 (AKI) are common in patients suffering from the 

 (COVID-19), its pathogenesis is poorly understood.

A team, led by Tariq U. Azam, Division of Cardiology, Department of Internal Medicine, University of Michigan, began to shed light on the pathogenesis between AKI and COVID-19.

The urokinase receptor system could be a key regulator of the intersection between inflammation, immunity, and coagulation, while the soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for acute kidney injuries. However, researchers do not know whether suPAR is linked with COVID-19-related AKI.

In the multinational, observational study, the investigators examined hospitalized adult COVID-19 patients. The researchers measured suPAR levels in plasma samples within 48 hours of hospital admission from 352 individuals and examined the association between suPAR levels and incident -in-hospital acute kidney injuries.

The mean age of the patient population was 61 years old.

A total of 91 (25.9%) individuals developed a AKI during hospitalization, 25 (27.4%) of which required dialysis. The median suPAR level was 5.61 ng/ml, while AKI incidence increased in conjunction with suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile).

However, no patient with a suPAR <4.60 ng/ml required dialysis during their hospitalization. In the multivariable analysis, the highest suPAR tertile was linked to a 9.15-fold increase in the odds of an acute kidney injury (95% CI, 3.64-22.93), as well as a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77-188.75). The investigators also found the association was independent of inflammatory markers and persisted across different subgroups.

“Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis,” the authors wrote. “SuPAR may be a key component of the pathophysiology of AKI in COVID-19.”

In a separate observational study of 3235 hospitalized patients with COVID-19 across the Mount Sinai Health System in New York, acute kidney injuries occurred in 1406 patients (46%), of whom 280 (20%) required dialysis. The researchers found about 66% of these injuries were moderate to severe and the majority of patients had evidence of proteinuria.

There have been other large studies conducted in both New York and China that produced similar findings regarding COVID-19 and acute kidney injuries.

Earlier this year, investigators found a mathematical way to forecast whether patients are at a high risk of developing an 

In the diagnostic study, the investigators examined 495,971 adult hospital admissions between 3 university hospitals in Illinois. The researchers used data from patients with serum creatinine (SCr) measurements from Loyola University Medical Center (LUMC) from 2007-2017 (n = 200,613), University of Chicago (UC) from 2008-2016 (n = 48,463), and at NorthShore University Health System (NUS) from 2006-2016 (n = 246,895).

In a time-to-event analysis, the investigators found a probability cutoff of at least 0.057 predicted the onset of a stage 2 AKI a median (IQR) of 27 hours prior to the eventual doubling in SCr concentrations in the University of Chicago cohort, 34.5 hours in the NUS cohort, and 39 hours in the LUMC cohort.

Soluble Urokinase Receptor (SuPAR) in COVID-19–Related AKI

Journal of the American Society of Nephrology

Articles

The highest suPAR tertile was linked to a 9.15-fold increase in the odds of an acute kidney injury.

Investigators Identify Key Component in COVID-19, Kidney Injury Link

Findings of a recent study showed house dust mites and grass allergens to be the most common triggers of 

 was found to be a comorbidity closely associated with the skin disease.

Currently, the global prevalence of atopic dermatitis stands at 20% in children and 3% in adults. The investigators of the study noted that although the disease is triggered by antigens, it is not clear which precise allergens are triggering factors.

Ömer Kutlu, MD, MRCP, and Ahmet Metin, MD, used file records from Kayseri Develi State Hospital of patients who underwent skin prick testing due to atopic dermatitis. They used the test results to determine the most common triggering allergens as well as any association with specific demographic factors.

Overall, they assessed 144 patients, with 73.6% being female. The median age of the population was 18 years (range, 3-51). Additionally, 63.2% of patients had a family history of allergic disease.

The skin prick test was administered by the same dermatologist so as to ensure standardization across all patients. Following administration of the test, positive results were evaluated and categorized into 4 levels of positivity degree– with 1 designating erythema ≤ 15 mm and no edema, and 5 designating edema > 6 mm as well as pseudopod development.

