SARS-CoV-2 vaccines will be deployed to countries with limited immunization systems. We assessed the effect of deploying SARS-Cov-2 vaccines on cold storage capacity and immunization workload in a simulated WHO African Region country using region-specific data on immunization, population, healthcare workers (HCWs), cold storage capacity (quartile values for national and subnational levels), and characteristics of an approved SARS-CoV-2 vaccine. We calculated monthly increases in vaccine doses, doses per vaccinator, and cold storage volumes for four-month SARS-CoV-2 vaccination campaigns targeting risk groups compared to routine immunization baselines. Administering SARS-CoV-2 vaccines to risk groups would increase total monthly doses by 27.0% for ≥ 65 years, 91.7% for chronic diseases patients, and 1.1% for HCWs. Assuming median nurse density estimates adjusted for absenteeism and proportion providing immunization services, SARS-CoV-2 vaccination campaigns would increase total monthly doses per vaccinator by 29.3% for ≥ 65 years, 99.6% for chronic diseases patients, and 1.2% for HCWs. When we applied quartiles of actual African Region country vaccine storage capacity, routine immunization vaccine volumes exceeded national-level storage capacity for at least 75% of countries, but subnational levels had sufficient storage capacity for SARS-CoV-2 vaccines for at least 75% of countries. In the WHO African Region, SARS-CoV-2 vaccination campaigns would substantially increase doses per vaccinator and cold storage capacity requirements over routine immunization baselines. Pandemic vaccination campaigns would increase storage requirements of national-level stores already at their limits, but sufficient capacity exists at subnational levels. Immediate attention to strengthening immunization systems is essential to support pandemic responses.

Background: After SARS-CoV-2 vaccines become available, they will be deployed to many countries with limited immunization systems. Methods: We conducted a cold chain capacity assessment of a simulated country in the WHO African Region. We combined region-specific data regarding immunization, population, healthcare workforce, and cold storage capacity (upper and lower range and quartile values for national and subnational levels). We used seasonal influenza vaccines as proxies for SARS-CoV-2 vaccines. We evaluated the increase in vaccine doses to be administered, doses administered per vaccinator, and cold storage volumes for SARS-CoV-2 campaigns targeting risk groups compared to routine immunization baselines. Findings: Compared to routine immunization, a SARS-CoV-2 vaccination campaign would increase monthly doses administered when targeting risk groups: ≥65 years (29.9%), chronic diseases patients (101.5%), and healthcare workers (1.2%). SARS-CoV-2 vaccination campaigns would increase doses administered per vaccinator for risk groups: ≥65 years (32.5%), chronic diseases patients (110.4%), or healthcare workers (1.4%). Routine vaccine volumes already exceed national level storage capacity for at least 75% of African Region countries, but subnational levels would have sufficient storage capacity for SARS-CoV-2 vaccines in all but the lower 25% of African Region countries. Interpretation: SARS-CoV-2 vaccination campaigns would substantially increase doses per vaccinator and cold chain capacity requirements over routine immunization baselines. Pandemic vaccination campaigns would add volume to national level stores already at their limits, but substantial capacity exists at subnational levels for SARS-CoV-2 vaccines. Immediate attention to strengthening delivery systems is essential to support pandemic vaccine responses in the African Region. Funding: None

Prolonged survival and durable responses in several late-stage cancers such as melanoma and lung cancer have been made possible with the use of immune checkpoint inhibitors targeting the programmed cell-death protein 1 (PD-1) or its ligand PD-L1. While it is prudent to focus on the unprecedented and durable clinical responses, there are subsets of cancer patients that do not respond to immunotherapies or respond early and then relapse later. Many pathways of resistance have been characterized, and more continue to be uncovered. To overcome the development of resistance, an in-depth investigation is necessary to identify alternative immune receptors and signals with the overarching goal of expanding treatment options for those with demonstrated resistance to PD1 checkpoint immunotherapy. In this mini-review, we will discuss the mechanisms by which tumors exhibit resistance to anti-PD-1/PD-L1 immunotherapy and explore strategies to overcome such resistances.

