Frequent Recurrence Research Articles

A new approach to immunosuppressive therapy in patients with glomerulonephritis with nephrotic syndrome

Glomerulonephritis (GN) is a group of immuno-inflammatory kidney diseases with predominant glomerular lesions that are difficult to treat. The greatest problems are caused by the treatment of GN with nephrotic syndrome, which often has a recurrent course. The aim of the research was to study the effectiveness of recombinant interleukin-2 (rIL-2) therapy in the GN patients with nephrotic syndrome. 62 patients with a nephrotic form of primary GN with frequent relapses admitted to the Nephrology Department have been recruited into the study. The age of patients was from 18 to 65 years. The patients underwent standard examinations, as well as immunological studies, before administration of the anti-relapse treatment, and 12 months after the treatment was started. Immunological testing included immunophenotyping of lymphocytes with counting of T and B lymphocytes, immunoregulatory and activated subpopulations of T lymphocytes, determination of urinary immunoglobulins (IgM, IgG, IgA) by immunoturbidimetric assays, proinflammatory cytokines – IL-1β, IL-8, IL-17A and anti-inflammatory cytokine IL-10 by ELISA tests. As a result of studies, the examined patients showed an increased contents of T helper cells, activated T lymphocytes (CD8+HLA-DR+CD45+, CD3+CD8brightCD38+) along with decreased numbers of Treg cells and an increased contents of proinflammatory cytokines IL-1β, IL-8, IL-17A and immunoglobulins of all three classes in urinary samples.The cohort of patients with GN selected for the study was divided in two groups (the main group and the comparison group). In addition to nephroprotective and steroid therapy, the treatment regimen of patients included rIL-2 in the main group, or cyclophosphamide in the comparison group. Regardless of the method used, the levels of protein, IgG and IL-17A in the urine proved to be decreased relative to the initial values; the contents of B cells and HLA-DR+ cytotoxic T lymphocytes in peripheral blood were found to be decreased. The revealed changes were more pronounced in the main group of patients. By 12 months after starting the treatment, the mentioned indexes began to differ significantly in the main group from those in the comparison group. Serum creatinine levels, numbers of T helper cells and Treg cells, IL-1β levels in urine did not undergo significant changes in the comparison group, whereas a decrease in serum creatinine and urinary IL-1β was registered in the main group of patients, along with decreased number of T helpers and increased numbers of Treg cells. In the main group of patients treated with rIL-2, the average number of relapses per year decreased by 4 times, showing only a 1.2-fold decrease in the comparison group. Hence, the low-dose therapy with rIL-2 may be considered an effective and safe alternative to conventional immunosuppressive therapy and a new option of the targeted treatment of glomerulonephritis with frequent recurrence of nephrotic syndrome.

Climate Projections Very Likely Underestimate Future Volcanic Forcing and Its Climatic Effects

AbstractStandard climate projections represent future volcanic eruptions by a constant forcing inferred from 1850 to 2014 volcanic forcing. Using the latest ice‐core and satellite records to design stochastic eruption scenarios, we show that there is a 95% probability that explosive eruptions could emit more sulfur dioxide (SO2) into the stratosphere over 2015–2100 than current standard climate projections (i.e., ScenarioMIP). Our simulations using the UK Earth System Model with interactive stratospheric aerosols show that for a median future eruption scenario, the 2015–2100 average global‐mean stratospheric aerosol optical depth (SAOD) is double that used in ScenarioMIP, with small‐magnitude eruptions (<3 Tg of SO2) contributing 50% to SAOD perturbations. We show that volcanic effects on large‐scale climate indicators, including global surface temperature, sea level and sea ice extent, are underestimated in ScenarioMIP because current climate projections do not fully account for the recurrent frequency of volcanic eruptions of different magnitudes.

