Jeff Temple, PhD, licensed psychologist, vice dean for research, UTMB School of Nursing, discusses the rising mental health crisis in adolescents and strategies for community stakeholders to mitigate this issue with AJMC® Associate Editor Matthew Gavidia.

Take a DEEP DIVE Into Medical World News

AJMC Associate Editor Matthew Gavidia sat down with Shannon Burke, SVP and general manager of health systems at Synchrony Health & Wellness, to discuss the importance of exercise on her physical and mental health and how it has improved her productivity.

Find Out What Managed Care Experts Like to Do AFTER HOURS

For our latest After Hours interview, Traci Thompson, MD, MBA, chief medical officer, Humana Healthy Horizons of Florida, discusses her drive to improve health equity in underserved east Tampa, with AJMC® Associate Editor Matthew Gavidia.

Learn About Managed Care Experts' AFTER HOURS Pursuits

Matthew is an associate editor for The American Journal of Managed Care® (AJMC®). He joined AJMC® in 2019 and creates content for 

, a 24-hour online program developed MJH Life Sciences® focusing on pressing topics within managed care, as well as the nonwork-related activities of health care stakeholders.

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Patients primarily treated by a dermatologist and those receiving biologic therapy were more likely to report satisfaction with treatment for 

 (HS), according to study findings published in 

HS is linked with a substantial quality of life burden among patients, with findings of the Global Survey Of Impact and Healthcare Needs (Global VOICE) project indicating that 23%, 30%, and 31% of patients experienced flare daily, weekly, or monthly, respectively. Despite nearly 50% of patients with HS reporting dissatisfaction with their medical treatment, factors related to adverse care management outcomes have not been explored.

“Treatment in HS remains the most fundamentally important gap in care for the disease state. To date, there is one regulatory approved treatment for moderate-to-severe HS, wherein about half of patients are expected to have approximately a 50% improvement from baseline count of inflammatory nodules and abscesses,” the study authors wrote.

“Information from patients with HS on factors influencing satisfaction with treatment may support patient-centred strategies to optimize outcomes.”


Researchers derived data from the cross-sectional Global VOICE survey to measure associations between treatment satisfaction and clinical and treatment-related characteristics. The questionnaire was administered to 27 institutions, mainly HS referral centers, in 14 countries from October 2017 to July 2018.

Fifty questions related to patient demographics, perspectives on diagnosis and care, pain and symptoms, life impact, comorbid conditions and treatment were part of the survey. The primary outcome investigated was patients’ self-reported overall satisfaction with their current treatments for HS, rated on a 5-point scale from “very dissatisfied” (1) to “very satisfied” (5).

Associations between treatment satisfaction and the following predictor variables were explored: age, sex, delay in HS diagnosis, body mass index (BMI), tobacco use (current, former, never), primary management of HS by a dermatologist (yes/no), depression, anxiety, number of comorbidities, treatment type, and flare frequency (every 6 months, every 3 months, monthly, weekly, daily).

Current treatment was classified as topical or injection only, nonbiologic systemic, biologic, or no medical treatment.

A total of 1418 patients with HS were included in the survey, in which a majority were European (55%) or North American (38%) and female (85%). Overall, 45% of participants reported being either dissatisfied or very dissatisfied with their current medical treatment.


After adjusting for potential covariates, findings showed that patients primarily treated by a dermatologist for HS were nearly twice as likely (odds ratio [OR], 1.99; 95% CI, 1.62–2.44; 

 < .001) to report being satisfied with current treatment vs those not primarily treated by a dermatologist.

Treatment with biologics was also associated with higher satisfaction (OR, 2.36, 95% CI, 1.74–3.19; 

 < .001) relative to treatment with nonbiologic systemic medications, as well as lower frequency of flares (every 6 months) vs higher frequency (3 months, monthly, weekly, or daily).


Conversely, tobacco smoking (OR, 0.78; 95% CI, 0.62–0.99; active vs never), depression (OR, 0.69; 95% CI, 0.54–0.87), and increasing number of comorbidities (OR, 0.88 per comorbidity; 95% CI, 0.81–0.96) were associated with lower treatment satisfaction.

Limitations of the analysis included its use of self-reported data and lack of data on disease severity.

“A number of factors appear to influence satisfaction with treatment among patients with HS…Awareness of these factors by physicians and patients may support partnered decision making, which may improve outcomes,” concluded the study authors.


Midgette B, Strunk A, Akilov O, et al. Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project. 

. Published online July 30, 2022. doi:10.1111/bjd.21798

Articles

Tobacco smoking, depression, and increasing number of comorbidities were associated with reduced treatment satisfaction among patients with hidradenitis suppurativa.