Thus, the investigators found that the most frequent allergens with ≥3 positivity (edema 3-6 mm), were grasses (31.2%), grasses mix (24.3%), Cynodon dactylon (15.3%), D. pteronyssinus (9.7%), D. farinae (7.6%), F. domesticus (7%), and Olea europaea (5.6%).

Furthermore, 65.3% of patients presented with a ≥1 degree of positivity, while 43.1% had a ≥3 positivity. Within both groups, 19.2% and 21.0%, respectively, demonstrated a reaction to only 1 allergen.

D. farinae and D. pteronysssinus positivity were much more frequent in patients >18 years than in those <18 years (

 .007, respectively). Besides these differences, there were no other statistical differences between other allergens and the age of the patients.

And finally, they found a statistical difference between ≥3 positivity and allergic rhinitis (

 = .006). Additionally, those with allergic rhinitis were much likelier to have a ≥1 and ≥3 positivity.

Those with atopic dermatitis who had comorbid allergic rhinitis and a ≥3 positivity were more typically triggered by grasses (44.5%), grasses mix (37.0%), Cynodon dactylon (27.2%), D. farinae (9.9%), D. pteronyssinus (8.6%), and Canis familiaris (8.6%).

“Detection of allergens, particularly in patients with atopic dermatitis, is crucial for the treatment and prevention of the disease,” Kutlu and Metin emphasized.

They concluded by referencing previous literature that assessed the associations among specific characteristics, such as geographic locations, various types of allergens, and patients with atopic dermatitis. Yet, they noted there is still potential for more in-depth research.

“Further multicenter, comprehensive SPT [skin prick test] based studies on atopic dermatitis will illuminate the possible triggers of the disease in atopic dermatitis in different geographies,” they wrote.

Evaluation of Skin Prick Test Results in Patients with Atopic Dermatitis

D. farinae and D. pteronyssinus positive skin prick test results were much more frequent in patients >18 years.

House Dust Mites and Grass Allergens Are Common Triggers for Atopic Dermatitis

New data analysis of the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry reveals a decline in hospital admission for 

Although the reasons for such findings can only be speculative, the investigators noted that this marked decrease should encourage public health officials to provide appropriate messages that especially target those that are wary of utilizing health services during the pandemic.

Jules Mesnier, MD, of the University of Paris, and colleagues used registry data to quantify changes in myocardial infarction-related hospital admissions following the lockdown in France. Their assessment also compared admission changes between patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI).

The FRENCHIE registry, which includes 21 participating centers, captures within 48 hours of symptom onset patients who present with either STEMI or NSTEMI. Therefore, Mesnier and colleagues used this timeframe to define recent acute myocardial infraction.

The investigators collected data over an 8-week period, which covered 4 weeks preceding lockdown and 4 weeks following it.

Patients admitted to the hospital due to COVID-19 who had subsequently developed myocardial infarction were excluded in their analysis. On the contrary, patients admitted for myocardial infarction who were then diagnosed with COVID-19 were included.

The primary outcome sought by the investigators was change in number of hospital admissions for all types of myocardial infarction, NSTEMI, and STEMI between the weeks preceding and following lockdown.

Additional objectives included further subgroup analyses of admission change and overall change in mortality between both periods.

Thus, the team reported that between February 17 and April 12, 2020, a total of 1167 patients were consecutively admitted to the hospital for recent acute myocardial infarction. Of the total, 583 had STEMI and 584 had NSTEMI.

Overall admission decreased from 686 to 481 between the periods (-30% [incidence rate ratio, 0.69; 95% CI, 0.51-0.70]).

Furthermore, admissions for STEMI decreased from 331 to 252 (-24% [IRR, 0.72; 95% CI, 0.62-0.85]), and admissions for NSTEMI decreased from 355 to 229 (-35% [IRR, 0.64; 95% CI, 0.55-0.76)].

Patients who were ≥80 years (n = 208) had a more noticeable decline than those who were younger (IRR, 0.64; 95% CI, 0.48-0.86).

They also noted that this decrease in admission had no association with regional COVID-19 prevalence or subgroup characteristics, such as gender, history of diabetes, history of hypertension, and smoking habits.

