients (RS: 5090, LS/VATS: 3240) from across 25 studies were included in the meta-analysis. Global QoL was significantly better after robotic surgery in the pooled analysis overall (SMD: - 0.28 [95% CI: - 0.49, - 0.08]), as well as in the prostatectomy and gastrectomy subgroups. GRADE certainty of evidence was low. Analysis of EPIC-26 subdomains also suggested greater sexual function after robotic versus laparoscopic prostatectomy. Robotic and conventional MIS approaches produce similar postoperative QoL after oncologic surgery for various tumor types, although advantages may emerge in some patient populations. Our results may assist surgeons in counseling patients who are undergoing oncologic surgery.

Real-world use of nirmatrelvir-ritonavir in COVID-19 outpatients during BQ.1, BQ.1.1., and XBB.1.5 predominant omicron variants in three U.S. health systems: a retrospective cohort study.

Background: Ritonavir-boosted Nirmatrelvir (NMV-r), a protease inhibitor with in vitro activity against SARS-CoV-2, can reduce risk of progression to severe COVID-19 among high-risk individuals infected with earlier variants, but less is known about its effectiveness against omicron variants BQ.1/BQ.1.1/XBB.1.5. We sought to evaluate effectiveness of NMV-r in BQ.1/BQ.1.1/XBB.1.5 omicron variants by comparing hospitalisation rates to NMV-r treated patients during a previous omicron phase and to contemporaneous untreated patients. Methods: We conducted a retrospective observational cohort study of non-hospitalised adult patients with SARS-CoV-2 infection using real-world data from three health systems in Colorado and Utah, and compared hospitalisation rates in NMV-r-treated patients in a BA.2/BA.2.12.1/BA.4/BA.5 variant-predominant (first) phase (April 3, 2022-November 12, 2022), with a BQ.1/BQ.1.1/XBB.1.5 variant-predominant (second) phase (November 13, 2022-March 7, 2023). In the primary analysis, we used Firth logistic regression with a two-segment (phase) linear time model, and pre-specified non-inferiority bounds for the mean change between segments. In a pre-specified secondary analysis, we inferred NMV-r effectiveness in a cohort of treated and untreated patients infected during the second phase. For both analyses, the primary outcome was 28-day all-cause hospitalisation. Subgroup analyses assessed treatment effect heterogeneity. Findings: In the primary analysis, 28-day all-cause hospitalisation rates in NMV-r treated patients in the second phase (n = 12,061) were non-inferior compared to the first phase (n = 25,075) (198 [1.6%] vs. 345 [1.4%], adjusted odds ratio (aOR): 0.76 [95% CI 0.54-1.06]), with consistent results among secondary endpoints and key subgroups. Secondary cohort analyses revealed additional evidence for NMV-r effectiveness, with reduced 28-day hospitalisation rates among treated patients compared to untreated patients during a BQ.1/BQ.1.1/XBB.1.5 predominant phase (198/12,061 [1.6%] vs. 376/10,031 [3.7%], aOR 0.34 [95% CI 0.30-0.38), findings robust to additional sensitivity analyses. Interpretation: Real-world evidence from major US healthcare systems suggests ongoing NMV-r effectiveness in preventing hospitalisation during a BQ.1/BQ.1.1/XBB.1.5-predominant phase in the U.S, supporting its continued use in similar patient populations. Funding: U.S. National Institutes of Health.

GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context.

INTRODUCTION: The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan. METHODS: We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context. RESULTS: The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves' Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management. CONCLUSION: Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients' finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.

Adolopment of clinical practice guidelines and creation of referral pathways for psychiatric conditions in Pakistan.

Psychiatric disorders are highly prevalent in Pakistan and burdens the scarce number of psychiatrists present in the country. The establishment of evidence-based clinical practice guidelines (EBCPGs) and primary-care referral pathways within the local context is imperative to make the process efficient. In this Health Policy, we aimed to develop EBCPGs and primary-care referral pathways that are specific to Pakistan's primary-care setting, with the aim of facilitating the management of psychiatric conditions. Ten EBCPGs were created through the GRADE-ADOLOPMENT process; two recommendations were adopted with minor changes, 43 were excluded, and all others were adopted without any changes. Ten primary-care referral pathways for managing ten psychiatric disorders were created and 23 recommendations were added which will help to bridge the gap in care provision. These psychiatric referral pathways and EBCPGs will bring Pakistan's healthcare system a step closer to achieving optimal health outcomes for patients.