Bacterial Profile and Antibiotic Use in Catheter-Associated Urinary Tract Infection Patients at a Tertiary Referral Hospital in Surabaya, Indonesia

Highlights: This study examined patients with catheter-associated urinary tract infections (CAUTI) to find the prevalent bacteria and the frequency of antibiotic use. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli sensitive to amikacin was found to be the most common pathogen in CAUTI, while ceftriaxone was the most commonly used antibiotic. Abstract Catheter-associated urinary tract infection (CAUTI) is the most typical type of infection associated with healthcare. This infection constitutes a significant health problem due to its complications and frequent recurrence. The high annual incidence of CAUTI leads to infectious complications and a high cost of treatment. Antibiotic-resistant bacteria further complicate the problem because multiresistant pathogenic bacteria are often responsible for these infections. Moreover, the lack of a comprehensive case reporting system in Indonesia hinders the determination of CAUTI incidence. This study aimed to determine the bacterial profile and antibiotic use in CAUTI patients (n=22) at the Internal Medicine Inpatient Unit of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. This retrospective descriptive study collected data from patient medical records to describe the incidence, type of bacteria, sensitivity patterns, and antibiotic use in CAUTI patients. The data collection process included collecting medical records, recording information on data collection sheets, and recapitulating and analyzing the data. The criteria for CAUTI diagnosis were a bacterial count of ≥105 CFU/mL and a catheterization that lasted more than 48 hours. Samples were selected using non-probability sampling, also known as saturation sampling. Meanwhile, variables analyzed in this study were the type of pathogenic bacteria, antibiotics used, age, and sex. Descriptive analysis was employed to analyze the data. The findings suggested that the most common bacteria were Escherichia coli, with eight of nine bacteria showing extended-spectrum beta-lactamase (ESBL) production. Female patients aged 35–65 years were the majority of the CAUTI patients. Amikacin was the antibiotic with the highest sensitivity (90.9%), while ceftriaxone was the most common type of antibiotic administered to the patients. In addition, intravenous (IV) administration was the most common route of antibiotic administration, with an average therapy duration of seven days. In conclusion, identifying the type of pathogenic bacteria and performing antibiotic susceptibility testing can help minimize antibiotic resistance and prevent more severe complications in CAUTI patients.

The role of stress reactions in the genesis of menstrual cycle disorders in recurrent urinary tract infections in minors

BACKGROUND. Extragenital diseases, including recurrent urinary tract infections, have an adverse effect on the reproductive health of children and adolescents. Vaginitis and menstrual cycle disorders, including primary oligomenorrhea, predominate in the structure of gynecological morbidity of minors suffering from recurrent UTIs.THE AIM: to study the role of stress reactions in the genesis of various variants of menstrual cycle disorders in minors suffering from recurrent UTIs to improve the dispensary management of this cohort of patients. PATIENTS AND METHODS. A prospective study was conducted in 98 adolescent girls aged 16 to 18 years. Taking into account the nature of the clinical course of UTI, all the subjects were divided into 3 groups: group 1 (n=41) – patients with UTI; group 2 (n=27) patients with frequent recurrence of UTI (more than 3 times a year (rIMP); group 3 (n=30) – minors, 1, 2 health groups with no IPM episode. A specialized gynecological examination, functional diagnostic tests, ultrasound examination of the placemark and ovaries, determination of cortisol, norepinephrine, adrenaline by enzyme immunoassay were carried out. Statistical analysis was performed using the program "SPSS Statistics 17.0 for Windows".RESULTS. Anovulation was observed in patients with frequent recurrence of UTI. Copious and prolonged menstruation, uterine bleeding and primary oligomenorrhea were observed only in patients with recurrent UTIs. In this cohort, inflammatory gynecological diseases take a chronic course. Polycystic ovarian syndrome (40.7 %) and chronic salpingoophoritis (44.4 %) were often detected in patients with frequently recurrent UTI. In patients suffering from UTI, in contrast to the data of the comparison group, there were significant violations of the nature of adaptive reactions, and changes in antistress reactions and their levels differed depending on the variant of the course of the microbial-inflammatory process. In patients with rare relapses of UTI, antistress reactions of a high level of reactivity prevailed, but there were reactions of calm and increased activation, training that took place at low levels of reactivity.CONCLUSION. Adaptive-compensatory disorders were revealed in almost every patient with recurrent UTI. Considering that stress is especially pathogenic during puberty, when hormonal and psychophysiological restructuring of the body occurs, prevention and complex therapy of microbial-inflammatory diseases of the urinary system in this category of patients should be carried out taking into account the formation of reproductive function and the severity of adaptation reactions.

