Inflammatory activity of rheumatoid arthritis linked to specific cognitive impairments

The inflammatory activity in the body caused by rheumatoid arthritis is linked to specific cognitive impairments, finds a small comparative study, published in the open access journal RMD Open.

These are diminished visuospatial abilities, recall, abstract thinking, and the executive functions of working memory, concentration, and inhibition.

Inflammatory activity in rheumatoid arthritis has been associated with various systemic effects, including on the brain, but it’s not clear which specific cognitive domains might be affected.

To try and find out, the researchers compared the cognitive function of 70 adults with rheumatoid arthritis (80% women, average age 56) under the care of one hospital and 70 volunteers without rheumatoid arthritis, and matched for age, sex, and educational attainment.

Nearly 3 out of 4 of the patients (49; 72%) had ongoing moderate to high levels of systemic inflammatory activity caused by their disease, as measured by levels of indicative proteins and the degree of joint inflammation, despite conventional drug treatment. They had had their disease for an average of 10.5 years.

All 140 participants underwent comprehensive neurological and psychological assessment, plus various validated cognitive tests, and assessments of mood and quality of life between June 2022 and June 2023.

Specific cognitive abilities tested were: ability to process and order visuospatial information; naming; attention; language; abstract thinking; delayed recall; and orientation, plus executive functions of working memory, concentration, and inhibition.

Cognitive impairment was defined as a Montreal Cognitive Assessment (MoCA) score of less than 26 out of a maximum of 30.

Information was collected on other influential risk factors. These included age; sex; smoking; alcohol intake; high blood pressure; obesity; blood fat levels; diabetes; and a history of heart disease/stroke.

In general, those who were cognitively impaired tended to be older, have lower educational attainment, and more coexisting conditions, such as obesity, unhealthy blood fat levels, and high blood pressure than those with intact cognition.

But patients with rheumatoid arthritis achieved lower average scores in the Montreal Cognitive Assessment than the volunteers (23 vs 25), and lower scores for executive function. Cognitive impairment was recorded in 60% of them compared with 40% of the volunteers.

Significantly more of the patients also scored more highly for anxiety and depression and had lower quality of life scores than the volunteers.

Cognitively impaired patients had more substantial and persistent inflammatory activity than those patients who maintained their cognitive function. And they were more likely to have symptoms of depression and poorer physical capacity.

The factors associated with the greatest risk of cognitive impairment among the patients were obesity (almost 6 times the risk) and inflammatory activity throughout the course of the disease (around double the risk). As in the general population, older age and lower educational attainment were also risk factors.

By way of an explanation for their findings, the researchers point to previous suggestions that the chronic inflammation, autoimmune processes, and persistent symptoms of pain and fatigue associated with rheumatoid arthritis could underpin the diminution of cognitive function.

This is an observational study, so no definitive conclusions about causal factors can be drawn. And the researchers acknowledge various limitations to their findings, including the lack of imaging tests to detect vascular damage associated with cognitive impairment.

But they conclude: “These results support the hypothesis that [rheumatoid arthritis] is a chronic systemic inflammatory disease that affects multiple systems, including neural tissue.

“[And the] results underline the importance of earlier and more stringent control of the activity of arthritis and the need for new therapeutic strategies aimed at associated factors, with the aim of mitigating the risk of cognitive impairment in patients with rheumatoid arthritis.”

Reference:

Mena-Vázquez N, Ortiz-Márquez F, Ramírez-García T, Cabezudo-García P, García-Studer A, Mucientes-Ruiz A, Lisbona-Montañez JM, Borregón-Garrido P, Ruiz-Limón P, Redondo-Rodríguez R, Manrique-Arija S, Cano-García L, Serrano-Castro PJ, Fernández-Nebro A. Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis. RMD Open. 2024 Jul 23;10(2):e004422. doi: 10.1136/rmdopen-2024-004422. 

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Vaping and smoking together increases lung cancer risk fourfold, reveals research

People who both vape and smoke are four times more likely to develop lung cancer than people who just smoke, according to new study published by The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and College of Public Health. These findings were consistent across gender and race.