In-hospital mortality was numerically higher after the lockdown than before it—25 (5%) of 481 patients vs 23 (3%) of 686, respectively. However, the team did not consider it statistically significant.

Such trends, therefore, may likely be attributed to patient fears of exposure to the virus in the hospital.

“These concerns might have been amplified by the general message that people should stay at home.,” they wrote.

Another notable explanation may involve reduced exposure to air pollution, a known trigger of acute myocardial infarction. The investigators did not consider both explanations to be mutually exclusive.

Mesnier and team acknowledged a need to conduct the study with a longer survey period beyond the first month and after the end of lockdown.

“Meanwhile, health authorities should be fully aware of the current situation in order to deliver appropriate public health messages,” they concluded. “This is crucial in countries still fighting COVID-19, but also in the case of a second wave in countries that are past the first wave of the pandemic, or in case another pandemic occurs in the future.”

Hospital admissions for acute myocardial infarction before and after lockdown according to regional prevalence of COVID-19 and patient profile in France: a registry study

This decrease in hospital admissions had no association with regional prevalence of COVID-19. 

COVID-19 Lockdown Linked to Decline in Acute Myocardial Infarction Hospitalizations

A better understanding of the cut points of 

 (IBD) biomarkers could help yield better pharmaceutical options for patients.

The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in IBD. While FCP has been evaluated as a biomarker for mucosal healing in the past, cut points for LCT and nCD64 are less known.

A team, led by Ruben J. Colman, MD, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, identified the cut points for LCT and nCD64 associated with FCP remission, while evaluating the relationship between biochemical outcomes and infliximab trough concentrations. 

The investigators analyzed FCP, LCT, and nCD64 both before and after infliximab induction in pediatric patients with Crohn’s disease. They defined week 14 FCP biomarker remission as FCP <250 µg/g and clinical response as a weighted Pediatric Crohn’s Disease Activity Index of an <12.5 or Δ>17.5 improvement.

Finally, the researchers calculated predictive outcomes by receiver operating characteristics (ROCs).

The study included a total of 56 patients with Crohn’s disease. The ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934; 

 = 0.02) as the ideal cut points for week-14 FCP biomarker remission.

Both the end of induction infliximab-trough of >9.4 µg/mL (AUROC, 0.799; 

 = 0.002) and >11.5 µg/mL (AUROC, 0.835; 

 = 0.003) were linked with a FCP <250 and FCP <100, respectively.

The investigators also found patients achieving end of induction trough greater than 5 µg/mL had a median FCP improvement (dose 1-4) of 90% compared with a median of 35% with levels <5 µg/mL (

 = 0.024) with a similar median reduction in nCD64 (48% vs 20%; 

“This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy,” the authors wrote. “Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.”

Last year, investigators discovered the allele HLA-DQA1*05 could be a useful biomarker in predicting anti-drug antibodies for 

A team, led by Alekseis Sazonovs, Wellcome Sanger Institute, performed a genome-wide association study to identify variants linked to the time of development of anti-drug antibodies of 1240 biologic-naïve patients with Crohn’s disease starting anti-tumor necrosis factor (anti-TNF) drugs such as infliximab or adalimumab.

Anti-TNF has become the most widely used biologic drug to treat immunemediated diseases.

However, repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies could facilitate the selection of therapy and use of preventative strategies.

The HLA-DQA1*05 allele, which significantly increases the rate of immunogenicity (HR, 1.90; 95% CI, 1.60—2.25; 

 =5.88 × 1013), is carried by approximately 40% of Europeans.

Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn’s Disease

The cut points for LCT and nCD64 in Crohn’s disease were not previously known. 

Infliximab Effective Improving Biomarkers for Pediatric Crohn's Disease

Findings of a recent analysis indicated frozen fecal material from universal donors may be related to a higher rate of clinical remission among patients with 

The results produced positive evidence of the use of frozen fecal material.

Luciane de Fatima Caldeira, MS, and colleagues conducted a systematic review and meta-analysis to gather evidence on the efficacy and safety of fecal microbiota transplantation for IBD. They conducted searches in PubMed, Scopus, and Web of Science databases. The team searched for phrases including fecal microbiota transplantation, fecal microbiota, foecal microbiota, and faecal microbiota. Studies evaluated the efficacy/effectiveness or safety of fecal microbiota transplantation in patients of any age or gender diagnosed with IBD, with or without a treatment comparator and reporting response, remission, or adverse events.