Evaluating Factors Associated With Treatment Satisfaction in Hidradenitis Suppurativa

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Certain gut microbiota are strongly associated with the pathophysiology of 

 (HE), according to research published in 

HE is a neuropsychiatric complication as a result of liver cirrhosis (LC). While past research has suggested gut microbiota plays a role in the pathogenesis of HE, this has not been explicitly confirmed.

In this study, the authors analyzed how the gut microbial profile changed among patients with HE or decompensated LC, compared with patients with compensated LC and patients without any health complications.

The study included 26 patients with decompensated LC, 27 patients with compensated LC, and 26 healthy controls.

All participants were aged 50 and older, with a mean (range) age of 68.4 (52−85), 67.6 (54−81), and 61.4 (50−79) in the decompensated LC, compensated LC, and healthy control groups, respectively. All 3 groups also had slightly more men than women, and mean BMI was slightly higher in both LC groups compared with the control group.

In an effort to clarify which functional gut microbial species are associated with HE, the authors focused on patient responses to being treated with rifaximin (RFX), a nonabsorbable antibiotic used to treat HE. Patients who experienced reduced plasma ammonia levels after RFX were defined as responders, and patients who saw no decrease were defined as nonresponders.

The authors also collected fecal samples from all patient groups and compared their fecal gut microbial profiles using 16S ribosomal RNA gene amplicon and metagenomic sequencing, and identify the specific species using linear discriminant analysis effect size.

, which can produce ammonia, was the most significantly abundant gut microbiota in the group of patients with HE. The microbiota’s ability to increase levels of blood ammonia and brain glutamine was experimentally verified in mice.

was also identified as a significantly abundant gut bacterium in patients with RFX-nonresponsive HE after RFX administration.

enhanced urease activity of recombinant urease itself, implying that 

could amplify ammonia production of surrounding 

-positive microbiota,” the authors noted. “Furthermore, the sensitivity of 

to RFX depended on conjugated secondary bile acid levels, suggesting a therapeutic potential of the combined use of secondary bile acid levels with RFX for enhancing the efficacy of RFX.”

According to the others, this may begin to explain why 

was found to be a dominant species among patients who were nonresponders, as these participants had plasma secondary bile acid levels much lower compared with responders.

According to the authors, targeting these identified bacteria is a potentially effective strategy to treat HE.

“In addition, although blood ammonia levels are generally thought to be unstable, future studies might be able to specify a new biomarker of HE through detailed characterization of specific gut microbiota, such as 

, identified here in patients with HE,” the authors concluded.

Yukawa-Muto Y, Kamiya T, Fujii H, et al. Distinct responsiveness to rifaximin in patients with hepatic encephalopathy depends on functional gut microbial species. 

. 2022;6(8):2090-2104. doi:10.1002/hep4.1954

Urease-positive Streptococcus salivarius was the most significantly abundant gut microbiota in patients with HE.

Study Identifies Gut Microbiota Linked to HE Pathophysiology

Rose is a freelance writer for The American Journal of Managed Care® (AJMC®), where she previously worked as an editor.

She has a BA in journalism & media studies and Spanish from Rutgers University. You can connect with Rose on 

 (BTC) expands, the clinical utility of comprehensive genomic profiling (CGP) to detect potential therapy targets warrants further research. A 

suggests that CGP can help with clinical decision-making and predict clinical outcomes in advanced BTC.

BTC, which encompasses cancers in the biliary tract—including intrahepatic and extrahepatic cholangiocarcinoma (ICC and ECC), gallbladder cancers, and ampullary cancer—has a 5-year survival rate lower than 15%. A lack of established early detection methods in tandem with a lack of curative therapies contribute to the poor prognosis patients with BTC face. With novel therapeutic strategies under investigation, review authors Takada, et al., aimed to evaluate the utility of CGP for patients with BTC and to identify genomic alterations that may help with prognostication.

The immunotherapy armamentarium for cancer overall has been growing, but combination gemcitabine and cisplatin chemotherapy is the current standard of care in advanced BTC. Recent research suggests that adding the immune checkpoint inhibitor (ICI) durvalumab to the gemcitabine-cisplatin regimen may be an effective approach, with a phase 3 study underway to confirm the benefit of adding durvalumab.

