Frequent Recurrence Research Articles

Therapeutic interventions and clinical efficacy in Ayurvedic management of Vipadika (Palmoplantar Psoriasis): A Case Report

Vipadika, a skin disorder mentioned in Ayurvedic literature as Kshudra Kustha attributed to Vata and Kapha Dosha imbalance, is analogous to palmoplantar psoriasis in contemporary science. It is a non-infectious chronic inflammatory disease of the skin bound to the palm and sole. It is characterized by pain, itching, and fissures in both soles. Contemporary treatment options often lead to temporary relief with frequent recurrence, leading patients to seek alternative therapies. The present case report aims to assess the therapeutic efficacy of Ayurvedic management in treating Vipadika. A 58-year-old female presented with pruritus, fissures in both sole and severe pain with oozing of bleeding from fissures across both soles; diagnosed as Vipadika. The treatment approach exclusively involved Shamana Chikitsa, including the oral administration of Panchatikta Ghrita, Gandhaka Rasayana, and Avipattikara Churna. Topical care was provided by washing the affected area with Panchavalkala Kwatha mixed with Shuddha Tankana for debridement. After washing, the patient was advised to use a foot scrubber for scrubbing the dead skin around the fissures followed by Jatyadi Malam for topical use. The patient's response was assessed over ten weeks, with follow-up for four weeks to determine using symptom improvement, patient-reported outcomes, and Auspitz sign. This case demonstrates the potential of Ayurvedic therapies for the effective management of Vipadika, suggesting a viable alternative to conventional treatment approaches.

Single-cell RNA sequencing analysis reveals the dynamic changes in the tumor microenvironment during NMIBC recurrence.

Due to the clinical characteristic of frequent recurrence in urothelial bladder cancer (UBC), patients face significant health impacts and economic burdens. Therefore, understanding the molecular mechanisms involved in UBC recurrence is crucial for reducing its recurrence rate. The aim of our study is to help urologists and clinical researchers gain a deeper understanding of the changes in the tumor microenvironment (TME) during UBC recurrence. We collected 10 samples from primary and recurrent non-muscle-invasive bladder cancer (NMIBC) and performed single-cell RNA sequencing. By distinguishing and annotating cell subpopulations, we identified tissue preferences of some novel cell subgroups. Next, pseudotime trajectory analysis, cell-cell communication analysis, and function enrichment analysis were applied to evaluate the dynamic changes in the TME and biological functions. Finally, we validated the distribution of some of these cell subgroups using multiplex immunofluorescence experiments. We identified a tumor-associated fibroblast (CAF) subtype with high COL18A1 expression that is highly expressed in recurrent NMIBC, suggesting that the stromal component of the tumor may play a crucial role in the recurrence process. Additionally, pseudotime trajectory analysis revealed a macrophage subtype with high IL-6 expression at the terminal stage of macrophage differentiation, exhibiting significant immunosuppressive features. This indicated the presence of immune exhaustion during NMIBC recurrence. Lastly, we found an upregulation of estrogen in recurrent urothelial cancer cells, which may partially explain the gender disparity observed in UBC. This study identified several cell subpopulations influencing NMIBC recurrence, which were heavily infiltrated in the TME of recurrent NMIBC. Additionally, the enrichment of estrogen in urothelial cancer cells from various sources suggested a role of sex hormones in NMIBC recurrence.

Cystine urolithiasis-free duration after first occurrence and treatment is longer for castrated dogs than for sexually intact male dogs.

