Cholecalciferol prevents low BMD in erythropoietic protoporphyria patients, reports research

A new study published in The Journal of Clinical Endocrinology & Metabolism showed that low bone mineral density (BMD) is more common in patients with erythropoietic protoporphyria (EPP) than in the general healthy population, however, BMD increases with cholecalciferol administration.

A rare hereditary metabolic condition of heme production is erythropoietic protoporphyria, which causes severe phototoxic responses that begin in childhood and last a lifetime. In order to prevent these responses, the patients wear sunblock and avoid the sun. Vitamin D insufficiency which is a known risk factor for early-onset osteoporosis, is increased by the EPP population’s lack of sun exposure.

Since 2016, adult patients with EPP have been treated with afamelanotide, a strong synthetic analogue of α-melanocyte-stimulating hormone (α-MSH) that agonistically binds to the melanocortin-1 receptor (MC1R) to boost eumelanin synthesis. Furthermore, the effectiveness of cholecalciferol supplementation in raising BMD in the general population is still up for debate.

According to earlier research, the individuals with EPP had a significant frequency of osteoporosis. Thus, to determine the individuals at risk for low bone mineral density (BMD) and which factors (cholecalciferol and afamelanotide medication) increase BMD in EPP, Louisa Kluijver and colleagues carried out this study. This single-center, longitudinal, ambispective cohort study was conducted between 2012 and 2023, and 2-time surveys and patient data from adult EPP patients who had at least one dual-energy x-ray absorptiometry (DXA) scan were utilized.

The key findings of this study suggest that EPP patients have poor BMD with a Z-score below 0 SD at baseline in 82.7% of the 139 patients. Of those with low BMD, 39.5% had osteopenia and 15.3% had osteoporosis. In 34.2% of patients, there were 50 fractures linked to osteoporosis. Also, BMD was not improved by afamelanotide.

Poor body mass index, aging, and chronic vitamin D insufficiency all raised the risk of poor BMD. The patients who had the best chance of changing their BMD were the patients who were vitamin D deficient and did not have cholecalciferol at baseline. Overall, the results demonstrate the high incidence of osteoporosis and fractures in EPP at a very early age, highlighting the need of appropriately treating vitamin D insufficiency for the prevention of osteoporosis and the improvement of bone mineral density.

Reference:

Kluijver, L. G., Wagenmakers, M. A. E. M., Wilson, J. H. P., & Langendonk, J. G. (2024). The impact of minimal sunlight exposure on bone health: Insights from a cohort study in erythropoietic protoporphyria. The Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgae729

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Study Identifies FGF23 as an Early Biomarker for Diabetic Kidney Disease Risk

China: A recent prospective study has highlighted the role of fibroblast growth factor 23 (FGF23) as an early biomarker for predicting the onset of diabetic kidney disease (DKD).

The study, published in Diabetes, Obesity and Metabolism, revealed that serum fibroblast growth factor 23 levels may serve as an independent biomarker for early diabetic kidney disease (DKD) detection. Researchers observed that elevated FGF23 levels were linked to the progression of kidney disease and could improve the predictive accuracy of traditional screening.

Diabetic kidney disease, a common complication of diabetes, is a leading cause of chronic kidney disease and end-stage renal failure worldwide. Early detection and intervention are crucial in slowing disease progression and preventing severe outcomes. While traditional biomarkers such as albuminuria and estimated glomerular filtration rate (eGFR) are widely used for DKD diagnosis, they often detect kidney damage at a later stage. FGF23 is a bone-derived phosphaturic hormone involved in regulating mineral metabolism and the progression of chronic kidney disease. Identifying FGF23 as an independent predictor of DKD offers a promising avenue for earlier risk assessment and preventive strategies.

Against the above background, Weiping Jia, Shanghai Jiao Tong University, Shanghai, China, and colleagues aimed to explore the relationship between FGF23 and diabetic kidney disease in a community-based prospective cohort study.

