Citations

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide including sub-Saharan Africa. The GALAD score, derived from Gender, Age, Lens culinaris agglutinin-reactive fraction of alpha fetoprotein, Alpha fetoprotein, and Des-carboxy-prothrombin, has high accuracy in diagnosing HCC in Asia, Europe, and North America; however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in sub-Saharan Africa. Clinical data from patients with cirrhosis (n = 93) or HCC (n = 78) from outpatient hepatology clinics at three teaching hospitals in Ghana were abstracted, and serum samples were analyzed. A logistic regression model predicting HCC status based on the GALAD score was constructed to obtain the ROC curve for GALAD. The AUC with 95% confidence interval (CI) was calculated. The median GALAD score was higher among patients with HCC versus cirrhosis controls (8.0 vs. −4.1, P < 0.01). The AUC of the GALAD score for HCC detection was 0.86 (95% CI, 0.79–0.92). At a cut-off value of −0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. The AUC (95% CI) was 0.87 (0.80–0.95) and 0.81 (0.67–0.94) in hepatitis B virus–positive and hepatitis B virus–negative patients, respectively. The GALAD score has a high accuracy for HCC detection. It has great potential to improve HCC surveillance in sub-Saharan Africa where imaging resources are limited. Significance: The GALAD score or its relevant modifications have the potential to aid in improving HCC surveillance efforts in low-resource settings in sub-Saharan Africa. This could enhance early detection rates of HCC and potentially improve survival rates in resource-limited settings.

Background: Rupture of the pectoralis major is most commonly seen with eccentric contraction mechanisms, and surgical options in the setting of acute tear include direct repair, endocortical buttons, suture anchors, and transosseous tunnel fixation. This technique video will detail repair using a unicortical endobutton fixation construct. Indications: Surgical repair is indicated for acute, complete pectoralis major tears; incomplete tears involving rupture of the sternal head with intact clavicular head; and tears in the young, active, high-demand demographic. Delay in diagnosis increases the risk of tendon retraction and fatty atrophy. Recent literature has shown that acute repair is superior to chronic repair in functional outcome, pain relief, and overall cosmesis. Technique Description: A beach-chair position and a deltopectoral approach are used to identify and mobilize the torn and retracted sternal head of the pectoralis major. A No. 2 SutureTape is then passed through the disrupted sternal head in a Krackow fashion to allow for a 6-strand repair. Two of the suture strands are then shuttled through the endocortical button. A drill is used to create a corticectomy for endobutton placement, which is secured into place by sequentially tightening each limb. Two additional endobuttons are placed in a similar fashion to complete the construct. Results: Outcomes studies regarding patients with pectoralis major tendon ruptures who underwent endocortical button fixation reveal that 83% of patients had good or excellent outcomes in a recent systematic review. Another study showed no significant difference in functional outcomes, return to activity, or complication rate with endocortical button fixation compared with other mechanisms of fixation. Discussion/Conclusion: Unicortical endobutton fixation can provide another fixation strategy for acute pectoralis major tears in young, active high-demand individuals. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background A higher number of recanalization attempts reduces the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke secondary to large vessel occlusion (LVO). We assessed the impact of switching EVT techniques after a failed first pass on procedural and clinical outcomes. Methods This multicenter international study, conducted between January 2013 and December 2022, included patients undergoing EVT for anterior circulation LVO (internal carotid artery or M1 segments) with failed first pass recanalization. Propensity score matching identified a 1:1 matched cohort of patients in whom EVT technique was changed after a failed first pass and those with the same technique repeated. The primary outcome was successful recanalization at second attempt defined as Thrombolysis in Cerebral Ischemia (TICI) score of 2B or higher. Secondary outcomes were 90-day modified Rankin Score (mRS) and postprocedural hemorrhage. Results Among 2167 patients, converting to an alternative technique after a failed first pass was associated with higher odds of successful recanalization (adjusted OR (aOR)=1.5, p=0.041), and higher odds of mRS 0–2 at 90 days (aOR=1.6, p=0.005) without additional risk of symptomatic hemorrhage (p=0.379). Using a propensity score matched cohort of 490 patients, technique conversion at second attempt increased odds of successful recanalization at second attempt (aOR=1.32, p=0.006) and 90-day mRS 0–2 (aOR=1.38, p=0.008). Conclusions Early conversion to an alternative EVT technique after a failed first pass recanalization in patients with AIS is associated with better technical success and clinical outcomes.

OBJECTIVES: Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are the most common causes of acute neuromuscular respiratory failure resulting in ICU admission. This synthetic narrative review summarizes the evidence for the prediction and management of acute neuromuscular respiratory failure due to GBS and MG. DATA SOURCES: We searched PubMed for relevant literature and reviewed bibliographies of included articles for additional relevant studies. STUDY SELECTION: English-language publications were reviewed. DATA EXTRACTION: Data regarding study methodology, patient population, evaluation metrics, respiratory interventions, and clinical outcomes were qualitatively assessed. DATA SYNTHESIS: No single tool has sufficient sensitivity and specificity for the prediction of acute neuromuscular respiratory failure requiring mechanical ventilation. Multimodal assessment, integrating history, examination maneuvers (single breath count, neck flexion strength, bulbar weakness, and paradoxical breathing) and pulmonary function testing are ideal for risk stratification. The Erasmus GBS Respiratory Insufficiency Score is a validated tool useful for GBS. Noninvasive ventilation can be effective in MG but may not be safe in early GBS. Airway management considerations are similar across both conditions, but dysautonomia in GBS requires specific attention. Extubation failure is common in MG, and early tracheostomy may be beneficial for MG. Prolonged ventilatory support is common, and good functional outcomes may occur even when prolonged ventilation is required. CONCLUSIONS: Multimodal assessments integrating several bedside indicators of bulbar and respiratory muscle function can aid in evidence-based risk stratification for respiratory failure among those with neuromuscular disease. Serial evaluations may help establish a patient’s trajectory and to determine timing of respiratory intervention.