This is the first study to provide evidence that smoking in combination with vaping increases the risk for cancer compared to smoking alone. Researchers reported their findings in the Journal of Oncology Research and Therapy.

Study design and methods

Lung cancer is the leading cause of cancer-related deaths worldwide, resulting in 1.8 million deaths in 2020 alone. The American Thoracic Society has found that about 87% of these cancers can be directly linked to persistent tobacco smoking.

For this case-control study, researchers analyzed cigarette smoking and use of electronic cigarettes (also known as vaping) in 4,975 people with lung cancer compared to a control group of 27,294 people without cancer. All study subjects were from the same general geographic location (treated in Columbus, Ohio) and had the same distribution of age, gender and race.

Researchers found that vaping combined with cigarette smoking was eight times more common in people with lung cancer compared to the control group of people without lung cancer. In addition, the data showed that the risk of developing lung cancer was four times higher among people who combined vaping and smoking compared to those who only smoked.

“Our findings provide the first evidence that smoking in combination with vaping significantly increases the risk of lung cancer compared to smoking alone. Most people know that tobacco smoke contains cancer-causing chemicals but, overall, there is less knowledge about the chemicals that are inhaled through vape vapors,” said Randall Harris, MD, PhD, corresponding author of the study and professor of epidemiology in the College of Public Health.

Researchers say it is critical that regulators consider these additional health exposures in their regulation of the tobacco product industry to further protect public health, particularly when it comes to inhaled flavorings and nicotine dose concentrations.

“From a public health perspective, we have always been concerned about dual-use of both traditional and e-cig products. This study presents clear evidence showing that vaping in addition to smoking can increase your risk for lung cancer. This is especially concerning given the rate of youth and young adults using these products,” said lead author Marisa Bittoni, PhD, a researcher in the medical oncology division in the College of Medicine. “More research about the health effects of alternative tobacco products is critically needed to put science behind the regulation of the tobacco industry.”

Reference:

 Bittoni MA, Carbone DP, Harris RE (2024) Vaping, Smoking and Lung Cancer Risk. J Oncol Res Ther 9: 10229. https://doi.org/10.29011/2574-710X.10229.

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IBS following gastroenteritis may last more than four years in around half of those affected, reveals research

Irritable bowel syndrome (IBS)-characterised by abdominal pain, bloating, and altered bowel habit-may last 4 or more years following a bout of gastroenteritis in around half of those affected, finds a pooled data analysis of the available evidence, published online in the journal Gut.

Aggressive and pro-inflammatory bacteria, such as Proteobacteria and Enterobacteriaceae, and the virus responsible for COVID-19 infection, SARS-CoV-2, are possible culprits, the findings suggest.

IBS and recurrent indigestion of unknown cause (functional dyspepsia), are disorders of the gut-brain axis. Although common worldwide, their causes remain poorly understood, note the researchers.

But a sudden bout of gastroenteritis, usually brought on by a viral infection or food poisoning, is thought to be one of the possible triggers, explain the researchers, who add that an estimated 179 million people around the globe succumb to gastroenteritis every year.

To explore this further, they trawled research databases, looking for published studies on the development of IBS or functional dyspepsia after a bout of gastroenteritis in people monitored for at least 3 months after the episode.

From a haul of 75 eligible studies, 45, involving a total of 21870 people mostly from Europe and North America, were suitable for pooled data analysis. Sixteen studies were judged to be of high quality, with the rest judged to be of fair quality.

The prevalence of IBS after a bout of gastroenteritis was 14.5%. This was based on 46 studies involving 14,446 people. And the prevalence of functional dyspepsia was nearly 13%, based on 13 studies involving 5636 people.

Compared with those who had not had gastroenteritis, those who had were more than 4 times as likely to develop IBS and 3 times as likely to develop functional dyspepsia afterwards.

