A Phase 1, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of HEV-239 (Hecolin) Vaccine in Healthy US Adults.

Background: Establishing the safety and immunogenicity of a hepatitis E virus vaccine in multiple populations could facilitate broader access and prevent maternal and infant mortality.

Methods: We conducted a phase 1, randomized, double-blinded, placebo-controlled (4:1 vaccine to placebo) trial of 30 µg HEV-239 (Hecolin, Xiamen Innovax Biotech Company Limited, China) administered intramuscularly in healthy US adults aged 18-45 years. Participants were vaccinated on days 1, 29, and 180.

Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study.

Background: The literature on first generation COVID-19 vaccines show they were less effective against new SARS-CoV-2 variants of concern including Omicron (BA.1, BA.2, BA.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.

Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial.

In the PREVENT-19 phase 3 trial of the NVX-CoV2373 vaccine (NCT04611802), anti-spike binding IgG concentration (spike IgG), anti-RBD binding IgG concentration (RBD IgG), and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks post-dose two are assessed as correlates of risk and as correlates of protection against COVID-19. Analyses are conducted in the U.S.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern.

Methods: We conducted a global Phase 3, multi-stage efficacy study (NCT04904549) among adults aged ≥18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 μg of ancestral (D614) and 5 μg of B.

Safety of Ceftazidime-Avibactam in Combination with Aztreonam (COMBINE) in a Phase I, Open-Label Study in Healthy Adult Volunteers.

This phase I study evaluated the safety of the optimal ceftazidime-avibactam (CZA) with aztreonam (ATM) regimens identified in hollow fiber infection models of MBL-producing Enterobacterales. Eligible healthy subjects aged 18 to 45 years were assigned to one of six cohorts: 2.5 g CZA over 2 h every 8 h (approved dose), CZA continuous infusion (CI) (7.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

Background: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.

Methods: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site).

Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial.

Background: Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15-50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.

Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA).

A Phase II Trial of Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Adrenocortical Carcinoma.

Background: Recurrent adrenocortical carcinoma (ACC) is an aggressive disease with few options offering durable survival benefit. Despite metastasectomy, recurrence is common. Cytoreduction and intraperitoneal chemotherapy have offered improved survival in other advanced cancers.

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases.

Purpose: There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver.

Unknown primary nasopharyngeal melanoma presenting as severe recurrent epistaxis and hearing loss following treatment and remission of metastatic disease: A case report and literature review.

Introduction: Primary nasopharyngeal melanoma is an exceedingly rare pathology with unclear etiology and oftentimes obscure clinical presentation. Despite improved diagnostic capabilities, these lesions are often diagnosed at an advanced stage and associated prognosis is poor, partly due to high rates of recurrences and metastasis.

Presentation Of Case: A 74-year-old woman was diagnosed with metastatic melanoma to the liver, of unknown primary.

Duodenal ischemia and upper GI bleeding are dose-limiting toxicities of 24-h continuous intra-arterial pancreatic perfusion of gemcitabine following vascular isolation of the pancreatic head: early results from the Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) study.

Background: Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is currently explored as an attractive approach for patients with locally advanced pancreatic ductal adenocarcinoma. To establish the feasibility and toxicity of regional intra-arterial gemcitabine delivered as a 24-h continuous infusion to the pancreas as a novel treatment option for patients with locally advanced PDAC a phase I clinical trial was conducted.

Methods: Between April 2011 and September 2013 six patients with biopsy confirmed, borderline or unresectable pancreatic adenocarcinoma, and having received at least one line of systemic chemotherapy, underwent vascular redistribution of the inflow to the head of the pancreas by arterial coil embolization followed by perfusion catheter placement within the splenic artery.

Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial.

Background: A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis.

Methods: Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum, and resectable to "no evidence of disease" were randomized to gastrectomy, metastasectomy, HIPEC, and systemic FOLFOXIRI (GYMS arm) or FOLFOXIRI alone (SA arm).

Results: Seventeen patients were enrolled (16 evaluable); 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction (CCR0).

A novel nomogram for peritoneal mesothelioma predicts survival.

Background: Malignant peritoneal mesothelioma (MPM) is a rare disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Estimation of personalized survival times can potentially guide treatment and surveillance.

Methods: We analyzed 104 patients who underwent CRS and cisplatin-based HIPEC for MPM.

Isolated hepatic perfusion with high-dose melphalan results in immediate alterations in tumor gene expression in patients with metastatic ocular melanoma.

Background: Patients with ocular melanoma liver metastases have a poor prognosis, treatment options are limited, and median survival is less than 1 year. In this study, we characterized the early molecular changes that occur in tumors immediately after vascular isolation perfusion with melphalan with hyperthermia in patients with hepatic metastases from ocular melanoma.

Methods: Patients underwent treatment on a clinical trial using a 60-min hyperthermic isolated hepatic perfusion (IHP) with melphalan.

Analysis of factors influencing outcome in patients with in-transit malignant melanoma undergoing isolated limb perfusion using modern treatment parameters.

PURPOSE In-transit disease afflicts approximately 10% of patients with extremity melanoma; no single treatment approach has been uniformly accepted as the most effective. We report long-term outcomes in patients with in-transit extremity melanoma who underwent isolated limb perfusion (ILP) in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular long-term follow-up. PATIENTS AND METHODS Between May 1992 and February 2005, 91 patients (median age, 57 years; 50 women, 41 men) underwent a 90-minute hyperthermic ILP (melphalan, 10 to 13 mg/L limb volume, tumor necrosis factor [TNF; n = 44], or interferon [n = 38]) using uniform operative technique and intraoperative leak monitoring.

Cytoreductive surgery and continuous hyperthermic peritoneal perfusion in patients with mesothelioma and peritoneal carcinomatosis: hemodynamic, metabolic, and anesthetic considerations.

Cytoreductive surgery and continuous hyperthermic peritoneal perfusion (CHPP) involve the conduct of a complex surgical procedure and delivery of high-dose hyperthermic chemotherapy to the peritoneum. This therapeutic modality has been shown to benefit patients with peritoneal carcinomatosis resulting from gastrointestinal and ovarian tumors and mesothelioma. However, it is unknown whether the primary disease (mesothelioma versus peritoneal carcinomatosis) affects hemodynamic and metabolic perturbations during the course of CHPP with cisplatin.

Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum.

Background: Generally, colorectal and high-grade appendiceal cancers are treated similarly; treatment approach is primarily based on tumor histology and stage of disease. Patients with adenocarcinoma of the lower gastrointestinal tract frequently experience diffuse metastases isolated to liver or peritoneum and have a poor survival. Identification of novel molecular pathways in metastases from these patients may identify novel targets and prognostic factors.

Isolated hepatic perfusion for the treatment of patients with advanced liver metastases from pancreatic and gastrointestinal neuroendocrine neoplasms.

Background: We report results of using isolated hepatic perfusion (IHP) in patients with advanced progressive liver metastases (LM) from pancreatic and gastrointestinal neuroendocrine neoplasms (NENs).

Methods: Thirteen patients with LM from NENs (mean percent hepatic replacement, 30; range, 10-60) were treated with a 1-hour hyperthermic IHP via a laparotomy with the use of 1.5 or 2.

Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy.

Purpose: Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy.

Patients And Methods: Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board.