For this purpose, the researchers analyzed data from 1,614 individuals with diabetes at baseline, selected from a cohort of 7,230 participants who completed a 4.6-year follow-up survey. Baseline serum FGF23 levels were assessed using an enzyme-linked immunosorbent assay. Multiple and ordinal logistic regression analyses were conducted to evaluate the predictive value of FGF23 for incident diabetic kidney disease.

The following were the key findings of the study:

  • Baseline serum FGF23 levels showed an early increase in the course of diabetic kidney disease (DKD) and continued to rise with disease progression.
  • There were no significant changes in serum calcium and phosphorus levels.
  • Over a 4.6-year follow-up, 198 individuals with diabetes developed incident DKD.
  • Elevated baseline FGF23 levels were significantly associated with an increased risk of developing DKD (odds ratio 1.290), even after adjusting for conventional DKD risk factors.
  • The association between FGF23 and DKD was particularly strong in individuals with a lower body mass index (<24 kg/m²), poor glycemic control (HbA1c ≥7%), and a shorter duration of diabetes (<5 years).
  • FGF23-based models demonstrated strong predictive performance for DKD risk and showed significant improvement over traditional DKD risk factor models.

The findings highlight a progressive increase in serum FGF23 levels during the early stages of diabetic kidney disease (DKD), establishing its significant association with the risk of incident DKD. The study suggests that FGF23 may be a reliable independent biomarker for predicting DKD risk and facilitating early identification of at-risk individuals.

‘Additionally, the study underscores the potential clinical utility of FGF23 in improving DKD screening strategies. Further research is warranted to explore the causal mechanisms, underlying pathways, and clinical implications of FGF23 in DKD progression,” the researchers concluded.

Reference:

Liu D, Yu S, Zhang Y, Li Q, Kang P, Wang L, Han R, Cheng D, Chen A, Hou X, Wu L, Zang S, Fang Q, Jia W, Li H. Fibroblast growth factor 23 predicts incident diabetic kidney disease: A 4.6-year prospective study. Diabetes Obes Metab. 2025 Feb 3. doi: 10.1111/dom.16224. Epub ahead of print. PMID: 39895483.

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CAR identified as Risk Factor for 28-Day ICU Mortality in Cardiac Surgery Patients: Study

Researchers have identified creatinine albumin ratio (CAR) as a risk factor for 28-day ICU mortality in patients undergoing cardiac surgery in a new study. The study revealed a complex dose-response relationship and subgroup-specific associations with mortality risk. Furthermore, CAR influenced 28-day ICU mortality through multiple key biomarkers, offering potential insights for targeted interventions. The study was conducted by Pengtao and fellow researchers published in the journal of BMC Cardiovascular Disorders.

The research, based on MIMIC-IV database information, examined the correlation between CAR levels and patient outcomes and found a clear dose–response relationship. CAR has been identified as a predictive marker in multiple postoperative contexts previously, but its prognostic association with cardiac surgery outcomes is not understood. This study sought to assess the correlation between CAR and ICU 28-day mortality, investigate subgroup-specific risk, and examine mechanisms through mediation analysis.

Methods

The research employed data from the MIMIC-IV database for 5,670 patients who were admitted to the ICU following cardiac surgery. Patients were divided into three groups according to CAR levels:

  • Low CAR (<0.23)

  • Intermediate CAR (0.23–0.31)

  • High CAR (≥0.31)

Kaplan–Meier survival analysis was used to compare differences in 28-day mortality across the groups. Multivariate Cox regression and RCS analyses were applied to investigate the dose–response relationship between CAR and risk of mortality. Receiver operating characteristic (ROC) curves were used to establish the predictive validity of CAR. Mediation analysis was employed to investigate the way CAR affects mortality via biochemical markers.

Key Results

  • Out of the 5,670 patients, those who had high CAR (≥0.31) had a mortality rate of 11.4% in ICU at 28 days, significantly greater than the patients with low CAR (<0.23) who had a mortality rate of 1.83%.

