Advanced Stages Of Disease Research Articles

Real-world characteristics and treatment of cardiac transthyretin amyloidosis: A multicentre, observational study.

Data on the clinical profiles of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) in the post-approval era of tafamidis 61mg are lacking. Study aims were characterization of contemporary ATTR-CM patients, analysis of potential eligibility for the 'Transthyretin Amyloidosis Cardiomyopathy Clinical Trial' (ATTR-ACT) and identification of factors associated with the decision on tafamidis 61mg treatment. This retrospective study analysed ATTR-CM patients seen at eight University Hospitals in the first year after approval of tafamidis 61mg for ATTR-CM in Germany (April 2020 to March 2021). The cohort comprised 366 patients (median age 79 [74; 82] years, 84% male), with 47% and 45% of the cohort being in National Amyloidosis Centre ATTR stage≥II and NYHA class≥III, respectively. Sixty-four per cent of patients met key eligibility criteria of the pivotal ATTR-ACT. In recently diagnosed patients (58% with diagnosis ≤6months), the rate of variant ATTR was significantly lower than in patients diagnosed more than 6months ago (9.3% vs. 19.7%). Of the 293 patients without prior ATTR specific treatment, tafamidis 61mg was newly initiated in 77%. Patients with tafamidis 61mg treatment were significantly younger, were more often eligible for ATTR-ACT, had lower NYHA class and higher serum albumin levels. These variables explained 16% of the variance of treatment decision. Unadjusted survival was higher in patients with than those without treatment (1-year survival 98.6% vs. 87.3%, P<0.001). Wild-type ATTR was the primary aetiology amongst contemporary ATTR-CM patients and almost two-thirds of patients were in an advanced disease stage. Clinical profiles of 64% of patients in routine care matched those of the ATTR-ACT. Further effort is needed to detect patients at an earlier disease stage and to validate criteria justifying treatment initiation.

Racial and ethnic disparities in outcomes of diffuse large B cell lymphoma in adolescent and young adults: a SEER database analysis.

Data regarding racial disparities in the incidence, treatment, and outcomes of diffuse large B-cell lymphoma (DLBCL) is limited in the adolescent and young adult (AYA) population. We utilized the surveillance, epidemiology, and end-result (SEER) registry research plus database to evaluate racial/ethnic disparities in 8605 AYA patients with DLBCL. Race/ethnicity was categorized into three main subsets: non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and 'other races' that included Hispanics (H), American Indian/Alaskan Native (AI/AN), Asian or Pacific Islander (A/PI). NHB were more likely to present with advanced stage disease (p < 0.001) and B symptoms (p < 0.001) and were less likely to receive chemotherapy(p < 0.001) compared to non-Hispanic white (NHW) patients and other races respectively. NHB patients had inferior 5-year disease specific survival (DSS) (70% vs 85% vs 80%, p < 0.001) and 5-year overall survival (OS) (66% vs 82% vs 77%, p < 0.001) compared to NHW and other races respectively. Black race was independently associated with both inferior DSS (HR 1.55, 95% CI 1.17-2.05, p = 0.002) and OS (HR 1.41, 95% CI 1.10-1.83, p = 0.007) after adjusting for age, gender, stage, presence of B symptoms, receipt of chemotherapy and radiation. NHB-DLBCL patients also had a lower 1-year relative survival rate (RSR) compared to NHW and other races. The low RSR in NHB patients persisted up to 5 years from diagnosis unlike NHW and other races. Our study shows that despite significant therapeutic advances in DLBCL over the last two decades, NHB AYA patients with DLBCL continue to have inferior survival outcomes compared to other ethnic and racial groups with disparities arising as early as the first year of diagnosis.

Health care resource utilization and costs across stages of amyotrophic lateral sclerosis in the United States.

