Think Globally, Adapt Locally: The ISCCM Guidelines and Position Statements.

How to cite this article: Myatra SN, Peter JV, Juneja D, Kulkarni AP. Think Globally, Adapt Locally: The ISCCM Guidelines and Position Statements. Indian J Crit Care Med 2024;28(S2):S1-S3.

ISCCM Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis.

Tuberculosis (TB) is an important cause of morbidity and mortality globally. About 3-4% of hospitalized TB patients require admission to the intensive care unit (ICU); the mortality in these patients is around 50-60%. There is limited literature on the evaluation and management of patients with TB who required ICU admission. The Indian Society of Critical Care Medicine (ISCCM) constituted a working group to develop a position paper that provides recommendations on the various aspects of TB in the ICU setting based on available evidence. Seven domains were identified including the categorization of TB in the critically ill, diagnostic workup, drug therapy, TB in the immunocompromised host, organ support, infection control, and post-TB sequelae. Forty-one questions pertaining to these domains were identified and evidence-based position statements were generated, where available, keeping in focus the critical care aspects. Where evidence was not available, the recommendations were based on consensus. This position paper guides the approach to and management of critically ill patients with TB. How to cite this article: Chacko B, Chaudhry D, Peter JV, Khilnani G, Saxena P, Sehgal IS, et al. isccm Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2024;28(S2):S67-S91.

Mild dehydration does not alter acute changes in sweat electrolyte concentrations during exercise.

The purpose of this study was to determine the effect of hydration status on the change in sweat sodium (Na+), chloride (Cl-), and potassium (K+) concentrations during exercise-heat stress. Fifteen subjects (Six female, nine male; 29 ± 9 y; 71 ± 14 kg) completed 90 min of cycling (81% HRmax) in the heat (~33°C, 42% rh) with fluid replacement to maintain euhydration (EUH) or without fluid to dehydrate to 2.4 ± 0.4% body mass loss (DEH). Sweat was collected from the forehead (FH), right scapula (SCAP), and left (LVFA) and right (RVFA) ventral forearms using the absorbent pad technique at the beginning (0-30 min) and end of exercise (60-90 min). Sweat was analyzed for Na+, Cl-, and K+ concentrations using ion chromatography. Data are reported as mean ± SD or median ± IQR. There were no differences (Paired t-tests or Wilcoxon signed-rank tests) between EUH and DEH in the change in sweat Na+ (FH: 24.3 ± 21.5 vs. 30.8 ± 22.4 mmol/L; SCAP: 9.7 ± 6.2 vs. 9.6 ± 8.2 mmol/L; LVFA: 7.5 ± 6.0 vs. 5.6 ± 5.9 mmol/L; RVFA: 8.2 ± 8.6 vs. 7.8 ± 5.2 mmol/L), sweat Cl-, or sweat K+ at any site (p = 0.07-0.99). The change in sweat electrolyte concentrations during 90 min of exercise in the heat was not significantly influenced by mild dehydration in recreational to moderately-trained male and female athletes.

Visual Performance of People With Albinism Assessed With Generalizable and Adaptive AIM and FInD Methods.

Purpose: People with albinism (PwA) are known to have visual impairments; however, little is known about whether these functions are disrupted across earlier and later stages of the visual pathway. We investigated distinct perceptual functions and fixation stability within each observer and compared the data with age- (±5 years) and sex-matched controls. Methods: Twenty-one self-reported PwA and twenty-one controls were recruited. Angular-indication measurement (AIM) and foraging-interactive-D-prime (FInD) psychophysical methods were deployed to measure OS, OD, and OU near visual acuity, spatial contrast sensitivity function (CSF), temporal contrast sensitivity (tCS; 0.5 c/°; horizontal grating: 0, 1, 2, 4, and 8 Hz), OU glare acuity, threshold-versus-contrast (2c/° vertical grating), long, medium, and short wavelength cone-isolated color detection, color discrimination, stereoacuity across spatial frequencies (1c/°, 2c/°, 4c/°, 8c/°), horizontal, circular, radial pattern and motion coherence, and equivalent-noise motion detection. Thresholds were determined by AIM and FInD and compared using N-ANOVAs, t-tests, planned multi-comparisons, correlations, and unsupervised, agglomerative hierarchical cluster analysis for each group. Results: We found significant differences between groups for most visual functions except for simple and complex form-coherence (two way-ANOVAs, P > 0.05) and complex motion coherence. Correlations between outcomes revealed more significant correlations for PwA and differences in the specific correlates between groups. Unsupervised hierarchical clustering revealed different functional clusters between groups. Conclusions: AIM and FInD successfully interrogated visual deficits in PwA. Overall, PwA showed impaired performance in achromatic, chromatic, temporal, and binocular functions, and had higher intrinsic noise levels. Midlevel vision was comparable between groups. Unsupervised cluster analysis and correlation between outcomes revealed a difference in functional outcome clusters between groups. The results may help to increase the efficiency of screening and identify target deficits for rehabilitation.