  • Kaplan–Meier analysis revealed that high CAR patients had the lowest survival rate among the three groups (p < 0.0001).

  • ROC curve analysis revealed that CAR had moderate predictive ability for 28-day ICU mortality (AUC = 0.748).

  • There was a strong dose–response relationship, with increasing CAR levels correlating with increased risk of death.

  • Subgroup analysis proved that the risk attributable to increased CAR was augmented in female patients and in the absence of chronic conditions such as CKD and T2DM.

Mediation analysis indicated that CAR affected 28-day ICU mortality via primary biomarkers, such as:

  • Chloride (39.8%)

  • Potassium (24.4%)

  • Sodium (28.3%)

  • Glucose (11.8%)

The study authors concluded that CAR is a reliable predictor of 28-day ICU mortality in cardiac surgery patients. The dose dependency and biochemical mediation effects indicate that CAR can potentially be used as an important instrument for early risk stratification.

Reference:

Shi, P., Rui, S. & Meng, Q. Association between serum creatinine—to—albumin ratio and 28-day mortality in intensive care unit patients following cardiac surgery: analysis of mimic-iv data. BMC Cardiovasc Disord 25, 100 (2025). https://doi.org/10.1186/s12872-025-04505-1

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Testing exhaled breath may reveal evidence of lung cancer, suggests study

Exhaled breath contains chemical clues to what’s going on inside the body, including diseases like lung cancer. And devising ways to sense these compounds could help doctors provide early diagnoses-and improve patients’ prospects. In a study in ACS Sensors, researchers report developing ultrasensitive, nanoscale sensors that in small-scale tests distinguished a key change in the chemistry of the breath of people with lung cancer. November is Lung Cancer Awareness Month.

People breathe out many gases, such as water vapor and carbon dioxide, as well as other airborne compounds.

Researchers have determined that declines in one exhaled chemical — isoprene — can indicate the presence of lung cancer.

However, to detect such small shifts, a sensor would need to be highly sensitive, capable of detecting isoprene levels in the parts-per-billion (ppb) range.

It would also need to differentiate isoprene from other volatile chemicals and withstand breath’s natural humidity.

Previous attempts to engineer gas sensors with characteristics like these have focused on metal oxides, including one particularly promising compound made with indium oxide.

A team led by Pingwei Liu and Qingyue Wangset out to refine indium oxide-based sensors to detect isoprene at the level at which it naturally occurs in breath.

The researchers developed a series of indium(III) oxide (In2O3)-based nanoflake sensors.

In experiments, they found one type, which they called Pt@InNiOx for the platinum (Pt), indium (In) and nickel (Ni) it contains, performed best.

These Pt@InNiOx sensors:

  • Detected isoprene levels as low as 2 ppb, a sensitivity that far surpassed earlier sensors.
  • Responded to isoprene more than other volatile compounds commonly found in breath.
  • Performed consistently during nine simulated uses.

More importantly, the authors’ real-time analysis of the nanoflakes’ structure and electrochemical properties revealed that Pt nanoclusters uniformly anchored on the nanoflakes catalyzed the activation of isoprene sensing, leading to the ultrasensitive performance.

Finally, to showcase the potential medical use of these sensors, the researchers incorporated the Pt@InNiOx nanoflakes into a portable sensing device. Into this device they introduced breath collected earlier from 13 people, five of whom had lung cancer. The device detected isoprene levels lower than 40 ppb in samples from participants with cancer and more than 60 ppb from cancer-free participants. This sensing technology could provide a breakthrough in non-invasive lung cancer screening and has the potential to improve outcomes and even save lives, the researchers say.