People living with ALS (plwALS) experience motor control loss, speech/swallowing difficulties, respiratory insufficiency, and early death. Advancing disease stage is typically associated with a greater burden on the health care system, and delays in diagnosis can result in substantial health care resource utilization (HCRU). To estimate HCRU and cost burden of plwALS across disease stages from a US payer perspective we assessed HCRU and costs in early-, mid-, and late-stage ALS. Using insurance claims data from the IBM MarketScan Databases between January 2013 and December 2019, we identified plwALS as having at least 2 claims at least 27 days apart with an ALS International Classification of Diseases, Ninth or Tenth Revision diagnosis code (335.20/G12.21) or at least 1 ALS diagnosis code and prescription filled for riluzole/edaravone. Eligible plwALS were aged at least 18 years and had at least 12 months of enrollment data before and at least 6 months after the index date (date diagnosis criteria met). plwALS were grouped into disease stages using an ALS severity-based staging algorithm developed using ALS symptom and staging survey data from 142 neurologists reporting on 880 plwALS. The starting date of each severity stage was defined as the first date of an ALS symptom within the early-, mid-, and late-stage categories, respectively. The ending date for a severity stage was defined as the day before the first date of an ALS symptom from a more severe category. plwALS could transition to more severe stages, with reverse transition of severity excluded. Mixed regression modeling was used to assess differences in HCRU and costs per person-year between severity stages, adjusted for age and sex. 2,273 plwALS were included in the total ALS study sample, with 1,215 early-stage, 1,511 midstage, and 1,186 late-stage plwALS. 90% of early-stage plwALS had ALS symptoms before diagnosis, and 27% of late-stage plwALS had a late-stage symptom before diagnosis. In the evaluation period, later-stage ALS groups had more overall hospital admissions (early = 0.15, middle = 0.23, and late = 0.74; P < 0.01), outpatient visits/service (early = 26.81, middle = 32.78, and late = 48.54; P < 0.01), emergency department visits (early = 0.46, middle = 0.69, and late = 1.03; P < 0.01), and total prescription count (early = 9.23, middle = 11.37, and late = 12.72; P < 0.01) over 12 months. Annualized costs increased as ALS progressed (early = $31,411, middle = $51,481, and late = $121,903; P < 0.01), which was primarily driven by higher frequency of and cost per hospital admission. HCRU and costs increased with ALS progression, with diagnosis frequently occurring even after experiencing late-stage symptoms. These findings highlight the potential value of delaying progression into a more resource-intensive stage by diagnosing and adequately treating plwALS earlier in the disease course.

Essential Considerations for Radiologists in Diagnosing Hidradenitis Suppurativa.

Hidradenitis suppurativa, also referred to as inverse acne, manifests as a persistent inflammatory skin disorder characterized by lesions such as deep nodules, abscesses, sinus tracts, and fibrotic scars. These manifestations predominantly occur in skin folds and intertriginous areas, notably in the axillary, inguinal, perianal, perineal, and inframammary regions. Due to similarities with other conditions in its initial stages, accurate diagnosis of hidradenitis suppurativa is often delayed, sometimes spanning several years. Diagnosis relies on identifying specific morphologic features (such as deep, inflamed, and painful nodules; sinus tracts; and scars), considering the affected sites (skin folds and areas with apocrine glands), and recognizing the chronic nature of the condition (persistent course with periods of exacerbation and remission). There are no definitive biologic or pathologic diagnostic tests, and biopsy of the affected area is not necessary. Treatment varies based on severity and may include topical and systemic antibiotics, hormonal therapy, immunomodulators, and surgery. Due to associated pain, increased site sensitivity, secretion drainage, odor, and scarring, this condition can have a negative psychosocial impact. Imaging studies, including high-frequency US and MRI with subsequent three-dimensional reconstruction, serve as valuable tools for precise staging, monitoring disease activity, and preoperative assessment. Currently, high-frequency US stands as the preferred method, incorporating sonographic classifications, while MRI and thee-dimensional imaging represent an emerging and promising approach. Imaging helps identify the extent of sinus tracts, assess involvement dimensions in advanced disease stages, and monitor proposed treatments. ©RSNA, 2024 Supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Comprehensive Clinicopathological and Immunohistochemical Analysis of Human Papillomavirus-independent Squamous Cell Carcinoma and Adenosquamous Carcinoma of the Uterine Cervix.