The FDA has already approved 2 novel targeted therapies: pemigatinib, a fibroblast growth factor receptor inhibitor; and ivosidenib, an isocitrate dehydrogenase 1 variant inhibitor. Tumor-agnostic ICIs and neurotrophic receptor tyrosine kinase (NTRK) inhibitors are also options in patients whose tumors fit certain genomic criteria. Human epidermal growth factor receptor-2 (EGFR-2)–targeted therapies for BTC with amplified Erb-B2 receptor tyrosine kinase 2 (

) is another emerging targeted therapy option. Overall, the increasing number of known targets and potentially applicable therapeutics supports the potential benefit of CGP in this patient population.

The study included 72 patients with advanced BTC at 5 hospitals in Japan who underwent CGP and met performance status and specimen eligibility criteria. Of these patients, 26 (36.1%) had ICC, 22 (30.6%) had ECC, 21 (29.2%) had gallbladder carcinoma, and 3 (4.2%) had ampullary carcinoma. The median patient age was 70 years, and all patients had undergone chemotherapy. Most samples (65.3%) were surgical specimens, but endoscopic ultrasound-guided fine needle aspiration and a cell block prepared from ascites were also feasible methods, the authors noted. In the study cohort, 66 samples underwent testing with F1CDx sequencing (91.7%), 5 were done with F1LCDx, and 1 (1.4%) was done with an NCC Oncopanel.

All patients in the cohort showed genomic alterations, with the most common being tumor protein p53, cyclin-dependent kinase inhibitor 2A (

) alterations. Of these patients, 42 (58.3%) had actionable genomic alterations and 14 (33.3%) had multiple actionable alterations. However, there were not distinct patterns associated with the 4 BTC subtypes as previous reports have suggested.

Eight (11.1%) of the 42 patients with actionable genomic alterations were treated with therapies matched to their genotypes in the second line or later. Gallbladder carcinoma patients with high TMB or MSI were given an ICI and experienced stable and progressive disease, respectively. Patients with ICC and an 

fusion gene were given pemigatinib, which elicited partial responses. Both treatments were covered by public insurance. Patients with high programmed death ligand 1 or 2 (

) expression, high TMB, breast cancer gene 2 (

 expression received investigational agents.

Genomic alterations found in the study cohort were not significantly associated with clinical features or overall survival (OS), except in the case of 

loss predicting poor prognosis and shorter OS in patients with ICC. Clinical features did not correlate to OS in most cases, although OS in patients with gallbladder carcinoma was notably shorter than OS in patients with ECC. The authors noted that normally, gallbladder carcinoma patients face a more positive prognosis than those with ICC or ECC, but the patients in the study cohort represent a cohort of patients with advanced cancer who did not respond to typical therapies.

While the study had a limited number of patients and no definitive conclusion, the findings support the use of CGP in clinical decision-making for advanced BTC.

“Although the Japanese health insurance system does not allow CGP before initial treatment, performing CGP in an earlier phase of therapy may improve clinical outcomes,” the authors wrote. “Further efforts are needed to delineate our results and combat this aggressive malignancy.”

Takada K, Kubo T, Kikuchi J, et al. Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study. 

. Published online September 2, 2022. doi:10.3389/fonc.2022.988527

A small study suggests that comprehensive genomic profiling can help with clinical decision-making and predicting clinical outcomes in advanced biliary tract cancer, but further research is needed.



Study Supports Comprehensive Genomic Profiling for Patients With Biliary Tract Cancer

 (DHA) that provides tailored self-management action advice to patients with inflammatory arthritis (IA) was linked to significant improvements in health-related quality of life (HRQOL) and disease activity, according to a small study published in 

Recent EULAR recommendations highlighted the importance of encouraging patient self-management strategies and the vital role of digital formats in helping patients do so.

Other research suggests most patients with rheumatic and musculoskeletal diseases regularly use smartphones. Because of this, the study authors claim DHAs are a strong potential format for patients to achieve and maintain disease remission through continuous, on-demand support.

The study focused on the Midaia Software, which was divided into a mobile app for patients (Mida Rheuma App) and a complementary app for the physician (DocBoard Web-App).

The study was small, with only 17 of 19 enrolled patients completing the study and a lack of control group.

Of these 17 patients with IA, 12 had rheumatoid arthritis, 1 had axial spondyloarthritis, and 4 had psoriatic arthritis. Seven patients were male, and the median (SD) age was 40.5 (12.2) years, with participants ranging in age from 19 to 63 years.

Treatments the patients received included nonsteroidal anti-inflammatory drugs, glucocorticoids, hydroxychloroquine, methotrexate, leflunomide, sulfasalazine, apremilast, Janus kinase inhibitors, tumor necrosis factor inhibitors, IL-6 receptor inhibitors, and IL-17 inhibitors. The authors observed no substantial intensification of antirheumatic treatment during the study.

