Intraoperative Aberrometry versus Preoperative Biometry for Intraocular Lens Power Calculations: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the published literature to compare intraoperative aberrometry (IA) with preoperative biometry-based formulas with respect to intraocular lens (IOL) power calculation accuracy for various clinical scenarios. METHODS: Literature searches in the PubMed database conducted in August 2022, July 2023, and February 2024 identified 157, 18, and 6 citations, respectively. These were reviewed in abstract form, and 61 articles were selected for full-text review. Of these, 29 met the criteria for inclusion in this assessment. The panel methodologists assigned a level of evidence rating to each of the articles; 4 were rated level I, 19 were rated level II, and 6 were rated level III. RESULTS: Intraoperative aberrometry performed better than traditional vergence formulas, including the Haigis, HofferQ, Holladay, and SRK/T, and similarly to the Barrett Universal II and Hill-RBF with respect to minimization of spherical equivalent (SE) refractive error. For toric IOLs, IA outperformed formulas that only considered anterior corneal astigmatism and was similar to formulas like the Barrett Toric Calculator (BTC), which empirically account for the contribution from the posterior cornea. In eyes with a history of corneal refractive surgery, IA performed similarly to the Barrett True-K and slightly better than other tested methods, including the Haigis-L, Shammas, and Wang-Koch-Maloney formulas. CONCLUSIONS: Intraoperative aberrometry corresponds well with modern vergence formulas, including the Barrett Universal II, Hill-RBF, BTC, and Barrett True-K. It has greater accuracy than traditional vergence-based IOL power calculation formulas in eyes with and without a history of corneal refractive surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Addressing Mental Health in Rural Settings: A Narrative Review of Blueberry Supplementation as a Natural Intervention.

Depression and anxiety are major public health issues; however, there is an unmet need for novel, effective, and accessible treatments, particularly in rural communities. Blueberries are an unexplored nutraceutical for these conditions due to their excellent nutritional profile, with particularly high levels of polyphenols and anthocyanins and benefits on mood, cognition, and health. Here, we present a narrative review of the literature concerning the etiology and treatments of major depressive disorder (MDD) and generalized anxiety disorder (GAD). In both animal and human studies, blueberry supplementation can ameliorate behavioral symptoms of both anxiety and depression. The mechanistic underpinnings of these behavioral improvements are not fully defined, but likely involve biochemical alterations in the gut-brain axis, including to inflammatory cytokines, reactive oxygen species, and growth factors. We also review the limitations of traditional therapies in rural settings. Finally, we assess the potential benefit of nutraceutical interventions, particularly blueberries, as novel therapeutics for these distinct, yet related mental health issues.

Morphologic Stages of Full-Thickness Macular Hole on Spectral Domain Optical Coherence Tomography.

OBJECTIVE: To describe the sequential morphological changes of the outer retina after full-thickness macular hole formation, utilizing a novel, objective staging system based on optical coherence tomography (OCT), and to determine its association with baseline visual acuity, duration of symptoms, and postoperative visual acuity at 3 months. DESIGN: Retrospective, observational, multicenter study. PARTICIPANTS: Patients with idiopathic full-thickness macular hole (FTMH) presenting to St. Michael's Hospital, Toronto, Canada, and Retina Consultants of Texas, Houston, USA, from 2009-2022. METHODS: The medical charts of 1000 patients with FTMH were reviewed and those with at least two preoperative SD-OCTs were analyzed. A staging system was developed by assessing outer retinal morphology on successive SD-OCT central foveal scans. MAIN OUTCOME MEASURES: Sequential outer retinal morphological changes with SD-OCT over time and their association with baseline visual acuity, duration of symptoms, and postoperative functional outcomes. RESULTS: Fifty-two eyes of 52 patients with a mean age of 65.4 ±8.4 years were included. Sequential outer retinal morphologic changes at the FTMH borders occurred in 4 distinct and reproducible stages as follows: Stage A: separation of the neurosensory retina from the RPE with the well-defined external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IDZ) (4/52, 7.6%); Stage B: thickening of EZ (27/52, 51.9%); Stage C: patchy (moth-eaten) photoreceptor loss (16/52, 30.7%) and Stage D: severe or complete loss of ISs and OSs and/or bare ELM (5/52, 9.6%). When assessing the preoperative OCT scans closest to the time of surgery, over a mean follow-up period of 288.9 days (SD 350.4,[5 -1841]), 28.8%(15/52 ) of eyes were in Stage B, 28.8% (15/52) were in Stage C and 42.3 %(22/52 ) were in Stage D. There was a statistically significant association between increasing stage at baseline and longer duration of macular hole symptoms (p=0.032) and worse visual acuity at baseline (p<0.001). Additionally, patients presenting with Stages B and C at the time point closest to surgery had better visual acuity outcomes three months postoperatively compared to those with Stage D(P=0.04). CONCLUSIONS: This SD-OCT staging system describes the sequential in vivo morphologic changes after FTMH formation providing a novel imaging biomarker.

