Category: 8. Health

WASHINGTON, D.C.—Replacing animal products with plant-based foods, even ultra-processed ones, leads to weight loss and improved insulin sensitivity in people with type 1 diabetes, according to new research by the Physicians Committee for Responsible Medicine published in Nutrition, Metabolism & Cardiovascular Diseases.

“Choosing a veggie burger instead of a cheeseburger—and other plant-based dietary swaps—can help people with type 1 diabetes who want to lose weight and improve how their body responds to insulin,” says Hana Kahleova, MD, PhD, the lead author of the study and director of clinical research at the Physicians Committee for Responsible Medicine. “The key to success is replacing all animal products with plant-based foods—whether unprocessed fruits and veggies or ultra-processed cereal, plant milks, and meat alternatives.”

The new research is a secondary analysis of a Physicians Committee study, which was the first randomized clinical trial to look at a vegan diet in people with type 1 diabetes. In the 12-week study, 58 adults with type 1 diabetes were randomly assigned to either a low-fat vegan group with no limits on calories or carbohydrates, or a portion-controlled group that reduced daily calorie intake for overweight participants and kept carbohydrate intake stable over time.

The secondary analysis examined if the level of processing in the foods the participants ate played a role in weight loss and insulin sensitivity. The participants’ dietary records were analyzed, and all foods—both animal products and plant-based foods—were categorized using the NOVA system, which assigns foods to categories based on their level of processing. NOVA category 1 is defined as unprocessed or minimally processed foods; category 2 includes processed ingredients; category 3 includes processed foods; and category 4 is composed of ultra-processed foods, greatly modified by industrial techniques and processes.

Consumption of animal foods decreased in all NOVA categories for participants in the vegan group, while their intake of NOVA category 1 plant-based foods—including fruits, vegetables, grains, and beans—increased. There were no significant changes in consumption of plant-based foods in categories 2, 3, and 4 in either the vegan or portion-controlled group.

In the vegan group, body weight decreased by 5.2 kg (about 11 pounds) and insulin sensitivity increased. There were no significant changes in weight or insulin sensitivity in the portion-controlled group.

The original study found that a vegan diet also reduced insulin needs and led to improvements in cholesterol levels and kidney function in people with type 1 diabetes.

Hisham Mehanna, Paul Nankivell, Kristien Boelaert, Rebecca Woolley, Neil Sharma, Paul S Sidhu, Gitta Madani, Philip Da Forno, Catherine Moreman, Andrew Palmer, Tessa Fulton-Lieuw, Judith Taylor, Kanchana Rajaguru, Jasper Bekker, Ram Vaidhyanath, Thaj Rehman, Jon Deeks
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 7, July 2025, Pages 1997–2006
https://doi.org/10.1210/clinem/dgae682

Abstract

Introduction

ElaTION is a large multicenter pragmatic randomized controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound alone (US) compared with US-FNAC to inform and update current practice guidelines.

Methods

Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) vs US-FNAC.

Results

Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US alone was the same as US-FNAC (0.91 [95% CI, 0.85–0.97] vs 0.87 [95% CI, 0.80–0.95] P = .37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, P < .0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%), respectively (P < .0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (nondiagnostic) FNAC and no definitive diagnosis.

Malignancy risk was higher in smaller nodules: < 10 mm 23/60 (38.3%), 10–20 mm 46/162 (28.4%), and >20 mm 80/466 (17.2%) (P < .0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) vs 42/113 (37.2%) respectively (P = .18).

Conclusion

Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the British Thyroid Association classification. However, findings also suggest caution regarding existing recommendations for conservative management of nondiagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3–U5) features may help identify high-risk subgroups for more proactive management.

 

The Oropouche virus (OROV), classified under the genus Orthobunyavirus and the family Peribunyaviridae, is recognized as the causative agent of a zoonotic vector-borne disease that presents clinical symptoms very similar to those caused by dengue virus, Zika virus, or other febrile illnesses. Endemic to the Amazon region and first identified in Trinidad and Tobago in 1955, the virus has spread throughout the Caribbean and Central and South America over the years, with several reassortants [1], including the new strain, responsible for the recent outbreaks in Brazil and Cuba.

OROV exhibits a sylvatic cycle in forested regions, where vertebrate hosts, such as nonhuman primates, sloths, rodents, and birds, contribute to its circulation, alongside an urban epidemic cycle involving humans [2]. The virus primarily spreads to humans through the anthropophilic biting midge Culicoides paraensis, while in the sylvatic cycle, the primary arthropod vector remains unidentified [1]. However, mosquitoes such as Culex quinquefasciatus, Coquillettidia venezuelensis, and Aedes serratus have been found infected in natural settings [2,3,4].

The OROV genome consists of three single-stranded negative-sense RNA segments: small (S), medium (M), and large (L). The S segment encodes an overlapping open reading frame (ORF) for nucleocapsid and a nonstructural protein, the M segment encodes for two glycoproteins and a nonstructural protein, and the L segment encodes for an RNA-dependent RNA polymerase [5]. Like other multi-segmented viruses, OROV can reassort its genome segments. This mechanism, which occurs during genome replication after the coinfection of a single cell with multiple viruses, can generate progeny capable of altered virulence or immune evasion. Reassortment can also occur during coinfection with different OROV strains, favoring evolution and viral spread by altering vector competence or virulence [6, 7].

Public health concerns about OROV intensified in 2024 following an unprecedented increase in the incidence of human infections in Central and South America, including reports of four fatalities and cases of vertical transmission of the virus linked to miscarriages, fetal deaths, and microcephaly [8,9,10]. Contextually, the detection of OROV in human semen has raised questions regarding its potential for sexual transmission, emphasizing the need for further research in this area [11].

In the same year, the first 19 imported cases of Oropouche (ORO) fever were reported in EU countries [12], and Italy identified its first five cases in travelers returning from Cuba and Brazil [13]. To assess the risk of potential local transmission of OROV in temperate continental Europe, where known competent OROV vectors are not present, research on the competence of other local vectors is necessary to evaluate the current and potential future adaptation of OROV to new ecological niches.

Prior to 2024, vector competence studies focused on OROV were limited in number and primarily conducted on insect species that circulate in endemic regions or North America [2, 14, 15]. To date, no experimental studies have been carried out on European mosquito populations, leaving a significant gap in knowledge regarding the virus’s ability to establish itself in nonendemic regions. The objective of this study is to investigate, through controlled experimental infections, the potential vectorial role of Italian populations of Aedes albopictus and Culex pipiens in transmitting the newly circulating OROV strain introduced by infected travelers. This particular reassortant has been found to be genetically distinct from the four previously known OROV genotypes, clustering into a highly supported monophyletic clade. This newly identified genotype V also includes viral sequences associated with the 2022–2024 Brazilian outbreak [16].

The experimental work was conducted in a Biosafety Level 3 (BSL-3) facility using two mosquito colonies derived from field populations collected in Rome. Culex pipiens colony originated from larvae and Ae. albopictus from eggs collected using ovitraps employed for Aedes surveillance.