Human papillomavirus-independent (HPVI) squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the uterine cervix are extremely rare. The aim of this study was to comprehensively describe the clinicopathological features, patient outcomes, and immunophenotypes of HPVI SCC and ASC. We found four and two patients with HPVI SCC and ASC, respectively, and reviewed their electronic medical records and pathology slides. We also performed immunostaining for p16 and p53. All except one patient underwent surgery. Two, one, and one patients with HPVI SCC were diagnosed as having IIIC1, IVA, and IVB diseases, respectively. Two patients with HPVI SCC experienced recurrences, and died of disease within nine months after treatment initiation. Both patients with HPVI ASC developed lung metastasis at four months post-operatively. HPVI SCCs and the squamous component of HPVI ASCs showed keratinizing, condylomatous, or poorly differentiated morphology. The glandular component of HPVI ASCs was gastric-type endocervical adenocarcinoma. None of the six tumors exhibited block positivity for p16. Two HPVI SCCs and one HPVI ASC displayed aberrant p53 expression. HPVI SCC is a rare and aggressive cervical malignancy that presents initially as advanced-stage disease with poor prognosis. Although the patients with initial stage I and II HPVI ASC were treated with curative intent, distant metastases appeared in the lungs during the early course of treatment. Further investigations are necessary to clarify the association between histological features and clinical behavior of HPVI ASC.

New insights on the link between Epstein‑Barr virus infection and cognitive decline in neurodegenerative diseases (Review).

Cognitive decline is a frequent complaint in healthy controls and neurological patients, regardless of the underlying pathology. Whilst cognitive impairment can be easily diagnosed in the more advanced stages of neurodegenerative diseases, early detection can be challenging. This is mainly the consequence of the incomplete understanding of the underlying pathophysiological mechanisms. In addition, currently available neurological treatments do not specifically target cognitive decline, since other motor and non-motor symptoms, such as bradykinesia, tremor, autonomic disturbances and depression, are of greater relevance from a therapeutic perspective. In this context, prospective studies must address a number of issues, including the risk factors associated with cognitive deficits in neurodegenerative diseases. The present review aims to offer a novel perspective on the association between Epstein-Barr virus infection and cognitive decline found in patients with neurodegenerative disorders. Specifically, relevant epidemiological studies and clinical trials explaining this connection were reviewed, focusing on the most frequent neurodegenerative disorders. They are namely Alzheimer's disease, Parkinson's disease and multiple sclerosis. Despite their limitations, possible underlying pathophysiological mechanisms that explain the impact of Epstein-Barr virus infection on cognitive decline are expected to offer novel study directions on this clinically relevant topic.

Frailty and associated outcomes in patients with transthyretin cardiac amyloidosis

Abstract Introduction Despite older age at diagnosis, the prevalence and clinical impact of frailty, an age-related geriatric syndrome, in patients with transthyretin cardiac amyloidosis (ATTR-CA) is poorly described. Purpose To determine: (1) the prevalence of frailty in ATTR amyloidosis patients; (2) the clinical frailty phenotype in ATTR amyloidosis (3) the independent and incremental prognostic value of frailty. Methods All consecutive patients diagnosed with ATTR-CA who underwent frailty assessment at two high-volume tertiary care centres from September 2019 to April 2023 were included in the study. Functional assessment was performed with the Rockwood Clinical Frailty Scale (CFS), an established frailty screening tool that stratifies patients on a nine-point scale ranging from 1 (very well) to 9 (terminally ill) providing a useful measure of physiological reserve. Frailty was defined as CFS &amp;gt;4. Functional status was further categorized as follows: 'non-frail' (CFS 1-3), ‘mild’ frailty (CFS 4-5), and 'moderate-to-severe' frailty (CFS 6-9). Logistic regression analysis was used to identify factors associated with CFS 6-9. Cox regression analysis was used to determine the independent and incremental prognostic value of frailty. Results The study comprised 880 patients with ATTR-CA (719 [81.7%] with wt-ATTR-CA, 85 [9.7%] with p.(V142I) hATTR-CA and 76 [8.6%] with a non-p.(V142I) hATTR-CA. Overall, 43.0% (N=378) were considered ‘non-frail’ (CFS 1-3). Prevalence of ‘mild’ frailty (CFS 4-5) was 41.4% (N=364), while prevalence of 'moderate-to-severe' frailty (CFS 6-9) was 15.7% (N=138). Frail patients were older, more symptomatic and with advanced disease stage as assessed with the National Amyloidosis Centre (NAC) staging system. At logistic regression analysis, age, female gender, non-p.(V142I) variants and NAC stage were associated with 'moderate-to-severe' frailty. Over a median 22 months, 16.8% died, with mortality rising with higher CFS levels. At Cox multivariable analysis, CFS was strongly associated with mortality (CFS 4-5 vs 1-3: Hazard Ratio [HR] 2.821, 95% C.I. 1.724-4.613; CFS 6-9 vs 1-3: HR 6.179, 95% C.I. 3.694-10.335, overall p-value&amp;lt;0.001), along with NAC stage and age. The addition of CFS to the NAC staging system significantly improved the goodness-of-fit of the model (X2: 73.26, p&amp;lt;0.00001), and significantly improved the discriminatory ability of the NAC alone (Figure, Harrell’s C statistics: 0.78, 95% C.I. [0.72-0.83] vs 0.69, 95% C.I. [0.64-0.75], p&amp;lt;0.0001). CONCLUSION Frailty is highly prevalent in patients with ATTR-CA, with up to 57% of patients living with some degree of frailty. Older age, female gender, non-p.(V142I) hATTR-CA variants and advanced disease stage were independently associated with moderate to severe frailty. Frailty was independently associated with all-cause mortality after adjusting for known predictors and increased the global predictivity of the NAC Score.Survival by Frailty Status and NAC