To evaluate outcome in 60 dogs with cystine urolithiasis treated with surgical removal with and without castration and postoperative therapeutic diet to determine frequency of recurrence and urolith-free duration. Patient records were reviewed for dogs with documented cystine urolithiasis from September 2010 to December 2020. Medical records, client interviews, and referring veterinarians were contacted to document the absence of clinical signs associated with subsequent urolith formation and to evaluate risk factors for urolith reoccurrence. 80 patients were identified with cystine uroliths, with 60 qualifying for inclusion in the study. Seven dogs were neutered prior to surgery, and 25 dogs were neutered at the time of the first surgery. Recurrence occurred in 20 dogs; 17 of those patients were intact (85%) at the time of recurrent urinary signs. Of the 20 dogs with recurrence, 50% (10 of 20) were being treated with dietary modifications. The risk of recurrence among neutered pets was 23% versus 47% for intact pets, but this difference was not statistically significant; however, neutered pets had a longer urolithiasis-free duration. There was no statistically significant difference in risk of recurrence and urolith-free duration between pets with and without therapeutic diet management, (30% vs 32.5%) respectively. Multivariant analysis showed no significant interaction between surgical intervention with therapeutic diet, with nonsignificant hazard ratios (HRs) for neuter status (HR = 0.503), diet (HR = 1.056), and their interaction (HR = 4.32 to 9). Sexually intact (vs castrated) male dogs should be monitored more closely for recurrence of surgical cystine urolithiasis.

Treatment of ulcerative colitis via the in situ restoration of local immune and microbial homeostasis by oral administration of Tremella polysaccharide drug-carrying hydrogel

Ulcerative colitis (UC) is a prevalent inflammatory bowel disease, and conventional treatments, such as anti-inflammatory medications and surgery, often prove inadequate due to frequent recurrences and various complications. To alleviate patient suffering, there is an urgent need for a therapeutic system that specifically delivers drugs to the colon for wound healing, inflammation relief, and restoration of microbial homeostasis. In this paper, we developed a Tremella polysaccharide drug-carrying hydrogel that adheres to the inflamed colonic mucosa, forming an effective artificial barrier and releasing the drug in situ to restore local immune and microbial balance. The hydrogel backbone was synthesized through the chemical cross-linking of Tremella polysaccharide with 1,4-butanediol diglycidyl ether in an alkaline environment. During this process, Soluplus® and TPGS-encapsulated ginsenoside compound K adhered to the hydrogel backbone due to electrostatic attraction. The enhanced adhesion following cross-linking enables the hydrogel to stably attach to the inflamed colonic mucosa, releasing mixed micelles that improve drug penetration and absorption by inhibiting the cellular efflux protein P-glycoprotein. This mechanism promotes local immune recovery and eliminates harmful intestinal flora, providing significant relief from UC symptoms. This natural polysaccharide-based hydrogel represents a highly effective oral treatment for UC.

Modified scarf osteotomy has a possible capability to be indicated against very severe hallux valgus deformity

BackgroundGenerally, scarf osteotomy is recommended for moderate-severe hallux valgus (HV) deformity. Although severe HV deformity is defined to be more than 40 degree (°), this definition of angular setting includes broad range of HV angle (HVA). Actually, very severe HV deformity such as more than 60° of the HVA is often seen. At present, whether scarf osteotomy would truly contribute to maintaining the correction status against such very severe deformity is elusive. Then, in this study corrective effectiveness of modified scarf osteotomy including very severe deformity (HVA ≥ 60°) was evaluated.MethodsA retrospective, observational study of 93 feet [mean follow-up: 56.0 months after the surgery] was performed. Hallux scores of the Japanese Society for Surgery of the Foot (JSSF), a self-administered foot evaluation questionnaire (SAFE-Q), and pre-postoperative radiographic parameters were evaluated. The patients were categorized into three groups [44 feet: (mildly severe) 40° ≤ HVA < 50°, 30 feet: (moderately severe) 50° ≤ HVA < 60°, 19 feet: (very severe) HVA ≥ 60°].ResultsBoth JSSF hallux and SAFE-Q score showed significant improvement in all groups, except social activity score in SAFE-Q, in very severe cases (P = 0.08). HVA also significantly improved in all groups without significant change of the HVA between post 1-month and final follow-up in each groups. No difference was seen among the three groups in complications after surgery and frequency of recurrence of HV deformity.ConclusionModified scarf osteotomy has sufficient potential to be indicated for very severe (HVA ≥ 60°) deformity, but it might be recommended before the HVA reaches > 60° from the perspective of clinical score improvement.Level of evidenceLevel III.