HRQOL was measured by the Short Form-36 (SF-36) Health Survey. The authors assessed SF-36 Total Score, Physical (PCS) and Mental Component Summary (MCS) scores, and 8 scales on physical function, role limitations due to physical function, bodily pain, general health, mental health, role limitations due to emotional health, social functioning, and vitality.

The study demonstrated a significant improvement in patients’ HRQOL assessed by Short Form-36 (SF-36) at day 34, with a 14.4% improvement in Total Score.

Statistically significant improvements were also reflected by a 23.6% increase in the Physical Component Summary (PCS) of SF-36 score (

= .024), a 76.9% increase in the role limitations due to physical health score (

= .022), and a 17.1% increase in the general health score (

Clinical significance was based on definitions of 5 points as minimal clinically important difference (MCID) in separate scores and 2.5 in SF-36 Total Score, PCS and MCS scores.

“According to 95% CIs and MCID relation, PCS, ‘role limitations due to physical health,’ and ‘general health’ demonstrated probable clinical significance,” the authors found. “For the SF-36 Total Score, ‘emotional well-being’ and ‘energy/fatigue’ clinical significance was not demonstrated for 95% CI, but it was probable for 90% CI.”

Disease activity also significantly improved, with a 38.4% decrease in Clinical Disease Activity Index and 39.9% decrease in Simple Disease Activity Index.

The Patient Health Questionnaire-9 also demonstrated significant improvements surrounding depression among patients with IA, with a 13.5% improvement.

The Mida Rheuma App also yielded high levels of usability by users.

“This suggests that using a personalized disease management program based on DHA significantly improves several measures of patient-reported outcomes and disease activity in patients with inflammatory arthritis in a timely manner,” the authors said. “These findings highlight the potential of complementary digital therapy in patients with inflammatory arthritis.”

However, the study’s pilot design, small sample size, short study duration of 34 days, and lack of a control group may very likely lead to bias and influence the findings.

“Since the pilot design of our study does not allow for final conclusions, a planned randomized controlled trial is needed to confirm these preliminary positive results,” the authors noted. “Furthermore, rheumatologists and patients need to be educated about the growing number of supportive digital tools available.”

Fedkov D, Berghofen A, Weiss C, et al. Efficacy and safety of a mobile app intervention in patients with inflammatory arthritis: a prospective pilot study. 

. 2022;1-14. doi:10.1007/s00296-022-05175-4

A mobile app providing self-management action advice to patients with inflammatory arthritis (IA) was linked to significant improvements in health-related quality of life (QOL) and disease activity.

Improved QOL, Disease Activity Seen in Patients With IA Using Tailored Self-management App

 (AD) with biologic therapy requires shared decision-making between the dermatologist and patient to ensure that the pros and cons of each therapy are known and the right drug is given, said Jason Ezra Hawkes, MD, MS, FAAD, board-certified dermatologist and associate professor of Dermatology at the University of California Davis in Sacramento

Can you discuss factors to consider in recommending biologic treatment for a patient with AD, whether as monotherapy or in combination with other medications?

When I think about biologics, I'm thinking about the severity of the patient. We were trying simpler things for maybe more localized disease or mild disease, but we need to sort of up our game in terms of treatment and management strategies as disease worsens. And so dupilumab was really a game changer for the treatment of AD, because it was so effective in so many patients, and the tolerability was actually very, very good.

So, I really rarely see lack of effectiveness or issues with tolerability with dupilumab, for example. So, it's been a big success for a lot of patients and we've seen other biologics that are coming out, specifically those that just block IL-13, for example, rather than IL-4 and IL-13. That also shows promise, but, as mentioned, these therapies don't always work for every patient. Some patients aren't responders, or it’s not covered by insurance, or they're afraid of injections. So, we also have to think about other strategies. Sometimes we have to use some of the oral medications or phototherapy; methotrexate or cyclosporine, for example, are sometimes required.

So, when we start thinking about these therapies, we want to have that shared decision-making conversation with patients and talk about the pros and cons. And most of the time, I'd say with biologics, we will sort of stick with monotherapy because it works for most patients. But occasionally, we need to add on other therapies like topical steroids, as I mentioned, methotrexate, which can be used safely with dupilumab, for example.

We're starting to see new therapies populate this space. Janus kinase (JAK) inhibitors are a class that'll be very exciting for this area, but it will also have its pros and cons. So, again, I think it comes back to having that shared decision-making conversation with our patients, so that they really understand what the ups and downs of the therapies are, but more importantly, we want to make sure that we ultimately find that therapy that alleviates the burden of this disease on our patients.