Lung cancer screening: Real screening site data, Vojvodina, Serbia

Abstract Background Lung cancer (LC) is the top cause of cancer-related deaths globally and in Serbia, often diagnosed in advanced stage of disease with when 5-year survival is 10% to 20%. LC screening with low-dose CT (LDCT) can decrease LC mortality and overall mortality. The first pilot LC screening program in Serbia started in the Institute for Pulmonary Diseases of Vojvodina in September 2020. The main objective of this study was to analyze LC patient characteristics according to their screening status. Methods This retrospective study utilized LC hospital registry data from September 2020 to December 2023, including gender, age at diagnosis, settlement area, smoking habits, cancer histological type, TNM classification, disease stage (1-4), and data on participation in LC screening. Group differences were assessed using chi-square and Student’s t-tests, with analyses conducted in SPSS v24.0. Results During observed period from a total of 4649 LC cases 2948 (63.4%) were males, and 73 (1.6%) were included in LC screening. Average age of all LC patients was 66 years, without differences between groups (p = 0.778). Significant differences between groups by gender were find (p = 0.042). Non-screened LC patients were significantly common males compared to females (63.6% vs 36.4%), while among screened difference by gender were lower (52.1% vs 47.9%, respectively). Screened compared to non-screened LC patients have significantly lower percentage of SCLC (9.6% vs 19.1%), and higher percentage of NSCLC (90.4% vs 80.9%), (p = 0.040). According to LC stage, screened compared to non-screened patients were significantly common diagnosed in stage I of disease (45.8% vs 7.8%), and significantly less common in higher LC stages; stage IIIB (11.1% vs 22.5%), and in stage IV (22.2% vs 45.7%), (p &amp;lt; 0.001). Conclusions LC screening with LDCT is proven secondary preventive measure with significant influence on decreasing LC mortality by increasing number of LC patients in early stages of disease. Key messages • Lung cancer screening with low-dose CT significantly increases early-stage diagnoses, improving survival chances. • Population strategies to prevent smoking and screening programs for high-risk groups are needed to reduce lung cancer incidence and mortality rates in Serbia.

Unexpected Findings: Cutaneous Metastasis in Squamous Cell Carcinoma of the Cervix – A Rare Case Report

Skin metastasis from squamous cell carcinoma of the uterine cervix is a rare occurrence with reported incidences ranging from 0.1% to 2%. This often indicates advanced-stage disease and poor prognosis. We present the case of a 50-year-old multiparous woman diagnosed with cervical squamous cell carcinoma FIGO stage 2A1 following a six-month history of abnormal uterine bleeding. Despite initial treatment with radical hysterectomy, the patient was noncompliant with postoperative radiotherapy and experienced disease recurrence manifesting as vaginal and cutaneous lesions. Subsequent chemotherapy failed to halt disease progression, leading to palliative care. The timing of skin metastasis onset following primary treatment is a crucial prognostic factor, with earlier appearances indicating poorer outcomes. Skin metastases are often preterminal, necessitating palliative care.

Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

Objective This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). Methods A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Results Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Conclusions Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

Extramammary Paget's disease treated with of anti-programmed cell death protein 1 therapy after docetaxel therapy failure.

Extramammary Paget's disease (EMPD) is a rare skin cancer with no standard treatment for advanced-stage disease. Although docetaxel-based chemotherapy is common, no standard treatment exists. Pembrolizumab is approved for solid tumors with a high tumor mutation burden (TMB) and/or high microsatellite instability, and nivolumab was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies. However, there is a lack of real-world data regarding the efficacy of anti-programmed cell death protein 1 (PD-1) therapy for EMPD. We present the case details of three EMPD patients treated with anti-PD-1 therapy after docetaxel treatment, with TMB values of 17.8, 14.3, and 5.0 mut/Mb, respectively, and we review similar reported cases. Even in the cases with a high TMB, the response to anti-PD-1 therapy was not sufficient. Most cases involve second-line or later treatments, so further research is needed to determine the precise effectiveness of anti-PD-1 therapy as a first-line treatment.

Exploring the complexity, treatment challenges, and outcomes in pediatric nodular lymphocyte predominant Hodgkin lymphoma: a perspective from a low–middle-income country

BackgroundIn children, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Given the lack of data on the best chemotherapy regimen, there is a knowledge gap in best management.MethodsThis retrospective study included all pediatric patients with NLPHL diagnosed and treated at the Children’s Cancer Hospital, Egypt (2007–2018). We analyzed the clinical characteristics, and treatment outcome according to disease stage (early and advanced), treatment strategy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and explored the prognostic factors for progression-free survival.ResultsThe median age at diagnosis was 12 years; 40 (68%) patients had early-stage disease, and 19 (32%) had advanced-stage disease. The median follow-up was 70 months; the 5-year EFS and OS were 75% and 97%, respectively. The 5-year EFS was 78% for early-stage disease and 60% for advanced-stage disease; the 5-year OS was 100% for early-stage disease and 88% for advanced-stage disease. The patients who underwent R-CHOP had a better 3-year EFS (100%) compared with those who underwent ABVD (65%) regimen (P = 0.01). Seventeen (25%) patients relapsed: 9/40 (22%) had early-stage disease, and 8/19 (42%) had advanced-stage disease. Splenic involvement, mediastinal disease, extranodal disease, and slow early response were independent predictors of relapse risk.ConclusionPediatric patients with early-stage NLPHL have an excellent prognosis, with a 5-year OS of 100%. However, those with advanced stages had a high relapse rate. R-CHOP was associated with a better response and relapse-free rate than ABVD.

Stemness in solid malignancies: coping with immune attack.

Immunotherapy has become a key new pillar of cancer treatment, and this has sparked interest in understanding mechanisms of cancer immune evasion. It has long been appreciated that cancers are constituted by heterogeneous populations of tumour cells. This feature is often fuelled by specialized cells that have molecular programs resembling tissue stem cells. Although these cancer stem cells (CSCs) have capacity for unlimited self-renewal and differentiation, it is increasingly evident that some CSCs are capable of achieving remarkable immune resistance. Given that most immunotherapy regiments have overlooked CSC-specific immune-evasive mechanisms, many current treatment strategies often lead to cancer relapse. This Review focuses on advancements in understanding how CSCs in solid tumours achieve their unique immune-evasive properties, enabling them to drive tumour regrowth. Moreover, as cancers often arise from tissue stem cells that acquired oncogenic mutations, we discuss how tissue stem cells undergoing malignant transformation activate intrinsic immune-evasive mechanisms and establish close interactions with suppressive immune cells to escape immune surveillance. In addition, we summarize how in advanced disease stages, CSCs often hijack features of normal stem cells to resist antitumour immunity. Finally, we provide insights in how to design a new generation of cancer immunotherapies to ensure elimination of CSCs.