Anti-urolithiatic Effect of Psiadia Punctulata Leaves Ethanolic Extracts Against Sodium Oxalate-Induced Urolithiasis in Rats

Kidney stones are rigid mineral and acidic salt deposits that accumulate in concentrated urine, leading to urolithiasis, the third most common urinary tract disorder. Current treatments for urolithiasis have limitations and frequent recurrences. This study aimed to investigate the anti-urolithiatic effects of ethanolic extracts from Psiadia Punctulata leaves on sodium oxalate-induced urolithiasis in rats. Rats were administered orally Psiadia Punctulata leaves ethanolic extract (PPEE) at 200 and 400 mg/kg doses for 14 days to assess its effectiveness against urolithiasis induced by sodium oxalate. Cystone (500 mg/kg) was used as a positive control. The effects of PPEE on body and kidney weights, urinary output and pH levels, urine and serum parameters, renal oxidative and antioxidative markers, and histopathological evaluations were examined. Oral administration of PPEE at 200 and 400 mg/kg doses showed a significant dose-dependent (P&lt;0.01) antiurolithiatic effect, reversing sodium oxalate-induced ion excretion and urinary calcium oxalate concentration. These findings support the traditional use of PPEE for renal calculi management, possibly due to its antioxidant properties identified through phytochemical screening. However, further research is needed to understand the exact mechanism of action

Adaptation of Satellite Remote Sensing Algorithms for Retrieval of Environmental Parameters in the Caspian Sea

The state of the Caspian Sea ecosystems causes serious concern due to anthropogenic (oil and gas production and transportation) and natural reasons (climatic changes, extreme meteorological and hydrological phenomena, natural hazards and their frequency of recurrence, etc.). Climatic changes have already led to a sharp drop in the Caspian Sea level, an increase in sea surface temperature, changes in ice conditions in the Northern Caspian, the intensity of phytoplankton blooms, especially in the Southern Caspian, an increase in turbidity in coastal areas due to river runoff, and changes in the frequency and intensity of wind patterns. As a rule, such phenomena have a significant specific (more often negative) impact on the natural systems and infrastructure of the coastal zone. To understand the current state and climatic changes in the main parameters of the marine environment in the Caspian Sea and to carry out its comprehensive analysis, it is necessary to use remote sensing data and to determine correctly different environmental parameters. Our experience shows that in many cases standard algorithms for retrieval of these parameters from the remote sensing data that are elaborated, calibrated and validated for the open ocean conditions, are not valid for inland seas which have their own specific physico-geographical, oceanographic and meteorological conditions. The paper presents a review of new algorithms and techniques developed during the past decade for correct retrieval of sea surface temperature, water turbidity, suspended particulate matter concentration, as well as determination of ice cover, river plumes, and wind surge areas based first of all on Ocean Color Data: MSI Sentinel-2A, -2B; OLI/TIRS Landsat-8 and OLI-2/TIRS-2 Landsat-9. These algorithms have been introduced into the specialized information and analytical system “See the Caspian Sea” (STCS), designed for collecting, analyzing and visualizing satellite and meteorological data for the Caspian Sea region.

Dermatophytes: Update on Clinical Epidemiology and Treatment.