Videos

Jason Ezra Hawkes, MD, MS, FAAD, board-certified dermatologist and associate professor of dermatology at the University of California Davis in Sacramento, spoke on the importance of shared decision-making in deciding which biologic would best alleviate disease burden in patients with moderate to severe atopic dermatitis.

Dr Jason Ezra Hawkes Discusses Clinical Considerations for Biologic Treatment in Atopic Dermatitis

Christina is the assistant managing editor for The American Journal of Managed Care® (AJMC®) and The American Journal of Accountable Care® (AJAC), and joined AJMC® in 2016. She oversees the entire process of the publication of the print journals, from manuscript submission to publication, and works with the editors in chief and editorial boards to promote the journals.

She has a BS in public health from Rutgers University. You can connect with Christina on 

A new study examined the potential of using dermoscopy to distinguish 

 (BCC) from benign skin tumors and found that despite some differences in the frequency of dermoscopic features between the conditions, dermoscopy alone is not sufficient for a reliable diagnosis.

, noted that although most cases of BCC can be diagnosed based on clinical and dermoscopic assessment, some presentations can overlap with benign adnexal skin tumors such as trichoblastic tumors (TT). The study authors noted that histopathological assessment is currently the gold standard for a differential diagnosis of TT and BCC, but they aimed to investigate whether dermoscopy could be used in clinical practice instead. Dermoscopy, a noninvasive technique using a handheld dermatoscope, is less time-consuming than excising and performing a histopathological assessment on a potential tumor.

Using medical records from the dermatology department at the Medical University of Gdańsk in Poland, the authors analyzed 502 cases of BCC and 61 cases of TT that were excised and histopathologically examined between May 2016 and August 2021. Two investigators who were blinded to the histopathological diagnosis graded clinical and dermoscopic pictures of the tumors according to predefined criteria. The clinical data included patient age and gender, as well as tumor location, size, visible pigmentation  and ulceration, and lesion morphology.

Patients with BCC tended to be older than those with TT (mean age, 71.4 vs 64.4 years, respectively; 

 = .0152), and women made up a higher proportion of the BCC group, although the difference was not statistically significant (52.0% vs 44.3%; 

 = .279). The BCC group had larger tumor size than the TT group (mean, 11.0 vs 8.2 mm; 

 = .001) and more often featured clinically visible ulceration (59.4% vs 19.7%; 

The analysis of dermoscopic variables revealed some characteristics associated with the different diagnoses: Dermoscopically visible ulceration was more common in the BCC group than the TT group (52.2% vs 14.8%; 

 < .0001) whereas pigmented structures (brown dots and brown globules), cloudy/starry milia-like cysts, and yellow globules were less common in the BCC group (all 

The study authors also created a binary classification algorithm that was tested and validated on the samples to distinguish BCC from benign tumors. It achieved an area under the curve of 79.23% (95% CI, 69.69%-88.76%), which the authors deemed insufficient for use in clinical practice, as very high sensitivity is needed when diagnosing malignant vs benign tumors given the serious consequences of false negatives.

The literature contains mixed evidence on the epidemiological and dermoscopic characteristics of TT, the authors noted, and their results contrast with some prior studies that had revealed differences in clinically observable pigmentation between BCC and TT cases.

The current study’s limitations included its retrospective and single-center design, as well as that the included patients had lighter skin phototypes.

The authors concluded that “despite differences in frequency of clinical and dermoscopic features between BCC and TT in the studied group, differential diagnosis based on these variables is not reliable based on the developed algorithm, as the overlap of the analyzed features was observed in both tumor types.” They recommended that histopathological examination remain the gold standard for diagnostic use in distinguishing BCC from TT.

Sławińska M, Płaszczyńska A, LakomyJ, et al. Significance of dermoscopy in association with clinical features in differentiation of basal cell carcinoma and benign trichoblastic tumours. 

. Published online August 17, 2022. doi:10.3390/cancers14163964

Despite some differences in the frequency of dermoscopic features between basal cell carcinoma (BCC) and benign skin tumors, dermoscopy alone is not sufficient for a reliable diagnosis, according to a recent study.

Dermoscopy Holds Limited Potential to Differentiate BCC From Benign Tumors

Julia is an associate editor for The American Journal of Managed Care® (AJMC®) and joined AJMC® in 2022. She produces written and video content covering multiple disease states, and assists in the screening process for manuscripts submitted to AJMC®.

She has a BA in English language and literature from Rutgers University. You can connect with Julia on 

 (CKD) has seen progress in the areas in which genomes can inform treatment. A review published in 

Current Opinion in Nephrology and Hypertension

 found that genomic testing could be applied in the treatment of CKD.