Both of the mosquito species were experimentally exposed to the first OROV strain isolated in Italy, obtained from a patient who had recently returned from Cuba in 2024 [16]. To initiate the infection process, adult female mosquitoes, aged 8–11 days, were allowed to feed for 1 h using a membrane feeder containing a mixture of rabbit blood and an OROV suspension. The final viral concentration of this suspension was 1.7 × 10⁶ TCID₅₀/ml, and the temperature of the blood meal was maintained at 37 °C using a circulating warm water system. After feeding, only fully engorged females were transferred to a controlled climate chamber, maintained at a temperature of 26 ± 1 °C, 70% relative humidity, and a 14 h light/10 h dark photoperiod cycle. These mosquitoes were then sustained on a saturated sucrose solution and monitored for 21 consecutive days. For each mosquito species, a subset of five individuals was sampled at day 0 (immediately after blood feeding). In the case of Ae. albopictus, 20 mosquitoes were randomly collected at 7, 14, and 21 days post-exposure (dpe). For Cx. pipiens, 20 mosquitoes were sampled at 7 dpe, but due to high mortality rates, only 15 mosquitoes were available for collection at 14 dpe. At each collection time, mosquitoes were immobilized by placing them on a petri dish on ice and dissected by removing the legs and wings. Saliva was then collected by inducing salivation with the application of 1 mL of 1% pilocarpine solution to the body and placing the proboscis in a finely drawn quartz capillary tube filled with mineral oil (Fig. 1).

The bodies, legs + wings, and saliva of each mosquito were processed and analyzed separately to determine the presence of the OROV genome, allowing for the calculation of infection rate (IR), dissemination rate (DR), and transmission rate (TR) [17]. After the infectious blood meal, all engorged female mosquitoes of both species were allowed to lay eggs (first gonotrophic cycle, F1). The eggs were allowed to hatch, and the larvae developed into adulthood. For each species, ten pools of five adults, divided by sex (five male and five female pools), were tested for possible transmission of the virus to the F1 generation. The main phases of the experiment are schematized in Fig. 2.

Fast Technology for Analysis of Nucleic Acids (FTA) cards were soaked in a sugar solution to collect mosquito saliva weekly and assess the potential presence of the virus throughout the experiment. The supernatant of samples that resulted in positive tests was filtered and inoculated onto Vero cell cultures to evaluate the viability of the virus. The development of cytopathic effects (CPE) in the cell cultures was used as a marker to confirm the presence of infectious virus particles.

The RNA was singularly extracted by each body, legs + wings, saliva, and FTA card specimens, and by pools of mosquitoes of the F1 generation by using the QIAsymphony DSP Virus/Pathogen Midi Kit in combination with the QIAsymphony SP (QIAGEN, Hilden, Germany). The OROV RNA presence in the different specimens was evaluated by the real Time RT-PCR protocol by RIVM Laboratory (National Institute for Public Health and the Environment, the Netherlands) modified from Weidmann et al. [18]. OROV quantification was obtained by comparing the crossing points of the values of the standard curve obtained from tenfold serial dilutions of OROV stocks, with estimated concentration by titration on Vero cells expressed as tissue culture infectious dose (TCID)₅₀/ml.

All results described below are reported in Table 1. Specimens belonging to both Cx. pipiens and Ae. albopictus, which were collected immediately after being exposed to the OROV infectious blood meal (specifically at day 0), were tested and found to be positive for the presence of the virus. The mean viral titers measured in these individuals were 1.3 × 10⁴ TCID₅₀/ml for Cx. pipiens and 1.4 × 10⁴ TCID₅₀/ml for Ae. albopictus, thereby confirming that these mosquitoes had successfully ingested infectious virus particles during the blood meal. For Cx. pipiens, all tested specimens—including their bodies, legs + wings, saliva samples, and FTA cards tested negative for the presence of viral RNA at all collection time points. As a consequence, IR, DR, and TR were all determined to be zero, indicating a lack of infection, dissemination, and transmission potential for this species. In contrast, regarding Ae. albopictus, viral RNA was detected by real-time RT-PCR in one body sample at 7 dpe and in another body sample at 21 dpe, with cycle threshold values equivalent to viral titers of 1.7 × 10⁵ TCID₅₀/ml and 1.15 × 10⁶ TCID₅₀/ml, respectively. These results led to a cumulative IR of 3.3%, calculated as the number of infected mosquito bodies divided by the total tested. When the supernatant of the two OROV-positive body homogenates was inoculated onto Vero cells, viable virus was confirmed to be present. This was demonstrated by the appearance of CPE at times consistent with the viral titers found in the bodies: 6 days after inoculation for the “7 dpe-positive” body, and 4 days after inoculation for the “21 dpe-positive” body.

However, viral RNA was not detected in any of the legs + wings, saliva samples, or FTA cards of this species, indicating a complete absence of disseminated infection as well as an inability to transmit the virus.

Finally, for both mosquito species examined in this study, no virus particles were detected in the F1 generation. Nevertheless, since the results obtained from the first gonotrophic cycle may not be indicative of potential viral transmission to the eggs, further studies in this direction would be advisable to definitively rule out vertical transmission, especially if these populations were to become competent for OROV transmission in the future.

In recent years, the OROV has re-emerged as a significant public health concern, posing a growing threat to human populations in various regions. This resurgence has been characterized by an increasing frequency of epidemics, some of which have occurred for the first time in certain South American and Caribbean countries, such as Cuba. The notable rise in the number of reported cases within endemic areas, combined with the occurrence of cases imported by travelers returning from affected regions to previously unaffected areas, such as Europe and the United States, suggests a broader pattern of viral expansion and circulation [19]. Although scientific evidence strongly supports the idea that C. paraensis midges are more effective vectors of OROV than mosquitoes in the urban cycle [20], the lack of detection of this species in Cuba—where one of the most recent outbreaks occurred—initially suggested a potential role for mosquitoes in transmitting OROV to humans. However, their presence was finally documented for the first time in Cuba in March 2025, following extensive surveillance conducted after the outbreak. While all previously used traps proved ineffective, the midges were caught by human landing catch [21]. Although this new evidence suggests that C. paraensis was likely already present at the start of the outbreak, the lack of detection could be due to the inadequate surveillance system or their low population density. This reinforces the importance of investigating the role of mosquitoes in OROV transmission and whether they may contribute to the establishment of an endemic circulation on the Island of Cuba [22]. Therefore, evaluating the vector competence of different mosquito populations remains a critical factor in preventing the virus’s potential spread to new geographic areas. A thorough understanding of the intricate virus–vector interactions is essential, particularly as the transmission and circulation of the virus could be influenced by the pathogen’s capacity to adapt to different vector species. In line with previous findings regarding American populations of Cx. pipiens and Ae. albopictus, our study indicates a lack of vector competence for the most recently circulating OROV strain in their Italian counterparts. Specifically, our results are consistent with those reported by Payne et al. [15], who demonstrated that experimentally infected American mosquito species were not competent vectors for either historical or recent OROV strains, as evidenced by an IR of 2% and the absence of transmission. Earlier research has demonstrated that multiple mosquito species, including Ae. albopictus and Cx. pipiens, fail to acquire the virus through natural feeding on infected mice. However, experimental thoracic microinjection of the virus into these mosquitoes leads to significantly increased viral titers, enabling subsequent transmission to naive immunodeficient mice [15]. In light of previous observations, our findings suggest that the primary barriers to infection and transmission are likely located at the midgut level. This finding is consistent with the conclusions drawn by Gallichotte et al. in their comprehensive systematic review of pre-2024 studies [14], which emphasized the importance of midgut barriers in restricting virus acquisition and dissemination rather than attributing these limitations to a fundamental molecular incompatibility between the virus and its mosquito hosts. Although our study did not detect any OROV infection in Cx. pipiens, a single positive saliva sample recently documented by Payne et al. [15], highlights the necessity for ongoing intraspecific surveillance among Cx. pipiens populations. While we acknowledge the limitations of this pioneering study—including the absence of biological replicates, limited sample sizes due to BSL-3 constraints, and the assessment of transmission only to the F1 generation—we consider these preliminary results important as they provide an early indication to health authorities of a negligible risk of OROV circulation by the two main arbovirus vectors in Italy and Europe. Future studies with expanded sample sizes, replicated experiments, different mosquito populations, and evaluation of subsequent gonotrophic cycles will be essential to elucidate the vector competence of these species fully. In summary, despite the experimental limits, our study provides evidence that does not support vector competence in Italian Cx. pipiens and Ae. albopictus mosquitoes for the recently circulating OROV strain in Cuba. Nevertheless, the possibility of co-evolutionary processes and shifts in vector–virus interactions facilitating the adaptation of OROV to new epidemiological contexts and promoting its geographical expansion should not be underestimated. The introduction of OROV fever cases into Italy and other nonendemic regions in 2024, along with the increasing circulation of the virus throughout much of Central and South America, reinforces the importance of maintaining a high level of vigilance as the 2025 vector activity season in Europe approaches. Sustained vector surveillance efforts, combined with comprehensive research on potential transmission dynamics, will be crucial in mitigating the public health risks associated with the continued spread of this emerging arbovirus.