There were insufficient data to pool study results for the length of time functional dyspepsia persisted after gastroenteritis, but the pooled data analysis for IBS indicated that symptoms had persisted for between 6 and 11 months in 100 out of 201 people (50%) in 5 studies, and for 1-4 years in 125 out of 239 (52%) people in 3 studies.

And symptoms lasted for more than 5 years in 187 out of 471 (40%) people in 4 studies.

The pooled data analysis pointed to certain risk factors for developing IBS after a bout of gastroenteritis, the most influential of which was a history of anxiety: this was associated with a three-fold heightened risk.

Diarrhoea lasting more than 3 weeks was associated with more than double the risk, while admission to hospital and female sex were associated with, respectively, 65% and 59% heightened risks.

Analysis of the infectious agents involved showed that viruses were implicated in nearly 11% of cases (13 studies; 3585 people), bacteria in just over 18% (20 studies; 7050 people), and parasites in 30% (2 studies of 779 people).

The highest prevalence of IBS following gastroenteritis was associated with Campylobacter infection (21%), reported by 6 studies. And the odds of developing IBS were 5 times as high after a Proteobacteria species infection and 4 times as high for infection with Enterobacteriaceae species. Those infected with SARS-CoV-2 or parasites were 5 times as likely to develop IBS.

The prevalence of functional dyspepsia following gastroenteritis was nearly 14% for bacterial infections (4 studies; 759 people) and 10% for SARS-CoV-2 infection (5 studies; 1269 people), with Enterobacteriaceae species, the most common source of infection.

Although theirs is the largest pooled data analysis to date of the prevalence of IBS and functional dyspepsia after a bout of gastroenteritis, the researchers acknowledge various limitations to their findings.

The study design, definitions used, participant numbers and length of follow-up varied considerably among the included studies. And most of the studies focused on Western populations, with limited data from the Asia-Pacific region and Africa. And there was no microbiological evidence of gastroenteritis in several of the studies.

But the researchers point out: “The pathophysiology of [disorders of gut-brain interaction] is poorly understood, and these disorders are traditionally perceived by healthcare professionals as being mostly psychological and less ‘valid’ diseases, with a potential risk of underestimating patients’ expectations and complaints.”

And they conclude: “Generally, as acute gastroenteritis is a common disorder worldwide, our findings may be relevant for public health, and physicians should pay heed if their patients present with a recent episode of infectious gastroenteritis.”

Reference:

Porcari S, Ingrosso MR, Maida M, et alPrevalence of irritable bowel syndrome and functional dyspepsia after acute gastroenteritis: systematic review and meta-analysisGut Published Online First: 16 July 2024. doi: 10.1136/gutjnl-2023-331835.

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Common blood tests could improve cancer diagnosis for people with stomach pain or bloating: Study

The results of routine blood tests could be used to speed up cancer diagnosis among people with stomach pain or bloating, suggests a new study led by UCL researchers.

Most people who report these symptoms to their GP are referred for blood tests. However, it is not known how well these blood tests, used to explore a range of possible causes of ill health, can predict cancer risk.

The new study, published in PLOS Medicine, looked at data from more than 400,000 people aged 30 or older in the UK who had visited a GP due to stomach pain and more than 50,000 who had visited their GP due to bloating. Two thirds of this group had blood tests following their appointment.

The researchers found that, in 19 commonly used blood tests, abnormal results were linked to a higher risk of being diagnosed with cancer within a year. They estimated that, if these abnormal results were taken into account, there would have been a 16% increase in the number of people with undiagnosed cancer who were given an urgent referral, compared to assessment based on symptoms, age and sex alone.

This translates as an extra six people with undiagnosed cancer being urgently referred out of 1,000 people who had visited the GP with stomach pain or bloating, on top of 40 people with cancer being urgently referred already, without using blood test results.*

Lead author Dr Meena Rafiq, of the UCL Department of Behavioural Science & Health, said: “Our study suggests we can improve cancer detection with blood tests that are already available and that are routinely given to patients with non-specific symptoms whose cause is unclear. This could be an efficient, affordable way to improve early cancer diagnosis and in some cases increase the likelihood of successful treatment.