The first area that genomic testing can be valuable in CKD care is in the understanding of which genes are associated with CKD or its phenotypes. This sector has expanded in recent years, and there is potential for each new gene discovered to work toward diagnosing a monogenic cause for CKD. Pathogenic variants in mtDNA causing a Gitelman-like syndrome brings together understanding and the identification of biallelic variants.

The identification of biallelic variants that are related to hypokalemic syndrome can fortify tubular potassium channel understanding and further link to extrarenal phenotypes. De novo heterozygous variant discovery can bring hypokalemic and hypomagnesemic kidney syndromes with dilated cardiomyopathy together.

Iterative progress continues in heritable structural kidney disorders. There are some challenges to whether the genetic variation in these genes relates to heritable phenotypes. Evidence for biallelic pathogenic 

 has emerged to suggest there is a causative relationship in various glomerular phenotypes, including nonsyndromic nephrotic syndromes and syndromic complex kidney phenotypes.

 have been identified resulting in mixed glomerular and tubulointerstitial kidney disease; 

 has been identified as linking disease entities with hepatic, kidney, and cardiac components. These gene relationships are helping to identify kidney ciliopathies.

Clinical effects of genomic testing for CKD have also been revealed through studies. A cohort of autosomal dominant tubulointerstitial kidney disease (ADTKD) families found that 29 of 45 achieved a genetic diagnosis through the genes known to be associated with the condition, although 9 of the 45 had diagnostic variants in genes not usually associated with ADTKD.

Researchers will have to collect and analyze cohorts of monogenic kidney disorders to further learn about prognostication factors. This includes in areas of broad genomic testing, which will need to be tested to determine whether it can have a diagnostic role in unexplained CKD or kidney failure.

Exome analysis in a retrospective study found that a broad kidney gene panel found new genetic diagnoses and could have a role in a diagnostic approach. Diagnosable phenocopy disorders could also be more common in genetic diagnosing. Broadened gene panels for complex phenotypes will be needed, as targeted gene panels fail to identify a genetic diagnosis in up to 20% of instances.

Understanding clinical utility for genomic testing is becoming the focus of further research, as there are less than 10 genes that account for many diagnoses made. A way that genomic testing could be applied is by replacing or acting synergistically with a kidney biopsy in certain situations, as some situations could avoid kidney biopsy altogether in favor of genomic testing. Genomic testing in conjunction with a kidney biopsy changes treatment in 1 of 4 patients who receive a genetic diagnosis.

Kidney donor assessment and reproductive planning could also be realizable goals for genomic testing clinical applicability. Key factors that indicate a higher likelihood of a monogenic cause of CKD include making clinical utility clearer. These factors could include the presence of a family history, younger age of onset, extrarenal features, and phenotype-specific factors.

Translating evidence into practice for integration into nephrology practice is the next step for genomic testing. A way that this can be implemented is in clinicians refining prevalence estimates and characterizing rarer subtypes to create revised and condition-specific diagnostic standards around genetic testing.

Digital health approaches to case identification, transcriptomic or RNA sequencing, and globally calibrated and verified gene-phenotype curation for monogenic CKD could be future innovations in genomic testing being applied to CKD.

The author concluded that the benefits of genomic testing and who it can benefit are becoming clearer and more likely to see positive effects than at any other point in history.

Mallett AJ. Which patients with CKD will benefit from genomic sequencing? synthesizing progress to illuminate the future. 

. Published online September 8, 2022. doi: 0.1097/MNH.0000000000000836

Genomic testing can benefit patients with chronic kidney disease (CKD) as more causative genes are identified and evidence for clinical utility is discovered.

Genomic Testing Could Be More Beneficial for Patients With CKD

Approximately 8.4 million people around the world lived with 

 (T1D) in 2021, and this number is predicted to rise to 17.4 million by 2040, according to a modelling study published in 

The study was conducted by researchers from the United States, Canada, Australia, and Luxembourg. These researchers also estimated around 3.1 million individuals with T1D would have been alive in 2021 if they had not died prematurely as a direct result of poor T1D care, and that an additional 700,000 individuals would still be alive if they had not died due to a lack of diagnosis.

 these findings have been entered into an open source database for the T1D Index Project, which was launched by the non-profit Juvenile Diabetes Research Foundation (JDRF) this month and shows how many people live with T1D around the world and what actions can be made to reduce its effects. The study was funded by JDRF.

The researchers set a discrete-time illness-death model (Markov model) to data on T1D incidence and associated mortality to estimate T1D incidence, prevalence, association mortality, and life expectancy in 201 countries.