Dermatophytes represent the largest and most common group of fungal infections, impacting 25% of the global population. Among them, Trichophyton rubrum has emerged as the predominant species, responsible for a range of conditions such as tinea corporis, tinea pedis, onychomycosis, tinea cruris, and tinea manuum. Although dermatophyte incidence varies geographically, there is a noticeable rise in cases caused by T. indotineae, a strain that exhibits resistance to terbinafine. In the past decade zoophilic dermatophyte T. mentagophytes genotype VII (now known as T. interdigitale) gains a growing importance, due to its increasing frequency, the severity of the clinical manifestation and mode of transmission. Tinea infections present with various clinical symptoms and can affect individuals of all ages, from tinea pedis in adults to tinea capitis in children. Among adults globally, tinea unguium (onychomycosis) is the most common form of dermatophytosis, affecting 5.5% of the general population. Tinea unguium is more frequently seen in developed countries, while tinea capitis is more common in developing nations. The COVID-19 pandemic has led to an increase in cases of tinea faciei, likely due to prolonged mask-wearing. Terbinafine remains the preferred treatment for dermatophyte infections worldwide due to its potent fungicidal properties, minimal risk of drug interactions, and fewer side effects compared to other oral antifungals. Itraconazole and terbinafine appear to be equally effective and safe for treating tinea cruris and tinea corporis. However, the rising resistance of dermatophytes to these antifungal drugs, along with frequent recurrences of dermatophytosis in certain regions, is becoming a significant public health concern.

Photodynamic therapy for early and recurrent oral cancers and pre-malignant lesions. Need of the hour for India

Oral cancer rates in India surpass those in any other nation, with patients manifesting varied disease stages, including pre-malignant phases. Tobacco chewing promotes field cancerization, and related surgical interventions can be remarkably morbid. Advanced-stage patients with frequent recurrences undergo treatments that significantly degrade their quality of life. In such instances, Photodynamic Therapy (PDT) emerges as an invaluable tool, enhancing both the longevity and quality of life. This paper elucidates two such cases benefiting from PDT, spotlighting its potential in transforming cancer care in India.

Клінічна характеристика та особливості хірургічного лікування пацієнтів із простими кістами нирок

Simple renal cysts are quite common in adults with an incidence that increases with age. Renal cysts are composed of enclosed liquid or semisolid fluid and are commonly identified through abdominal imaging. The purpose of this study was to compare the clinical and laboratory characteristics of patients with simple renal cysts who underwent aspiration sclerotherapy or laparoscopic resection and establish the association between these parameters. The research was conduc­ted on the basis of the urology department of the St. Panteleimon Hospital between 2021 and 2023, 46 patients who underwent surgical removal of a renal cysts were analyzed. The main methods of treating kidney cysts were aspiration sclerotherapy and laparoscopic unroofing. Patients were divided into groups depending on the treatment method (aspiration sclerothe­rapy or laparoscopic unroofing). In order to establish the differences, a comparative analysis was carried out by age, sex, results of clinical parameters, cyst localization and recurren­ces. The association between clinical parameters and treatment methods was assessed using Pearson’s χ2 test. Statistical analysis of the obtained data was carried out with the help of software packages SPSS v. 25.0 and EXCEL. There were 13 men (62 %) and 8 women (38 %) among patients who underwent lapa­roscopic unroofing. Right renal cysts were found in 8 patients (38 %), and left renal cysts were found in 13 patients (62 %). The mean age of the patients was 56±2.6 years. Among the patients undergoing aspiration sclerotherapy, there were 11 men (44 %) and 14 women (56 %). The right kidney cyst was found in 14 patients (56 %), and the left kidney cyst was found in 11 patients (44 %). The mean age of the patients was 63±2.2 years. The mean size of kidney cysts in patients who underwent laparoscopic unroofing was 70±3.6 mm. In patients undergoing aspiration sclerotherapy, the size of kidney cysts was 72±5.4 mm. There was no statistically significant difference in age, sex, and size of kidney cysts in patients who underwent aspiration sclerotherapy and laparoscopic unroofing. It was established that there was no statistically significant difference in age, sex, or size of renal cysts in patients undergoing surgical treatment. In patients after laparoscopic unroofing, relapses have not been established in the clinic. However, the frequency of recurrence in patients after aspiration sclerotherapy is 74±9 % of the total number of patients, which is a fairly high rate of recurrence of renal cysts. We found that laparoscopic unroofing was associated with a lower recurrence rate compared with aspiration sclerotherapy. It should be noted that laparoscopic unroofing is a more effective method of treatment compared to aspiration sclerotherapy. We emphasize that laparoscopy is a modern approach to renal cyst surgery, which not only reduces trauma, shortens the recovery time of patients, but also ensures high accuracy and efficiency of treatment.