Previous research has shown that the personalities of people who engage in different types of organized sport tend to vary. But what is less clear is how personality affects the types of exercise people actually enjoy doing.

The new study, published in Frontiers in Psychology, explored whether individual personality traits corresponded to the enjoyment of different types of exercise, whether participants completed a prescribed exercise program, and the subsequent impact on their fitness levels.

The study found several correlations between exercise type and personality traits, including extroverts’ enjoyment of high intensity exercise and the preference of those with the neuroticism trait – associated with people prone to worrying – for short bursts of activity rather than prolonged effort.

Dr Flaminia Ronca, first author of the study from UCL Surgery & Interventional Science and the Institute of Sport, Exercise and Health (ISEH), said: “We know that the global population is becoming increasingly sedentary. You often hear about people trying to become more active, but struggling to make lasting changes. In this study, we wanted to understand how personality can influence this to support the development of effective interventions for changes in health behavior.

“We found some clear links between personality traits and the type of exercise the participants enjoyed most, which I think is important because we could potentially use this knowledge to tailor physical activity recommendations to the individual – and hopefully help them to become and remain more active.”

For the study, the team assessed 132 volunteers from the general public with a range of fitness levels and backgrounds, who were assigned either to an eight-week cycling and strength training program (intervention group), or to a resting control group¹.

Participants’ benchmark fitness levels were assessed at the beginning of the programme. Strength was tested via press ups, performing a plank to failure, and countermovement jumps (jumping again immediately after landing). This was followed by a low intensity cycling session for 30 minutes, and then a cycling test to measure their peak oxygen capacity (V̇O₂ max test) after a short rest.

The team also assessed their perceived stress levels on a scale of one to 10, as well as their personality traits using the Big 5 model, a common personality test in the field of sport and exercise psychology. The Big 5 model groups individuals according to whether their dominant trait is extroversion, agreeableness, conscientiousness, neuroticism or openness².

During the exercise programme, participants were asked to rate their enjoyment of each exercise session, before having their fitness level tested again once the program had been completed.

Of the 132 starters, 86 people completed the intervention and all of these participants got fitter and stronger regardless of personality.

How personality trait influences exercise enjoyment

While not all personality traits had a link to exercise enjoyment, several connections were uncovered by the study.

Extroverts tended to particularly enjoy high intensity exercise, such as high intensity interval training (HIIT) and a fitness test of maximum intensity cycling.

Those with a strong neuroticism trait engaged well with the exercise intervention, but preferred bursts of intensity rather than prolonged intensity. They also preferred not being monitored, such as not recording their heart rate while undertaking the program, suggesting that these individuals might appreciate being given space for independence and privacy when engaging in exercise.

Those who were conscientious tended to have a well-rounded fitness level, meaning that they tended to score more highly on aerobic fitness as well as core strength, and were generally more physically active. However, conscientiousness didn’t predict higher enjoyment of a specific form of exercise. The authors say this might be because conscientious individuals tend to be driven by the health-related outcomes of engaging in physical activity rather than enjoyment, suggesting that adherence to the program may be less about enjoyment than because it was ‘good for them’.

The impact of personality and exercise on stress

At the beginning of the study, the stress levels of the intervention group and the control group were similar. However, the only group to experience a significant reduction in stress levels after exercising were those who scored highly in the neuroticism trait.

Professor Paul Burgess, an author of the study from the UCL Institute of Cognitive Neuroscience, said: “We found that people who scored more highly in the neuroticism personality trait showed a particularly strong reduction in stress when they undertook the fitness training recommended in the study. This suggests that there may be particular benefits in stress reduction for those with this trait.”

The researchers concluded that the most important thing people can do to improve their activity levels is to find something that they enjoy, which will make it more likely that they’ll stick with it.

Notes

1. The program consisted of:
   • Three weekly cycling sessions of varying intensity: a 60-minute light ride at an easy pace, a 30 min threshold ride at a moderate but sustainable effort, or a High Intensity Interval Training session where the level of exertion varied.
   • One weekly bodyweight strength session.
2. The five traits measured in The Big 5 model are:
   • Extroversion: how energetic, outgoing, and sociable an individual is, including how much they seek company and stimulation.
   • Agreeableness: Involves attributes related to cooperation, trust, compassion, and a considerate nature toward others.
   • Conscientiousness: Reflects traits like orderliness, reliability, and the drive to achieve goals through careful planning and persistence.
   • Neuroticism: Measures emotional stability and the tendency to experience negative emotions like anxiety, mood swings, or irritability.
   • Openness: Describes a person’s willingness to try new experiences, curiosity about the world, and imagination.

CHICAGO, July 8, 2025 /PRNewswire/ — The American Lung Association is launching a new campaign to support and empower individuals living with chronic obstructive pulmonary disease (COPD) in rural and other communities across the U.S.

Approximately 16 million people are living with COPD in the United States, a chronic, progressive lung disease that limits air flow and causes difficulty breathing. There is no cure for COPD; however, there are treatments—including supplemental oxygen, inhalers and medication, and lifestyle changes—that can improve daily symptoms and quality of life. Unfortunately, many people with lower incomes and education levels face barriers to optimal treatment and care. This includes individuals living in rural areas where COPD rates are twice that of those in urban communities, resulting in more hospitalizations and deaths.

The Lung Association’s Living Well with COPD campaign provides free one-on-one COPD support, education and resources tailored for every stage of the disease. The campaign is created for all families across the U.S. affected by COPD, with a focus on people in rural communities who may not be close to physical hospitals and other resources.

“Living well with COPD requires an evolving treatment plan, regular visits with a healthcare provider, and lifestyle modifications that can help you breathe better,” said Harold Wimmer, President and CEO of the American Lung Association. “Unfortunately, many individuals, especially those living in rural communities, lack the support and access to essential care and resources that could greatly enhance their daily lives. For these individuals and their families, the Lung Association can help.”

Working with rural partners and referral networks, along with local healthcare providers, the Lung Association is:  

• Expanding access to the free Lung Health Navigator program. Lung Health Navigators are licensed healthcare professionals, including registered nurses and respiratory therapists, who offer free and customized one-on-one support to help people throughout their COPD journey. People can meet with a Lung Health Navigator over the phone, through an online chat, or a video call, depending on an individual’s preference and schedule. To connect with a Lung Health Navigator, call 866-252-2959, or visit Lung.org/navigator.
• Creating and distributing new educational materials for people with COPD to empower them to improve communication with their healthcare provider, better understand available COPD treatments, and improve their quality of life.
• Supporting rural and other healthcare providers to improve COPD care, better understand COPD treatment options, and build strong, trusting relationships with their patients.

For more information, contact the Lung Association’s HelpLine at 1-800-LUNGUSA. To learn more about COPD, visit Lung.org/copd. 

Support for the Living Well with COPD educational campaign was provided by Sanofi and Regeneron, AstraZeneca, Genentech and GlaxoSmithKline.

