Since its inception, the Hemoglobin, Albumin, Lymphocyte, Platelet Score (HALP) has gained attention as a new prognostic biomarker to predict several clinical outcomes in a multitude of cancers. In our review, we searched PubMed for articles between the first paper on HALP in 2015 through September 2022, yielding 32 studies in total that evaluated HALP's association with various cancers, including Gastric, Colorectal, Bladder, Prostate, Kidney, Esophageal, Pharyngeal, Lung, Breast, and Cervical cancers, among others. This review highlights the collective association HALP has with demographic factors such as age and sex in addition to TNM staging, grade, and tumor size. Furthermore, this review summarizes HALP's prognostic ability to predict overall survival, progression-free survival, recurrence-free survival, among other outcomes. In some studies, HALP has also been able to predict response to immunotherapy and chemotherapy. This review article also aims to serve as a comprehensive and encyclopedic report on the literature that has evaluated HALP as a biomarker in various cancers, highlighting the heterogeneity surrounding HALP's utilization. Because HALP requires only a complete blood count and albumin - already routinely collected for cancer patients - HALP shows potential as a cost-effective biomarker to aid clinicians in improving outcomes for immuno-nutritionally deficient patients.

Study Need and Importance: Patients who undergo radical cystectomy (RC) are at risk for malnutrition for a variety of reasons. A prognostic marker for underlying nutritional and immune status is of much value in urologic oncology because patients can be better screened and targeted with pre-/perioperative immunonutritional therapy, with the goal being to improve post-RC outcomes. Our paper sought to validate the hemoglobin, albumin, lymphocyte, platelet score (HALP) as a surrogate for immunological and nutritional status to predict RC postoperative outcomes. What We Found: We found that low HALP scores are a predictor for shorter overall survival (see Figure ). HALP remained predictive even when adjusting for comorbidities, TNM staging, and neoadjuvant chemotherapy. We determined that an optimum HALP cutoff of 25.0 is clinically meaningful to preoperatively screen patients for nutritional deficiency. This finding is in line with a previous study which identified 22.2 as an optimum threshold in RC, which further lends credence to the utility of HALP. Limitations: This study is limited by a small sample size (n[50) and clinical data collected from only a single institution. Furthermore, some of the patients in our sample underwent neoadjuvant chemotherapy, which has an unknown effect on the HALP score. Although our study adjusted for neoadjuvant chemotherapy, neoadjuvant chemotherapy may have nevertheless impacted HALP scores across groups. Interpretation for Patient Care: HALP is potentially a powerful predictor of overall survival following RC.Given that HALP evaluates nutritional and immunological status, it is possible to use HALP to screen for patients who may be in need of preoperative nutritional and immune therapy. Future research should investigate if preoperative HALP score can be improved by administrating preoperative nutritional supplementation, with the goal of improving the arsenal of preoperative interventions to aid malnourished patients undergoing surgery. Figure. Kaplan-Meier estimates of overall survival by low and high hemoglobin, albumin, lymphocyte, and platelet (HALP) scores prior to radical cystectomy. Cum indicates cumulative; High HALP, 25.0; Low HALP, <25.0.

Vibrio cholerae uses cholera toxin (CT) to cause cholera, a severe diarrheal disease in humans that can lead to death within hours of the onset of symptoms. The catalytic activity of CT in target epithelial cells increases cellular levels of 3′,5′-cyclic AMP (cAMP), leading to the activation of the cystic fibrosis transmembrane conductance regulator (CFTR), an apical ion channel that transports chloride out of epithelial cells, resulting in an electrolyte imbalance in the intestinal lumen and massive water loss. Here we report that when administered perorally, benzopyrimido-pyrrolo-oxazinedione, (R)-BPO-27), a potent small molecule inhibitor of CFTR, blocked disease symptoms in a mouse model for acute diarrhea caused by toxigenic V. cholerae. We show that both (R)-BPO-27 and its racemic mixture, (R/S)-BPO-27, are able to protect mice from CT-dependent diarrheal disease and death. Furthermore, we show that, consistent with the ability of the compound to block the secretory diarrhea induced by CT, BPO-27 has a measurable effect on suppressing the gut replication and survival of V. cholerae, including a 2010 isolate from Haiti that is representative of the most predominant ‘variant strains’ that are causing epidemic and pandemic cholera worldwide. Our results suggest that BPO-27 should advance to human Phase I studies that could further address its safety and efficacy as therapeutic or preventative drug intervention for diarrheal syndromes, including cholera, that are mediated by CFTR channel activation.

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