“Given that in practice it may be challenging for GPs to interpret a range of blood test data, our study points to the need for an automated tool that could assess cancer risk based on multiple variables.”

The study used anonymised patient data from the Clinical Practice Research Datalink (CPRD), collected from a network of GP practices across the UK between 2007 and 2016.

The researchers found that one in 50 (2.2%) people who went to the GP reporting stomach pain were diagnosed with cancer over the next 12 months. Precisely the same proportion (2.2%) of people reporting bloating were also diagnosed with cancer within a year.

In the UK, guidelines from the National Institute for Health and Care Excellence (NICE) say that people should be given an urgent cancer referral (i.e. referred to a specialist or for tests) if their risk of cancer is higher than 3%.

In the new study, the researchers found that people aged 60 or over who had gone to the GP with either stomach pain or bloating had a high enough risk to warrant an urgent cancer referral (that is, their risk was higher than 3%) regardless of blood test results. Currently, over-60s with stomach pain or bloating are only given a cancer referral in the UK if they have an additional potential cancer signal such as weight loss.

Risk of cancer was estimated to be 3.1% for men in their 60s reporting stomach pain, rising to 8.6% for men in their 80s with this symptom. For women in these age groups, the risk was 3.1%, rising to 6.1%.

The researchers cautioned that the incidence of cancer was likely to be higher in the study sample than among a broader group of people experiencing stomach pain or bloating who would not necessarily go to their GP or have blood tests.

In the UK study sample, the researchers found that, among people aged 30 to 59 years with abdominal pain or bloating, anaemia, low albumin, raised platelets, abnormal ferritin, and increased inflammatory markers strongly predicted a risk of undiagnosed cancer.

For example, in women aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to 10% with raised ferritin, to 9% with low albumin, to 8% with raised platelets, to 6% with raised inflammatory markers and to 4% with anaemia.

Currently, only raised platelets and anaemia are included in guidelines for cancer referral. The guidelines, the researchers noted, focused on the presence of ‘alarm’ symptoms and risk of cancer of a single organ, with limited guidance existing for vague symptoms that could be a sign of cancer in a number of different organs.

Dr Rafiq added: “Half of all people with as-yet-undetected cancer will first go to the doctor with vague symptoms that can be challenging to diagnose. Many of these patients are investigated in primary care with commonly used blood tests that could help to identify which patients are most likely to have underlying cancer and should be prioritised for referral.

“This research shows these common tests can substantially enhance assessment of cancer risk.”

The study also showed which types of cancer were most common for people with these symptoms and how this varied depending on age and sex. Overall, bowel cancer was most common, followed by prostate and pancreatic cancer in men, while in women bowel cancer was followed by breast and ovarian cancer.

The researchers said the findings on the predictive value of blood tests for cancer could not be extrapolated to other health systems with higher or lower rates of blood test use.

Reference:

Meena Rafiq ,Cristina Renzi,Becky White,Nadine Zakkak,Brian Nicholson,Georgios Lyratzopoulos,Matthew Barclay, Predictive value of abnormal blood tests for detecting cancer in primary care patients with nonspecific abdominal symptoms: A population-based cohort study of 477,870 patients in England, PLoS Medicine, https://doi.org/10.1371/journal.pmed.1004426.

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Hydroxychloroquine treatment effective against anogenital lichen sclerosus: Study

A new study published in the recent issue of the International Journal of Dermatology unveiled the positive potential of hydroxychloroquine in treating anogenital lichen sclerosus because of its high response rates and low frequency of side effects. Few studies in the past have examined the effectiveness of hydroxychloroquine in the management of anogenital or extragenital lichen sclerosus. Ignoring this disease might result in more severe scarring and the development of malignant transformation. In order to examine the clinicopathological characteristics, treatment response, outcomes of patients diagnosed with extragenital or anogenital lichen sclerosus, and treatment with hydroxychloroquine therapy, the team led by Christeebella Akpala conducted this comprehensive study.