Outcomes Following Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus at 10-Year Follow-Up: A Retrospective Review.

OBJECTIVE: The purpose of this study was to evaluate outcomes following autologous osteochondral transplantation (AOT) for the treatment of osteochondral lesions of the talus (OLT) at a minimum of 10-year follow-up. DESIGN: Retrospective chart review identified patients who underwent AOT for the treatment of OLT. Pre-operative magnetic resonance imaging (MRI) scans were obtained in all patients. Clinical outcomes assessed included: pre- and post-operative foot and ankle outcome score (FAOS), visual analog scale (VAS), patient satisfaction, complications, failures and secondary surgical procedures. RESULTS: Thirty-nine patients with a mean lesion size was 122.3 ± 64.1 mm2 and mean follow-up time of 138.9 ± 16.9 months were included. The mean FAOS scores improved from a preoperative score of 51.9 ± 16.0 to 75.3 ± 21.9 (P < 0.001). Increasing lesion size was variable associated with inferior FAOS scores (R2 = 0.2228). There was statistically significant higher mean T2 relaxation values at the superficial layer at the site of the AOT graft (42.9 ± 5.2 ms) compared to the superficial layer of the adjacent native cartilage (35.8 ± 3.8 ms) (P < 0.001). Seventeen complications (43.6%) were observed, the most common of which was anterior ankle impingement (25.6%). There were 2 failures (5.1%), both of which had a history of prior bone marrow stimulation via microfracture and post-operative cysts identified on MRI. CONCLUSION: This retrospective review found that AOT for the treatment of large OLTs produced a 94.9% survival rate at a minimum of 10-year follow-up. Increasing lesion size was associated with inferior clinical outcomes. The findings of this study indicates that AOT is a viable long-term surgical strategy for the treatment of large OLTs.

Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan.

Current genome-wide association studies (GWAS) for kidney function lack ancestral diversity, limiting the applicability to broader populations. The East-Asian population is especially under-represented, despite having the highest global burden of end-stage kidney disease. We conducted a meta-analysis of multiple GWASs (n = 244,952) on estimated glomerular filtration rate and a replication dataset (n = 27,058) from Taiwan and Japan. This study identified 111 lead SNPs in 97 genomic risk loci. Functional enrichment analyses revealed that variants associated with F12 gene and a missense mutation in ABCG2 may contribute to chronic kidney disease (CKD) through influencing inflammation, coagulation, and urate metabolism pathways. In independent cohorts from Taiwan (n = 25,345) and the United Kingdom (n = 260,245), polygenic risk scores (PRSs) for CKD significantly stratified the risk of CKD (p < 0.0001). Further research is required to evaluate the clinical effectiveness of PRSCKD in the early prevention of kidney disease.

Epithelioid trophoblastic tumor in male patients with germ cell tumor: A clinicopathologic analysis of five cases.