INNV-09. DISTANT PARENCHYMAL RECURRENCE DURING LONG-TERM USE OF TTFIELDS TREATMENT FOR GLIOBLASTOMA

Abstract BACKGROUND Tumor treating fields (TTFields) treatment has been an important option for the treatment of glioblastoma. The introduction of novel treatment options may lead to distinct recurrence patterns compared to those observed with conventional therapies; however, the specific recurrence pattern during TTFields treatment has not been elucidated. METHODS AND RESULTS Here, we analyzed 39 cases of glioblastoma treated with TTFields. Although a usage rate of more than 75% is recommended, among 39 cases, 18 discontinued TTFields treatment owing to requests by patients with lower usage rates. In these discontinued cases, patients exhibiting sensory aphasia were more frequently included compared to those who continued TTFields (44.4%, p&amp;lt;0.001). Among 21 cases involving patients who continued TTFields, tumor recurrence was observed in 15 of those cases. Five out of 15 cases (33.3%) exhibited recurrence in distant parenchyma from the primary lesion. A higher usage rate and relatively longer use of TTFields were observed in these five cases, along with more favorable progression-free survival than those in the other 10 cases (p=0.019, p=0.040, and p=0.024, respectively). In one case, recurrent tumors with lower-grade glioma histology but molecular markers characteristic for glioblastoma, IDH-wildtype were identified. This tumor arose in an area that received a lower local minimum power density of TTFields compared to the primary lesion, following long-term TTFields therapy CONCLUSIONS Long-term use of TTFields might be correlated with a high frequency of distant parenchymal recurrence in cases with favorable response.

EXTH-74. COOLING GLIOBLASTOMA WITH A NEURAL IMPLANT

Abstract Survival rates for glioblastoma (GBM) patients are low due to the difficulty in eradicating all tumor cells, leading to frequent recurrence. This recurrence is frequently within 2-cm from the original site. Studies indicate that supra-total resection improves survival, and non-destructive local therapies show promise in preventing GBM recurrence. Our research demonstrates that non-freezing, ‘cytostatic’ hypothermia is effective against GBM in rats and can be scaled to pig models. This method, unlike ablative cryogenic hypothermia, safely inhibits GBM growth without damaging healthy tissue. Using in vitro culture models and in vivo rat models via a Peltier device, we tested cytostatic hypothermia. This was followed by finite-element modeling (FEM) to simulate bioheat transfer in human and pig brains. The system consists of a neural implant with a multiprobe array, a Peltier chip, a water block, and an artificial internal circulation system with a piezoelectric pump. In vitro tests identified a cytostatic window of 20–25°C. Miniature Peltier devices were fabricated to achieve this in rats to inhibit GBM growth and extend survival. Rats whose tumors received cytostatic levels of hypothermia survived their full study period. FEM simulations confirmed that multiprobe arrays could cool brain tissue to 25°C without significantly raising skin temperature. Portable systems were successfully fabricated and tested in pigs, achieving safe target temperatures with minimal EEG and OCTA changes. Our findings suggest that cytostatic hypothermia can be scaled to larger animals and made implantable and portable, offering a promising non-destructive approach to halting GBM growth and prolonging survival, moving closer to becoming a viable treatment option for patients with GBM.

Targeted RNA Sequencing of Head and Neck Adenoid Cystic Carcinoma Reveals SEC16A::NOTCH1 Fusion and MET Exon 14 Skipping as Potentially Actionable Alterations.