Posterior Reversible Encephalopathy Syndrome (PRES) is a neurological condition presenting with encephalopathy, seizures and headache with concurrent edema in the posterior cerebral circulation. While hypertension is the most common associated, PRES has been reported in patients receiving chemotherapy for various cancers such as AML. We report a 61-year-old female with history of hypertension who presented with sepsis and a new diagnosis of Acute Myeloid Leukemia (AML). She was started on broad spectrum antibiotics for her sepsis concurrently with Azacitidine and Venetoclax for treatment of sepsis and AML, respectively. Shortly after initiation of her AML treatment, patient became encephalopathic and experienced tonic clonic seizures. She had clinical and imaging features consistent with PRES. PRES has been reported as rare complication of chemotherapy of various cancer generally, and AML specifically. It is important to recognize it in a timely manner to prevent further damage. This case report highlights this important complication of the chemotherapy initiation in AML especially in elderly patient who presented with sepsis.

Background and Clinical Significance: Hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL), have been associated with the development of Guillain–Barré syndrome (GBS). Specifically, treatment with the immunomodulator rituximab, which is used in the backbone of DLBCL treatment, has increasingly been used in this patient population. Case Presentation: We present the case of a man in his 60s with DLBCL who presented to the hospital with the progressive weakness of the bilateral upper and lower extremities within 6 weeks of the completion of treatment including rituximab. The temporal relationship between the completion of rituximab and subsequent polyradiculoneuropathy, as well as a favorable response to intravenous immunoglobulin (IVIG), affirmed the diagnosis of treatment-induced GBS. Conclusions: The increased use of rituximab as part of a standard treatment regimen for hematologic malignancies demonstrates the need for an awareness of a possible association between rituximab and the subsequent paradoxical development of GBS, which will allow for expeditious evaluation for better patient outcomes.

PURPOSE: The VISION study ¹ found that Lutetium-177 ( ¹⁷⁷ Lu)–PSMA-617 (“Lu-177”) improved overall survival in metastatic castrate resistant prostate cancer (mCRPC). We assessed whether artificial intelligence enhanced PSMA imaging in mCRPC patients starting Lu-177 could identify those with better treatment outcomes. PATIENTS AND METHODS: We conducted a single site, tertiary center, retrospective cohort study in 51 consecutive mCRPC patients treated 2022-2024 with Lu-177. These patients had received most standard treatments, with disease progression. Planned treatment was Lu-177 every 6 weeks while continuing androgen deprivation therapy. Before starting treatment, PSMA images were analyzed for SUVmax and quantified tumor volume using artificial intelligence software (aPROMISE, Exinni Inc.). RESULTS: Fifty-one mCRPC patients were treated with Lu-177; 33 (65%) received 4 or more treatment cycles and these 33 had Kaplan-Meier median overall survival (OS) of 19.3 months and 23 (70%) surviving at 24 month data analysis. At first cycle Lu-177, these 33 had significantly more favorable levels of serum albumin, alkaline phosphatase, calcium, glucose, prostate specific antigen (PSA), ECOG performance status, and F18 PSMA imaging SUV-maximum values – reflecting PSMA “target expression”. In a “protocol-eligibility” analysis, 30 of the 51 patients (59%) were considered “protocol-eligible” and 21 (41%) “protocol-ineligible” based on initial clinical parameters, as defined in Methods. “Protocol-eligible” patients had OS of 14.6 mo and 63% survival at 24 months. AI-enhanced F18 PSMA quantified imaging found “protocol-eligible” tumor volume in mL to be only 39% of the volume in “ineligible” patients. CONCLUSION: In this cohort of mCRPC patients receiving Lu-177, pre-treatment AI-assisted F18 PSMA imaging finding higher PSMA SUV / lower tumor volume associated with the patient’s ability to have four or more treatment cycles, protocol eligibility, and better overall survival. KEY POINTS: Question: In mCRPC patients initiating Lu-177 therapy, can AI-assisted F18 PSMA imaging identify patients who have better treatment outomes? Findings: 33 (65%) of a 51 consecutive patient mCRPC cohort were able to receive 4 or more cycles Lu-177. These patients had significantly more favorable serum albumin, alkaline phosphatase, calcium, glucose, PSA, performance status, and higher AI-PSMA scan SUV-maximum values, with a trend toward lower PSMA tumor volumes in mL. They had Kaplan-Meier median OS of 19.3 months and 70% survived at 24 months. AI-enhanced PSMA tumor volumes (mL) in “protocol eligible” patients were significantly lower - only 40% - than tumor volumes of “protocol ineligible” patients. Meaning: In this cohort of mCRPC patients receiving Lu-177, pre-treatment AI-assisted F18 PSMA imaging finding higher PSMA SUV / lower tumor volume associated with the patient’s ability to have four or more treatment cycles, protocol eligibility, and better overall survival.