Epithelioid trophoblastic tumor (ETT) is an extremely rare chorionic-type neoplasm in the testis, with only seven cases reported in the literature. Here, we report five cases of testicular ETT from a single institution, constituting the largest series of this rare tumor to date. The patients had a mean age of 44 years (range, 20-68 years). Four patients had a previous history of testicular germ cell tumor (GCT) treated with chemotherapy, and they developed ETT in metastatic sites in a mean of 11 years (range, 3-15 years) after the initial diagnosis of testicular GCT. Only one patient had ETT in the testis. Three patients had a normal serum beta-human chorionic gonadotropin (ß-hCG) level, and two patients had a level that was slightly elevated, but far below that typically seen in patients with choriocarcinoma. ETT was characterized by a proliferation of intermediate trophoblastic cells with abundant eosinophilic cytoplasm, and the tumors frequently had coagulative necrosis with eosinophilic debris, mimicking keratinizing squamous cell carcinoma. The trophoblastic phenotype of ETT was supported by its immunoreactivity for trophoblastic markers, including GATA-3 (3 of 3 cases tested), α-inhibin (3/4), p63 (3/5), and ß-hCG (3/4). ETT was also positive for cytokeratin (4/4) and GCT marker SALL4 (3/3). Despite surgery and chemotherapy, two patients died of disease 17 months after ETT diagnosis, and three patients were alive with metastatic disease at a mean of 20 months (range, 15-28 months). Our results demonstrate that ETT may be an aggressive disease associated with distinct pathologic features and poor clinical outcome.

Surviving septic patients endotyped with a functional assay demonstrate active immune responses.

Introduction: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that ex vivo functional TNF expression as well as an immunologic endotype based on both IFNγ and TNF expression could be used to model clinical outcomes in sepsis patients. Methods: This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing facility, long-term acute care facility, or hospice. Whole blood ELISpot assays were conducted to quantify TNF expression [stimulated by lipopolysaccharide (LPS)] and IFNγ expression (stimulated by anti-CD3/CD28 mAb), which were then used for assignment to one of four subgroups including an 'immunocompetent', 'immunosuppressed endotype', and two 'mixed' endotypes. Results: Whole blood TNF spot-forming units were significantly increased in septic and CINS patients on days 4 and 7 compared to healthy subjects. In contrast, TNF expression per cell on days 1, 4, and 7 was significantly lower in both septic and critically ill non-septic (CINS) patients compared to healthy subjects. Early increases in total TNF expression were associated with favorable discharge disposition and lower in-hospital mortality. 'Immunocompetent' endotype patients on day 1 had a higher proportion of favorable to non-favorable discharges compared to the 'immunosuppressed' endotype. Similarly, 'immunocompetent' endotype patients on day 4 had a higher in-hospital survival compared to the 'immunosuppressed' endotype patients. Finally, among septic patients, decreased total TNF and IFNγ expression were associated with 180-day mortality. Conclusions: Increased ex vivo whole blood TNF expression is associated with improved clinical outcomes. Further, the early 'immunocompetent' endotype is associated with favorable discharge and improved in-hospital and 180-day survival. The ability to functionally stratify septic patients based on blood cell function ex vivo may allow for identification of future immune modulating therapies.

Traumatic chylothorax: a case report, treatment options and an update of the literature.

Background: Chylothorax is an uncommon condition defined by the escape of lymphatic fluid into the pleural space originating from the thoracic duct. Case Description: Our case involves a male patient in his 60s who developed traumatic chylothorax after being involved in a bicycle collision. The total body computed tomography (CT) showed multiple fractures of the ribs and spine, including a fracture of the anterior column of the Th12 vertebra. The patient was placed under observation in the intensive care unit and because of the instability of the Th12 fracture operative stabilization was performed with a percutaneous dorsal pedicle screw-rod spondylodesis. One day postoperatively, the patient suffered from acute respiratory distress; vital signs and hemoglobin levels remained stable. CT angiography was performed showing a large amount of fluid in the right pleural cavity. A chest tube was placed and a total of 3 L of fluid was evacuated. The next day a chylous production of 2 to 3 L per 24 hours was observed. Initiation of nutritional management for the patient involved a medium-chain triglyceride (MCT) diet in conjunction with total parenteral nutrition (TPN) administration. Due to the ongoing chylous leakage, despite the MCT diet and TPN, the patient underwent video-assisted thoracic surgery (VATS); the thoracic duct was identified and clipped. In addition, a VATS chemical pleurodesis with talc was performed. The chylous drainage ceased and after a total of 8 weeks the MCT diet was stopped. Conclusions: This case report encompasses relevant diagnostic evaluations and the array of medical treatments applicable to a chylothorax resulting from trauma.