About the American Lung Association
The American Lung Association is the leading organization working to save lives by improving lung health and preventing lung disease through education, advocacy and research. The work of the American Lung Association is focused on four strategic imperatives: to defeat lung cancer; to champion clean air for all; to improve the quality of life for those with lung disease and their families; and to create a tobacco-free future. For more information about the American Lung Association, which has a 4-star rating from Charity Navigator and is a Platinum-Level GuideStar Member, call 1-800-LUNGUSA (1-800-586-4872) or visit: Lung.org. To support the work of the American Lung Association, find a local event at Lung.org/events or donate today at Lung.org/donate. 

American Lung Association • 55 W. Wacker Drive, Suite 1150 • Chicago, IL 60601
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CONTACTS:
Jill Dale | American Lung Association
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SOURCE American Lung Association

Introduction

Whipple’s disease, first described by George Whipple in 1907, is a chronic systemic infection caused by the gram-positive bacterium Tropheryma whipplei, a member of the Actinomycetota phylum.¹ Although classically characterized by gastrointestinal involvement, extraintestinal manifestations—such as arthralgia, central nervous system disorders, and endocarditis—have been increasingly recognized.²

Severe infections caused by T. whipplei, including endocarditis, meningitis, and pneumonia, though uncommon, can be life-threatening and require prompt diagnosis and treatment. Pulmonary involvement is particularly rare and often presents with nonspecific respiratory symptoms, contributing to delays in diagnosis.

Given this rarity and clinical ambiguity, pulmonary infection with T. whipplei may be misdiagnosed, especially in immunocompetent individuals. Delayed recognition can result in disease progression to acute respiratory distress syndrome (ARDS), increasing the risk of adverse outcomes. Early use of molecular diagnostic tools such as metagenomic next-generation sequencing (mNGS) can be critical for accurate identification and timely intervention.Here, we report a rare case of ARDS caused by T. whipplei in an immunocompetent young adult, confirmed by mNGS of bronchoalveolar lavage fluid, and provide a comprehensive review of the literature.

Case Presentation

A 28-year-old man presented to the emergency department with a 4-day history of progressive dyspnea, productive cough with purulent sputum, and fever (39.6°C). The patient has a clear history of aspiration, with symptoms beginning after occupational exposure to wastewater, initially manifesting as mild fatigue and a nonproductive cough. He self-administered febuxostat and over-the-counter combination tablets containing paracetamol and amantadine hydrochloride, without clinical improvement. A chest CT performed at a local hospital revealed bilateral patchy and flocculent opacities in both lungs (Figure 1A–C). The patient had no notable past medical history, including no history of autoimmune diseases (eg, rheumatoid arthritis), chronic infections, malignancies, or use of immunosuppressive agents. Immunologic evaluation revealed normal lymphocyte subsets, including CD3+, CD4+, and CD8+ T cells, with a normal CD4/CD8 ratio. Serum immunoglobulin levels (IgG, IgA, and IgM) were also within normal limits, indicating no evidence of immunodeficiency. Due to worsening hypoxemia, he was transferred to our tertiary care center for advanced management.

Figure 1 Chest CT scans. (A–C) Images on hospital day 1 showing bilateral patchy opacities. (D–F) Images after 3 weeks of treatment showing resolution of pulmonary exudates.

On admission, the patient exhibited severe respiratory distress (SpO₂: 91% on room air). Laboratory findings included leukocytosis (12.33 × 10⁹/L; 96.30% neutrophils), elevated C-reactive protein (256 mg/L), and procalcitonin (2.2 ng/mL). Arterial blood gas analysis demonstrated severe hypoxemia (PaO₂/FiO₂ ratio: 118). Repeat chest CT showed bilateral ground-glass opacities and consolidations, predominantly in the lower lobes, consistent with ARDS. High-flow nasal cannula (HFNC) oxygen therapy was initiated, and empiric antimicrobial therapy with meropenem (2 g every 8 hours), azithromycin (500 mg daily), and levofloxacin (750 mg daily) was administered.

Despite these interventions, the patient developed worsening hypoxemia (PaO₂/FiO₂ ratio: 69) and delirium, necessitating mechanical ventilation with lung-protective strategies and prone positioning. Bronchoscopy revealed hyperemic bronchial mucosa with submucosal hemorrhages and scant white secretions. Bronchoalveolar lavage fluid (BALF) was sent for microbiological analysis, including NGS. Antifungal (caspofungin: 70 mg loading dose, then 50 mg daily) and antiviral (oseltamivir: 75 mg twice daily) therapies were added empirically, alongside sivelestat sodium (0.2 mg/kg/hour) to attenuate pulmonary inflammation. Sedation was achieved with sufentanil (0.1 µg/kg/hour) and midazolam (2 mg/hour), with neuromuscular blockade using atracurium (5 µg/kg/minute).

A diagnostic breakthrough occurred on hospital day 5 when metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF), performed using the IDseq™ Ultra platform (Vision Medicals, China), detected Tropheryma whipplei DNA with 12,373 sequence reads, confirming Whipple’s disease-associated ARDS. A low abundance of Staphylococcus aureus (69 sequence reads) was also identified but was deemed clinically insignificant due to the low read count and lack of supporting clinical or microbiological evidence. Antimicrobial therapy was subsequently revised to intravenous ceftriaxone (2 g daily) and sulfamethoxazole-trimethoprim (SMZ-TMP; 15 mg/kg/day of the trimethoprim component). Follow-up blood cultures grew Staphylococcus epidermidis, prompting a switch from linezolid to vancomycin (15 mg/kg every 12 hours).

Over the following week, the patient’s oxygenation improved (PaO₂/FiO₂ ratio: 212), allowing gradual weaning from mechanical ventilation to HFNC on hospital day 18. Inflammatory markers normalized, with procalcitonin decreasing to 0.3 ng/mL and C-reactive protein dropping to 8 mg/L prior to discharge. The patient’s body temperature returned to normal (<37.5°C) within 72 hours after the initiation of targeted antibiotic therapy. He was subsequently discharged on day 28 with a planned 12-month course of oral SMZ-TMP. Follow-up CT demonstrated significant resolution of pulmonary exudates (Figure 1D–F).

Discussion

Whipple’s disease (WD) is a rare, multisystemic infection that poses diagnostic challenges due to its protean manifestations. While pulmonary involvement is uncommon, this case illustrates a life-threatening presentation of WD as ARDS. Although WD typically affects immunocompromised hosts, this patient had no known immunosuppression, aligning with prior reports of WD in immunocompetent individuals exposed to environmental reservoirs.

The nonspecific respiratory symptoms and radiographic findings in pulmonary WD—such as bilateral consolidations and ground-glass opacities—often mimic more common etiologies (eg, bacterial pneumonia, COVID-19).³ Conventional diagnostic methods, including cultures and serology, frequently fail to identify Tropheryma whipplei, as exemplified here. NGS emerged as a pivotal tool, enabling rapid pathogen identification and timely therapeutic adjustment. This underscores the growing role of molecular diagnostics in managing critically ill patients with atypical presentations.