A new, adaptive, self-administered, and generalizable method used to measure visual acuity.

SIGNIFICANCE: Angular Indication Measurement (AIM) is an adaptive, self-administered, and generalizable orientation-judgment method designed to interrogate visual functions. We introduce AIM Visual Acuity (VA) and show its features and outcome measures. Angular Indication Measurement VA's ability to detect defocus was comparable with that of an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter chart and showed greater sensitivity to astigmatic blur. PURPOSE: This proof-of-concept study introduces Angular Indication Measurement and applies it to VA. METHODS: First, we compared the ability of AIM-VA and ETDRS to detect defocus and astigmatic blur in 22 normally sighted adults. Spherical and cylindrical lenses in the dominant eye induced blur. Second, we compared repeatability over two tests of AIM-VA and ETDRS. RESULTS: A repeated-measure analysis of variance showed a main effect for defocus blur and test. For the astigmatism experiment, an interaction between blur and orientation was found. Pairwise comparisons showed that AIM was more sensitive to astigmatic-induced VA loss than ETDRS. Bland-Altman plots showed small bias and no systematic learning effect for either test type and improved repeatability with more than two adaptive steps for AIM-VA. CONCLUSIONS: Angular Indication Measurement VA's ability to detect defocus was comparable with that of an ETDRS letter chart and showed greater sensitivity to induced astigmatic blur, and AIM-VA's repeatability is comparable with ETDRS when using two or more adaptive steps. Angular Indication Measurement's self-administered orientation judgment approach is generalizable to interrogate other visual functions, e.g., contrast, color, motion, and stereovision.

Incidence and Risk Factors for Deep Venous Thrombosis and Its Impact on Outcome in Patients Admitted to Medical Critical Care.

Objectives: This study evaluated the incidence and risk factors for deep venous thrombosis (DVT) while on thromboprophylaxis, in patients admitted to the medical intensive care unit (MICU), and to assess its impact on outcomes. Methods: Consecutive patients admitted to the MICU underwent compression ultrasound of the jugular, axillary, femoral, and popliteal veins at admission, day 3 and 7 to screen for DVT. All patients were on pharmacological and/or mechanical thromboprophylaxis as per protocol. The primary outcome was the incidence of DVT (defined as occurrence on day 3 or 7). Secondary outcomes were death and duration of hospitalization. Risk factors for DVT were explored using bivariate and multivariable logistic regression analysis and expressed as risk ratio (RR) with 95% confidence intervals (CIs). Results: The incidence of DVT was 17.2% (95% CI 12.0, 22.3) (n = 35/203); two-thirds were catheter associated (23/35). There was no difference in mortality between those with and without incident DVT (9/35 vs 40/168, p = 0.81). The mean (SD) duration of hospitalization was longer in the DVT group (20.1 (17) vs 12.9 (8.5) days, p = 0.007). Although day 3 INR (RR 2.1, 95% CI 0.9-5.3), age >40 years (2.1, 0.8-5.3), vasopressor use (1.0, 0.4-2.9) and SOFA score (0.9, 0.85-1.1) were associated with the development of DVT on bivariate analysis, only central venous catheters (15.97, 1.9-135.8) was independently associated with DVT on multivariable analysis. Conclusions: Despite thromboprophylaxis, 17% of ICU patients develop DVT. The central venous catheter is the main risk factor. DVT is not associated with increased mortality in the setting of prophylaxis. How to cite this article: Krishnamoorthy A, Hansdak SG, Peter JV, Pichamuthu K, Rajan SJ, Sudarsan TI, et al. Incidence and Risk Factors for Deep Venous Thrombosis and Its Impact on Outcome in Patients Admitted to Medical Critical Care. Indian J Crit Care Med 2024;28(6):607-613.

Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis.

OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

Real-world evidence study on the early use of cemiplimab in the UK: REACT-CEMI (Real World evidence of advanced CSCC treatment with cemiplimab).

Background: Cemiplimab was licensed in the United Kingdom (UK) in 2019 for the treatment of patients with locally advanced and metastatic CSCC not suitable for curative surgery or radiotherapy (advanced CSCC [aCSCC]). No UK multi-center studies have investigated the real-world experience of cemiplimab post marketing authorization in aCSCC. Methods: This non-interventional retrospective study (10 UK centers) involved data collection from medical records of patients with aCSCC who initiated cemiplimab treatment between 2 July 2019 and 30 November 2020. The study period was a minimum of 12 and a maximum of 36 months post cemiplimab initiation. The primary objective was to describe the real-world clinical effectiveness of cemiplimab (primary outcome: overall response rate [ORR]). Results: Of 105 patients, 70% (n=73/105) were male (median [range] age at index of 78.5 [55.4-93.2] years); most patients (63% [n=50/80]) had an Eastern Cooperative Oncology Group (ECOG) score of 1 and 62% (n=63/102) had metastatic disease. The ORR within 12 months was 42% (95% confidence interval [CI] 32%-51%) and the disease control rate was 62% (n=65/105). The median (95% CI) real-world progression-free survival and overall survival from index was 8.6 (6.0-18.7) and 21.0 (14.7-25.2) months, respectively. The median (range) number of cemiplimab infusions was 11.0 (1.0-44.0). Eighty-seven percent experienced no cemiplimab treatment interruptions; 13% (n=14/105) interrupted treatment due to immune-related adverse reactions (irARs) (47% [n=9/19] of treatment interruption events). Eighty-five percent (n=89/105) of patients had discontinued cemiplimab treatment by the end of the study; where reasons for discontinuation were recorded, 20% (n=17/87) discontinued due to the completion of their 2-year treatment course. Nineteen percent (n=20/105) of patients experienced irARs. Conclusion: Effectiveness and safety data in this study are broadly similar to previous real-world studies of cemiplimab and the EMPOWER-CSCC1 clinical trial; with our cohort representing a broader population (included immunocompromised and transplant patients). Results support the use of cemiplimab for the treatment of aCSCC in a real-world setting.

A systematic review of cognitive and behavioral tools to differentiate behavioral variant frontotemporal dementia from other conditions.

The behavioral variant of frontotemporal dementia (bvFTD) is thought to be the commonest clinical presentation of frontotemporal lobar degeneration and is predominantly characterized by changes in behavior. In patients lacking unequivocal biomarker evidence of frontotemporal neurodegeneration, the clinical diagnosis of bvFTD is often unstable. In response, we conducted a systematic review and critical appraisal of cognitive and behavioral tools that have sought to differentiate bvFTD from other conditions. A systematic literature review of PubMed, Scopus, and Web of Science was conducted on December 31, 2023 for cognitive and behavioral tools that differentiated bvFTD from other cohorts. Ninety-six studies were included. The quality appraisal of almost all studies was low and introduced a high risk of bias. The few studies that were of high quality had a prospective study design and recruited patients suspected (but not yet confirmed) to have bvFTD. These studies reported that behavioral tools (e.g., the Frontal Behavioral Inventory) and social cognition tests (e.g., the Ekman's Faces Test) had good test performance in differentiating bvFTD from a broad range of psychiatric and neurological conditions. Importantly, the review highlighted the extreme paucity of studies that have evaluated methods where, in Bayesian terms, there is genuine clinical uncertainty regarding a diagnosis of bvFTD. Most studies used healthy controls of typical Alzheimer's disease as comparators-groups that often have negligible pretest probability of bvFTD. In response, we propose a study design checklist for studies seeking to develop diagnostic algorithms in bvFTD research.