Adenoid cystic carcinoma (AdCC) of the head and neck harbors MYB/MYBL1::NFIB fusions in around 60% of cases, with unfavorable long-term survival due to frequent recurrences and metastases, currently lacking effective targeted therapy. The study aims to identify actionable alterations and to elucidate the molecular underpinnings of MYB/MYBL1::NFIB-negative AdCC using a large targeted RNA sequencing panel. We retrospectively searched our MSK-Solid Fusion clinical sequencing database for head and neck AdCC sequenced between2016and 2023. Of a total of 55 cases, 28 showed MYB::NFIB, 7 showed MYBL1::NFIB, and one case each harbored MYB::MPDZ (case 1) and FUS::MYB (case 2). One base of tongue tumor expressed both MYB::NFIB fusion and MET exon 14 skipping transcripts due to concurrent MET splice site mutation, D1010N (case 3). One parotid tumor lacked MYB/MYBL1 rearrangement but instead showed an in-frame SEC16A::NOTCH1 fusion that preserved the secretase cleavage site (case 4). Clinical records on 4cases with non-canonical sequencing findings were reviewed. Distant metastases were present at the initial diagnosis (case 2) or at recurrence (cases 1, 3, and 4). Disease-related mortality occurred in cases 2 and 4 despite radiotherapy and immunotherapy. The study improved the understanding of AdCC providing the first documentation of tumor clinical behavior associated with MYB::MPDZ and FUS::MYB fusions and reporting potentially actionable SEC16A::NOTCH1 fusion and MET exon 14 skipping mutation. Further research is needed to explore the therapeutic utility of MET inhibition and the efficacy of γ-secretase inhibitors against rare NOTCH1fusions in AdCC.

Thyroid cancer in a child with Cowden syndrome

Cowden disease (Cowden syndrome) refers to PTEN-associated hamartoma tumor syndromes. It arises due to a mutation in the phosphatase and tensin homolog gene, one of the main functions of which is cell cycle regulation. The presence of a mutation in the gene leads to uncontrolled cell growth, and patients have a lifelong increased risk of neoplasms of various degrees of malignancy. This article presents a clinical case of Cowden syndrome with an early debut at the age of 7 years. The combination of macrocephaly (SDS of head circumference &gt;2) with various skin manifestations (facial trichilemmomas, acral keratosis, papillomatous papules) and the presence of benign and/or malignant neoplasms are pathognomonic for Cowden syndrome. Of the malignancies, breast and thyroid cancer, colorectal cancer, renal cell carcinoma, and endometrial cancer are the most common. Thyroid carcinoma has been shown to have an earlier age of manifestation and often occurs already in childhood. This determines the need to screen patients with a proven mutation in the PTEN gene for nodal neoplasms from an early age. If surgical treatment is necessary, thyroidectomy remains preferable due to the frequent recurrence of nodules, as well as the uncertain potential for malignancy due to the low study of thyroid nodules in patients with mutations in the PTEN gene.

QUERCETIN AS A POTENTIAL THERAPEUTIC AGENT IN HYPERTENSION COMPLICATED BY CONNECTIVE TISSUE DYSPLASIA

This article summarizes data on the effect of quercetin during the treatment of arterial hypertension, complicated by connective tissue dysplasia. Currently, numerous studies are being conducted to study the role of various genes in the development of arterial hypertension. One of the risk factors for hypertension, which remains insufficiently studied, is collagen pathology - undifferentiated connective tissue dysplasia (UND). The presence of connective tissue in all organs and systems, its common origin with mesenchyme, smooth muscle, blood, and lymph leads to dysplastic changes in any organ and system. Among the many metabolic agents in the treatment of hypertension in combination with DST, the bioflavonoid quercetin, which has a pronounced antioxidant effect, deserves the most attention. The use of water-soluble quercetin in the complex therapy of patients with hypertension in combination with DST reduces the frequency of recurrence of hypertensive crises in the post-hospital period, reduces the number of complications, leads to a decrease in blood stabilization, pressure, additional hypotensive effect.

Protection against Clostridioides difficile disease by a naturally avirulent strain.