Comparing redo surgery and stereotactic radiosurgery for recurrent, residual, and/or tumors showing progression in nonfunctioning pituitary adenomas: A systematic review and meta-analysis.

Background: Non-functioning pituitary adenomas (NFPAs) are well-differentiated benign tumors originating from the adenohypophyseal cells of the pituitary gland. They present with headaches, visual disorders, or cranial nerve deficits. NFPAs can recur, progress, or present as residual tumors. We, therefore, conducted this review to compare the effects of both revision surgery and stereotactic surgery on tumor size, visual status, endocrine status, and complications. Methods: A systematic review of published literature on recurrent, residual, or progressing NFPAs that underwent redo surgery or stereotactic radiosurgery from the inception till June 2020 was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirteen records (1209 patients) were included, and risk ratio (RR) and 95% confidence intervals (CIs) estimated from each study were pooled using a random-effects meta-analysis model. Results: Redo surgery was the preferred intervention in patients presenting with larger tumor sizes and was more effective in reducing the tumor size as compared to stereotactic radiosurgery (SRS) (risk ratio [RR] 56.14; 95% CI, 16.45-191.58). There was more visual loss with revision surgery as compared to SRS (risk ratio [RR] 0.08; 95% CI, 0.03-0.20). However, SRS was associated with fewer complications, such as new diabetes insipidus, as compared to the redo surgery (risk ratio [RR] 0.01; 95% CI 0.01-0.03). Conclusion: Redo surgery is the superior choice in the treatment of recurrent/residual or progressing NFPAs if the tumor size is large and an immediate reduction in tumor burden through debulking is warranted. However, redo surgery is associated with a higher risk of visual loss, new endocrinopathies, and other complications, in contrast to SRS.

Association between monoclonal antibody therapy, vaccination, and longer-term symptom resolution after acute COVID-19.

Effective therapies for reducing post-acute sequelae of COVID-19 (PASC) symptoms are lacking. Evaluate the association between monoclonal antibody (mAb) treatment or COVID-19 vaccination with symptom recovery in COVID-19 participants. The longitudinal survey-based cohort study was conducted from April 2021 to January 2022 across a multihospital Colorado health system. Adults ≥18 years with a positive SARS-CoV-2 test were included. Primary exposures were mAb treatment and COVID-19 vaccination. The primary outcome was time to symptom resolution after SARS-CoV-2 positive test date. The secondary outcome was hospitalization within 28 days of a positive SARS-CoV-2 test. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. COVID-19 vaccination, but not mAb therapy, was associated with a shorter time to symptom resolution. Both were associated with lower 28-day hospitalization.

Novel Journal Metrics in Cardiothoracic Surgery: How Different Are Contemporary Metrics From the Impact Factor?

OBJECTIVE: Despite shortcomings, impact factor (IF) remains the "gold standard" metric for journal quality. However, novel metrics including the h-index, g-index, and Altmetric Attention Score (AAS; mentions in mainstream/social media) are gaining traction. We assessed correlations between these metrics among cardiothoracic surgery journals. METHODS: For all cardiothoracic surgery journals with a 2021 Clarivate IF (N = 20), the 2-year IF (2019 to 2020) and 5-year IF (2016 to 2020), h-index, and g-index were obtained. Two-year journal-level AAS (2019 to 2020) was also calculated. Journal Twitter presence and activity was sourced from Twitter and the Twitter application programming interface. Correlations were assessed using Spearman correlation, and coefficients of determination were calculated. RESULTS: IF demonstrated a moderate-strong positive correlation with the h-index (rs = 0.48 to 0.77) and g-index (rs = 0.49 to 0.79) and a moderate correlation with AAS (rs = 0.53 to 0.58). The 2-year IF accounted for 25% to 49% of variability in the h-index, 27% to 55% of variability in the g-index, and 32% of variability in the AAS. Among journals with a Twitter account (N = 10), IF was strongly correlated with Twitter following (rs = 0.81 to 0.86), which was in turn strongly correlated with journal AAS (rs = 0.79). Article-level AAS was moderately correlated with citation count (rs = 0.47). CONCLUSIONS: IF accounted for only between 25% and 55% of variability in the h-index and g-index, indicating that these newer metrics measure unique dimensions of citation-based impact. Thus, the academic community must familiarize itself with these newer journal metrics. Social media attention may be associated with scholarly impact, although further work is needed to understand these relationships.