Incidence and mortality data were available from 97 and 37 countries, respectively, and data from an expert survey were used to estimate T1D diagnosis rates. Random-forest regression of published T1D mortality data was used to model estimated mortality, and life expectancy was calculated using life tables.

These estimates were validated against observed prevalence data from 15 countries.

The authors found between 8.1 and 8.8 million people lived with T1D globally in 2021.

Of this group, 1.5 million (18%) were aged younger than 20 years, 5.4 million (64%) were aged between 20 and 59 years, and 1.6 million (19%) were aged 60 and older.

“There is a systemic trend towards other published estimates having lower paediatric prevalence and higher adult prevalence than in our model,” the authors noted.

In 2021, half a million new cases of T1D were diagnosed, with a median age of onset of 39 years. Further, roughly 35,000 individuals who did not receive a T1D diagnosis died within 12 months of symptom onset.

“The burden of type 1 diabetes in 2021 is vast and is expected to increase rapidly, especially in resource-limited countries,” the authors said, noting 1.8 million, or one-fifth, of individuals living with T1D globally in 2021 lived in low-income or lower–middle-income countries.

Additionally, the mean remaining life expectancy for a 10-year-old diagnosed with T1D in 2021 ranged from 13 years in low-income countries to 65 years in high-income countries.

In 2040, researchers predict between 13.5 and 17.4 million prevalent type 1 diabetes (T1D) cases, reflecting a 60% to 107% increase in global cases compared with 2021.

The researchers also estimated 3.7 million missing prevalent cases of T1D in 2021.

“The substantial missing prevalence highlights the premature mortality of type 1 diabetes and an opportunity to save and extend lives of people with type 1 diabetes,” the authors said. “Our new model, which will be made publicly available as the Type 1 Diabetes Index model, will be an important tool to support health delivery, advocacy, and funding decisions for type 1 diabetes.”

Gregory GA, Robinson TIG, Linklater SE, et al. Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. 

. 2022;S2213-8587(22)00218-2. doi:10.1016/S2213-8587(22)00218-2

In 2040, researchers predict between 13.5 and 17.4 million type 1 diabetes (T1D) cases globally, reflecting a 60% to 107% increase in cases compared with 2021.

Number of T1D Cases Expected to Double Worldwide by 2040

details a case of intrahepatic sarcomatoid 

 (s-CCC), a very rare malignancy of the hepatobiliary system, in a 32-year-old man who is the youngest reported patient with s-CCC. The 

 aims to provide insight into the diagnosis and treatment of the condition, as well as raise awareness to facilitate accurate diagnosis of s-CCC versus other hepatobiliary cancers.

A subtype of intrahepatic cholangiocarcinoma, s-CCC comprises less than 1% of hepatobiliary cancers overall. While its pathogenesis is not well understood, s-CCC can affect various organs, including the urinary tract, uterus, thyroid, breast, skin, pancreas, lung, upper digestive tract, and gall bladder. It is easily confused for hepatocellular carcinoma (HCC) and other liver malignancies, and the most common symptoms are nonspecific, such as fever and abdominal pain. Accurate diagnosis of s-CCC requires immunohistochemical staining to differentiate it from other liver cancers.

The highest risk group for s-CCC mainly encompasses patients older than 40 years, and the case report of a 32-year-old individual represents the youngest recorded s-CCC patient thus far. The patient presented with occasional pain in the upper abdomen and nausea at night, but without other symptoms such as fever or chills. He was seen at a different hospital and found to have an occupancy in segment 5 of his liver 3 days prior. He had a history of chronic hepatitis B spanning more than 20 years and had undergone entecavir treatment, but did not have any notable family history.

A physical examination was uneventful, and alanine aminotransferase (ALT), serum carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), serum total bilirubin, and serum aspartate aminotransferase (AST) were all within normal ranges based on initial lab results. Abnormalities in common serological markers, including CEA and AFP, were previously thought to distinguish s-CCC, but this case and several other studies suggest that these markers are not reliable. CT scans showed a hypodense mass in segment 5 of the patient’s liver, and MRI scans showed a similarly sized mass.

The patient underwent a laparoscopic segmentectomy of segment 5 and cholecystectomy. Recovery was smooth with no bleeding events or biliary fistula, and the patient was discharged after 8 days. Histology reports identified a primary high-grade malignant tumor that showed patchy necrosis and abundant lymphocyte infiltration, but no infiltration into nerves, vessels, or the margin of the hepatectomy.