First-line therapy for WD involves prolonged antibiotic regimens to prevent relapse. Intravenous ceftriaxone (2–4 weeks) followed by oral SMZ-TMP (12 months) remains the cornerstone of treatment.⁴ In this case, SMZ-TMP’s efficacy was evident, with rapid clinical improvement after its initiation. However, emerging reports of SMZ-TMP resistance highlight the need for alternative regimens (eg, Meropenem combined with SMZ -TMP) in refractory cases.^5,6

These cases in the table elucidate the similar clinical manifestation and the evolution of the cases in the literature. Patients’ ages ranged from 26 to 62, with a median of 39 years. SMZ-TMP was a consistent component of the antimicrobial regimen across most cases, emphasizing its efficacy as a cornerstone drug for treating Tropheryma whipplei infections.^5–9 This reflects its well-documented ability to inhibit Tropheryma whipplei growth and its broad-spectrum activity. Intravenous ceftriaxone is currently recommended as part of the initial treatment phase for rapid control of systemic infection, and Trimethoprim-sulfamethoxazole (SMZ-TMP) was then recommended as primary oral maintenance therapy for at least 1 year.³ However, Cases of resistance to SMZ-TMP have been documented, prompting the need for alternative or combination therapies (Table 1).¹⁰

Table 1 Cases of Resistance to SMZ-TMP

Limitations

This case report has several limitations. First, while conventional diagnostic methods failed to identify the causative pathogen, the definitive diagnosis relied on metagenomic next-generation sequencing (mNGS), underscoring the limited sensitivity of traditional microbiological tools in detecting Tropheryma whipplei. Second, although the patient was considered immunocompetent based on medical history, a detailed immunological workup was performed and only included basic parameters such as lymphocyte subset analysis and immunoglobulin levels; more comprehensive immune profiling was not conducted. Third, the lack of long-term follow-up data precludes assessment of potential disease relapse or chronic sequelae. These factors should be addressed in future studies to better understand the pathophysiology and management of T. whipplei-associated ARDS. Furthermore, given the potential for central nervous system (CNS) involvement in Whipples’ disease, long-term follow-up is essential. Although our patient showed no neurological symptoms during hospitalization, future monitoring for CNS relapse or delayed complications remains clinically important.

Conclusion

This case highlights the indispensable role of advanced molecular diagnostics, particularly next-generation sequencing, in identifying rare and atypical pathogens such as Tropheryma whipplei in critically ill patients with ARDS. Timely and precise pathogen detection enables targeted therapy, significantly improving patient outcomes even in severe and life-threatening conditions. Importantly, this report underscores the necessity of considering Tropheryma whipplei as a potential etiology of ARDS, even in immunocompetent individuals, especially when conventional diagnostic approaches fail.

The therapeutic challenge posed by emerging resistance to standard regimens, such as trimethoprim-sulfamethoxazole, further highlights the need for ongoing research into alternative or combination antibiotic therapies. Future studies should aim to deepen our understanding of the pathophysiological mechanisms underlying Tropheryma whipplei-induced pulmonary involvement and refine clinical guidelines for the diagnosis and management of such cases. By integrating cutting-edge diagnostics with personalized therapeutic strategies, clinicians can advance the care of patients with rare and complex infectious diseases in critical care settings.

Ethics Approval Consent to Participate

This study has been reviewed and approved by the First Affiliated Hospital of Dalian Medical University. The patient provided informed consent for publication of the clinical details and written informed consent was obtained. Written informed consent was provided by the patient for the publication of the case details and images. Details of the case can be published without institutional approval.

Consent to Publish

The study participant gave consent to publish.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This study did not receive any funding.

Disclosure

The authors declare that they have no competing interests in this work.

References

1. Wilson KH, Blitchington R, Frothingham R, Wilson JA. Phylogeny of the whipple’s-disease-associated bacterium. Lancet. 1991;338(8765):474–475. doi:10.1016/0140-6736(91)90545-z

2. Patil S, Fantry GT. Connecting the dots: the many systemic manifestations of whipple disease. Gastroenterol Hepatol (N Y). 2012;8(1):63–66.

3. Lagier JC, Fenollar F, Raoult D. Acute infections caused by tropheryma whipplei. Future Microbiol. 2017;12(3):247–254. doi:10.2217/fmb-2017-0178

4. Dolmans RA, Boel CH, Lacle MM, Kusters JG. Clinical manifestations, treatment, and diagnosis of tropheryma whipplei infections. Clin Microbiol Rev. 2017;30(2):529–555. doi:10.1128/CMR.00033-16

5. Deng Y, Zhang H, Lu J, Zhou Z, Zhang T, Cui X. Whipple’s disease of the respiratory system: a case report. Exp Ther Med. 2024;27(4):133. doi:10.3892/etm.2024.12421

6. Li W, Zhang Q, Xu Y, Zhang X, Huang Q, Su Z. Severe pneumonia in adults caused by Tropheryma whipplei and Candida sp. infection: a 2019 case series. BMC Pulm Med. 2021;21(1):29. doi:10.1186/s12890-020-01384-4

7. Zhu B, Tang J, Fang R, et al. Pulmonary coinfection of mycobacterium tuberculosis and tropheryma whipplei: a case report. J Med Case Rep. 2021;15(1):359. doi:10.1186/s13256-021-02899-y

8. Shan X, Li Z, Dong L. A case of pneumonia caused by infection with tropheryma whipplei complicated by cryptococcus during treatment with a Janus kinase inhibitor: a case report. BMC Pulm Med. 2024;24(1):625. doi:10.1186/s12890-024-03401-2

9. Lu Z, Zhang A, Guo J, Ni H. An unusual case of severe pneumonia caused by Tropheryma whipplei combined with Legionella pneumophila. World J Emerg Med. 2023;14(6):492–494. doi:10.5847/wjem.j.1920-8642.2023.095

10. Bakkali N, Fenollar F, Biswas S, Rolain JM, Raoult D. Acquired resistance to trimethoprim-sulfamethoxazole during Whipple disease and expression of the causative target gene. J Infect Dis. 2008;198(1):101–108. doi:10.1086/588706

11. Zhang WM, Xu L. Pulmonary parenchymal involvement caused by Tropheryma whipplei. Open Med. 2021;16(1):843–846. doi:10.1515/med-2021-0297

Introduction

Nesidioblastosis is the most common cause of hyperinsulinemic hypoglycemia in infants but is extremely rare in adults.^1,2 Insulinoma is the most frequent cause of hyperinsulinemic hypoglycemia in adult.² Nesidioblastosis is pathologically characterized by diffuse neoformation of the islets of Langerhans islets from the pancreatic ductal epithelium, a disease that does not exhibit neoplastic proliferation, unlike insulinoma.³ While insulinomas can be identified with various imaging modalities, adult-onset nesidioblastosis is difficult to detect using imaging modalities.^4–7 To diagnose adult-onset nesidioblastosis, it is necessary to suspect the disease based on clinical findings, endocrine examinations, and imaging studies and then perform a selective arterial calcium injection (SACI) test.^8–13 The present study describes a rare case of adult-onset nesidioblastosis in a patient with heterochronic repeated severe hypoglycemic symptoms that was cured by pancreatic resection twice, resulting in total pancreatectomy.

Case Report

A 37-year-old woman was referred to our hospital with complaints of weight loss (height: 160.4 cm, weight dropped from 90 to 66 kg in half a year) and repeated disturbances of consciousness. She was diagnosed with manic depression at a previous hospital. She had Whipple’s triad but did not take oral hypoglycemic agents or receive insulin injection therapy. She had no medical or family history of endocrine-related diseases including insulinoma, diabetes mellitus, or multiple endocrine neoplasia type 1.

Laboratory data showed that the serum levels of fasting plasma glucose (PG), immunoreactive insulin (IRI), connecting peptide immunoreactivity (CPR), and hemoglobin A1c, and a urine levels of CPR were 31 mg/dl, 11.6 μU/mL, 6.6 mg/mL, 5.2%, and 115.2 μg/day, respectively. Fajan’s index (IRI / PG), Grunt’s index (PG / IRI), and Turner’s index [(IRI × 100) / (PG – 30)] were 0.37, 2.7, 1160, respectively (Table 1a). In the fasting test, the PG level was decreased to 45 mg/dl and IRI was increased to 10.0 μU/mL after 12 hours (Table 1b). In the octreotide loading test, the PG level was increased to 155 mg/dl after 120 minutes and IRI was decreased to 0.3 μU/mL after 30 minutes (Table 1c). Antiinsulin antibodies were absent. The function and imaging studies of the pituitary, adrenal, parathyroid, and thyroid glands were within normal limits. On imaging studies, including ultrasonography, contrast-enhanced computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, no tumor was identified in the pancreas (Figure 1). In addition, upper gastrointestinal endoscopy and colonoscopy revealed no findings in the gastrointestinal tract, suggesting ectopic insulinoma. The SACI test revealed that step-up was detected only in the gastroduodenal artery (GDA) and not in the proper hepatic, splenic, and superior mesenteric arteries (Figure 2).