Close to 70 patients with lichen sclerosus who received hydroxychloroquine therapy at the host institution between the period of 2018 and 2023 were included in a retrospective analysis. A total of 3 male patients and 67 female patients made up the entire cohort. Of the 23 individuals identified with extragenital lichen sclerosus, 16 underwent concurrent morphea overlap. The most common clinical manifestation was itching which was observed in 67% of the study group. A significant fraction of patients required hydroxychloroquine medication due to a connective tissue disease, this summed up to 36%. Of the 30 patients treated just for lichen sclerosus, 9 patients had no reaction and 21 patients showed a response.

Anogenital response rate to hydroxychloroquine was 84.6% overall when compared to 50% in extragenital lichen sclerosus, according to a more comprehensive study. 4 months was the median delay from the first reaction. 10 individuals (14.3%) experienced adverse effects, the most of which were moderate. Due to its retrospective design and dependence on data from a single institution, this study had a small sample size, making it one of the limitations. Overall, hydroxychloroquine shows potential as a treatment for anogenital lichen sclerosus due to its high response rates and minimal prevalence of side effects. However, further research and dedicated prospective trials, especially with large-scale are required to determine its definite efficacy.

Reference:

Akpala, C. O., Tekin, B., Torgerson, R. R., Wetter, D. A., & Nguyen, G. H. (2024). Treatment of lichen sclerosus with hydroxychloroquine: a Mayo Clinic experience. In International Journal of Dermatology. Wiley. https://doi.org/10.1111/ijd.17394

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Opioid-free propofol anesthesia may reduce postoperative nausea and vomiting after thyroid and parathyroid surgery: Study

A new study published in the journal of Anaesthesia found that patients having parathyroid and thyroid surgery underwent less postoperative vomiting and nausea when under opioid-free propofol anesthesia. The use of opioids for perioperative analgesia is common. Also, the postoperative hyperalgesia and increased analgesic consumption may be linked to the intraoperative administration of high bolus doses or continuous infusions of powerful opioids. Postoperative nausea and vomiting (PONV), extended sedation, ileus, and urine retention are examples of opioid-related side effects that might postpone the recovery and release or result in an unplanned return to the hospital. After thyroid and parathyroid surgery, postoperative nausea and vomiting are common and are linked to poorer patient outcomes. Thereby, Dan Wang and colleagues undertook this study to analyze if opioid-free propofol anesthesia would be less likely to cause postoperative nausea and vomiting in patients having who have undergone these operations when compared to opioid-inclusive propofol anesthesia.

At two medical facilities in mainland China, this research enrolled adult patients slated for thyroid and parathyroid surgeries. The patients were randomized 1:1, stratified by study location and sex, to either the opioid-inclusive group (sufentanil and propofol) or the opioid-free group (esketamine, lidocaine, dexmedetomidine, and propofol). Bispectral index 45 to 55 was reached by titrating propofol infusions and the patients were given multimodal analgesia with paracetamol and flurbiprofen axetil as well as prophylactic treatment for nausea and vomiting with dexamethasone and ondansetron. The prevalence of postoperative vomiting and nausea in the first 48 hours following surgery was the main result.

Out of the total 557 people nearly 394 individuals were deemed eligible for this study. The opioid-free anesthesia group (10/197, 5%) had a lower incidence of postoperative nausea and vomiting in the first 48 hours after surgery than the opioid-inclusive group (47/197, 24%). Furthermore, fewer instances of hypotension and desaturation following tracheal extubation, as well as greater patient satisfaction, were associated with opioid-free propofol anesthesia.

The opioid-free group faced a small delay in the time to tracheal extubation. The 30-day results and postoperative pain ratings for the two groups were comparable. Overall, the findings of this study found that the incidence of postoperative nausea and vomiting following thyroid and parathyroid operations was much lower when propofol anesthesia was opioid-free. Despite somewhat delayed tracheal extubation, the opioid-free regimen also resulted in lower rates of hypotension and desaturation, fewer rescue anti-emetics and increased patient satisfaction.