Members of the team screened the titles and abstracts to identify irrelevant records. They used a standardized form to collect data on the general characteristics and clinical outcomes of the included studies.

The investigators included 60 studies for the qualitative synthesis and 36 were able to be used in the quantitative synthesis. The mean Newcastle-Ottawa Scale score for the quasi-experimental studies was 6 (range, 6-8).

The team noted 6 of 9 randomized controlled trials presented comparable data and were assessed in 2 meta-analyses—1 for clinical remission and 1 for clinical response. There were statistically significant differences observed for both outcomes, favoring fecal microbiota transplantation over placebo (355 patients, clinical remission: RR, 1.7 [95% CI, 1.12-2.56], I2=45%; clinical response: RR, 1.68 [95% CI, 1.04-2.72], I2=55%).

Overall, 24 quasi-experimental studies assessed clinical remission. An analysis resulted in a clinical remission prevalence of 32.3% (95% CI, 23.1-43.1), while the 9 randomized controlled trials resulted in a rate of 46% (95% CI, 31.4-61.4). There was an overall remission rate of 37% (95% CI, 28.8-45.9) and there was no significant difference between the 2 study designs (

In a stool type subgroup analysis, the clinical remission rate for fresh fecal material was 29.1%, while rates were 44.2% for frozen fecal matter, 57.2% when both types of stool were used, and 66.5% for capsules, with a statistical difference observed among the groups (

=.036).Patients who had Crohn disease presented a remission rate of 47.6% and those with ulcerative colitis demonstrated a remission rate of 35%.

For clinical response, 26 quasi-experimental studies and 7 randomized controlled trials resulted in a response of 53.5% and 54.4%, respectively. Those who received fresh fecal material had a clinical response of 52.1%, while patients who received frozen fecal material presented a response of 52.8%. If fecal material was received from relatives or acquaintances, the pooled clinical response was 37.1%. Those who received fecal material from universal donors had a response rate of 59.7%.

There was a frequency of 26.9% and 48.2% for adverse events among the quasi-experimental studies and randomized controlled trials, respectively. Among studies where fresh fecal material was transplanted, the frequency of any adverse event was 30.2%, while it was 43.2% among studies using frozen fecal material and 22.6% in those using capsules.

The investigators found fecal material transplantation for the management of patients with IBD demonstrated a response rate of 53.8% with a complete remission of 37%.

Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis

Fecal material transplantation for the management of patients with IBD demonstrates a response rate of 53.8% with a complete remission of 37%.

Positive Effects of Fecal Material Transplantation for IBD Management

In late May, a surgery team at the Northwestern Medicine Lung Transplant Program executed a medical marvel: the first double lung transplant in the US for a severely ill patient with 

Ankit Bharat, MD, chief of thoracic surgery and surgical director for the program, shared the incredible story on the 

, highlighting what his team has found to be foundational evidence for a last-ditch procedure for patients failing to recover from the virus.

Though the successful transplant set a precedent for COVID-19 care, Bharat also sees it helping to confront another great US public health issue: the underutilization of donor lungs.

“Only 15% of all the lungs coming from donors get utilized,” he explained. “We have a huge opportunity to understand donor management and improve the utilization of those lungs.”

Approximately 2700 lung transplants were performed in the US last year, Bharat said—with many more opportunities for procedures left unanswered, and an even greater count of donor lungs expired.

Many factors influence the minimal rate of lung transplants, and one that seems to be a self-perpetuating issue is the mortality risk, which Bharat said is approximately 10% now.

“But the gap can absolutely be overcome by how many donors are already there,” Bharat said. “I don’t personally think that’s a challenge we can’t overcome.”

Along with showing capability to better a respiratory distress-generating disease like COVID-19, surgeons have become capable of safely transplanting hepatitis C patient donor lungs—a previously taboo practice—as well as using ex vivo lung perfusion circuits to give second life to donor lungs.