Table 1 Endocrine Examinations

Figure 1 Contrast-enhanced computed tomography at initial diagnosis. There were no tumorous lesions from pancreatic uncus to head (a) and from pancreatic body to tail (b) on contrast-enhanced computed tomography.

Figure 2 The results of selective arterial calcium injection test. The serum level of insulin status based on a selective arterial calcium injection test SACI (Calcium gluconate hydrate: 0.025 mEq/kg injection). Abbreviations: SACI, selective arterial calcium injection; CHA, common hepatic artery; GDA, gastroduodenal artery; SpA, splenic artery; SMA, superior mesenteric artery.

Based on the above examination results, the patient was clinically diagnosed with adult-onset nesidioblastosis originating from the pancreatic head. Initially, she was treated with diazoxide (300 mg, taken daily) for 1 months; however, but symptoms of impaired consciousness persisted. Subsequently, she received octreotide acetate therapy (30mg, once every 4 weeks; Sandostatin LAR; Novartis, Basel, Switzerland) and had no hypoglycemic symptoms for 1 year. However, the patient subsequently experienced relapse of hypoglycemic symptoms. The patient’s home blood glucose levels were not measured. The results of the SACI test were the same as the previous time, with a step-up only in the GDA, and no tumor was detected in the imaging studies. She underwent pancreatoduodenectomy for adult-onset nesidioblastosis with the pancreatic head region as the culprit, which was poorly controlled with drug therapy.

Pathological examination of the resected pancreas revealed no neoplastic proliferation of pancreatic β-cells, or an obvious increase in the size or number of islets. Immunohistochemical examination revealed numerous isolated insulin-producing cells in the pancreatic parenchyma. Therefore, insulinoma was not thought to be the cause of the hypoglycemia in this patient. The numerous isolated insulin-producing cells in the pancreatic parenchyma may have caused the hyperinsulinemia and hypoglycemia in this patient (Figure 3). Although the patient pathologically did not fully meet the diagnostic criteria for nesidioblastosis, she was clinically diagnosed with adult-onset nesidioblastosis. After the first operation, the hypoglycemic symptoms disappeared; however, 1 year later, she gradually complained of the same symptoms. Therefore, the patient underwent remnant total pancreatectomy for heterochronic recurrent adult-onset nesidioblastosis, with the remnant pancreas as the responsible lesion. The resected remnant pancreas showed the same pathological features as those of the preceding pancreatectomy specimen, with no islet tumors but numerous isolated insulin-producing cells in the parenchyma (Figure 4). After the second surgery, the patient had no hypoglycemic symptoms for > 5 years (Figure 5). However, seven years later, the patient died of sepsis due to Fournier’s gangrene.

Figure 3 Histopathological findings of resected specimen at the first surgery. (a) On hematoxylin and eosin staining of the resected pancreas, there were no neoplastic proliferation of pancreatic beta cells and increasing in the number or size of pancreatic islet cells. (b) On immunostaining staining for insulin of the resected pancreas, there were numerous isolated insulin-producing cells in the pancreatic parenchyma.

Figure 4 Histopathological findings of resected specimens at the second surgery. (a) On hematoxylin and eosin staining, tumorous proliferation of pancreatic beta cells and increasing in the number or size of pancreatic islet cells failed to show. (b) On immunostaining staining for insulin of resected pancreas, there were numerous isolated insulin-producing cells in the pancreatic parenchyma.

Figure 5 Clinical course. Initially, she was treated with diazoxide for 1 months. However, symptoms of impaired consciousness persisted. Subsequently, she received octreotide acetate therapy and had no hypoglycemic symptoms for 1 year. However, the patient subsequently experienced relapse of hypoglycemic symptoms. She underwent pancreatoduodenectomy. One year later, she gradually complained of the same symptoms. Therefore, the patient underwent remnant total pancreatectomy. After the second surgery, the patient had no hypoglycemic symptoms for > 5 years.

Discussion

There are a wide variety of diseases that cause consciousness disturbance and weight loss, including endocrine and psychiatric diseases; however, hypoglycemia due to hyperinsulinemia is also an important differential diagnosis. Causes of hyper-insulinemic hypoglycemia include such as insulinoma, insulin autoimmune syndrome, the use of insulin secretagogues, and nesidioblastosis.^1,2,14 Nesidioblastosis, first named by Laidlaw in 1938,³ has been reported to cause intractable hypoglycemia due to the diffuse proliferation of pancreatic beta cells. Nesidioblastosis is a disease characterized by severe postprandial hypoglycemia and hyperinsulinemia unresponsive to dietary therapy, and its mechanism is characterized by an abnormal increase in β-cell mass and diffuse neoformation of the islets of Langerhans islets from the pancreatic ductal epithelium.³ Though, nesidioblastosis is recognized as the most common cause of hyper-insulinemic hypoglycemia in infants, it is very rare in adults, and the first adult case of nesidioblastosis has been reported in 1975.^1,2,15 In an epidemiological survey conducted in Japan from 2017 to 2018, 205 cases of insulinoma were reported, of which 95% were aged 20 years or older, whereas only 9 cases of nesidioblastosis occurred in patients aged 20 years or older.¹⁶ In recent years, adult-onset nesidioblastosis has also been reported after gastric bypass surgery for bariatric surgery and gastrectomy with Roux-en-Y anastomosis,¹⁷ these conditions are now collectively described as non-insulinoma pancreatogenous hypoglycemia syndrome.¹⁸ However, the developmental mechanism of adult-onset nesidioblastosis remains unclear, and several causes have been speculated, including dysregulation of beta cell function,¹⁹ increased production of growth factors,²⁰ and unidentified genetic mutations.²¹ In recent years, mutations have been identified in several β-cell genes involved in insulin secretion, the most common of which are in the ABCC8 or KCNJ11 genes. A better understanding of the functions of these genes may help elucidate the pathogenesis of nesidioblastosis.²² Conversely, insulinoma is the most common cause of hyperinsulinemic hypoglycemia in adults and a rare disease in infants.^1,2 In both diseases, it is important to first diagnose the existence of hypoglycemia due to hyperinsulinemia and then determine the localization of the responsible lesion. Whipple’s triad is a classical feature of hyper-insulinemic hypoglycemia.⁸ In addition, insulin secretion indices using PG and IRI, such as Fajan’s, Grunt’s, and Turner’s indices, fasting test, and octreotide loading test, are helpful in the initial diagnosis.^9–12 Misdiagnosis of nesidioblastosis as a psychiatric disorder is likely to delay appropriate treatment and result in detrimental effects on the patient’s quality of life. This patient had repeated disturbances of consciousness, but was misdiagnosed with manic depression. In this case, the patient had Whipple’s triad, and all indices except Grunt’s index met the diagnostic criteria for hyperinsulinemic hypoglycemia. Although the sensitivity and specificity of these tests are not sufficient,²³ it is clinically important to consider that the positive results of these tests can raise suspicions about nesidioblastosis or insulinoma. In addition, hypoglycemia results in various symptoms, including confusion, loss of consciousness, and seizures, so when these symptoms appear, it is necessary to consider whether hypoglycemia and the hyperinsulinemia that causes it may be the underlying cause.