Source:

Wang, D., Sun, Y., Zhu, Y., Shan, X., Liu, H., Ji, F., & Peng, K. (2024). Comparison of opioid‐free and opioid‐inclusive propofol anaesthesia for thyroid and parathyroid surgery: a randomised controlled trial. In Anaesthesia. Wiley. https://doi.org/10.1111/anae.16382

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IM progesterone improves success rate of IVF in women with low progesterone levels, reveals research

A new study published in the International Journal of Fertility and Sterility found that among women with low progesterone levels, IM injection of 50 mg progesterone dramatically boosts the success rate of in vitro fertilization (IVF).

Long recognized for its critical role in the early stages of pregnancy, exogenous progesterone therapy was found to be able to prevent abortions caused by the removal of the corpus luteum before the seventh week of pregnancy, according to a series of elegant studies conducted in the early 1970s. Also, the antiprogesterone medication mifepristone works well to induce abortions in the first few weeks of pregnancy. Therefore, progesterone has long been the interest of scientists, who have concentrated on its therapeutic uses in the field of assisted reproductive technology (ART) as well as infertility therapy generally. Further studies show that, on the day of embryo transfer (ET), a low progesterone level dramatically lowers the likelihood of getting pregnant. Thus, Mahbod Ebrahimi and team wanted to determine how adding 50 mg of intramuscular progesterone per day to an 800 mg progesterone suppository might affect the success rate of IVF in women with low progesterone levels.

Infertile women who were candidates for IVF and had progesterone levels less than 9.2 ng/ml on the ET day were included in this concurrent open-label clinical study. These women were assigned randomly to either the intervention group or control group. In addition to 400 mg of progesterone suppository every 12 hours starting on the day of ET, the intervention group was provided 50 mg of progesterone intramuscularly once daily. Just 400 mg of progesterone suppositories were given to the control group every 12 hours. These medications were taken up until 12 weeks following the ET in the case of pregnancy.

There was a significant difference (P=0.035) between the number of women who had clinical pregnancy which was around 54 (50.0%) in the intervention group and 39 (36.8%) in the control group. There was a significant difference (P=0.042) in the number of women who had ongoing pregnancy in the intervention group (47, 43.5%) and the control group (33, 31.1%). The incidence of multiple pregnancies and abortions did not significantly differ between the two groups. The intramuscular administration of 50 mg progesterone considerably boosts the clinical and continuing pregnancy rates. Overall, this study suggests that IM injection of 50 mg progesterone increases the clinical and ongoing pregnancy outcomes.

Reference:

Ebrahimi, M., Akbari Asbagh, F., Davari Tanha, F., Amirkhanloo, F., Sahraiyan, G., Feizabad, E., & Lotfi, S. (2024). The Effect of Adding Daily 50 mg Intramuscular Progesterone to 800 mg Progesterone Suppository on The In Vitro Fertilization Success Rate in Women with Low Progesterone Levels: A Clinical Trial Study. International Journal of Fertility and Sterility, 18(Suppl 1). https://doi.org/10.22074/ijfs.2023.2008438.1506

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Using custom abutments and permanent cement tied to better retention of zirconia and metal-ceramic single crowns: Study

Using custom abutments and permanent cement tied to better retention of zirconia and metal-ceramic single crowns suggests a study published in the Clinical Oral Implant Research. 

A study was done to evaluate the effect of different cement types on the incidence of failure and loss of retention of zirconia and metal-ceramic single crowns (SCs) cemented on implant abutments. They placed 567 implant-supported SCs in 358 patients and retrospectively evaluated long-term retention for up to 12.8 years. The frameworks were made from metal alloy (n = 307) or zirconia (n = 260). SCs were cemented with permanent (glass-ionomer cement; n = 376) or semipermanent cement (zinc oxide non-eugenol cement; n = 191) on standardized (n = 446) or customized (n = 121) abutments. Kaplan–Meier curves were used to calculate the incidence of decementation. Differences between survival curves were assessed with log-rank tests. Cox-regression analysis was performed to evaluate multiple risk factors. Results: Of the 567 SCs, 22 failed because of technical complications and four because of implant loss. Loss of retention was observed in 50 SCs. Analysis revealed a 7% probability of loss of retention for zirconia and 16% for metal-ceramic SCs after 10 years (p = .011). After 5 years, loss of retention was higher for standardized abutments than for customized abutments (p = .014). The probability of loss of retention was higher with semipermanent than with permanent cement (p = .001). Cox-regression analysis revealed semipermanent cement as the only significant risk factor for SC failure (p = .026). In contrast to semipermanent cement, permanent cement provides acceptable long-term retention of cemented implant-supported SCs. These possible positive effects of customized abutments have to be controlled with larger sample sizes.