Clostridioides difficile is a leading cause of healthcare infections. Gut dysbiosis promotes C.difficile infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence. Although therapies preventing recurrent CDI have been developed, including live biotherapeutic products, existing therapies are costly and do not prevent primary infections. Here, we show that an avirulent C.difficile isolate, ST1-75, protects mice from developing colitis induced by a virulent R20291 strain when coinfected at a 1:1 ratio. In metabolic analyses, avirulent ST1-75 depletes amino acids more rapidly than virulent R20291 and supplementation with amino acids ablates this competitive advantage, indicating that ST1-75 limits the growth of virulent R20291 through amino acid depletion. Overall, our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI and reveals that the ST1-75 strain may be a biotherapeutic agent that can prevent CDI in high-risk patients.

VCAN in the extracellular matrix drives glioma recurrence by enhancing cell proliferation and migration.

Gliomas are the most prevalent primary malignant intracranial tumors, characterized by high rates of therapy resistance, recurrence, and mortality. A major factor contributing to the poor prognosis of gliomas is their ability to diffusely infiltrate surrounding and even distant brain tissues, rendering complete total resection almost impossible and leading to frequent recurrences. The extracellular matrix (ECM) plays a key role in the tumor microenvironment and may significantly influence glioma progression, recurrence, and therapeutic response. In this study, we first identified the ECM and the Versican (VCAN), a key ECM protein, as critical contributors to glioma recurrence through a comprehensive analysis of transcriptomic data comparing recurrent and primary gliomas. Using single-cell sequencing, we revealed heterogeneous distribution patterns and extensive intercellular communication among ECM components. External sequencing and immunohistochemical (IHC) staining further validated that VCAN is significantly upregulated in recurrent gliomas and is associated with poor patient outcomes. Functional assays conducted in glioma cell lines overexpressing VCAN demonstrated that VCAN promotes cell proliferation and migration via the PI3K/Akt/AP-1 signaling pathway. Furthermore, inhibiting the PI3K/Akt pathway effectively blocked VCAN-mediated glioma progression. These findings provide valuable insights into the mechanisms underlying glioma recurrence and suggest that targeting both VCAN and the PI3K/Akt pathway could represent a promising therapeutic strategy for managing recurrent gliomas.

Recurrence patterns and evolution of submicroscopic and asymptomatic Plasmodium vivax infections in malaria-endemic areas of the Peruvian Amazon.

In the Peruvian Amazon, Plasmodium vivax malaria transmission is maintained due to the high frequency of recurrences. By understanding the recurrence rates of submicroscopic and asymptomatic cases, we can develop informed strategies to prevent transmission more efficiently and disrupt the silent transmission cycle. A three-year, population-based cohort study was conducted in two sites, Cahuide and Lupuna, within the Loreto region in Peru from 2013 to 2015. The study included 385 individuals and aimed to examine the temporal dynamics of malaria recurrences and their impact on transmission and control. Individuals from Lupuna presented a higher risk of P. vivax infections compared to Cahuide, where most recurrences were asymptomatic and submicroscopic. It is estimated that a great proportion of these recurrences were due to relapses in both communities. The application of molecular diagnostic method proved to be significantly more effective, detecting 2.3 times more episodes during the follow-up (PCR, 1068; microscopy, 467). PCR identified recurrences significantly earlier, at 151 days after an initial infection, compared to microscopy, which detected them on average after 365 days. Community, occupation and previous malaria infections were factors associated with recurrences. Finally, potential infection evolution scenarios were described where one frequent scenario involved the transition from symptomatic to asymptomatic infections with a mean evolution time of 240 days. This study explores the contrast in malaria recurrence risk among individuals from two endemic settings, a consequence of prolonged exposure to the parasite. Through the analysis of the evolution scenarios of P. vivax recurrences, it is possible to have a more complete vision of how the transmission pattern changes over time and is conditioned by different factors.