Factors associated with safe and successful postoperative day 1 discharge after lung operations: a systematic review and meta-analysis.

BACKGROUND: A shorter length of stay (LOS) is associated with fewer hospital-acquired adverse conditions and decreased utilization of hospital resources. While modern perioperative care protocols have enabled some ambitious surgical teams to achieve discharge as early as within postoperative day 1 (POD1), most other teams remain cautious about such an approach due to the perceived risk of missing postoperative complications and increased readmission rates. We aimed to identify factors that would help guide surgical teams aiming for safe and successful POD1 discharge after lung resection. METHODS: We searched the PubMed, Embase, Scopus, Web of Science and CENTRAL databases for articles comparing perioperative characteristics in patients discharged within POD1 (DWPOD1) and after POD1 (DAPOD1) following lung resection. Meta-analysis was performed using a random-effects model. RESULTS: We included eight retrospective cohort studies with a total of 216,887 patients, of which 22,250 (10.3%) patients were DWPOD1. Our meta-analysis showed that younger patients, those without cardiovascular and respiratory comorbidities, and those with better preoperative pulmonary function are more likely to qualify for DWPOD1. Certain operative factors, such as a minimally invasive approach, shorter operations, and sublobar resections, also favor DWPOD1. DWPOD1 appears to be safe, with comparable 30-day mortality and readmission rates, and significantly less postoperative morbidity than DAPOD1. CONCLUSIONS: In select patients with a favorable preoperative profile, DWPOD1 after lung resection can be achieved successfully and without increased risk of adverse outcomes such as postoperative morbidity, mortality, or readmissions.

Socio-demographic characteristics of children and young people with primary brain tumours: comparison between a public and private sector tertiary hospital in Karachi, Pakistan.

Primary brain tumours (PBTs) are the commonest solid tumours in children and young people (CYP). A study was conducted at a private and a public sector hospital in Karachi, Pakistan, to determine the socio-demographic and tumour-related characteristics of CYP with PBTs between those presenting to the public and private hospitals. A total of 49 patients were included. The commonest PBT was pilocytic astrocytoma (29%). There were no differences in tumour-related characteristics between the two groups. However, parents of CYP with PBTs presenting to the public sector hospital were significantly less educated and had lower household incomes. No significant differences in age, gender, educational status, and ethnicity of CYP with PBTs were observed. Since CYP with PBTs presenting at the public sector hospital were from significantly lower socioeconomic backgrounds and their parents were less educated, it suggests socio-economic disparities in PBT care for CYPs in Karachi, Pakistan.

Effectiveness of subcutaneous monoclonal antibody treatment in emergency department outpatients with COVID-19.

Objectives: To evaluate whether subcutaneous neutralizing monoclonal antibody (mAb) treatment given in the emergency department (ED) setting was associated with reduced hospitalizations, mortality, and severity of disease when compared to nontreatment among mAb-eligible patients with coronavirus disease 2019 (COVID-19). Methods: This retrospective observational cohort study of ED patients utilized a propensity score-matched analysis to compare patients who received subcutaneous casirivimab and imdevimab mAb to nontreated COVID-19 control patients in November-December 2021. The primary outcome was all-cause hospitalization within 28 days, and secondary outcomes were 90-day hospitalization, 28- and 90-day mortality, and ED length of stay (LOS). Results: Of 1340 patients included in the analysis, 490 received subcutaneous casirivimab and imdevimab, and 850 did not received them. There was no difference observed for 28-day hospitalization (8.4% vs. 10.6%; adjusted odds ratio [aOR] 0.79, 95% confidence intervals [CI] 0.53-1.17) or 90-day hospitalization (11.6% vs. 12.5%; aOR 0.93, 95% CI 0.65-1.31). However, mortality at both the 28-day and 90-day timepoints was substantially lower in the treated group (28-day 0.6% vs. 3.1%; aOR 0.18, 95% CI 0.08-0.41; 90-day 0.6% vs. 3.9%; aOR 0.14, 95% CI 0.06-0.36). Among hospitalized patients, treated patients had shorter hospital LOS (5.7 vs. 11.4 days; adjusted rate ratio [aRR] 0.47, 95% CI 0.33-0.69), shorter intensive care unit LOS (3.8 vs. 10.2 days; aRR 0.22, 95% CI 0.14-0.35), and the severity of hospitalization was lower (aOR 0.45, 95% CI 0.21-0.97) compared to untreated. Conclusions: Among ED patients who presented for symptomatic COVID-19 during the Delta variant phase, ED subcutaneous casirivimab/imdevimab treatment was not associated with a decrease in hospitalizations. However, treatment was associated with lower mortality at 28 and 90 days, hospital LOS, and overall severity of illness.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Bailout Surgery for Difficult Gallbladders: Surgical Approach and Outcomes.