A definitive diagnosis of nesidioblastosis was made postoperatively, based on histopathological findings. Pathological criteria have been proposed for the diagnosis of adult-onset nesidioblastosis, and consist of four major criteria and some minor criteria.²⁴ The four major criteria are as follows. First, insulinomas were excluded by macroscopic, microscopic, and immunohistochemical examination. Second, there were multiple β-cells with enlarged hyperchromatic nuclei and abundant clear cytoplasms. Third, islet cells have a normal spatial distribution among the different cell types. Finally, there is no endocrine cell proliferation activity. The identification of a ductuloinsular complex, characterized by the neoformation of islet cells arising from the pancreatic ductal epithelium, is also conclusive evidence of nesidioblastosis. However, as in this case, some cases do not completely meet these pathological criteria but show clinically similar symptoms, and the pathogenesis of adult-onset nesidioblastosis has not yet been fully established. In contrast, insulinomas are characterized by neoplastic proliferation of pancreatic beta cells.⁴ Therefore, insulinoma is typically identified as a hypervascular tumor in imaging studies, whereas nesidioblastosis cannot be detected on imaging studies. The localized diagnostic accuracy of insulinoma by ultrasonography, computed tomography, magnetic-resonance imaging, endoscopic ultrasonography, and somatostatin receptor scintigraphy was reported to be 60–95% and With a recent advances in diagnostic technologies, a high pretreatment diagnostic rate for insulinoma has been reported by combining these imaging modalities.^8–13 The SACI test is an existing and localized diagnosis using insulin secretion function and plays an extremely important role in identifying the region responsible for hyperinsulinemic hypoglycemia.¹³ The SACI test involves selective arteriography of the gastroduodenal, splenic, superior mesenteric, and hepatic arteries, and insulinomas are identified using tumor-enhancing staining. Calcium was injected into each artery (0.025 mEq/kg body weight) to assess endocrine function, and insulin was sampled from a catheter placed in the hepatic vein. When an insulinoma or nesidioblastosis is present, calcium injection releases insulin and decreases PG levels only if the specific artery that feeds the area of the pancreas containing these diseases is tested. In the SACI test, blood vessels with plasma insulin levels that were more than double the basal level after calcium injection were considered positive. In this case, the step-up was initially confirmed only in the GDA region; therefore, it was determined that the region responsible for hyperinsulinemia was in the pancreatic head. Therapeutic strategies for nesidioblastosis include pancreatectomy and drug therapy, and the former is considered as the optimal and curative treatment.^25,26 It has also been reported that a high-carbohydrate diet with appropriate protein adjustment and reduced fat intake is effective in controlling of hypoglycemia in patients with nesidioblastosis;²⁷ however, it has also mentioned that although these medications and dietary therapies have reduced severe hypoglycemic episodes, manageable hypoglycemic episodes still occur.²⁷ In nesidioblastosis, partial pancreatic resection may cause continuous hypoglycemic symptoms, whereas total pancreatectomy leads to insulin-dependent diabetes mellitus. It has been reported, including in this case, that hyperinsulinemic hypoglycemia recurs over time after the culprit lesion is removed, but the mechanism is still unclear. Therefore, it may be important to continue follow-up for the recurrence of hypoglycemic symptoms after surgery. Recently, nesidioblastosis due to pancreatic islet hyperplasia after gastric Roux-en-Y bypass surgery has been reported,¹⁷ and this may help elucidate the changes that occur in the remnant pancreas over time after the initial pancreatectomy. Previous literatures suggested that when the disease persists, a 70–90% resection of the pancreatic tissue is advisable in order to avoid the possibility of developing post-operative diabetes and cure the hyperinsulinemic hypoglycemia.^25,26 We believe that adult-onset nesidioblastosis might improve if the responsible region is removed. Since total pancreatectomy eliminates the exocrine and endocrine functions of the pancreas, various complications may occur after surgery. When we searched for the keyword “nesidioblastosis, adult, total pancreatectomy” in PubMed, three case reports were found.^28–30 The age at the time of total pancreatectomy ranged from 22 to 32 years, and all the patients were women. Two cases with records of treatment history were similar to this case in that they had undergone two-stage total pancreatectomy.^28,29 One of these was a report of pyoderma gangrenosum after total pancreatectomy due to nesidioblastosis.³⁰ Therefore, in our opinion, regional pancreatectomy should be performed for the responsible lesion initially rather than total pancreatectomy, and secondly to remnant pancreatectomy if hyperinsulinemic hypoglycemia symptoms reappear during the post-operative period. In adult-onset nesidioblastosis, in which hypoglycemia cannot be controlled by subtotal pancreatectomy or drug therapy, total pancreatectomy may be a treatment option given the current advances in insulin preparations and pancreatic enzyme replacement therapy. However, in such cases, it is important to ensure that patients fully understand the importance of continuing the diabetes treatment.

In patients who did not show normalization of glycemia by surgery or did not undergo pancreatectomy, chronic use of somatostatin analogs, diazoxide, or verapamil hydrochloride has been reported.^31,32 Diazoxide is a frequently used drug for nesidioblastosis; however, it has some adverse effects, including fluid retention, hypotension, hypertrichosis, and bone marrow suppression.³¹ However, these treatments are primarily aimed at palliating the symptoms rather than curatively. In this case, diazoxide did not improve the symptoms; therefore, the patient was promptly transferred to the next treatment. Although octreotide acetate therapy was subsequently able to alleviate the symptoms to a certain extent, the control worsened over time; therefore, surgical resection was selected.

Conclusion

In conclusion, the present study reports a case of heterochronic adult-onset nesidioblastosis that was cured twice with pancreatectomy, resulting in total pancreatectomy. When an adult patient presents with repeated hypoglycemic symptoms and insulinoma cannot be identified on imaging, adult-onset nesidioblastosis should be considered as a differential diagnosis. It is important to perform an existing and localized diagnosis, treat the responsible lesion, and be mindful of the possibility of recurrence in the residual pancreas.

Ethics Statement

Written informed consent was obtained from the patient for the publication of this report and accompanying images prior to death. Institutional ethics committee approval was not required to publish this manuscript. All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

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Inside a bright new building in the heart of Skid Row, homeless people hung out in a canopy-covered courtyard — some waiting to take a shower, do laundry, or get medication for addiction treatment. Others relaxed on shaded grass and charged their phones as an intake line for housing grew more crowded.

The Skid Row Care Campus officially opened this spring with ample offerings for people living on the streets of this historically downtrodden neighborhood. Pop-up fruit stands and tent encampments lined the sidewalks, as well as dealers peddling meth and fentanyl in open-air drug markets. Some people, sick or strung out, were passed out on sidewalks as pedestrians strolled by on a recent afternoon.

For those working toward sobriety, clinicians are on site to offer mental health and addiction treatment. Skid Row’s first methadone clinic is set to open here this year. For those not ready to quit drugs or alcohol, the campus provides clean syringes to more safely shoot up, glass pipes for smoking drugs, naloxone to prevent overdoses, and drug test strips to detect fentanyl contamination, among other supplies.

As many Americans have grown increasingly intolerant of street homelessness, cities and states have returned to tough-on-crime approaches that penalize people for living outside and for substance use disorders. But the Skid Row facility shows Los Angeles County leaders’ embrace of the principle of harm reduction, a range of more lenient strategies that can include helping people more safely use drugs, as they contend with a homeless population estimated around 75,000 — among the largest of any county in the nation. Evidence shows the approach can help individuals enter treatment, gain sobriety, and end their homelessness, while addiction experts and county health officials note it has the added benefit of improving public health.