Age above all: The impact of storage duration in mice resuscitated with whole blood or packed red blood cells and plasma in a hemorrhagic shock model.

BACKGROUND: The use of whole blood compared with a balanced ratio of components in trauma resuscitation remains an area of ongoing investigation. One factor that may affect outcomes is the age of the blood product transfused. We used a murine model of blood banking and hemorrhagic shock resuscitation to compare the effect of storage duration in whole blood and packed red blood cells on the recipient inflammatory response. METHODS: Murine whole blood or packed red blood cells were evaluated for the red blood cells storage lesion up to 14 days. Mice underwent hemorrhagic shock followed by resuscitation with whole blood or packed red blood cells combined with equal volume of thawed plasma (1:1) stored for 1, 7, or 14 days. Serum and lung cytokine/chemokine levels were measured and leukocyte infiltration determined via immunohistochemistry. RESULTS: Both whole blood and packed red blood cells develop a blood storage lesion. Four hours after resuscitation, mice resuscitated with either day 14 whole blood or 1:1 demonstrated increased inflammatory cytokines and chemokines with similar findings within lung tissue compared with mice resuscitated with whole blood and 1:1 products stored for 1 or 7 days. CONCLUSIONS: Resuscitation with murine packed red blood cells or whole blood stored for 14 days produces a pronounced recipient inflammatory response compared with those units stored for lesser durations. Given the shorter storage duration of human whole blood to packed RBCs, resuscitation with whole blood within current storage limits may represent an advantageous resuscitation strategy compared with older packed red blood cells.

Morphology of true lumen and surgical outcomes of acute type A aortic dissection repair with superior mesenteric artery malperfusion.

BACKGROUND: Acute type A aortic dissection (ATAD) can cause visceral malperfusion. Central aortic repair may resolve malperfusion, but some require further intervention. This study aimed to review outcomes after ATAD presenting with visceral malperfusion and to evaluate the predictive value of true lumen (TL) morphologies in preoperative computed tomography scan for persistent superior mesenteric artery (SMA) ischemia after central repair. METHODS: Open surgical repair of ATAD performed between 2008 and 2023 at our institution was reviewed retrospectively. Patients with central repair first approach were included for analysis. Patients with inadequate computed tomography scan data to assess luminal morphology were excluded. TL morphology was reviewed at the diaphragm level and categorized as concave or convex. The malperfusion pattern, static vs dynamic, was assessed at SMA orifices. Data were analyzed using a contingency table and parametric and nonparametric methods. RESULTS: A total of 543 open ATAD repairs were performed. Of these, 263 patients were eligible under the inclusion criteria and, subsequently, analyzed. The mean age was 57±14, and 83 (31%) patients were female. SMA malperfusion developed in 42 (16%) of the 263 patients, including 26 patients with dynamic obstruction, 6 patients with static obstruction, and 10 patients with dynamic and static obstruction. Regarding dissection flap morphology, 78 patients (30%) exhibited concave morphology, while 185 patients (70%) had convex morphology. TL diameter was significantly larger in convex than concave (concave: 6 mm vs convex: 16 mm; P < .0001). The prevalence of clinically significant SMA malperfusion was higher in concave-shaped TL (concave 41% vs convex 5%; P < .0001). Dynamic SMA obstruction was more frequently observed in the concave group (concave 72% vs convex 30%; P < .001). However, significantly more patients with convex-shaped TL required bowel resection than concave (concave 13% vs convex 70%; P < .001). The operative mortality was higher in the convex group, although statistically insignificant (concave 19% vs convex 50%; P = .0059). CONCLUSIONS: Central repair first strategy could resolve more than 80% of SMA malperfusion in ATAD when the TL is concave-shaped at the level of the diaphragm. Convex-shaped TL morphology was associated with less incidence of SMA malperfusion but was more frequently associated with static obstruction and higher incidence of bowel resection. The morphology evaluation of the TL at the diaphragm level may be simple and beneficial for surgical planning for ATAD presenting with SMA malperfusion.

Arthroplasty treatment options for femoral neck fractures in the elderly: A network meta-analysis of randomized control trials.