INTRODUCTION: Inflammation in acute cholecystitis may cause a cholecystectomy to be more challenging. Due to the difficult dissection, conversion to subtotal cholecystectomy via laparoscopic or open procedure may be required. This is done to reduce the risk of bile duct injury and hemorrhage. We sought to describe the incidence and risk factors, safety, morbidity, and outcomes associated with bailout procedures. METHODS: A single academic center, retrospective review of laparoscopic cholecystectomies that resulted in bailout procedures performed between January 2015 and December 2020. Data collected from the chart review included demographics, comorbidities, length of presenting symptoms, vital signs, laboratory and imaging, intraoperative findings, length of surgery, and outcome. RESULTS: A total of 1892 cholecystectomies were performed with 147 bailout procedures. For bailout 92 (63.4%) were converted to open, with 66% resulting in complete cholecystectomy. Hypertension and diabetes were the most common comorbidities. The median duration of symptoms was 4 days. Difficult anatomy in the hepatocystic triangle (66%) and dense adhesions (31%) were the most common reasons for bailout. The mean duration of surgery was 145.76 (SD 102.94) minutes. There were 2 bile duct injuries, both in open total cholecystectomy subgroup. Bile leak occurred in 23.8% with majority in subtotal cholecystectomy group. There was no difference in hospital length of stay, surgical site infection, or mortality among different bailout procedures. CONCLUSIONS: Subtotal cholecystectomy represents a safe alternative to total cholecystectomy during challenging cases to avoid damaging surrounding structures. The choice of laparoscopic or open subtotal approach is dependent on the surgeons' expertise.

Neoadjuvant vs Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer.

BACKGROUND: In patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant vs adjuvant chemoimmunotherapy for resectable stage II-IIIB NSCLC. METHODS: We queried the National Cancer Database for patients who had undergone an operation for stage II-IIIB NSCLC and who had received neoadjuvant or adjuvant chemoimmunotherapy between 2015 and 2020. We used inverse probability weighting to adjust for confounding variables and used Kaplan-Meier survival curves and Cox regression to explore the relationship between treatment groups and overall survival (OS) at 3 years postoperatively. RESULTS: The inverse probability-weighted cohort represented 2119 weighted patient cases (neoadjuvant, 1034; adjuvant, 1085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared with adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [95% CI, 71%-83%] vs 68% [95% CI, 64%-72%]; P = .035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (hazard ratio, 0.70; 95% CI, 0.50-0.96; P = .027). Among patients for whom pathologic stage data were available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. CONCLUSIONS: Neoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable stage II-IIIB NSCLC. Although randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.

Hospital Resources and Practice Patterns for Congenital Cardiac Surgery in Pakistan: A Nationwide Status Report.

Objective: Low- and middle-income countries such as Pakistan bear the brunt of the global burden of congenital heart disease (CHD), This nationwide study assessed hospital resources and surgical practice patterns pertaining to CHD surgery across Pakistan. Methods: A nationwide hospital facility survey was conducted, targeting all health centers performing CHD surgery in Pakistan. Descriptive data analysis was performed, with categorical variables being presented as frequencies and percentages and continuous variables being reported as means and standard deviations. Results: Seventeen surgeons across 17 different centers participated in the study. Eight of 17 (47%) surgeons were under 45 years of age, while the rest were older than 45 years. More respondents were employed at public/government-owned hospitals (11/17, 65%) and at specialized cardiac centers (13/17, 76%), with a majority of centers reported as having a special ICU designated for congenital cardiac patients (11/17, 65%). With regard to operative volume, 7 of 17 (41%) centers reported more than 350 cases per year, with 7 of 17 reported >10 neonatal cases per year (6/12, 50%). Only one center reported national and international collaborations for research, most centers carrying out less than five research projects in a year. Conclusion: This study has identified key areas that require the attention of local administrative bodies as well as international organizations and societies. The existing centers in Pakistan are unable to meet the demands of the population, leaving a large number of untreated patients, especially for neonatal lesions.