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by stromal fibrosis, hypoxia, and nutritional deprivation. Nutritional metabolic interventions may fundamentally change the tumor microenvironment and improve outcomes. A ketogenic diet (KD) (lower carbohydrate, moderate protein, higher fat) can significantly reduce glucose and insulin and stimulate ketogenesis. Triplet chemotherapy with gemcitabine/cisplatin/nab-paclitaxel has been associated with a median OS 16.4 months, PFS 10.1 months in patients with metastatic PDAC in the first-line setting. Recently, KD plus triplet chemotherapy was shown to inhibit murine pancreatic KPC tumor growth and prolong animal survival over chemotherapy alone (Yang et al, Med, 2022). Tumor growth inhibition was associated with glucose depletion, altered TCA substrate use and NADH elevation. Methods: In this Phase II trial, patients with treatment-naive metastatic PDAC were randomized to triplet chemotherapy with a medically supervised ketogenic diet (MSKD) or continuing their usual diet (non-MSKD). The MSKD is supported by Virta Health, who offers tracking of daily ketone (beta-hydroxybutyrate, BHB) and glucose levels, a web-based application, education, and communication with a remote care team to ensure sustained nutritional ketosis (BHB 0.5–3.0mM). Patients with BMI < 18, type 1 DM or history of DKA were excluded. Primary endpoint was PFS. Secondary endpoints: DCR (PR+CR+SD ≥ 9 weeks), change in CA 19-9 (CA125, CEA if not CA 19-9 expressers), average fasting insulin levels, HbA1c, body weight, gut microbiome, serum metabolites, QOL (QLQ- C30). Results: A total of 36 patients with untreated metastatic PDAC were enrolled. Among 32 evaluable patients (median age 65.9 years; 53% male), 16 were randomized to each arm. Both groups had similar baseline weight, HgbA1c, insulin and BHB levels (all p>0.05). Nine patients had type 2 DM; 6 required insulin. In the MSKD group, 15/16 achieved nutritional ketosis at any point during the study, with mean BHB of 0.57 mM (95% CI 0.40–0.73) and median proportion of days in ketosis of 39.4% (range 0-95.8%) by daily ketone tracking. Lab data showed significantly higher mean ± SD maximum change in BHB in the MSKD (0.5 ± 0.9 mmol/L) versus non-MSKD (–0.2 ± 0.3 mol/L) group (p = 0.018). There were no significant differences between groups in maximum change in weight, HbA1C, or insulin (all p > 0.05). The most common MSKD-related adverse events were Gr 1-2 fatigue (n=4), constipation (n=3), weight loss (n=3), and none stopped MSKD due to adverse events.Conclusion: A medically supervised ketogenic diet is feasible in patients with metastatic PDAC receiving triplet chemotherapy, with median proportion of days in ketosis of 39.4% and an acceptable safety profile. The MSKD is associated with comparable changes in insulin and HgbA1c levels compared to the non-MSKD diet, and sustained ketosis does not result in significantly greater weight loss. MSKD warrants further prospective exploration and analyses of the primary endpoint and correlative studies are ongoing. Citation Format: Gayle S Jameson, Erkut Borazanci, Diana L Hanna, Caroline GP Roberts, Meredith S Pelster, Richard C Frank, Angela T Alistar, Julia E Wiedmeier-Nutor, Sandra D Algaze, Brandon Fell, Sarah J Hallberg, Denise J Roe, Betsy C Wertheim, Derek Cridebring, Joshua D Rabinowitz, Stephen Gately, Daniel D Von Hoff, Drew W Rasco. Randomized phase II trial of two different nutritional approaches for patients receiving treatment for their advanced pancreatic cancer: initial results of safety and feasibility of the medically supervised ketogenic diet [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B012.

Abstract Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12–36 h post-MT. Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

Background The benefit of intravenous thrombolysis (IVT) is well established. We aim to study the benefits of IVT in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) who underwent unsuccessful mechanical thrombectomy (MT). Methods We included AIS patients who underwent MT for anterior circulation LVO with failed recanalization (modified treatment in cerebral ischemia [mTICI] score ≤ 2A). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score matching using demographic, clinical, radiographic and procedural variables was used to match patients with and without IVT. The primary outcome was favorable 90-day good functional outcome (defined as modified Rankin scale of 0–2), and secondary outcomes included intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Results Totally, 610 AIS patients with unsuccessful MT were included. After propensity matching, 219 patients were identified in each group. Median age was 70 years and 73 years in the IVT + MT and MT alone groups, respectively. In the IVT + MT group, final mTICI scores of 0, 1, and 2A were achieved in 92 (42.0%), 33 (15.1%), and 94 (42.9%) patients, respectively, versus 76 (34.7%), 29 (13.2%), and 114 (52.1%) in the MT alone group. The IVT + MT group had greater odds of 90-day good functional outcome (adjusted odds ratio 2.54, 95% confidence interval 1.53–4.32). There were no significant differences in secondary outcomes. Conclusions IVT is associated with improved functional outcomes in AIS patients with LVO despite unsuccessful MT.