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The new 2021 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with CKD who are not receiving dialysis advises treating to a target systolic blood pressure of <120 mmHg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target — largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) — represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of ≤130/80 mmHg for patients with albuminuria or ≤140/90 mmHg for patients without albuminuria.

Source: Medscape

IL-10 to TNFα Ratio: Strong predictor of rejection found in the blood.

A total of 244 kidney transplant recipients from the University of Pittsburgh School of Medicine participated in the study, 162 in the training set, and 82 in the internal validation set.

The investigators determined the ratio of interleukin-10 (IL-10) to tumor necrosis factor–α (TNFα) produced by transitional-1 B cells (T1B) in peripheral blood 3 months after transplant.

Their main goal was to see whether that ratio could serve as an early predictor of T-cell-mediated rejection (TCMR) in kidney transplant recipients. As the authors explain, B cells secrete IL-10 and TNFα. The ratio of these two molecules is a measure of regulatory B-cell activity, which has been implicated in organ rejection.

Source: Science Translational Medicine

KarXT – a novel combination of xanomeline with trospium.

A novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent is associated with a greater reduction in psychosis symptoms compared with placebo, new research shows.

In a randomized phase 2 trial comprised of nearly 200 participants, xanomeline-trospium (KarXT) was generally well tolerated and had none of the common side effects linked to current antipsychotics, including weight gain and extrapyramidal symptoms such as dystonia, parkinsonism, and tardive dyskinesia.

The results showing robust therapeutic efficacy of a nondopamine targeting antipsychotic drug is an important milestone in the advance of the therapeutics of schizophrenia and other psychotic disorders.

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.

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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.

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

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.

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

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

Researchers from the National Institutes of Health (NIH) have discovered a new inflammatory disorder called Vacuoles, E1 enzyme, X-linked, Autoinflammatory and somatic Syndrome (VEXAS), which is caused by mutations in the UBA1 gene.

VEXAS causes symptoms that included blood clots in veins, recurrent fevers, pulmonary abnormalities and vacuoles (unusual cavity-like structures) in myeloid cells.