“We certainly hope with the success we’ve had, and other centers on the east coast and west coast similarly performing these transplants and getting these patients through, the OPTN (Organ Procurement and Transplantation Network) includes COVID-19 as a diagnosis code in their registration of these recipients,” Bharat said.

Listen to Bharat’s perspective on improving lung transplants, as well as his team’s miraculous procedure, on Lungcast.

Low annual donor use and high mortality rates could be correlatively improved with greater embrace of opportunities.

How a COVID-19 Procedure Helps the Case for Better Lung Transplant Use

Findings of a recent study do not indicate nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with chronic obstructive pulmonary disease (COPD).

Still, the trial was underpowered as it did not reach full enrollment.

Yves Lacasse, MD, and colleagues designed a double-blind, placebo-controlled, randomized trial to determine whether nocturnal oxygen provided for a period of 3-4 years would decrease mortality or the worsening of disease so patients could meet current specifications for long-term oxygen therapy. Patients included had COPD with nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy. All patients had stable disease for at least 6 weeks before enrollment and had been nonsmokers for at least 6 months. The team defined nocturnal desaturation as a nocturnal home oximetry recording of at least 30% of the recording time with an oxygen saturation of less than 90%.

Lacasse and the investigators randomly assigned patients 1:1 to receive either home nocturnal oxygen from an oxygen concentrator or ambient air from a sham concentrator (placebo). At baseline, the team took clinical measurements including the Charlson comorbidity index, spirometry, lung volumes, carbon monoxide diffusion capacity, and arterial blood gas.

The nocturnal oxygen was delivered overnight from an electrically powered oxygen concentrated. Patients used supplemental oxygen throughout the night. The goal was to maintain a nocturnal oxygen saturation of more than 90% for at least 90% of the recording time. Oxygen adjustment was performed at home, starting with a rate of 2 liters per minute during a first test night and increased by increments of 1 liter per minute per night, up to 4 liters per minute.

Those in the control group received ambient air delivered through identical concentrators rendered ineffective by bypassing the sieve beds. Patients in this group also underwent a sham flow-rate adjustment procedure.

The primary outcome of the study was a composite of death from any cause or a requirement for long-term oxygen therapy. Additional outcomes included adherence to the intervention, exacerbation and hospitalization rates, and quality of life.

Overall, 243 patients were enrolled in the study—123 were randomly assigned to receive nocturnal oxygen and 120 received placebo. Of the patients, 79% met the definition for nocturnal desaturation on the 2 oximetry studies. There were 242 patients at the three-year follow-up and 231 patients at the four-year follow-up.

A majority of the patients, 97.5% who received oxygen had nocturnal saturation during the treatment within the target flow rate and 78.2% were given oxygen at a flow rate of 2 liters per minute. At 3 years of follow-up, 39% of those assigned to nocturnal oxygen and 42% of those assigned to placebo met the NOTT-defined criteria for long-term oxygen therapy or died (difference, -3 percentage points; 95% CI, -15.1 to 9.1; 

The investigators noted at 3 and 4 years of follow-up, the absolute differences between the 2 trial groups in the percentage of patients with a primary outcome event, the separate component of death, or the separate component of a requirement for long-term oxygen therapy were all no more than 6.5 percentage points. There was no significant difference between nocturnal oxygen and placebo in the composite outcome (HR, .87; 95% CI, .61-1.25; 

=.44) or its separate components of death (HR, .98; 95% CI, .6-1.63) and a requirement for long-term oxygen therapy (HR, .87; 95% CI, .57-1.34).

Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease

Unclear Whether Nocturnal Oxygen Positively Affects COPD Patients

Findings from a new study demonstrated that infants exposed to 

prior to birth had a two times higher odds of developing 

The results underscore the necessity of maintaining close follow up care in this vulnerable patient population.

In the past 10 years, prenatal opioid exposure (POE) has seen a dramatic increase among the US newborn population. As many as 100 infants are born daily with Neonatal Opioid Withdrawal Syndrome (NOWS). Therefore, there lies a great need in investigating long-term outcomes in such patients.