Explainable text-tabular models for predicting mortality risk in companion animals.

As interest in using machine learning models to support clinical decision-making increases, explainability is an unequivocal priority for clinicians, researchers and regulators to comprehend and trust their results. With many clinical datasets containing a range of modalities, from the free-text of clinician notes to structured tabular data entries, there is a need for frameworks capable of providing comprehensive explanation values across diverse modalities. Here, we present a multimodal masking framework to extend the reach of SHapley Additive exPlanations (SHAP) to text and tabular datasets to identify risk factors for companion animal mortality in first-opinion veterinary electronic health records (EHRs) from across the United Kingdom. The framework is designed to treat each modality consistently, ensuring uniform and consistent treatment of features and thereby fostering predictability in unimodal and multimodal contexts. We present five multimodality approaches, with the best-performing method utilising PetBERT, a language model pre-trained on a veterinary dataset. Utilising our framework, we shed light for the first time on the reasons each model makes its decision and identify the inclination of PetBERT towards a more pronounced engagement with free-text narratives compared to BERT-base's predominant emphasis on tabular data. The investigation also explores the important features on a more granular level, identifying distinct words and phrases that substantially influenced an animal's life status prediction. PetBERT showcased a heightened ability to grasp phrases associated with veterinary clinical nomenclature, signalling the productivity of additional pre-training of language models.

Successful Embolization of a Direct Carotid Cavernous Fistula under Gadolinium-Based Angiography.

Endovascular neurointervention is typically performed with iodinated contrast medium (ICM) under fluoroscopy. However, some patients may be contraindicated to such procedures based on their sensitivity to ICM. In this report, we describe a case of successful coil embolization of a direct carotid cavernous fistula using angiography with gadolinium-based contrast agents in a patient with severe allergic reaction to ICM. The clinical decision-making for this patient was further complicated by comorbidities of renal impairment, drug allergies, and previously severe gastrointestinal bleeding.

Cost-effectiveness of craniotomy versus decompressive craniectomy for UK patients with traumatic acute subdural haematoma.

OBJECTIVE: To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH). DESIGN: Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial. SETTING: UK secondary care. PARTICIPANTS: 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122). INTERVENTIONS: Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery). MAIN OUTCOME MEASURES: In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists. RESULTS: In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be -£5520 (95% CI -£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be -£4536 (95% CI -£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE. CONCLUSIONS: In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant). ETHICS: Ethical approval for the trial was obtained from the North West-Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076). TRIAL REGISTRATION NUMBER: ISRCTN87370545.

A comparison between full-length 16S rRNA Oxford nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues.

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing.

No effect of tattoos on local sweat concentrations of select cytokines, cortisol, glucose, blood urea nitrogen, or lactate during exercise.

Due to growing interest in the investigation of exercise induced sweat biomarkers to assess an individual's health and the increasing prevalence of tattoos in the world's population, investigators sought to determine whether local sweat concentrations and excretion rates of epidermal growth factor (EGF), interleukin (IL) -1α, IL-6, IL-8, cortisol, glucose, blood urea nitrogen (BUN), and lactate differ between tattooed and contralateral non-tattooed skin during exercise. Sixteen recreational exercisers [female (50%)] (age = 25-48 years) with ≥ 1 unilateral permanent tattoo [median tattoo age = 6 years, IQR = 5] on the arm/torso completed an outdoor group fitness session. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate concentrations. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate excretion rate. Findings suggest that permanent tattoos older than 1 year may not impact local sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, and lactate concentrations or excretion rates during exercise.Clinical trial identifier NCT04920266 was registered on June 9, 2021.

Increased antibiotic resistance of Pseudomonas aeruginosa isolates from chronic rhinosinusitis patients grown in anaerobic conditions.