INTRODUCTION: Treatment options for displaced intracapsular femoral neck fractures in elderly patients include unipolar hemiarthroplasty (UHA), bipolar hemiarthroplasty (BHA), unipolar total hip arthroplasty (UTHA), and dual-mobility total hip arthroplasty (DMTHA). This network meta-analysis (NMA) of randomized controlled trials (RCTs) quantitatively compares these treatments to identify the optimal surgical technique. METHODS: Following PRISMA guidelines, a comprehensive literature search in Medline (PubMed), Cochrane, and EMBASE databases was conducted. RCTs comparing UHA, BHA, UTHA, or DMTHA were included. Interventions were ranked using the SUCRA score. RESULTS: Among 5,542 studies, 12 RCTs met inclusion criteria, involving 1,490 patients. Procedures were ranked by prosthetic dislocation, mortality, operating time, intraoperative blood loss, revision rate, Harris Hip Score (HHS). BHA ranked the best in dislocation rate, intraoperative blood loss and mortality. UHA had the shortest operating time. DMTHA had the greatest ranking for HHS. However, the differences between these treatment modalities were rarely statistically significantly different. CONCLUSION: A variety of arthroplasty procedures can be used to treat displaced intracapsular femoral neck fractures. Our results indicate that while BHA resulted in the best post-operative ranking amongst the compared treatment strategies in terms of dislocation rates, blood loss and mortality, the differences between the treatment options does not clearly favor a specific treatment option.

Evidence-based guidelines for drug dosing in intravitreal injections in silicone oil-filled eyes: Pharmacokinetics, safety, and optimal dosage.

We evaluate the pharmacokinetics, safety, and optimal dosages of intravitreal agents in silicone oil (SO)-filled eyes, addressing challenges in administering such therapies. We assessed the pharmacological properties and safety profiles of intravitreal drugs in SO-filled eyes, deriving conclusions and guidance from available literature and expert consensus. Preclinical data suggest comparable half-lives of anti-vascular endothelial growth factoragents in SO-filled eyes, but clinical evidence is mainly from case reports and small series. Available research prioritizes standard dosages, particularly for bevacizumab (1.25 mg), supported by stronger evidence than aflibercept (2 mg) or ranibizumab (0.5 mg). Intravitreal steroids, especially dexamethasone at 0.7 mg, show efficacy and safety, while evidence for fluocinolone acetonide at 0.19 mg is limited. Intravitreal methotrexate has been reported at the dosage of 250-400 µg, with keratitis as the primary expected side effect. Case reports indicate tolerability of standard dosages of antivirals (foscarnet 1.2-2.4 mg/0.1 mL, ganciclovir 4 mg/0.1 mL) and the antibiotic combination piperacillin/tazobactam (250 µg/0.1 mL). We offer guidance based on current, but limited, literature. Standard dosage of intravitreal agents should be carefully considered, along with close monitoring for potential side effects, which should be discussed with patients.

Suprachoroidal Drug Delivery for Macular Edema Associated With Noninfectious Uveitis.

Purpose: To evaluate clinical trials in the literature that focus on suprachoroidal drug delivery for the treatment of noninfectious uveitis and other posterior segment diseases. Methods: A synthesis of the literature was performed. Results: In 2021, suprachoroidal space triamcinolone acetonide, a corticosteroid delivery system used for the treatment of uveitic macular edema (ME), was approved by the US Food and Drug Administration. The drug-delivery system targets the suprachoroidal space using a microneedle-based device and has a favorable pharmacokinetic profile. Suprachoroidally administered investigational therapies have also been assessed in clinical trials for other posterior segment diseases, including diabetic ME, retinal vein occlusion, age-related macular degeneration, and choroidal melanoma. Conclusions: The safety and efficacy of suprachoroidal corticosteroid injections to treat uveitic ME have been shown in recent phase III clinical trials. Multiple programs are also investigating this modality of drug delivery for use in many other retinal and choroidal pathologies.

A Pilot Study of the CD38 Antagonist Daratumumab in Patients with Metastatic Renal Cell Carcinoma or Muscle-Invasive Bladder Cancer.