Reference:

Ye Cheng, Raquel Portela, Pingli Wang, Pingwei Liu, Yupeng Mao, Khak Ho Lim, Jieyuan Zheng, Xuan Yang, Gensheng Zhang, Liren Ding, Wen-Jun Wang, Bo-Geng Li, Miguel A. Bañares, Qingyue Wang. Ultrasensitive In2O3-Based Nanoflakes for Lung Cancer Diagnosis and the Sensing Mechanism Investigated by Operando Spectroscopy. ACS Sensors, 2024; DOI: 10.1021/acssensors.4c01298

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One-Stage Microsurgical Reconstruction tied to improved ankle joint function for Achilles Tendon Defects: Study

Researchers have found in a new study that the one-stage microsurgical reconstruction method for open Achilles tendon defects promotes better tendon healing and improves long-term ankle joint function. Using vascularized tendon tissue for repair is an effective approach, as it supports both anatomical and physiological functional reconstruction of the Achilles tendon.

A study was done to explore the differences in long-term ankle joint function between one-stage and staged microsurgical repair of open Achilles tendon defects. A retrospective analysis of the surgical treatment and follow-up data of 147 patients with open Achilles tendon defects from January 2007 to September 2023 was conducted. Patients were divided into a one-stage reconstruction group (n = 81) and a staged reconstruction group (n = 66) on the basis of whether one-stage microsurgical repair was used. In the one-stage reconstruction group, 43 patients underwent vascular anastomosed fascia lata free anterolateral thigh perforator flap transplantation for repair, and 38 patients underwent descending genicular artery free flap transplantation with the adductor magnus tendon. In the staged reconstruction group, the sural neurovascular flap was used to repair the soft tissue defect in the heel area in the first stage. In the second stage, 31 patients underwent flexor hallucis longus tendon transfer, and 35 patients underwent peroneus longus muscle tendon transfer with the lateral calcaneal artery. Observations included evaluation of the continuity and healing of the Achilles tendon via colour Doppler ultrasound 3 months postoperatively and assessment of ankle joint function 2 years postoperatively using the American Orthopedic Foot and Ankle Society ankle-hindfoot score (AOFAS) and the Achilles tendon total rupture score (ATRS). RESULTS: Three months after surgery, colour Doppler ultrasound revealed good continuity of the Achilles tendon in all patients, with slight thickening and irregular fibre orientation. Two years after surgery, the ATRS and AOFAS scores of the one-stage reconstruction group were superior to those of the staged group (PATRS < 0.05, PAOFAS < 0.05). Among the one-stage reconstruction group, patients who underwent descending genicular artery-free flap transplantation with the adductor magnus tendon presented better performance in walking on uneven surfaces, fast stair climbing, abnormal gait, plantar flexion and dorsiflexion, and inversion and eversion than did those who underwent vascular anastomosed fascia lata free anterolateral thigh perforator flap transplantation, although there was no overall functional difference (PAOFAS = 0.792; PATRS < 0.001). In the staged repair group, patients who underwent peroneus longus muscle tendon transfer with the lateral calcaneal artery in the second stage had better postoperative follow-up ankle joint function than did those who underwent flexor hallucis longus tendon transfer (PAOFAS < 0.001; PATRS < 0.001). Preoperative injury classification of the heel region (P < 0.001), size of the defect area in the heel region (PAOFAS < 0.001, RAOFAS = -0.397; PATRS < 0.001, RATRS = -0.436), and length of the Achilles tendon defect (PAOFAS < 0.001, RAOFAS = -0.429; PATRS < 0.001, RATRS = -0.280) were associated with postoperative follow-up ankle joint function, whereas preoperative wound infection was not associated with postoperative follow-up ankle joint function (PAOFAS = 0.690, PATRS = 0.759). The surgical method (OR = 49.725, 95% CI: 16.996 ~ 145.478) and the preoperative heel region defect area (OR = 0.947, 95% CI: 0.903 ~ 0.992) were found to be independent risk factors affecting the postoperative follow-up of ankle joint function in patients with open Achilles tendon defects. The use of a one-stage microsurgical reconstruction method for open Achilles tendon defects is more conducive to Achilles tendon healing and results in a better long-term ankle joint function prognosis. The use of vascularised tendon tissue to repair Achilles tendon defects is a good choice that meets the needs of anatomically and physiologically functional reconstruction of the Achilles tendon.