Relative burden of cancer and noncancer mortality among long-term survivors of differentiated thyroid cancer in the US

BackgroundLimited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC).MethodsIn this retrospective study, nationwide data from the Surveillance, Epidemiology, and End Results database (1992-2020) were utilized. The Accelerated Failure Time Model was applied to calculate Survival Time Ratios (TR), with the primary focus on mortality resulting from DTC. The competing risks model was employed to investigate the relative risks of various outcomes in DTC patients with a survival duration of 5 years or more.ResultsIn our cohort, 279 patients succumbed to DTC, while 748 died from other diseases. Notably, in DTC cohorts, noncancer-specific mortality rates were consistently higher than DTC-specific mortality rates across different age groups and genders. The risk of DTC and noncancer-specific mortality varied based on the TNM stage. With more advanced disease stages, the risk of DTC and other cancer-specific mortality gradually increased. The cumulative mortality from other cancer-specific causes was consistently the lowest.ConclusionsIn long-term surviving DTC patients, noncancer-specific mortality outweighed DTC-specific mortality irrespective of age and gender. For stage I and II patients, increased attention should be directed toward noncancer-specific mortality in postoperative follow-ups. Conversely, for stage III and IV patients, greater consideration should be given to DTC-related causes of death. In addition, for stage III and IV DTC patients, the risk of death from other cancers was significantly higher than for stages I and II.

Treatment and survival differences between patients with invasive lobular carcinoma versus invasive ductal carcinoma of the breast.

Invasive lobular carcinoma (ILC) exhibits differences in molecular and biological characteristics compared to invasive ductal carcinoma (IDC). We aim to compare breast cancer-specific survival (BCSS) between patients with ILC and IDC. We used data from the Surveillance, Epidemiology, and End Results database (1992-2020). Logistic regression analyses were conducted to identify factors associated with treatment modalities. We examined BCSS at different time points using a cox regression model with time-dependent coefficient. 343,397 patients with IDC and 39,859 patients with ILC were included. Patients with ILC had more advanced stage disease (stage II, 35% vs. 34%; stage III, 16% vs.11%), and higher rate of hormone receptor-positive disease (97% vs. 81%). Compared to patients with IDC, patients with ILC had better BCSS in the first five years (Hazard ratio [HR]=0.71, p <0.001), but worse BCSS in later years (HR=1.30, p<0.001 in year 6-10; HR=1.75, p<0.001 in year 11-15; HR=2.17, p<0.001 in year 16-20). Patients with ILC survive better in early years but worse in later years compared to patients with IDC. Future studies are required to identify patients with ILC who are at risk of late recurrence or mortality. The results of this study add to the currently conflicting literature of survival of ILC and demonstrate the importance of evaluating novel therapeutic approaches and extended therapy for patients with ILC.

Neuroleptic malignant syndrome in Huntington disease.

Despite the wide use of dopamine receptor blocking agents (DRBAs) in Huntington disease (HD), neuroleptic malignant syndrome (NMS) is rarely described in this population. The aim of this study was to assess NMS prevalence in a large cohort of HD patients and explore the main associated risk factors. In 2023, an HD patient was admitted to our neurology department due to NMS. Starting from the case description, we performed a narrative review of the literature of NMS cases in HD, reviewed data from the fifth dataset of the Enroll-HD (a longitudinal, observational, global study of families with HD) study (PDS5) selecting HD patients treated with DRBAs and/or tetrabenazine (TBZ) who presented at least one of the core symptoms of NMS (rigidity and hyperthermia), and collected data to investigate prevalence of NMS and identify risk factors. In the Enroll-HD PDS5 dataset, we identified 5108 of 11,569 HD patients who were undergoing DRBA and/or TBZ treatment. Only one patient, a Caucasian man of 46 years, undergoing clozapine and valproate treatment, had a registered diagnosis of NMS. NMS in HD patients is seldom described. This could be due to an underestimation of this condition. There are no available objective NMS diagnostic criteria at present, and the existence of atypical forms of NMS further complicates diagnosis. Advanced disease stage, rigid-akinetic phenotype, abrupt therapy changes, polytherapy, and dehydration are key risk factors, most of which are preventable through awareness and caution in managing medications in the HD population.

The role of ethnic enclaves and neighborhood socioeconomic status in invasive breast cancer incidence rates among Asian American, Native Hawaiian, and Pacific Islander females in California.