CD207 Expression Level is a New Prognostic Marker for Condyloma Acuminatum.

Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians. A total of 40 male patients with CA and their skin lesions were collected, as well as 40 healthy male penile tissue samples. The skin lesions of CA were clinically and histologically confirmed by acetic acid test. The expression of CD207 in epidermal tissues was detected using immunohistochemistry. The difference in the number of CD207 positive cells between CA skin lesions and healthy skin controls was compared, and the association between the number of CD207 positive cells in CA skin lesions and the duration of disease course and the frequency of recurrence was determined through Spearman correlation analysis. In CA skin lesions, CD207 positive cells were found to have morphological abnormalities and the number of cells was significantly reduced compared to healthy skin, suggesting that there may be antigen presentation dysfunction in CA skin lesions, which may be the reason for the prolonged and unresolved condition of the disease. The fewer CD207 positive cells in CA skin lesions, the longer the disease course and the more frequent the recurrence, therefore, the expression level of CD207 can be used as a new prognostic marker for predicting the outcome of CA.

CO208 Recurrence Rates and Survival Among Patients with Early-Stage Cancers: A Systematic Literature Review

Since the frequency of recurrences is not well known across different early-stage tumours, a systematic review was conducted to assess the recurrence rates and overall survival (OS) of patients diagnosed with early-stage cancers.

P-367 The frequency and pattern of metachronous recurrence after endoscopic submucosal dissection for dysplasias and adenocarcinoma of stomach

P-367 The frequency and pattern of metachronous recurrence after endoscopic submucosal dissection for dysplasias and adenocarcinoma of stomach

Indicators of immune status in women with different recurrence rates of nonspecific inflammatory diseases of the genital organs

Non-specific inflammatory diseases of the female genital organs (NIDFGO) are an important problem of modern gynecology due to their high frequency in the population, the tendency to frequent recurrences, and many cases of resistance to recommended antimicrobial and anti-inflammatory drugs. Aim: to study indicators of immune status in women with different recurrence rates of NIDFGO and biomarkers of recurrences to improve potential therapeutic approaches and prevent recurrences in the further. Materials and methods. A prospective single-center controlled non-randomized clinical study was conducted with the participation of 98 adult women. Out of them, 80 patients with NIDFGO had one-year recurrence rate of 1, 2–3, 4 or more events, and 18 age-matched women without NIDFGO were assigned to the control group. Immunogram and hemogram were performed for all study participants using standardized methods. Statistical analysis of the results was performed using IBM SPSS 23 statistical package software. Results. The mean serum concentration of IgE in patients with frequent relapses was 3 times (p < 0.05) lower than that in women with only one recurrence, 2.6 times (p < 0.05) lower than that in patients with medium recurrence rate, and 3.4 times (p < 0.05) less than in the control. In women with frequent recurrences, the mean relative number of blood NKT cells was 3.5 times (p < 0.05) less than that in patients with only one recurrence, 2.3 times (p < 0.05) less than that in persons with medium recurrence rate, and 3 times (p < 0.05) less as compared to women of the control group. Conclusions. Selective deficiencies of IgE and NKT cells in women with NIDFGO are factors that lead to a higher frequency of disease exacerbations per year. T he development and clinical approval of immunotherapeutic approaches to compensate for deficiencies of IgE and NKT cells in women with NIDFGO will contribute to the imposition of immune control over the inflammatory process, increase the effectiveness of antimicrobial treatment, resulting in a decrease in the recurrence rate.

Role of Vitamin D in Head and Neck Cancer-Immune Function, Anti-Tumour Effect, and Its Impact on Patient Prognosis.