PURPOSE: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC). EXPERIMENTAL DESIGN: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring design for toxicity was used for excessive toxicity. RESULTS: In both the MIBC (n = 8) and mRCC (n = 8) cohorts, no toxicity events were encountered. In the MIBC cohort, one patient experienced pathologic complete response rate. In the mRCC cohort, no objective responses were reported, and the median progression-free survival was 1.5 months (95% confidence interval, 1.1-1.8 months). Immune monitoring found significant reductions in NK cells in circulation in both cohorts after treatment. In the tissue analysis, IHC found evidence of diminished CD38 presence in mRCC with treatment, whereas the baseline levels in MIBC were low. CONCLUSION: Treatment with daratumumab was safe. No signal of efficacy was detected in mRCC, and conclusions on the activity in MIBC were limited. Evidence of daratumumab targeting CD38 was detected in circulating immune cells and within the tumor microenvironment of mRCC and MIBC. SIGNIFICANCE: In this prospective clinical trial of daratumumab, treatment in patients with MIBC and mRCC was safe. Limited efficacy was observed. Treatment with daratumumab resulted in CD38-expressing immune cell subsets to be targeted both in circulation and within the tumor microenvironment.

Functional and radiological sinonasal outcomes of CFTR modulators for sinus disease in cystic fibrosis: A meta-analysis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease. METHODS: English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements. RESULTS: Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030). CONCLUSIONS: CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.

Non-Invasive Ventilatory Support in Preterm Neonates in the Delivery Room and the Neonatal Intensive Care Unit: A Short Narrative Review of What We Know in 2024.

BACKGROUND: Guidelines recommend non-invasive ventilatory (NIV) support as first-line respiratory support mode in preterm infants as NIV is superior to intubation and mechanical ventilation in preventing death or bronchopulmonary dysplasia. However, with an ever-expanding variety of NIV modes available, there is much debate about which NIV modality should ideally be used, how, and when. The aims of this work were to summarise the evidence on different NIV modalities for both primary and secondary respiratory support: nCPAP, nasal high-flow therapy (nHFT), and nasal intermittent positive airway pressure ventilation (nIPPV), bi-level positive airway pressure (BiPAP), nasal high-frequency oscillatory ventilation (nHFOV), and nasally applied, non-invasive neurally adjusted ventilatory assist (NIV-NAVA) modes, with particular focus on their use in preterm infants. SUMMARY: This is a narrative review with reference to published guidelines by European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. nCPAP is currently the most commonly used primary and secondary NIV modality for premature infants. However, there is increasing evidence on the superiority of nIPPV over nCPAP. No beneficial effect was found for BiPAP over nCPAP. For the use of nHFT, nHFOV, and NIV-NAVA, more studies are needed to establish their place in neonatal respiratory care. KEY MESSAGES: The superiority of nIPPV over nCPAP needs to be confirmed by contemporaneous trials comparing nCPAP to nIPPV at comparable mean airway pressures. Future trials should study NIV modalities in preterm infants with comparable respiratory pathology and indications, at comparable pressure settings and with different modes of synchronisation. Importantly, future trials should not exclude infants of the smallest gestational ages.

Bladder-sparing Therapy for Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection.

BACKGROUND AND OBJECTIVE: There has been a recent surge in the development of agents for bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options. METHODS: A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions. KEY FINDINGS AND LIMITATIONS: There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials. CONCLUSIONS AND CLINICAL IMPLICATIONS: The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC.

Development and optimization of a diluted whole blood ELISpot assay to test immune function.

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis ('SPIES') is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay. In contrast, we developed a diluted whole blood (DWB) ELISpot protocol that has been validated across multiple laboratories. Heparinized whole blood was collected from healthy donors and septic patients and tested under different stimulation conditions to evaluate the impact of blood dilution, stimulant concentration, blood storage, and length of stimulation on ex vivo IFNγ and TNFα production as measured by ELISpot. We demonstrate a dynamic range of whole blood dilutions that give a robust ex vivo cytokine response to stimuli. Additionally, a wide range of stimulant concentrations can be utilized to induce cytokine production. Further modifications demonstrate anticoagulated whole blood can be stored up to 24 h at room temperature without losing significant functionality. Finally, we show ex vivo stimulation can be as brief as 4 h allowing for a substantial decrease in processing time. The data demonstrate the feasibility of using ELISpot to measure the functional capacity of cells within DWB under a variety of stimulation conditions to inform clinicians on the extent of immune dysregulation in septic patients.