Reference:

Rammelsberg, P., & Klotz, A. L. (2024). Long-term retention and survival of cemented implant-supported zirconia and metal-ceramic single crowns: A retrospective study. Clinical Oral Implants Research, 00, 1–8. https://doi.org/10.1111/clr.14321

Keywords:

Using, custom, abutments, permanent, cement, retention, zirconia, metal-ceramic, single, crowns, study, Rammelsberg, P., & Klotz, A. L.

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NSAIDs Unlikely to Cause AKI After Urinary Surgery in Children, Study Finds

USA: In a recent study published in the Journal of Pediatric Urology, researchers found that postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) was unlikely to be a primary cause of acute kidney injury (AKI).cute kidney injury

Nonetheless, AKI remained a notable risk following lower urinary tract reconstruction surgeries. This risk is attributed to factors such as underlying health conditions, prolonged duration of surgeries, and significant fluid shifts during the procedure.

“There was no significant difference in the incidence of postoperative AKI between patients who received NSAIDs and those who did not follow lower urinary tract reconstruction, except for individuals with advanced chronic kidney disease (CKD),” the researchers reported.

The opioid crisis has prompted a shift towards greater use of non-opioid analgesics for postoperative pain management. Despite this trend, some pediatric urologists remain hesitant to prescribe NSAIDs due to concerns about potential AKI. Although earlier research has established the safety and effectiveness of NSAIDs in pediatric patients, their safety profile, specifically after lower urinary tract reconstruction procedures has not been thoroughly examined.

Against the above background, Darren Ha, Department of Pediatric Urology, Children’s Hospital Colorado, Aurora, CO, USA, and colleagues hypothesized there would be a difference in the incidence of postoperative AKI between patients who did and did not receive NSAIDs following surgery. For this purpose, they used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI (increase in creatinine ≥0.3 mg/dL or increase in creatinine ≥1.5x baseline or urine output <0.5 mL/kg/hr for six h).

A retrospective review was conducted on patients aged 2 to 18 who underwent lower urinary tract reconstruction procedures—such as bladder augmentation or creation of a catheterizable channel—between 2009 and 2021 and who had documented urine output.

The stage of CKD was evaluated using creatinine and cystatin C levels obtained within six months of surgery, based on the CKiD U25 equations. Patients who received NSAIDs were matched with those who did not, based on 11 characteristics, to evaluate differences in outcomes. The primary focus of the study was the incidence of AKI occurring within 48 hours post-surgery.

The study led to the following findings:

  • The unmatched cohorts included 243 patients. Propensity matching identified 166 patients in the NSAID arm and 41 in the no NSAID arm. Twenty-six patients with CKD stage 2–3 were included.
  • There was no significant difference in the incidence of postoperative AKI based on any KDIGO criteria (17.1% no NSAID versus 16.3% NSAID).
  • Median postoperative opioids fell from 0.88 mg/kg in the no NSAID arm to 0.37 mg/kg morphine equivalents in the NSAID arm, although this was not statistically significant.
  • Log-rank testing by Kaplan–Meier analysis demonstrated no difference in time to incidence of low urine output between the groups.
  • In the whole population not stratified by NSAID use, there were no differences in AKI between those with and without CKD (16.7% with versus 17.9% without CKD).

