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Researchers have discovered a new type of bone cells “osteomorphs”

Researchers have discovered a new type of bone cells, called “osteomorphs,” which may be targeted for osteoporosis and other skeletal diseases.

The discovery came when Dr. Tri Giang Phan of the Garvan Institute of Medical Research in Darlinghurst, New South Wales and colleagues were studying osteoclasts, cells that resorb bone.

The osteomorphs were able to fuse together to form osteoclasts in a process the team calls “cellular recycling.”

As reported in Cell, the researchers performed single cell RNA sequencing to profile the genes that were highly expressed by osteomorphs. Those genes were shown to be important in bone structure and function in mice.

“Working with colleagues at Imperial College in London,” Dr. Phan said, “we showed that when 17 of these genes were knocked out, the mice developed abnormal bones.” Specifically, the deletions impacted the amount of bone, as well as bone strength.

Genes upregulated by osteomorphs also were shown to be important in human bone diseases. Specifically, investigation of human orthologues of osteomorph-upregulated genes were found to be involved in rare skeletal dysplasias caused by single-gene defects. Seventy-one of the genes also were found to be involved in the regulation of bone mineral density in a large population cohort, the UK Biobank Study, and may therefore be important in osteoporosis.

Source: Reuters

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More disappointing results for Vitamin C, Thiamine & Hydrocortisone in Sepsis

Among critically ill patients with sepsis, treatment with hydrocortisone, vitamin C (ascorbic acid) and thiamine (HAT) did not improve outcome in the randomized controlled VICTAS trial.

The VICTAS trial enrolled 501 adults in the intensive-care units at 43 U.S. hospitals with sepsis-induced respiratory dysfunction, cardiovascular dysfunction, or both; 252 were randomly allocated to the combination of vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) and 249 to placebo or placebo every six hours for 96 hours or until death or discharge from the ICU. Patients could receive open-label corticosteroids at the discretion of the clinical team; about a third of patients in each group were given corticosteroids.

The results showed no statistically significant difference in the HAT and placebo groups in the primary outcome, the number of consecutive ventilator- and vasopressor-free days in the first 30 days.

Source:

Clinic Hours In Article, New Drug

FDA approves treatment for rare Duchenne Muscular Dystrophy Mutation

The U.S. Food and Drug Administration granted approval for Amondys 45 (casimersen) injection for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping (Exons are pieces of DNA that provide information for making proteins in a person’s genome). The agency approved Amondys 45 based on an increase in dystrophin (a protein that helps keep muscle cells intact) production in skeletal muscle observed in patients treated with the therapy. This is the first FDA-approved targeted treatment for patients with this type of mutation. Approximately 8% of patients with DMD have a mutation that is amenable to exon 45 skipping.

Dose: 30 mg/kg IV

Side effects: Upper respiratory tract infections, cough, fever, headache, joint pain and throat pain.

Source: FDA

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Russia detects first case of H5N8 bird flu in humans

The H5N8 strain is deadly for birds, and this marks the first transmission of the strain from animals to humans and has reported the matter to the World Health Organization (WHO).

Humans and other mammals normally are not susceptible to infection by avian influenza A viruses. Nevertheless, several subtypes of avian influenza or bird-origin influenza viruses have infected humans; 3 of these subtypes have caused pandemics within the past century. At present, HPAI H5N1 is entirely an avian influenza subtype. Humans can become infected, but so far as is known, they must inhale or ingest massive viral doses from excreta or tissues of infected birds to do so.

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Zika vaccine candidate shows promise in Phase 1 Trial

The researchers randomized 100 healthy adult volunteers to an experimental Zika vaccine candidate known as Ad26.ZIKV.001 in either one-dose or two-dose regimens of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) or placebo. Approximately half (55%) of the participants were women, and 72% were White.

Approximately 80% of patients in both two-dose groups showed antibody responses for a year after vaccination. Geometric mean titers (GMTs) reached a peak of 823.4 in the low-dose/low-dose group and 961.5 in the high-dose/high-dose group. On day 365, the GMTs for these groups were 68.7 and 87.0, respectively.

A single high-dose vaccine achieved a similar level of neutralizing antibody titers, but lower peak neutralizing responses than the two-dose strategies, the researchers noted.

Source: Medscape

Clinic Hours In Article, COVID-19

FDA: COVID-19 not transmitted by food or packaging

“After more than a year since the coronavirus disease 2019 (COVID-19) outbreak was declared a global health emergency, the U.S. Department of Agriculture, the U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention continue to underscore that there is no credible evidence of food or food packaging associated with or as a likely source of viral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19,” said the statement attributed to Janet Woodcock, MD, acting commissioner of food and drugs at the U.S. Food and Drug Administration.

The statement noted that COVID-19 is a respiratory illness spread from person to person. Some researchers found small amounts of virus particles on food or food packaging, but the infection usually requires a much higher number of particles, the statement said.

Source: FDA

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Tocilizumab cuts deaths in hospitalized COVID-19 patients

Tocilizumab, sold under the brand name Actemra, is an intravenous anti-inflammatory monoclonal antibody drug used to treat rheumatoid arthritis. It was added to the trial in April 2020 for patients with COVID-19 who required oxygen and had evidence of inflammation.

The study data were from 2,022 COVID-19 patients who were randomly allocated to receive tocilizumab by intravenous infusion and who were compared with 2,094 patients randomly allocated to usual care alone. Researchers said 82% of all patients were taking a systemic steroid such as dexamethasone.

Results showed that treatment with tocilizumab significantly reduced deaths – with 596 (29%) of the patients in the tocilizumab group dying within 28 days, compared with 694 (33%) patients in the usual care group.

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FDA approves Evinacumab-dgnb for Homozygous familial hypercholesterolemia

The US FDA has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying meds in patients aged 12 and older with homozygous familial hypercholesterolemia (HoFH).

Mechanism: Evinacumab-dgnb is a fully-human monoclonal antibody that binds to and blocks the function of ANGPTL3.

Dose: 15 mg/kg) once a month via intravenous infusion.

Adverse Effects: Nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, nausea, pain in extremity and asthenia.

Cost: $450,000 per year

Extra notes: Reductions in LDL-C seen were observed as early as week 2 and maintained throughout the double-blind treatment period (week 24) and open-label trial period (through week 48).

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Pembrolizumab ‘Preferred Choice’ in MSI-H/dMMR Metastatic CRC

Pembrolizumab significantly improved progression-free survival compared with chemotherapy among patients with microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) metastatic colorectal cancer, according to results from the KEYNOTE-177 study.

Study Details: The KEYNOTE-177 trial included 307 patients with confirmed, untreated MSI-H/dMMR metastatic colorectal cancer who were randomly assigned to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles (n = 153) or the investigators’ choice of chemotherapy (n = 154). Chemotherapy regimens included modified FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) alone or in combination with either bevacizumab or cetuximab, or FOLFIRI (leucovorin, fluorouracil, irinotecan) alone or in combination with either bevacizumab or cetuximab. Patients in the chemotherapy group could cross over to pembrolizumab therapy after disease progression.

Source: Medscape

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Ruxolitinib as second line drug in Chronic GVHD

Ruxolitinib, a JAK inhibitor first marketed for use in myelofibrosis, is already approved for acute GVHD. The US Food and Drug Administration approved that indication last year on the basis of data from two previous trials, REACH 1 and REACH 2. The trials found that ruxolitinib was superior to best available therapy for treating patients with acute GVHD.

In the current REACH 3 study, Zeiser and colleagues compared ruxolitinib with best available therapy in 329 patients with moderate-to-severe cGVHD (both steroid dependent and steroid resistant).

Source: Medscape