“We get a really bad rap for this, but this is the safest way to use drugs,” said Darren Willett, director of the Center for Harm Reduction on the new Skid Row Care Campus. “It’s an overdose prevention strategy, and it prevents the spread of infectious disease.”

Despite a decline in overdose deaths, drug and alcohol use continues to be the leading cause of death among homeless people in the county. Living on the streets or in sordid encampments, homeless people saddle the health care system with high costs from uncompensated care, emergency room trips, inpatient hospitalizations, and, for many of them, their deaths. Harm reduction, its advocates say, allows homeless people the opportunity to obtain jobs, taxpayer-subsidized housing, health care, and other social services without being forced to give up drugs. Yet it’s hotly debated.

Politicians around the country, including Gov. Gavin Newsom in California, are reluctant to adopt harm reduction techniques, such as needle exchanges or supervised places to use drugs, in part because they can be seen by the public as condoning illicit behavior. Although Democrats are more supportive than Republicans, a national poll this year found lukewarm support across the political spectrum for such interventions.

Los Angeles is defying President Donald Trump’s agenda as he advocates for forced mental health and addiction treatment for homeless people — and locking up those who refuse. The city has also been the scene of large protests against Trump’s immigration crackdown, which the president has fought by deploying National Guard troops and Marines.

Trump’s most detailed remarks on homelessness and substance use disorder came during his campaign, when he attacked people who use drugs as criminals and said that homeless people “have no right to turn every park and sidewalk into a place for them to squat and do drugs.” Health and Human Services Secretary Robert F. Kennedy Jr. reinforced Trump’s focus on treatment.

“Secretary Kennedy stands with President Trump in prioritizing recovery-focused solutions to address addiction and homelessness,” said agency spokesperson Vianca Rodriguez Feliciano. “HHS remains focused on helping individuals recover, communities heal, and help make our cities clean, safe, and healthy once again.”

A comprehensive report led by Margot Kushel, a professor of medicine at the University of California-San Francisco, this year found that nearly half of California’s homeless population had a complex behavioral health need, defined as regular drug use, heavy drinking, hallucinations, or a recent psychiatric hospitalization.

The chaos of living outside, she said — marked by violence, sexual assault, sleeplessness, and lack of housing and health care — can make it nearly impossible to get sober.

Skid row care campus

The new care campus is funded by about $26 million a year in local, state, and federal homelessness and health care money, and initial construction was completed by a Skid Row landlord, Matt Lee, who made site improvements on his own, according to Anna Gorman, chief operating officer for community programs at the Los Angeles County Department of Health Services. Operators say the campus should be able to withstand potential federal spending cuts because it is funded through a variety of sources.

Glass front doors lead to an atrium inside the yellow-and-orange complex. It was designed with input from homeless people, who advised the county not just on the layout but also on the services offered on-site. There are 22 recovery beds and 48 additional beds for mostly older homeless people, arts and wellness programs, a food pantry, and pet care. Even bunnies and snakes are allowed.

John Wright, 65, who goes by the nickname Slim, mingled with homeless visitors one afternoon in May, asking them what they needed to be safe and comfortable.

“Everyone thinks we’re criminals, like we’re out robbing everyone, but we aren’t,” said Wright, who is employed as a harm reduction specialist on the campus and is trying, at his own pace, to stop using fentanyl. “I’m homeless and I’m a drug addict, but I’m on methadone now so I’m working on it,” he said.

Nearby on Skid Row, Anthony Willis rested in his wheelchair while taking a toke from a crack pipe. He’d just learned about the new care campus, he said, explaining that he was homeless for roughly 20 years before getting into a taxpayer-subsidized apartment on Skid Row. He spends most of his days and nights on the streets, using drugs and alcohol.

The drugs, he said, help him stay awake so he can provide companionship and sometimes physical protection for homeless friends who don’t have housing. “It’s tough sometimes living down here; it’s pretty much why I keep relapsing,” said Willis, who at age 62 has asthma and arthritic knees. “But it’s also my community.”

Willis said the care campus could be a place to help him kick drugs, but he wasn’t sure he was ready.

Research shows harm reduction helps prevent death and can build long-term recovery for people who use substances, said Brian Hurley, an addiction psychiatrist and the medical director for the Bureau of Substance Abuse Prevention and Control at the Los Angeles County Department of Public Health. The techniques allow health care providers and social service workers to meet people when they’re ready to stop using drugs or enter treatment.

“Recovery is a learning activity, and the reality is relapse is part of recovery,” he said. “People go back and forth and sometimes get triggered or haven’t figured out how to cope with a stressor.”

Swaying public opinion

Under harm reduction principles, officials acknowledge that people will use drugs. Funded by taxpayers, the government provides services to use safely, rather than forcing people to quit or requiring abstinence in exchange for government-subsidized housing and treatment programs.

Los Angeles County is spending hundreds of millions to combat homelessness, while also launching a multiyear “By LA for LA” campaign to build public support, fight stigma, and encourage people to use services and seek treatment. Officials have hired a nonprofit, Vital Strategies, to conduct the campaign including social media advertising and billboards to promote the expansion of both treatment and harm reduction services for people who use drugs.

The organization led a national harm reduction campaign and is working on overdose prevention and public health campaigns in seven states using roughly $70 million donated by Michael Bloomberg, the former mayor of New York.

“We don’t believe people should die just because they use drugs, so we’re going to provide support any way that we can,” said Shoshanna Scholar, director of harm reduction at the Los Angeles County Department of Health Services. “Eventually, some people may come in for treatment but what we really want is to prevent overdose and save lives.”

Los Angeles also finds itself at odds with California’s Democratic governor. Newsom has spearheaded stricter laws targeting homelessness and addiction and has backed treatment requirements for people with mental illness or who use drugs. Last year, California voters approved Proposition 36, which allows felony charges for some drug crimes, requires courts to warn people they could be charged with murder for selling or providing illegal drugs that kill someone, and makes it easier to order treatment for people who use drugs.

Even San Francisco approved a measure last year that requires welfare recipients to participate in treatment to continue receiving cash aid. Mayor Daniel Lurie recently ordered city officials to stop handing out free drug supplies, including pipes and foil, and instead to require participation in drug treatment to receive services. Lurie signed a recovery-first ordinance, which prioritizes “long-term remission” from substance use, and the city is also expanding policing while funding new sober-living sites and treatment centers for people recovering from addiction.

‘Harm encouragement’

State Sen. Roger Niello, a Republican who represents conservative suburbs outside Sacramento, says the state needs to improve the lives of homeless people through stricter drug policies. He argues that providing drug supplies or offering housing without a mandate to enter treatment enables homeless people to remain on the streets.

Proposition 36, he said, needs to be implemented forcefully, and homeless people should be required to enter treatment in exchange for housing.

“I think of it as tough love,” Niello said. “What Los Angeles is doing, I would call it harm encouragement. They’re encouraging harm by continuing to feed a habit that is, quite frankly, killing people.”

Keith Humphreys, who worked in the George W. Bush and Barack Obama administrations and pioneered harm reduction practices across the nation, said that communities should find a balance between leniency and law enforcement.

“Parents need to be able to walk their kids to the park without being traumatized. You should be able to own a business without being robbed,” he said. “Harm reduction and treatment both have a place, and we also need prevention and a focus on public safety.”

Just outside the Skid Row Care Campus, Cindy Ashley organized her belongings in a cart after recently leaving a local hospital ER for a deep skin infection on her hand and arm caused by shooting heroin. She also regularly smokes crack, she said.

She was frantically searching for a home so she could heal from two surgeries for the infection. She learned about the new care campus and rushed over to get her name on the waiting list for housing.

“I’m not going to make it out here,” she said, in tears.

This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. 

This article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.