Isabella Cervantes, BA, of the University of New Mexico School of Medicine, and colleagues designed a retrospective cohort study to determine the association between POE and the likelihood of an altered immune response by 8 years of age. Immune response was measured by the development of asthma.

To do this. Cervantes and team pulled data from a comprehensive CERNER HealthFacts® U.S. national database, which captures de-identified, longitudinal health record data from 800 hospitals across the country.

The investigators used ICD-9-CM and ICD-10-CM diagnostic codes to identify infant patients born at term who had confirmed prenatal exposure to opioids or Neonatal Opioid Withdrawal Syndrome (NOWS).

Then they compared this population of patients with infants who had neither diagnoses at birth. Data was analyzed using IBM Statistical Package for Social Sciences, and Pearson’s Chi-Square test analysis was conducted to determine any association between POE and asthma diagnosis.

Overall, the study included 3021 patient records between 2000-2016. A majority of the population was male (50.7%), with Caucasian (61%) being the most represented race/ethnicity.

The investigators also noted that a majority of patients had Medicaid insurance (41.9%) and were raised in urban communities (92.5%).

As many as 50.4% of patients presented with POE—versus 49.6% who had no known exposure.

In their analysis, the investigators found that up to 66.3% of all asthma patients (n = 172) were prenatally exposed to opioids.

Thus, after controlling for race, gender demographics, and insurance type, they determined that the odds of developing asthma were two times higher for the prenatally exposed group (OR, 21; 95% CI, 1.4-3.0; 

They considered a major strength of the study to be the vastness of the national database. Therefore, the results could be consistent across different regions in the US.

A limitation, however, were the diagnostic codes used to identify their patient population of interest. For example, the codes used to identify infants with prenatal opioid exposure included other diagnoses such as Drug Withdrawal Syndrome in Newborn. Other confounding variables included smoking in the household, among others.

To address such limitations, they highlighted a need to undertake a longitudinal, prospective, multisite study for the future.

“These emerging results suggest infants with POE may have altered immune reactivity that not only impacts the newborn period but persists into childhood,” they wrote.

Future investigations should aim to characterize in greater detail the impact of POE on the immune system so that new follow-up strategies or effective interventions can be developed, they concluded.

Increased Incidence of Asthma in Children with Prenatal Opioid Exposure

​, was published online in The Univeristy of New Mexico Digital Repository. 


About 2/3 of children with asthma had been exposed to opioids prior to birth, according to a new retrospective study.

Prenatal Opioid Exposure Associated with Development of Asthma in Children

mark-timberlake-n8Bepoi9YRc-unsplash.jpg

 duration and the trajectory of cognitive decline, it has not been extensively studied in the past.

A team, led by Yanjun Ma, BA, Peking University Clinical Research Institute, Peking University First Hospital, investigated the link between sleep duration and cognitive decline in 

 individuals from a pooled analysis of a pair of nationally representative aging cohorts in China and the UK.

In the cohort, the investigators used data from waves 4-8 (2008-2009 to 2016-2017) in the English Longitudinal Study of Ageing and waves 1-3 (2011-2015) in the China Health and Retirement Longitudinal Study in a population-based setting.

There was a total of 28,756 participants in the 2 randomly enrolled cohorts, each of which was either living in England and at least 50 years or living in China and at least 45 years old.

Each participant self-reported sleep duration per night in face-to-face interviews.

The investigators sought main outcomes of global cognitive z scores, calculated according to immediate and delayed recall test, an animal fluency test, the serial sevens test, an intersecting pentagon copying test, and a date orientation test.

The team analyzed the from 20,065 total patients, 9254 from the English Longitudinal Study of Ageing with a mean age of 64.6 years old and 10,811 from the China Health and Retirement Longitudinal Study with a mean age of 57.8 years old.

In the English Longitudinal Study of Ageing the medial follow-up was 8 years and in the China Health and Retirement Longitudinal Study the mean follow-up was 4 years.

During the 100,000 person-years of follow-up, the global cognitive z scores in individuals with 4 hours or less (pooled β = −0.022; 95% CI, −0.035 to −0.009 SD per year; 

 = 0.001) and 10 hours or more (pooled β = −0.033; 95% CI, −0.054 to −0.011 SD per year; 

 = 0 .003) of sleep per night declined faster than in the reference group of 7 hours per night after adjusting for a number of covariates.