Head and neck squamous cell carcinoma (HNSCC) describes a heterogeneous group of human neoplasms of the head and neck with high rates of morbidity and mortality, constituting about 3% of all cancers and ~1.5% of all cancer deaths. HNSCC constituted the seventh most prevalent human malignancy and the most common human cancer in the world in 2020, according to multi-population observations conducted by the GLOBOCAN group. Since approximately 60-70% of patients present with stage III/IV neoplastic disease, HNSCC is still one of the leading causes of death in cancer patients worldwide, with an overall survival rate that is too low, not exceeding 40-60% of these patients. Despite the application of newer surgical techniques and the implementation of modern combined oncological treatment, the disease often follows a fatal course due to frequent nodal metastases and local neoplastic recurrences. The role of micronutrients in the initiation, development, and progression of HNSCC has been the subject of considerable research. Of particular interest has been vitamin D, the pleiotropic biologically active fat-soluble family of secosteroids (vitamin-D-like steroids), which constitutes a key regulator of bone, calcium, and phosphate homeostasis, as well as carcinogenesis and the further development of various neoplasms. Considerable evidence suggests that vitamin D plays a key role in cellular proliferation, angiogenesis, immunity, and cellular metabolism. A number of basic science, clinical, and epidemiological studies indicate that vitamin D has multidirectional biological effects and influences anti-cancer intracellular mechanisms and cancer risk, and that vitamin D dietary supplements have various prophylactic benefits. In the 20th century, it was reported that vitamin D may play various roles in the protection and regulation of normal cellular phenotypes and in cancer prevention and adjunctive therapy in various human neoplasms, including HNSCC, by regulating a number of intracellular mechanisms, including control of tumour cell expansion and differentiation, apoptosis, intercellular interactions, angio- and lymphogenesis, immune function, and tumour invasion. These regulatory properties mainly occur indirectly via epigenetic and transcriptional changes regulating the function of transcription factors, chromatin modifiers, non-coding RNA (ncRNAs), and microRNAs (miRs) through protein-protein interactions and signalling pathways. In this way, calcitriol enhances intercellular communication in cancer biology, restores the connection with the extracellular matrix, and promotes the epithelial phenotype; it thus counteracts the tumour-associated detachment from the extracellular matrix and inhibits the formation of metastases. Furthermore, the confirmation that the vitamin D receptor (VDR) is present in many human tissues confirmed the physiopathological significance of vitamin D in various human tumours. Recent studies indicate quantitative associations between exposure to vitamin D and the incidence of HNC, i.e., cancer risk assessment included circulating calcidiol plasma/serum concentrations, vitamin D intake, the presence of the VDR gene polymorphism, and genes involved in the vitamin D metabolism pathway. Moreover, the chemopreventive efficacy of vitamin D in precancerous lesions of the head and neck and their role as predictors of mortality, survival, and recurrence of head and neck cancer are also widely discussed. As such, it may be considered a promising potential anti-cancer agent for developing innovative methods of targeted therapy. The proposed review discusses in detail the mechanisms regulating the relationship between vitamin D and HNSCC. It also provides an overview of the current literature, including key opinion-forming systematic reviews as well as epidemiological, prospective, longitudinal, cross-sectional, and interventional studies based on in vitro and animal models of HNSCC, all of which are accessible via the PubMed/Medline/EMBASE/Cochrane Library databases. This article presents the data in line with increasing clinical credibility.

Iron Rim Lesions as a Specific and Prognostic Biomarker of Multiple Sclerosis: 3T-Based Susceptibility-Weighted Imaging.

