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New guideline for replacement of ART: CAB/RPV LA not for everyone

Approved by the FDA in late January 2021, CAB/RPV LA (cabotegravir/rilpivirine) is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections versus daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86% to 91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.

With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6-11.5 weeks for CAB and 13-28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.

CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius) and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common.

Source: Medscape

Restoring pulmonary endothelial cells reverses emphysema in mice

Correcting endothelial dysfunction in both human tissue and an elastase-induced murine model of emphysema shows promise in stopping and reversing the course of the disease, according to an international group of researchers.

EC loss and dysfunction were also hallmarks of emphysematous lungs harvested from the elastase-treated mice. The team found that intravenous delivery of healthy lung ECs from genetically identical mice reversed these phenotypes.

“We also found,” continued Dr. Racanelli, “that removing a specific molecule from the cells had a similar result.” In particular the researchers observe that “Leucine-rich a-2-glycoprotein- 1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression.” LRG1 upregulation, they note ,”directly correlated with severity of the COPD phenotype.”

Source: Journal of Experimental Medicine

New investigational helmet device shrinks glioblastoma

A case report describes a novel helmet device that generates a noninvasive oscillating magnetic field and that shrunk a glioblastoma tumor by about a third.

The patient had end-stage recurrent glioblastoma and had undergone all standard therapy options. He wore the device for 5 weeks but died from an unrelated injury, so the treatment period was cut short.

A brain scan showed a 31% reduction of contrast-enhanced tumor volume, and an autopsy of his brain confirmed the rapid response to the treatment.

Source: Frontiers in Oncology

Delta variant of COVID-19 as contagious as chickenpox

Internal Centers for Disease Control and Prevention (CDC) documents support the high transmission rate of the delta variant and put the risk in easier to understand terms. The documents also show that breakthrough infections in the vaccinated make people about as contagious as those who are unvaccinated. In addition to being more transmissible, the delta variant likely causes more severe COVID-19 illness.

Source: Medscape

Lenvatinib plus Gefitinib therapy promising in liver cancer

In patients with advanced liver cancer who were unresponsive to lenvatinib, adding gefitinib (an EGFR inhibitor) led to a clinically meaningful response in a proof-of-concept study. 12 patients with advanced liver cancer who were unresponsive to lenvatinib treatment showed meaningful clinical responses after treatment with lenvatinib plus geftinib. Specifically, after 4-8 weeks of combination treatment, four patients had a partial response, four had stable disease and four showed disease progression.

 

Source: Reuters Health

Urinary thromboxane B2 may be marker of aggressive prostate cancer in black men

Upregulation of urinary thromboxane B2 may be a new marker of aggressive prostate cancer in African American men, a group that bears a disproportionately high burden of lethal prostate cancer.

Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. Dr. Stefan Ambs and colleagues with the National Cancer Institute investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men.

Using mass-spectrometry, they measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, in 977 men with prostate cancer (490 AA and 487 EA) and 1,022 controls (479 AA and 543 EA). During a median follow-up of 8.4 years, 246 men with prostate cancer died.

Source: Reuters Health

Corneal changes may signal long COVID

Nerve fiber loss and an increase in dendritic or key immune cells on the cornea may help identify Long COVID, according to a small study published online today in the British Journal of Ophthalmology.

Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.

Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.

Source: British Journal of Ophthalmology

Ficlatuzumab + chemo shows early promise in refractory AML

The combination of ficlatuzumab plus chemotherapy showed considerable early promise in relapsed/refractory acute myeloid leukemia (AML) in a small phase-1 study.

Ficlatuzumab is an investigational, first-in-class monoclonal antibody that binds to extracellular hepatocyte growth factor (HGF) to prevent it from activating MET signaling and stimulating tumor growth.

Febrile neutropenia was the most common adverse event with the ficlatuzumab/cytarabine combination. Serious adverse events occurred in two patients, and there was one death deemed unrelated to the investigational therapy.

Source: Reuters Health

FDA approves spinal cord stimulation for diabetic neuropathy pain

The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).

The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment.

The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.

Source: Medscape

China’s first human infection case with Monkey B virus dies

A Beijing-based veterinarian who was confirmed as China’s first human infection case with Monkey B virus (BV) has died. The 53-year-old male vet, who worked for an institution researching on non-human primates, showed early-onset symptoms of nausea and vomiting, a month after he dissected two dead monkeys. The virus, initially isolated in 1932, is an alphaherpesvirus enzootic in macaques of the genus Macaca.

B virus (Cercopithecine herpesvirus 1; BV) is a macaque α-herpesvirus that is similar to the herpes simplex viruses (HSV1 and HSV2) of humans. From an animal health standpoint, BV is not a serious problem in its natural macaque host. However, the fatal effect of zoonotic BV infection in humans has driven the effort to eliminate BV from research macaques. Historically, the case fatality rate in untreated human BV infection has been greater than 70%, a rate similar to untreated HSV encephalitis in humans.

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