Few studies have examined whether the incidence rates of invasive breast cancer among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations differ by the neighborhood social environment. Thus, we examined associations of ethnic enclave and neighborhood socioeconomic status (nSES) with breast cancer incidence rates among AANHPI females in California. A total of 14,738 AANHPI females diagnosed with invasive breast cancer in 2008-2012 were identified from the California Cancer Registry. AANHPI ethnic enclaves (culturally distinct neighborhoods) and nSES were assessed at the census tract level using 2007-2011 American Community Survey data. Breast cancer age-adjusted incidence rates and incidence rate ratios (IRRs) were estimated for AANHPI ethnic enclave, nSES, and their joint effects. Subgroup analyses were conducted by stage of disease. The incidence rate of breast cancer among AANHPI females living in lowest ethnic enclave neighborhoods (quintile (Q)1) were 1.21 times (95% Confidence Interval (CI) 1.11, 1.32) that of AANHPI females living highest ethnic enclave neighborhoods (Q5). In addition, AANHPI females living in highest vs. lowest SES neighborhoods had higher incidence rates of breast cancer (Q5 vs. Q1 IRR = 1.30, 95% CI 1.22 to 1.40). The incidence rate of breast cancer among AANHPI females living in low ethnic enclave + high SES neighborhoods was 1.32 times (95% CI 1.25, 1.39) that of AANHPI females living in high ethnic enclave + low SES neighborhoods. Similar patterns of associations were observed for localized and advanced stage disease. For AANHPI females in California, incidence rates of breast cancer differed by nSES, ethnic enclave, when considered independently and jointly. Future studies should examine whether the impact of these neighborhood-level factors on breast cancer incidence rates differ across specific AANHPI ethnic groups and investigate the pathways through which they contribute to breast cancer incidence.

A panoramic view of the strategies for epithelial ovarian cancer: a review of current challenges

Epithelial ovarian cancer (EOC) remains a formidable challenge in the field of gynecological oncology, accounting for a significant proportion of cancer-related deaths among women worldwide. Despite advances in surgical techniques and chemotherapeutic regimens, the prognosis for patients with advanced-stage disease continues to be dismal, underscoring the urgent need for novel and more effective treatment strategies. This editorial review examines intriguing therapeutic modalities that have the potential to improve treatment outcomes as well as overcome the current difficulties in managing EOC. It presents a brief but comprehensive examination of current research literature about epithelial ovarian cancer, challenges, disease recurrence, molecular complexity, and emerging therapeutic modalities. The importance of gene- and stem-cell therapy in pursuing effective ovarian cancer treatments still holds the platform. While traditional chemotherapy remains crucial for advanced cases, surgical interventions remain pivotal for early-stage patients. Treatment options include innovative DNA polymerase (alpha/delta/epsilon) inhibitors, personalized treatments, and immunotherapies toward advanced cases for quality survival. The challenges posed by epithelial ovarian cancer and late diagnosis necessitate a continuous quest for improved therapeutic options. Emerging approaches such as gene and stem cell therapies show promise in reshaping treatment paradigms. Further exploring localized treatment modalities presents avenues for enhancing improved patient payoff.

The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Are people with HIV at advanced disease stages being left behind? A global survey.

A substantial percentage of people with HIV are still admitted for care at advanced disease stages. Here, we investigate the availability of the supplies and infrastructure required to provide care for this population in healthcare facilities and explore correlations with local demand. AIDS Healthcare Foundation's partner facilities were invited to respond to a survey addressing the availability of services to support clients with advanced HIV. We present results per continent and according to gross national income per capita using frequencies and percentages. We generated country-level scores taking the average percentage of facilities with available resources on 10 key items and used Spearman's correlation to investigate relationships between country scores and local demand, depicted by the percentages of people with HIV newly enrolled in care with a CD4 T-cell count <200/mm3 in 2022. A total of 643 facilities from 37 countries responded to the survey between September and December 2021. Overall, services requiring more costly equipment and/or supplies were less frequently available. Facilities in Africa, Asia, and Latin America/Caribbean and those with lower gross national income had a somewhat lower availability of diagnostic and therapeutic resources. Availability of services was not correlated with local demand: 14 countries (42%) had scores below the 50% percentile despite having >20% of newly enrolled people with HIV with a CD4 T-cell count <200/mm3. Appropriate care can mitigate the morbidity and mortality associated with advanced HIV. We found that the healthcare services recommended by the World Health Organization as essential to support clients with advanced HIV are often unavailable in facilities providing HIV care, despite high local demand.