This study aimed to identify the clinical significance of iron rim lesions (IRLs) in distinguishing multiple sclerosis (MS) from other central nervous system (CNS) demyelinating diseases, determine the relationship between IRLs and disease severity, and understand the long-term dynamic changes in IRLs in MS. We retrospectively evaluated 76 patients with CNS demyelinating diseases. CNS demyelinating diseases were classified into three groups: MS (n = 30), neuromyelitis optica spectrum disorder (n = 23), and other CNS demyelinating diseases (n = 23). MRI images were obtained using conventional 3T MRI including susceptibility-weighted imaging. Sixteen of 76 patients (21.1%) had IRLs. Of the 16 patients with IRLs, 14 were in the MS group (87.5%), indicating that IRLs were significantly specific for MS. In the MS group, patients with IRLs had a significantly higher number of total WMLs, experienced more frequent recurrence, and were treated more with second-line immunosuppressive agents than were patients without IRLs. In addition to IRLs, T1-blackhole lesions were observed more frequently in the MS group than in the other groups. IRLs are specific for MS and could represent a reliable imaging biomarker to improve the diagnosis of MS. Additionally, the presence of IRLs seems to reflect more severe disease progression in MS.

Phosphorylation of IWS1 by AKT maintains liposarcoma tumor heterogeneity through preservation of cancer stem cell phenotypes and mesenchymal-epithelial plasticity

Chemotherapy remains the mainstay of treatment for patients with advanced liposarcoma (LPS), but response rates are only 25% and the overall survival at 5 years is dismal at 20–34%. Translation of other therapies have not been successful and there has been no significant improvement in prognosis for nearly 20 years. The aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the aggressive clinical behavior LPS and in resistance to chemotherapy, but the precise mechanism remains elusive and efforts to target AKT clinically have failed. Here we show that the AKT-mediated phosphorylation of the transcription elongation factor IWS1, promotes the maintenance of cancer stem cells in both cell and xenograft models of LPS. In addition, phosphorylation of IWS1 by AKT contributes to a “metastable” cell phenotype, characterized by mesenchymal/epithelial plasticity. The expression of phosphorylated IWS1 also promotes anchorage-dependent and independent growth, cell migration, invasion, and tumor metastasis. In patients with LPS, IWS1 expression is associated with reduced overall survival, increased frequency of recurrence, and shorter time to relapse after resection. These findings indicate that IWS1-mediated transcription elongation is an important regulator of human LPS pathobiology in an AKT-dependent manner and implicate IWS1 as an important molecular target to treat LPS.

Relation Between Baseline CXCR1 Expression And Neoadjuvant Chemotherapy Response In Breast Cancer Patients.

To examine the C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues prior to neo-adjuvant chemotherapy, and its relationship to neo-adjuvant chemotherapy effectiveness and other prognostic variables. The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised patients with recent histopathologically proven breast cancer cases eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained by immunohistochemicalstain using concentrating rabbit anti-human C-X-C Motif Chemokine Receptor 1 polyclonal antibody kits. C-X-C Motif Chemokine Receptor 1 expression was classified into low and high categories. Patients were followed for 2 years for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25. Of the 100 females with mean age 50.2±12.1 years, 52(52%) had their left side affected, while 48(48%) had their rightside affected. There were 52(52%) cases with mean age 49.2±12.9 years having high C-X-C Motif Chemokine Receptor 1 expresssion, while 48(48%) with mean age 51.4±11.2 years had low expression. There was a significant association between high expression and advanced tumour grade, advanced tumourstage, higher frequency of triple negative breast cancer and higher frequency of Ki-67-positive cancers (p<0.05). Patients with high C-X-C Motif Chemokine Receptor 1 expression had significantly lower frequency of complete pathological response when compared with patients with low expression (p<0.001). Patients with high expression had higher frequency of recurrence, shorter disease-free survival, higher mortality and shorter overall survival, but the difference was not significant (p>0.05). Multivariate logistic regression analysis identified triple negative hormonal status (p=0.031) and high baseline C-X-C Motif Chemokine Receptor 1 expression (p<0.001) as significant predictors of complete pathological response. There was found to be a link between baseline C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues and pathological response to neoadjuvant therapy in breast cancer patients.

How different very late recurrence of atrial fibrillation 5 years after catheter ablation?