Reference:

Mao, Jianjie, et al. “Comparison of Long-term Ankle Joint Function After One-stage and Staged Microsurgical Repair of Open Achilles Tendon Defects.” Journal of Orthopaedic Surgery and Research, vol. 20, no. 1, 2025, p. 149.

Keywords:

One-Stage, Microsurgical, Reconstruction, improved, ankle, joint, function, Achilles, Tendon, Defects, study, Mao, Jianjie

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Routine incisional negative pressure wound therapy fails to reduce SSIs in adults undergoing emergency laparotomy: JAMA

According to a new study researchers have found that routine incisional negative pressure wound therapy (iNPWT) does not significantly reduce surgical site infections (SSIs) more than standard wound dressings in patients undergoing emergency laparotomy with primary skin closure. The study was conducted by the SUNRRISE trial study group published in the journal of JAMA.

SSI is still a significant concern after emergency abdominal surgeries, potentially increasing morbidity and healthcare costs for patients.However, evidence of its effectiveness in reducing the incidence of SSI in emergency laparotomies is deficient. Therefore, this study aimed to assess whether iNPWT reduces the rates of SSIs and improves outcomes following surgery for such a high-risk population.

The SUNRRISE trial was a phase 3, assessor-masked, pragmatic, randomized clinical trial conducted between December 18, 2018, and May 25, 2021. A total of 840 adult patients undergoing emergency laparotomy in 22 UK hospitals and 12 Australian hospitals were enrolled. Participants were randomized 1:1 to receive either iNPWT (n=411) or the surgeon’s choice of standard wound dressing (n=410).

The main outcome was SSI at 30 days after surgery, which was evaluated by assessors blinded to the groups by US Centers for Disease Control and Prevention criteria. Secondary outcomes were readmission to hospital, length of stay in hospital, wound pain, quality of life, and postoperative complications.

Results

  • A total of 840 patients were enrolled; 394 participants per group were included in the primary analysis after post randomization exclusions.

  • SSI rates were similar between the two groups: 112 of 394 patients (28.4%) in the iNPWT group and 108 of 394 (27.4%) in the surgeon’s preference group (relative risk: 1.03; 95% CI, 0.83-1.28; p=0.78).

  • No significant differences were found in six of the seven secondary outcomes, including hospital readmissions, quality of life, and length of hospital stay (median: 8 days in the iNPWT group vs. 9 days in the standard dressing group; p=0.21).

  • These results were consistent across subgroup analyses, including degree of contamination, stoma presence, BMI, and skin preparation.

Researchers concluded that routine use of iNPWT for closed surgical wounds in emergency laparotomies does not reduce SSIs or improve secondary outcomes compared to standard dressings.

Reference:

SUNRRISE Trial Study Group. Negative Pressure Dressings to Prevent Surgical Site Infection After Emergency Laparotomy: The SUNRRISE Randomized Clinical Trial. JAMA. Published online January 27, 2025. doi:10.1001/jama.2024.24764

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Topical corticosteroids Prescribed more for Vulvar lichen sclerosus Patients Without a History of VSCC Compared to Post-Surgery LS Patients: Study

Vulvar lichen sclerosus (LS) is a long-term skin condition that can advance to vulvar squamous cell carcinoma (VSCC) via differentiated vulvar intraepithelial neoplasia (dVIN). Symptoms of LS are managed with topical corticosteroids (TCS), which can also impede the progression to dVIN and VSCC. Nonetheless, existing global guidelines do not provide specific recommendations for treating LS following VSCC surgery. Recent study aimed to evaluate the management of vulvar lichen sclerosus (LS) patients without a history of vulvar squamous cell carcinoma (VSCC) and those with LS following surgery for VSCC, particularly regarding the prescribing of topical corticosteroids (TCS) for these patient groups. The study conducted a survey among registered gynecologic oncologists in the Netherlands to assess the frequency, type, and duration of TCS treatment prescribed for these patient groups and the reasons for initiating TCS treatment.