Inflammasome-targeted therapy might prevent adverse perinatal outcomes of recurrent chronic intervillositis of unknown etiology

Chronic histiocytic intervillositis of unknown origin (CHI) is a rare placental disorder associated with adverse pregnancy outcomes, frequent recurrence, and a lack of effective preventive strategies. Recent insights indicate a potential link between CHI-associated inflammatory lesions and the inflammasome pathway, suggesting innovative therapeutic avenues. Here we show a potential role of the inflammasome pathway in CHI through comprehensive transcriptomic analysis of grade 2 or 3 histopathologic CHI samples, paired with placental controls. Additionally, we present case studies of three individuals with recurrent CHI, who have undergone treatment with anakinra and colchicine throughout pregnancy, resulting in improved perinatal outcomes. Notably, all cases are characterized by the birth of healthy, full-term infants, with reduced or absent intervillositis recurrence. Placental assessment unveils heightened activation of the NLRP3-PYCARD inflammasome pathway and IL-1β processing in CHI samples, with downregulation observed in treated pregnancy samples, devoid of intervillositis. Collectively, these findings suggest a potential therapeutic role for targeting the inflammasome pathway in preventing recurrent CHI in pregnant individuals.

Multi-year recurrent pericarditis disease duration in Italian patients: clinical outcomes after cessation of long-term IL-1 pathway inhibition provide insights for chronic management

Abstract Background Recurrent pericarditis (RP) is a chronic disease mediated by IL-1 often lasting for years, and specific tools to guide treatment duration with IL-1 pathway inhibition at the individual patient (pt) level are limited. The Phase 3 trial RHAPSODY and 2-year long-term extension (LTE) demonstrated that rilonacept reduced risk of recurrence over long-term treatment (1,2). At the conclusion of the LTE, after a median of 28 months of rilonacept treatment (non-US pts), Italian pts returned to standard management because rilonacept was not commercially available. Clinical outcomes after rilonacept cessation and washout were followed to inform disease persistence and time to recurrence. Purpose Multicentric analysis of RP event rates in Italian pts after stopping long-term rilonacept. Methods Clinical records from Italian RHAPSODY pts were examined for the 18-month period post-LTE (To). Primary outcome: pericarditis recurrence (defined by tertiary-center experts as pericarditis pain plus c-reactive protein [CRP] elevation). Secondary outcomes: time to recurrence and proportion of pts requiring re-initiation of IL-1 pathway inhibition. Safety outcomes: serious adverse events (SAEs). Results 17 Italian pts were observed (Table 1). At To, median [Q1-Q3] disease duration (time from index episode) was 48 [41-56] months, during which pts had received a median 28 [27-30] months of continuous rilonacept treatment (all were in Clinical Response, i.e., no pain, normalized CRP, and on rilonacept monotherapy). After rilonacept cessation at To, no pts received prophylactic treatment. 82.4% (14/17) of pts experienced confirmed pericarditis recurrences, with time to recurrence 8 [6-9] weeks. Half of these pts (n=7) were given oral medications (NSAIDS, colchicine [n=3] and/or steroids [n=4], of whom 1 steroid-treated pt failed and resumed IL-1 pathway inhibition). The other half (n=7) resumed IL-1 pathway inhibition directly upon recurrence. The remaining 17.6% (3/17) of pts had no pericarditis recurrences after To and remained off treatment during the observation period. No pts experienced SAEs. Neither recurrence frequency nor time to recurrence was significantly related to baseline disease characteristics or demographics. Conclusions This exploratory analysis shows that in pts with RP of even 4-years’ duration (including a median 28-months’ rilonacept treatment), the 80% recurrence rate after treatment cessation was indicative of severe persistent underlying disease. Time to pericarditis recurrence after rilonacept cessation (median 8 weeks) was consistent with the predicted gradual pharmacokinetic washout and previously-reported 8.6-week time to flare in RHAPSODY (1). Pericarditis recurrences in these pts with long disease duration and systemic inflammation were severe enough to necessitate re-initiation of advanced therapy. Further studies could quantify optimal treatment duration for pts achieving prolonged remission on IL-1 pathway inhibition.