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health and Welfare the Basic Science Research Program run by the National Research Foundation of Korea (NRF). Background Atrial fibrillation (AF) is a chronic progressive disease that recurs continuously even after successful AF catheter ablation (AFCA). Objective We explored the mechanism of this long-term recurrence by comparing the patient characteristics and redo-ablation findings. Methods Among 4,248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at single centers, we enrolled 1,417 patients (71.7% male, age 60.0 [52.0–67.0] years, 57.9% paroxysmal AF) who experienced clinical recurrences (CRs) of the disease, and divided them according to the period of recurrence: within one year (n=645), 1–2 years (n=339), 2–5 years (n=308), and after 5-years (CR&amp;gt;5yr, n=125). We also compared the redo-mapping and ablation outcomes in 198 patients. Results In patients with a CR&amp;gt;5yr, the proportion of paroxysmal AF was higher (p=0.031); however, the left atrial (LA) volume (computed tomography, p=0.003), LA voltage (p=0.003), frequency of early recurrence (p&amp;lt;0.001), and use of post-procedure anti-arrhythmic drugs (p&amp;lt;0.001) were lower. A CR&amp;gt;5yr was independently associated with the low LA volume (odds ratio [OR] 0.99 [0.99–1.00], p=0.019), low LA voltage (OR 0.62 [0.41–0.95], p=0.030), and lower early recurrence (OR 0.39 [0.23–0.64], p&amp;lt;0.001). Extra-pulmonary vein (PV) triggers (P for trend 0.003) during repeat procedures were significantly greater in patients with a CR&amp;gt;5yr, despite no difference in the de novo protocol. The rhythm outcome of repeat ablation procedures did not differ with the timing of the CR (log-rank p=0.330). Conclusions Patients with a later CR showed a smaller LA volume, lower LA voltage, and higher extra-PV triggers during the repeat procedure, suggesting progression of AF.

Retrospective study of lameness in beef cattle in northeastern Sardinia, Italy.

Lameness is one of the most prevalent diseases affecting dairy and beef cattle, resulting in decreased animal performance, decreased animal welfare, and substantial economic loss. In extensive beef cattle farming, the risk factors for this multifactorial disease are largely unexplored. This study aims to conduct a preliminary epidemiological survey of risk factors in beef cattle in extensive breeding, evaluate the farmer's perception of lameness, and determine the recurrence frequency of the pathologies under investigation in treated animals. The study was conducted in Sardinia, Italy. The population of the study consisted of 14379 cattle from 230 farms. An ad hoc questionnaire was developed to collect all the necessary data. A strong association was found between breed and the occurrence and recurrence of lameness (p < 0.0001). In addition, the Country of origin of both bulls and cows was found to be correlated with the incidence of lameness (p < 0.0001 and 0.0001, respectively). Farmers who indicated on the questionnaire that lameness was not important on their farm had more animals with recurrences (p < 0.0001) than other farmers. The veterinarian's treatment choice differed significantly by farmer concern (p = 0.007) and was associated with less disease recurrence (p < 0.0001), resulting in greater farmer satisfaction (p < 0.007). Pure cow breed, French bull origin, and farmer's age were detected as significant predictors of lameness issues, with pure cow breed and French bull origin having the strongest associations (p = 0.009). Even though the results of this study are preliminary, they indicate that breed selection is crucial in extensive beef farms to reduce lameness prevalence. In addition, it would be reasonable to train breeders to prevent and diagnose lameness early in order to collaborate with veterinarians to prevent recurrence.

Activation of persistent pathogenic microflora after ascending pyelolithotripsy and the recurrence rate of nephrolithiasis

We’ve studied the activation of persistent pathogenic microflora in 28 patients after retrograde pyelolithotripsy and the frequency of recurrence of kidney stones during the year under the conditions of traditional drug treatment in the early and late postoperative periods. We’ve studied the recurrence of kidney stones during the year under conditions of use in another group of patients (26 patients), in addition to traditional drug treatment, phytouroantiseptic (herbal extract BNO 1045). It has been confirmed that persistent pathogenic microflora is found in the structures of urinary stones, which is released after operative crushing of stones and reverses into active forms that are insensitive to the main groups of antibiotics, which long-term support a chronic inflammatory process in the kidneys, and is the cause of exacerbation of chronic pyelonephritis and relapse. It has been proven that the use of a phytouroantiseptic (herbal extract BNO 1045) in the complex treatment is the effective method for eliminating the infectious and inflammatory process in the kidneys caused by persistent pathogenic microflora, for decreasing the level of uric acid in the blood and normalization of urine’s pH, which leads to effective prevention of stone relapse.