“Our findings reinforce the safety and effectiveness of NSAIDs as a viable alternative to opioid analgesics for postoperative pain management. However, acute kidney injury continued to pose a significant risk following these surgeries, independent of NSAID use, likely due to factors such as underlying health conditions, extended surgery durations, and fluid shifts,” the researchers wrote.

“Therefore, enhanced monitoring of patients is essential to mitigate the risk of postoperative complications,” they concluded.

Reference:

Ha, D., Halstead, N. V., Blanchette, E. D., Wilcox, D. T., Vemulakonda, V. M., Wood, D. N., & Rove, K. O. (2024). Risk of acute kidney injury after lower urinary tract reconstruction with early NSAID therapy: A propensity matched retrospective analysis. Journal of Pediatric Urology. https://doi.org/10.1016/j.jpurol.2024.07.005

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Cendakimab Shows Efficacy and Safety in Treating Moderate to Severe Atopic Dermatitis: Results from Clinical Trial

USA: In a phase 2 randomized clinical trial of 221 patients with moderate to severe atopic dermatitis (AD), treatment with cendakimab, an investigational anti-interleukin (IL)-13 monoclonal antibody, demonstrated efficacy after 16 weeks.

The findings, published in JAMA Dermatology, demonstrated improvements in pruritus, skin clearance, and the extent and severity of AD compared with placebo. Cendakimab was generally safe and well-tolerated.

Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine involved in the pathogenesis of atopic dermatitis (AD), by blocking its binding to IL13R-α1 and IL13R-α2 receptors. Proof-of-concept studies in AD endorse cendakimab as a potential treatment for type 2 inflammatory diseases. Considering this, Andrew Blauvelt, Oregon Medical Research Center, Portland, Oregon, and colleagues aimed to evaluate the safety and efficacy of cendakimab compared with placebo in patients with moderate to severe AD.

For this purpose, the researchers conducted a phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial from 2021 to 2021. It enrolled adult patients with moderate to severe AD and inadequate response to topical medications at 69 sites in 5 countries (Japan [n = 17], US [n = 26], Czech Republic [n = 8], Poland [n = 9], and Canada [n = 9]).

Patients were randomized in a 1:1:1:1 ratio to receive subcutaneous cendakimab, 360 mg, every two weeks; 720 mg, every two weeks; 720 mg, once weekly; or placebo.

The study evaluated the mean percentage change in Eczema Area and Severity Index (EASI) scores from baseline to week 16. Hierarchical testing with adjustment for multiple comparisons was conducted for the following comparisons: 720 mg once weekly versus placebo, followed by 720 mg every two weeks vs placebo, and finally, 360 mg every two weeks vs placebo.

The study led to the following findings:

  • Two-hundred twenty-one patients were randomized, and 220 received the study drug (43% women; mean age, 37.7 years; 720 mg, once weekly [24%]; 720 mg, every two weeks [25%]; 360 mg, every two weeks [25%]; placebo [26%]).
  • The primary efficacy endpoint was met for cendakimab, 720 mg, once weekly versus placebo (–84.4 versus –62.7) but missed statistical significance for 720 mg, every two weeks (–76.0 versus –62.7).
  • The treatment effect for 360 mg every two weeks (−16.3 versus placebo) was comparable with 720 mg once weekly (−21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted.
  • Of patients with treatment-emergent adverse events leading to discontinuation, 7.4% received 720 mg once weekly; 3.6% 720 mg every two weeks; 1.8% 360 mg every two weeks; and 3.6% placebo.

“In the randomized clinical trial, cendakimab proved effective, safe, and well-tolerated for patients with moderate to severe atopic dermatitis (AD). The primary endpoint, a significant reduction in Eczema Area and Severity Index (EASI) scores at week 16, was achieved with the 720 mg once-weekly dose. Across all doses, cendakimab showed continuous improvement in AD over the 16-week treatment period,” the researchers concluded.

Reference:

Blauvelt A, Guttman-Yassky E, Lynde C, et al. Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. Published online July 17, 2024. doi:10.1001/jamadermatol.2024.2131

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