The findings of the study demonstrate that Dutch gynecologic oncologists prescribed TCS more often to patients with LS without a history of VSCC compared to patients with LS following surgery for VSCC. Specifically, TCS were prescribed more frequently to LSnoVSCC patients (86%) compared to LSVSCC patients (52%). When TCS treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most common reasons for treating patients in both groups with TCS were symptoms, followed by clinical aspects of the lesion and prevention of progression to differentiated vulvar intraepithelial neoplasia (dVIN) and VSCC. The study highlighted that LS is a chronic skin condition with the potential to progress to VSCC through dVIN. LS symptoms are commonly treated with TCS, which can also prevent progression to dVIN and VSCC. The survey revealed that Dutch gynecologic oncologists prescribed TCS more frequently to LSnoVSCC patients than to LSVSCC patients, indicating a variation in TCS prescription practice between these patient groups.

Factors Influencing Prescription Behavior

The study provided insights into the different factors influencing the prescription behavior of gynecologic oncologists for LSnoVSCC and LSVSCC patients. The findings will contribute to the evolving understanding of the management of patients with LS, especially following VSCC, and could inform further prospective studies and potential integration of TCS use in (inter)national LS and vulvar cancer guidelines.

Conclusion

In conclusion, the study highlighted variations in TCS prescription patterns for LS patients without a history of VSCC compared to those with LS following surgery for VSCC among Dutch gynecologic oncologists. These findings underscore the evolving clinical practice and expert clinical opinions concerning the management of LS patients, indicating the need for further research and prospective studies to inform guidelines and enhance patient care.

Key Points

– The study aimed to evaluate the management of vulvar lichen sclerosus (LS) patients without a history of vulvar squamous cell carcinoma (VSCC) and those with LS following surgery for VSCC, particularly regarding the prescribing of topical corticosteroids (TCS) for these patient groups.

– Dutch gynecologic oncologists prescribed TCS more often to patients with LS without a history of VSCC compared to patients with LS following surgery for VSCC. TCS were prescribed more frequently to LS without VSCC patients (86%) compared to LSVSCC patients (52%).

– Ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups when TCS treatment was initiated.

– The most common reasons for treating patients in both groups with TCS were symptoms, followed by clinical aspects of the lesion and prevention of progression to differentiated vulvar intraepithelial neoplasia (dVIN) and VSCC.

– LS is a chronic skin condition with the potential to progress to VSCC through dVIN. TCS treatment is commonly used to manage LS symptoms and can also prevent progression to dVIN and VSCC.

– The study highlighted variations in TCS prescription patterns for LS patients without a history of VSCC compared to those with LS following surgery for VSCC among Dutch gynecologic oncologists. These findings underscore the need for further research and prospective studies to inform guidelines and enhance patient care, contributing to the evolving understanding of the management of patients with LS.

Reference –

Féline O. Voss, Karelina L. Groenewegen, Hester Vermaat, Maaike C.G. Bleeker & Marc van Beurden (2024) Prevalence of prescribing topical corticosteroids to patients with lichen sclerosus following surgery for vulvar cancer: a survey among gynaecologiconcologists in The Netherlands, Journal of Obstetrics and Gynaecology, 44:1, 2294330, DOI:10.1080/01443615.2023.2294330

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Study suggests that hematological markers may aid early TB detection in people living with HIV