The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8+ T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of the expression of cGAS-STING in tumor cells on the infiltration of CD8+ T cells and clinical outcomes in mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC remains largely unknown. Our findings reveal that 56.8% of all pMMR CRC cases were cGAS-negative/STING-negative expressions (cGAS-/STING-) in tumor cells, whereas only 9.9% of all pMMR CRC showed cGAS-positive/STING-positive expression (cGAS+/STING+) in tumor cells. The frequency of cGAS+/STING+ cases was reduced in the advanced stages of pMMR/MSS CRC, and histone methylation might be involved in the down-regulation of STING expression in tumor cells. Since the expression level of cGAS-STING in tumor cells has been associated with the infiltration of CD8+ and/or CD4+ T cells and the frequency of recurrence in pMMR/MSS CRC, decreased expression of cGAS-STING in tumor cells might lead to poor immune cell infiltration and worse prognosis in most pMMR/MSS CRC patients. Our current findings provide a novel insight for the treatment of patients with pMMR/MSS CRC.

Is there any association between the frequency of wet age-related macular degeneration recurrences and the seasons of the year?

To investigate whether a seasonal distribution of the frequency of exudative age-related macular degeneration (wet AMD) recurrences exists. In total, 129 eyes with 171 recurrences in patients suffering from wet AMD were included in the study. All the patients had been treated with intravitreal anti-VEGF injections according to Pro Re Nata treatment regimen. Recurrence was defined as the re-detection of sub-retinal fluid, intraretinal fluid, and/or sub-macular hemorrhage in optical coherence tomography scans, after at least two consecutive monthly examinations with a "dry" macula. The year was divided in three 4-month periods (zone A: June-September, zone B: October-January, and zone C: February-May) based on the weather conditions prevailing in each period. Mean temperature and hours of sunlight exposure were the main weather markers recorded. Eighty-two recurrences (48%) occurred during the period June-September, 50 (29.2%) during the period October-January, and 39 (22.8%) during the period February-May (Chi-square = 17.5, p < 0.001). Among the groups, neither patients' age (78 ± 8years A, 76 ± 7years B, and 79 ± 8years C, p = 0.15) nor gender status (40% men A, 36% men B, and 51% men C, p = 0.35) differed significantly. Mean temperature was 27.6 ± 1.8°C, 15.1 ± 4.6°C, and 16.5 ± 4.4°C in zones A, B, and C, respectively. Hours (h) of sunlight exposure (average hours/month) were 344 ± 34h, 188 ± 42h, and 223 ± 57h in zones A, B, and C. We demonstrated that the frequency of wet AMD recurrences is significantly elevated during the warmer months, possibly due to the higher levels of UV radiation and mean temperature. Further research is necessary to validate our findings.

Clinical features and surgical outcomes of Rathke cleft cysts with suprasellar components: a single-center experience of 157 cases.