“Immunohistochemical examinations further showed positive staining for vimentin, CK19, CK7, CD34 (vessels), CD31 (vessels) and PD-L1 while results for AFP, Glypican-3, CK20, PD-L1 and HepPar-1 were negative,” the authors wrote. “The latter, as a marker of hepatocytes, helps to distinguish cholangiocarcinoma and metastatic carcinoma in the liver from HCC and as such, it is of diagnostic value.”

With the s-CCC diagnosis confirmed, the patient was started on adjuvant therapy with albumin-paclitaxel in combination with gemcitabine for 8 cycles. At 17 months post-surgery, there was no recurrence.

Relevant case reports and series were also reviewed by the authors to gain insight into common characteristics of s-CCC, and 76 cases were identified in PubMed. Most patients in the dataset reported their main complaints, and the most common was abdominal pain. This was more common than fever and weight loss. In immunohistochemical analyses, HepPar-1 and AFP were found to be useful diagnostic markers based on data from 50 patients.

“Electron microscopy is also used to diagnose neoplasms of s-CCC and in this case, irrespective of their hepatocyte origin, the tumors are characterized by the presence of microvilli and basement membranes,” the authors wrote. “Hence, based on results from electron microscopy, immunohistochemistry as well as histological examinations, sarcomatoid cholangiocarcinoma can be accurately diagnosed.”

Tumor treatment data was available for 74 patients, 35 (47.3%) of whom underwent surgical intervention. Radiotherapy or chemotherapy was given in 15 (20.3%) cases, and 8 patients (10.8%) received supportive treatment or palliative care. Five patients (6.8%) had surgery plus chemotherapy or radiotherapy, 2 (2.7%) had transcatheter arterial embolization, 1 (1.3%) underwent viscum album treatment, and 1 (1.3%) had transcatheter arterial infusion chemotherapy and surgical treatment. Seven patients (9.5%) were untreated. Of 73 patients with follow-up data available, 44 (60.3%) experienced disease progression leading to death, and 15 (20.5%) survived. Disease recurred in 12 patients (16.4%) and 2 patients (2.7%) were lost to follow-up.

Overall, the report stresses a need for established guidelines in this rare disease, as well as further research on the effectiveness of chemotherapy or radiation therapy for these patients. The progression of s-CCC is still unclear, and surgical resection with or without adjuvant chemotherapy remains the standard treatment route.

Xi LF, Jin Y, Li JT. Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the condition's characteristics. 

. Published online September 1, 2022. doi:10.3389/fsurg.2022.963952

The rare condition can easily be confused with hepatocellular carcinoma, but immunohistochemical studies can help accurately diagnose intrahepatic sarcomatoid cholangiocarcinoma.



Case Report Describes Youngest Recorded Patient With Intrahepatic Sarcomatoid Cholangiocarcinoma

Metabolic syndrome (MetS) is a disease that is diagnosed in those who have metabolic abnormalities, such as hypertension and abdominal obesity. Short and long 

 duration are known predictors of adverse medical outcomes.

 found that sleep duration and insomnia had an effect on the current and future risk of MetS in postmenopausal women.

Data from the Women’s Health Initiative (WHI), a prospective study of postmenopausal women aged 50 to 79 years, was used for this study. All women reported their own sleep duration, from 6 or fewer hours per night to  10 or more hours per night. The WHI Insomnia Rating Score was also used to determine how often the participants had trouble falling asleep; if they woke up several times a night, woke up earlier than planned, or had trouble getting back to sleep; and how restful sleep was in the past 4 weeks.

Age, race, education level, marital status, and chronic disease presence were collected from the group. All participants were also asked if they used any medication or alcohol at night to help sleep. Waist circumference and body mass index (BMI) were taken for each participant. Participants were excluded if they had a history of diabetes or were missing baseline information.

There were 5159 participants with sleep duration data that were included in the study, of which 5063 had data on insomnia. Women with MetS were more likely to have a higher BMI, depression, low alcohol consumption, low levels of physical activity, longer sleep hours, insomnia, and more frequent use of sleep medication.

Positive associations were found between the following:

Sleep duration of 8 to less than 9 hours with a waist circumference greater than 88 cm (odds ratio [OR], 1.18; 95% CI, 1.01-1.40) and triglycerides (TG) of 150 mg/dL or higher (OR, 1.23; 95% CI, 1.05-1.46)

Sleep duration of 9 or more hours with MetS (OR, 1.51; 95% CI, 1.12-2.04), waist circumference greater than 88 cm (OR, 1.40; 95% CI, 1.04-1.90), and TG of 150 mg/dL or more (OR, 1.42; 95% CI, 1.04-1.92).

A recent study used longitudinal data to investigate current and future risks of metabolic syndrome and its potential links with sleep duration and insomnia.