An Indian study suggests that hematological markers may aid early TB detection in people living with HIV (PLHIV). Tuberculosis (TB) remains a significant health challenge among people living with HIV (PLHIV), underscoring the need for early diagnosis and prompt treatment. Hematological parameters have emerged as potential markers for predicting and monitoring TB disease. This study aimed to assess the utility of hematological parameters in predicting TB disease among PLHIV. This retrospective cohort study was conducted at an Antiretroviral Therapy (ART) Centre in Gujarat, India, including PLHIV registered between January 2018 and March 2024. Hematological parameters, including hemoglobin levels, platelet counts, white blood cell differentials, and derived ratios (monocyte-lymphocyte ratio [MLR] and neutrophil-lymphocyte ratio [NLR]), were extracted from medical records. TB diagnosis was based on bacteriological confirmation or clinical criteria. Cox proportional hazards models and Kaplan-Meier survival analyses were performed to assess the association between hematological parameters and TB disease, adjusting for potential confounders. Results: Among 810 PLHIV, 202 (25%) had TB disease. PLHIV with TB had a higher prevalence of anemia (91.6% vs. 60.0%, p < 0.001), leucocytosis (16.3% vs. 7.6%, p = 0.0004), and neutrophilia (25.2% vs. 9.4%, p < 0.0001) compared to those without TB. A higher MLR ratio (> 0.23) was associated with an increased risk of TB (HR: 5.44, 95% CI: 3.94-7.50, p < 0.001), independent of anemia. Anemia was also an independent predictor of TB. Hematological parameters, particularly MLR ratio and anemia status, showed strong associations with TB disease among PLHIV. An MLR > 0.23 was associated with a 5.44-fold increased risk of TB, while anemia increased the risk by 4.37-fold. These readily available and cost-effective markers could enhance early TB detection and risk stratification in PLHIV, especially in resource-limited settings. Integration of these parameters into existing screening protocols may improve targeted interventions and patient outcomes.

Reference:

M Y, Vamja R, Makwana N, Parmar PA, Sundar RNS. Haematological markers as predictive tools for tuberculosis in PLHIV: a retrospective cohort study in Gujarat, India. BMC Infect Dis. 2025 Feb 17;25(1):228. doi: 10.1186/s12879-025-10625-y. PMID: 39962402; PMCID: PMC11834239.

Keywords:

Anemia; Biomarkers; HIV; Hematological Parameters; Monocyte-to-Lymphocyte Ratio; Tuberculosis, M Y, Vamja R, Makwana N, Parmar PA, Sundar RNS, BMC Infect Dis, BMC Infectious Diseases

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Inhaled Therapy with Ensifentrine Significantly may Reduce COPD Exacerbations, unravels research

A new study published in the CHEST journal found that ensifentrine, an innovative inhaled therapy, significantly reduces the rate and risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). The findings from a pooled analysis of two phase 3 clinical trials highlighted the drug’s potential to improve the quality of life for COPD patients with serious exacerbations.

COPD exacerbations are sudden worsening of symptoms which can lead to irreversible lung damage, increased hospitalization rates, and a decline in overall health. Medications that effectively reduce these exacerbations remain an unmet need, as exacerbations tend to increase the risk of further episodes and diminish the patients’ quality of life.

Ensifentrine is a first-in-class dual inhibitor of phosphodiesterase (PDE) 3 and 4, offering both bronchodilatory and nonsteroidal anti-inflammatory benefits. The drug was evaluated in two large clinical trials (ENHANCE-1 and ENHANCE-2) which enrolled symptomatic patients aged 40 to 80 with moderate to severe COPD. The participants received either 3 mg of ensifentrine twice daily or a placebo over 24 weeks, with the study assessing the impact of drug on exacerbation rates and the time to first exacerbation.

The pooled analysis included a total of 975 patients treated with ensifentrine and 574 who received placebo. Also, 62% of participants were also using either long-acting muscarinic antagonists (LAMA) or long-acting β2-agonists (LABA), while 18% were on inhaled corticosteroids.

These results showed a 41% reduction in the rate of moderate to severe exacerbations among patients taking ensifentrine when compared to the placebo group (rate ratio: 0.59, 95% confidence interval [CI]: 0.43-0.80; p < .001). Similarly, the risk of experiencing an exacerbation was also reduced by 41% (hazard ratio: 0.59, 95% CI: 0.44-0.81; p < .001).