The investigators also observed an inverted U-shaped association between sleep duration and global cognitive decline.

“In this pooled cohort study, an inverted U-shaped association between sleep duration and global cognitive decline was found, indicating that cognitive function should be monitored in individuals with insufficient (≤4 hours per night) or excessive (≥10 hours per night) sleep duration, the authors wrote. “Future studies are needed to examine the mechanisms of the association between sleep duration and cognitive decline.”

Previously, researchers have reported a strong association between sleep and cognitive function in older adults and while a number of cohort studies have examined whether baseline sleep duration was linked to cognitive decline and incident dementia, the results have been inconsistent.

Association Between Sleep Duration and Cognitive Decline

Those who slept more than 10 hours or less than 4 hours per night declined faster than those who slept about 7 hours per night.

Sleep Duration Linked to Cognitive Decline for Geriatric Individuals

 and transfusion-dependent thalassemia offers promise for those unresponsive to standard care, there still remain great challenges in advancing this relatively novel treatment domain.

A new review co-authored by Joachim Kunz, MD, and Andreas Kulozik, MD, PhD, of the Department of Pediatric Oncology, University of Heidelberg, Germany, laid out the potential for gene therapy, such as gene editing and addition. They also commented on the current roadblocks for making such practices available worldwide.

As a result of large migration from areas of high sickle cell disease and ß-thalassemia prevalence, such pathological mutations have become the most common genetic disorders globally. Thus, the authors noted that shifting demographics in countries with once low prevalence of hemoglobinopathies have led to a rising in patient numbers.

The current standard of care for these disorders, then, includes disease-modifying treatment with red blood cell transfusions, iron chelation, and pharmacologic induction of fetal hemoglobin (HbF), which require a combining with treatment of symptoms and complications.

Nonetheless, a gene therapy option for transfusion-dependent thalassemia has emerged in the past few years.

In 2019, the European Medicine Agency (EMA) conditionally licensed gene addition therapy (Zynteglo) for the European Union, based on data showing lentiviral transduction of hematopoietic stems cells.

The licensing was supported by the HGB-204 and HGB-205 trials run by bluebird bio, which found that 12 of 13 evaluable patients with a non-ß

 genotype became independent from red blood cell transfusions (HGB-204 median duration, 38 months).

The treatment is indicated for patients with transfusion dependent non-ß° thalassemia major, aged ≥12 years old and who have a non-ß

 genotype. Additionally, these patients must have no available HLA-matched sibling as a stem donor.

Kunz and Kulozik referenced various other clinical trials aimed at providing gene therapy in patients with sickle cell disease.

“In [sickle cell disease], successful gene therapy must reduce the frequency and severity of vasoocclusive complications such as pain crises or acute chest syndrome and ultimately prevent or even reverse end organ damage,” they wrote.

After optimization of therapy protocols, the study investigators were able to use gene addition to reduce the frequency of vasocclusive complications.

The review also acknowledged current advanced preclinical studies focused on gene editing and repair. However, such clinical experience with these techniques is limited in its availability. 

Despite the various techniques being developed under the umbrella of gene therapy, the authors suggested that a combination of strategies might be necessary to optimize patient outcomes.

And finally, there are still 2 major obstacles that they noted must be addressed before use of gene therapy can become widespread.

The first is that current protocols still require myeloablative conditioning. Even if the cumulative dose of chemotherapy is reduced, especially in comparison to allogeneic stem cell transplantation, there remains the risk of infertility and secondary neoplasms.

Furthermore, the sophisticated logistics and high cost of therapy can certainly pose a challenge in countries and healthcare systems with limited resources and a high prevalence of hemoglobinopathies.

“Obviously, the development of conditioning regimens with reduced toxicity and lowering the costs of gene therapy are the most important steps required to bring this treatment option to more than a small number of selected patients,” Kunz and Kulozik concluded.

Gene addition and editing strategies have potential of curing sickle cell disease and transfusion-dependent thalassemia, but there are still many obstacles that must be overcome.

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