Both intrasuprasellar and suprasellar Rathke cleft cysts (RCCs) have suprasellar components, and we aimed to explore their clinical features and surgical outcomes. Patients with surgically treated intrasuprasellar or suprasellar RCCs were retrospectively analyzed. All patients with intrasuprasellar RCCs were treated with the standard endoscopic endonasal approach (EEA, group I); the patients with suprasellar RCCs received the extended EEA (group II) or supraorbital keyhole approach (SKA, group III) according to the relevant indications. A surgical strategy of maximal safe resection aiming to protect neuroendocrine function was adopted. In addition, patients (distinguished from the above 3 groups) who had aggressive resection of suprasellar RCC were also enrolled for comparison of different surgical strategies. A total of 157 patients were eligible, including 121 patients with intrasuprasellar RCCs in group I, 19 patients with suprasellar RCCs in group II, and 17 patients with suprasellar RCCs in group III. Preoperatively, the patients with suprasellar RCC (groups II and III) more commonly presented with visual dysfunction, diabetes insipidus (DI), and hyperprolactinemia than the patients with intrasuprasellar RCCs (all p<0.05). A higher incidence of hypopituitarism and a larger diameter were observed for intrasuprasellar RCCs (both p<0.05). Postoperatively, group II had a higher rate of new-onset DI, hyponatremia, and recurrence than group I (all p<0.025) and similar outcomes to group III. For suprasellar RCCs, comparison of the maximal safe resection vs. aggressive resection (supplementary patients: 14 with extended EEA, 12 with SKA) showed similar improvement and recurrence, with higher rates of DI and hyponatremia with the latter strategy (all p<0.05). Suprasellar RCC is associated with more complicated preoperative presentations, intricate postoperative complications, and frequent recurrence compared with intrasuprasellar RCC. Under rational indications, both extended EEA and SKA achieve satisfactory outcomes. The strategy of maximal safe resection is recommended for greatest functional preservation.

What is known about the diagnosis and treatment of herpes labialis?

Herpes labialis is one of the most common skin infections. In most people it is asymptomatic or mildly symptomatic, but very severe cases do occur. Herpes remains latent and can recur. Herpes labialis is a clinical diagnosis. If in doubt, additional testing can be carried out, usually polymerase chain reaction. There are no treatments that can eliminate the virus. In case of more severe symptoms and frequent recurrences, there may be an indication for treatment. In case of mild complaints, topical zinc sulphate/zinc oxide and analgesics (systemic or topical lidocaine) will suffice. More severe complaints and frequent recurrences can be treated with antiviral creams (Aciclovir) or with systemic antiviral medication (Valaciclovir). In frequent recurrences, prophylactic Valaciclovir can also be given for a period of many months. Treatment should be started as soon as possible and will slightly shorten the duration of the disease.

Centrosome amplification-related signature correlated with immune microenvironment and treatment response predicts prognosis and improves diagnosis of hepatocellular carcinoma by integrating machine learning and single-cell analyses.

Centrosome amplification is a well-recognized oncogenic driver of tumor initiation and progression across a variety of malignancies and has been linked with tumor aggressiveness, metastasis, and adverse prognosis. Nevertheless, the significance of centrosome amplification in HCC is not well understood. The TCGA dataset was downloaded for centrosome amplification-related signature construction using the LASSO-penalized Cox regression algorithm, while the ICGC dataset was obtained for signature validation. Single-cell RNA sequencing from GSE149614 was analyzed to profile gene expression and the liver tumor niche. A total of 134 centrosome amplification-related prognostic genes in HCC were detected and 6 key prognostic genes (SSX2IP, SPAG4, SAC3D1, NPM1, CSNK1D, and CEP55) among them were screened out to construct a signature with both high sensitivity and specificity in diagnosis and prognosis of HCC patients. The signature, as an independent factor, was associated with frequent recurrences, high mortality rates, advanced clinicopathologic features, and high vascular invasions. Moreover, the signature was intimately associated with cell cycle-related pathways and TP53 mutation profile, suggesting its underlying role in accelerating cell cycle progression and leading to liver cancer development. Meanwhile, the signature was also closely correlated with immunosuppressive cell infiltration and immune checkpoint expression, making it a vital immunosuppressive factor in the tumor microenvironment. Upon single-cell RNA sequencing, SSX2IP and SAC3D1 were found to be specially expressed in liver cancer stem-like cells, where they promoted cell cycle progression and hypoxia. This study provided a direct molecular link of centrosome amplification with clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of centrosome amplification in liver cancer development and therapy resistance, thereby providing valuable insights into prognostic prediction and therapeutic response of HCC.