The study further revealed that the benefits of ensifentrine extended across multiple patient subgroups, regardless of age, sex, race, disease severity, history of exacerbations, eosinophil count, or background COPD medication use.

This data suggested that ensifentrine may help delay progression of patients from infrequent exacerbators (Global Initiative for Chronic Obstructive Lung Disease Group B) to frequent exacerbators (Group E), indicating a potential role in slowing disease progression. Overall, these findings underline the potential of ensifentrine as a strong addition to COPD management, addressing the urgent need for therapies that reduce exacerbation rates and improve long-term outcomes.

Reference:

Sciurba, F. C., Christenson, S. A., Rheault, T., Bengtsson, T., Rickard, K., & Barjaktarevic, I. Z. (2025). Effect of dual phosphodiesterase 3 and 4 inhibitor ensifentrine on exacerbation rate and risk in patients with moderate to severe COPD. Chest, 167(2), 425–435. https://doi.org/10.1016/j.chest.2024.07.168

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Optimizing TIRp and Mean Glucose Levels in second trimester Reduces Fetal Risks in T1D Pregnancies: Study

Tight metabolic control during pregnancy, mainly keeping time in range during pregnancy (TIRp) and mean glucose levels within target ranges, may reduce the risk of large for gestational age (LGA) infants in women with Type 1 Diabetes (T1D). A recent study was conducted by Ana Maria and colleagues and was published in the journal Diabetes Research and Clinical Practice.

Through optimizing their blood glucose levels, pregnant women can significantly reduce risks for the fetus and the mother to suffer complications related to pregnancy. TIRp (63–140 mg/dL) and mean glucose thresholds that can contribute to better fetal outcomes in Latin American women with T1D were assessed in this study.

This was a prospective cohort study conducted on 62 pregnant women with T1D. All these women were on AID systems managing their glucose levels during pregnancy. The mean age of the patients was 31.9 years (±5.9), and their mean HbA1c was 7.57% (±1.29%). Establishing optimum TIRp and mean glucose cut-off points for predicting LGA with the Liu method in measurement at second-trimester, analyzing the strongest predictors of LGA. The analysis included comparisons of TIRp metrics, glucose levels, fetal outcomes, and the device types used, specifically examining outcomes with AHCL systems versus other AID systems.

  • LGA was higher among those with TIRp < 59.1% (50%) compared with those with TIRp > 59.1% (17.9%) (p = 0.010).

  • Hyperbilirubinemia was also more common in the former where TIRp < 59.1% (45%) in comparison to TIRp better the latter groups (11.8%) (p = 0.016).

  • The optimal TIRp cut-off point which identified as being able to reduce risk for LGA was > 59.1 % during the second trimester with a measure of sensitivity at 75% and specificity at 61% and an AUC of 0.68 (CI 0.48 – 0.88).

  • It reflected a reduced risk for LGA with sensitivity at 69%, specificity 70%, and an AUC at 0.70 (CI 0.51-0.88).

  • The third trimester was attained with improved metabolic control in women with AHCL devices compared to those on other devices of insulin delivery.

In conclusion, it is evident that keeping TIRp > 59.1% and mean glucose < 133 mg/dL during the second trimester confers reduced risks of LGA in the pregnancy outcomes of women with T1D. AHCL systems also support better metabolic control hence promising as a tool in the management of T1D pregnancies. Further research into the observed outcomes may validate the adoption of these metrics as the standard in handling these pregnancies.

Reference:

Medina, A. M. G., Carrillo, D. C. H., Macías, M. N. S., Chávez, M. J. S., Gómez, M. A. R., Parra, D., González, J. A. G., Grassi, B., Imitola, A., Cob, A., Rondón, M., García, M., & Velandia, O. M. M. (2024). Time in range and mean glucose cut-off points for reduction of fetal outcomes in pregnant women with type 1 diabetes using automated insulin delivery systems. Diabetes Research and Clinical Practice, 217(111902), 111902. https://doi.org/10.1016/j.diabres.2024.111902

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