Introduction: In chronic rhinosinusitis (CRS), the congestion and blockage of the nose can cause anaerobic conditions within the sinus cavities which may promote the expression of virulence and antibiotic resistance genes in invading pathogens. Pseudomonas aeruginosa is a facultative anaerobic bacteria and causes severe recalcitrant CRS. In this study, we aimed to evaluate the antimicrobial resistance of P. aeruginosa isolates of CRS patients in planktonic and biofilm form grown in aerobic and anaerobic conditions. Methods: P. aeruginosa clinical isolates of CRS patients (n = 25) were grown in planktonic and biofilm form in aerobic and anaerobic conditions. Minimum inhibitory concentrations (MIC) of planktonic forms and minimum biofilm eradication concentrations (MBEC) were determined. Additionally, metabolic activity by fluorescein diacetate assay, biofilm biomass by crystal violet assay and eDNA concentration were assessed in both conditions. Results: P. aeruginosa planktonic cells grown in anaerobic condition exhibited increased gentamicin resistance (p < .01), whereas P. aeruginosa biofilms grown in anaerobic condition displayed significantly increased MBEC values for gentamicin (p < .0001) and levofloxacin (p < .001). The metabolic activity of anaerobic biofilms was significantly higher compared with aerobic biofilms (p < .0001). However, the biofilm biomass of isolates grown in aerobic conditions was higher than anaerobic conditions (p < .5). Conclusion: P. aeruginosa isolates from CRS patients grown in anaerobic conditions showed significantly increased resistance to antibiotics with an increased metabolic activity but decreased biofilm biomass. Level of Evidence: NA.

Developing a selective culturing approach for Campylobacter hepaticus.

Campylobacter hepaticus, the causative agent of Spotty Liver Disease (SLD) is an important disease in cage-free egg producing chickens causing mortality and production drops. C. hepaticus is a slow growing Campylobacter easily overgrown by fecal bacteria. It is currently only reliably isolatable from bile samples. A selective media for isolation from feces or environment would assist diagnosis and impact assessment. Growth of five Australian C. hepaticus isolates was studied using Horse blood agar (HBA), sheep blood agar (SBA), Bolton, Preston and Brain Heart Infusion (BHI) base media. Blood and/or bile were added to Bolton, Preston and BHI medias. C. jejuni was used as a positive control. Plates were incubated in duplicate under microaerophilic conditions at 42°C for 10 days and examined at days 3-5 and 7-10 of incubation. Each isolate was examined for sensitivity to 14 antimicrobials using HBA sensitivity plates. Growth was inhibited by BHI and by added bile, while blood improved growth. Further replicates using SBA, HBA, Bolton and Preston media showed best growth on Bolton agar with blood. All five C. hepaticus isolates were resistant to trimethoprim and vancomycin, while four were also resistant to rifampicin and bacitracin. Media based upon Bolton plus blood supplemented with vancomycin and trimethoprim might be used as the most appropriate media for selective growth of C. hepaticus. The addition of bile to media for C. hepaticus isolation and growth will inhibit growth and is not advised.

Pilot Validation of a 3-Dimensional Printed Pituitary Adenoma, Vascular Injury, and Cerebrospinal Fluid Leak Surgical Simulator.