Testicular Germ Cell Tumors with Venous Tumor Thrombus: Prevalence, Presentation, and Management.

BACKGROUND AND OBJECTIVE: There are limited data on the prevalence and management of testicular germ cell tumor (TGCT) cases presenting with venous tumor thrombus (VTT). Our objectives were to describe the prevalence of TGCT with VTT, to identify a multicenter retrospective cohort, and to ascertain expert opinion regarding optimal management of this entity. METHODS: Using the IBM Marketscan database, we identified men with testicular cancer who underwent retroperitoneal lymph node dissection (RPLND) with concurrent VTT or inferior vena cava (IVC) tumor thrombectomy to estimate the prevalence of VTT in TGCT. To identify a multicenter retrospective cohort of patients, we surveyed surgeons and described the presentation, management, and outcomes for the cohort. KEY FINDINGS AND LIMITATIONS: The prevalence of TGCT with VTT in the IBM Marketscan database was 0.3% (n = 7/2517) when using stringent criteria and 3.1% (n = 79/2517) when using broad criteria. In response to our survey, 16 surgeons from ten centers contributed data for 34 patients. Most patients (n = 29, 85%) presented with nonseminomatous germ cell tumor. Surgical management was used for 93.9% (n = 31), including postchemotherapy tumor thrombectomy with primary cavorrhaphy in 63%. The Marketscan analysis was limited to insured individuals and did not include clinicopathological details, and use of billing codes may have included patients with stromal tumors. In addition, lack of responses to the anonymous survey limited data capture, and the RedCap survey did not address symptoms specific to IVC obstruction or allow central review of the imaging leading to VTT diagnosis. CONCLUSIONS AND CLINICAL IMPLICATIONS: VTT among males with TGCT is rare and requires complex multidisciplinary management, including venous tumor thrombectomy at the time of postchemotherapy RPLND. PATIENT SUMMARY: Using a medical database, we estimated that the frequency of testicular cancer cases in which the tumor extends into a blood vessel (called venous tumor thrombus, VTT) is just 0.3-3.1%. We carried out a survey of surgeons with experience of this condition. Our results indicate that although testicular cancers respond well to chemotherapy, VTT is less responsive and complex surgery is necessary for this rare condition.

Knowledge and awareness of cervical cancer and human papillomavirus vaccination among female university students.

BACKGROUND:  Prevention strategies for reducing cervical cancer incidence rely on informed populations, particularly those most at risk. This study assesses the knowledge and awareness of female university students towards cervical cancer, human papillomavirus (HPV) and its vaccination. METHODS:  A validated self-administered questionnaire was used in a descriptive cross-sectional study among female university students. The data were analysed with Statistical Package for Social Sciences version 26, and p  0.05 was considered significant. RESULTS:  The total participants were 190 with a mean age of 22.6 ± 4.35 years. The majority (90%) were aware of cervical cancer, and 78.9% agreed it is a terminal illness, but fewer participants knew it was associated with infection (63.7%), and that it had effective risk-reducing methods (70.5%). Only 32.6% were aware of the Pap smear test, less than half (43.2%) were aware of the cervical cancer vaccine and only 43.7% knew it was available locally. Although fewer (39.5%) considered themselves susceptible to cervical cancer, many (62.1%) would like a Pap smear test. Overall, 88.9% of the participants possessed adequate knowledge of cervical cancer, 67.9% of the HPV vaccine and only 33.7% of HPV. Ethnicity (p = 0.03), year of study (p = 0.001) and institution (p = 0.002) were all significantly associated with knowledge levels, vaccine awareness and Pap smear test awareness. CONCLUSION:  Participants showed low HPV knowledge and varying awareness levels regarding cervical cancer, HPV and HPV vaccine.Contribution: This study provides insights into female university students' knowledge and awareness gaps, highlighting the need for targeted interventions.