BACKGROUND AND OBJECTIVES: Endoscopic skull base surgery is a subspecialty field which would benefit significantly from high-fidelity surgical simulators. Giving trainees the opportunity to flatten their learning curve by practicing a variety of procedures on surgical simulators will inevitably improve patient outcomes. METHODS: Four neurosurgeons, 8 otolarynologists, and 6 expert course faculty agreed to participate. All participants were asked to perform a transsphenoidal exposure and resection of a pituitary adenoma, repair a cerebrospinal fluid (CSF) leak, control a carotid injury, and repair a skull base defect. The content, face, and construct validity of the 3-dimensional printed model was examined. RESULTS: The heart rate of the participants significantly increased from baseline when starting the carotid injury simulation (mean 90 vs 121, P = .029) and significantly decreased once the injury was controlled (mean 121 vs 110, P = .033, respectively). The participants reported a significant improvement in anxiety in facing a major vascular injury, as well as an increase in their confidence in management of major vascular injury, resecting a pituitary adenoma and repair of a CSF leak using a 5-point Likert scale (mean 4.42 vs 3.58 P = .05, 2 vs 3.25 P < .001, 2.36 vs 4.27 P < .001 and 2.45 vs 4.0 P = .001, respectively). The mean Objective Structured Assessment of Technical Skills score for experienced stations was 4.4, significantly higher than the Objective Structured Assessment of Technical Skills score for inexperienced stations (mean 3.65, P = .016). CONCLUSION: We have demonstrated for the first time a validated 3-dimensional printed surgical simulator for endoscopic pituitary surgery that allows surgeons to practice a transsphenoidal approach, surgical resection of a pituitary adenoma, repair of a CSF leak in the diaphragma sellae, control of a carotid injury, and repair of skull base defect.

Challenges and patient outcomes in chronic subdural haematoma at the level of a regional care system A multi-centre, mixed-methods study from the East of England.

BACKGROUND: Chronic subdural haematoma (cSDH) is a common neurosurgical pathology affecting older patients with other health conditions. A significant proportion (up-to 90%) of referrals for surgery in neurosciences units (NSU) come from secondary care. However, the organisation of this care and the experience of patients repatriated to non-specialist centres are currently unclear. OBJECTIVES: This study aimed to clarify patient outcome in non-specialist centres following NSU discharge for cSDH surgery and to understand key system challenges. The study was set within a representative neurosurgical care system in the east of England. DESIGN AND METHODS: We performed a retrospective cohort analysis of patients referred for cSDH surgery. Alongside case record review, patient and staff experience were explored using surveys as well as an interactive c-design workshop. Challenges were identified from thematic analysis of survey responses and triangulated by focussed workshop discussions. RESULTS: Data on 381 patients referred for cSDH surgery from six centres was reviewed. One hundred and fifty-six (41%) patients were repatriated following surgery. Sixty-one (39%) of those repatriated suffered an inpatient complication (new infection, troponin rise or renal injury) following NSU discharge, with 58 requiring institutional discharge or new care. Surveys for staff (n = 42) and patients (n = 209) identified that resourcing, communication, and inter-hospital distance posed care challenges. This was corroborated through workshop discussions with stakeholders from two institutions. CONCLUSIONS: A significant amount of perioperative care for cSDH is delivered outside of specialist centres. Future improvement initiatives must recognise the system-wide nature of delivery and the challenges such an arrangement presents.

S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis.

Staphylococcus aureus mucosal biofilms are associated with recalcitrant chronic rhinosinusitis (CRS). However, S. aureus colonisation of sinus mucosa is frequent in the absence of mucosal inflammation. This questions the relevance of S. aureus biofilms in CRS etiopathogenesis. This study aimed to investigate whether strain-level variation in in vitro-grown S. aureus biofilm properties relates to CRS disease severity, in vitro toxicity, and immune B cell responses in sinonasal tissue from CRS patients and non-CRS controls. S. aureus clinical isolates, tissue samples, and matched clinical datasets were collected from CRS patients with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. B cell responses in tissue samples were characterised by FACS. S. aureus biofilms were established in vitro, followed by measuring their properties of metabolic activity, biomass, colony-forming units, and exoprotein production. S. aureus virulence was evaluated using whole-genome sequencing, mass spectrometry and application of S. aureus biofilm exoproteins to air-liquid interface cultures of primary human nasal epithelial cells (HNEC-ALI). In vitro S. aureus biofilm properties were correlated with increased CRS severity scores, infiltration of antibody-secreting cells and loss of regulatory B cells in tissue samples. Biofilm exoproteins from S. aureus with high biofilm metabolic activity had enriched virulence genes and proteins, and negatively affected the barrier function of HNEC-ALI cultures. These findings support the notion of strain-level variation in S. aureus biofilms to be critical in the pathophysiology of CRS.

Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study.

INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.