Negative Patients Research Articles

397 Treatment outcomes of swallowing sparing VMAT in HPV negative Head and Neck Carcinoma patients.

397 Treatment outcomes of swallowing sparing VMAT in HPV negative Head and Neck Carcinoma patients.

Effect of nucleos(t)ide analogue discontinuation on the prognosis of HBeAg-negative hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A propensity score matching analysis.

Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

NEUT-RI, a surrogate marker of NETosis is lower in patients with strong IgM antiphospholipid antibodies.

Antiphospholipid antibody syndrome (APS) is an acquired autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy complications. Recently, thrombotic APS was linked to increased neutrophil extracellular traps (NET) formation, suggesting an association between NETs and the severity of APS-related thrombosis. We performed a retrospective study on patients tested for presence of antiphospholipid antibodies (990 negative and 374 positive) to evaluate the association between the neutrophil activation state, estimated by the neutrophil reactive index (NEU-RI), a parameter routinely available from some haematology analysers, and antiphospholipid antibodies. We do not observe a difference in NEU-RI values between positive and negative patients globally. However, interestingly, we highlight an association between high titers of IgM and low NEU-RI values indicating a lower neutrophil activation. Our data are in line with the recent questioning about the putative clinical consistency of positive solid-phase aPL IgM.

Pre-injury methamphetamine use is associated with increased length of hospital stay in rural orthopaedic trauma patients

ObjectivesThe primary focus of this study is to determine if rural methamphetamine positive patients experience longer hospital length of stays compared to urban methamphetamine positive patients following an orthopaedic trauma. MethodsPatients presenting with traumatic orthopaedic injuries and urine drug screen were categorized into urban, suburban, and rural cohorts found in the Rural Urban Commuting Area codes based on home residence zip codes. Demographic, injury, hospital stay, and follow-up data were collected from the medical records. Comparisons between cohorts were determined by Chi square, Fisher exact, unpaired t-Tests, or ranked sum tests. DesignA retrospective cohort analysis. SettingAcademic Level I Trauma Center. Patient selection criteriaPatient records were examined between January 2013 to January 2023 for a traumatic orthopaedic injury and a urine drug screen result at the time of presentation to an academic Level I trauma center. Outcome measures and comparisonsMethamphetamine use status, patient age at time of admission, sex, marital status, insurance status, home zip code, orthopaedic injury location, complications, if the patient underwent surgery for orthopaedic injuries, admission date, discharge date, and discharge location were measured. Results249 patients met inclusion criteria for this analysis. Methamphetamine positive patients are significantly more likely to be younger, more likely to have surgery for orthopaedic injuries, experience a medical complication, or be discharged to home or a rehabilitation facility compared to methamphetamine negative patients. Urban patients experienced a shorter length of stay compared to suburban and rural patients, regardless of methamphetamine use status. Patients with Medicare, military, workers compensation, or commercial insurance are significantly more likely to attend follow-up appointments than patients with Medicaid or self-pay. ConclusionsMethamphetamine positive patients overall do not experience a longer length of hospital stay compared to methamphetamine negative patients. Rural methamphetamine positive patients experience a longer length of hospital stay compared to urban methamphetamine positive patients.

Cognitive Targeted Prostate Biopsy Alone for Diagnosing Clinically Significant Prostate Cancer in Selected Biopsy-Naïve Patients: Results from a Retrospective Pilot Study.

(1) Background: To identify a particular setting of biopsy-naïve patients in which it would be reasonable to offer only cognitive targeted prostate biopsy (PBx) with a transrectal approach. (2) Methods: We designed an observational retrospective pilot study. Patients with a prostatic specific antigen (PSA) level > 10 ng/mL, either a normal or suspicious digital rectal examination (DRE), and a lesion with a PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone were included. All patients underwent a transrectal PBx, including both systematic and targeted samples. The detection rate of clinically significant prostate cancer (csPCa) (Gleason Score ≥ 7) was chosen as the primary outcome. We described the detection rate of csPCa in systematic PBx, targeted PBx, and overall PBx. (3) A total of 92 patients were included. Prostate cancer was detected in 84 patients (91.30%) with combined biopsies. A csPCa was diagnosed in all positive cases (100%) with combined biopsies. Systematic PBxs were positive in 80 patients (86.96%), while targeted PBxs were positive in 84 men (91.30%). Targeted PBx alone would have allowed the diagnosis of csPCa in all positive cases; systematic PBx alone would have missed the diagnosis of 8/84 (9.52%) csPCa cases (4 negative patients and 4 not csPCa) (p = 0.011). (4) Conclusions: Cognitive targeted PBx with a transrectal approach could be offered alone to diagnose csPCa in biopsy-naïve patients with PSA ≥ 10 ng/mL, either normal or suspicious DRE, and a lesion with PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone.

HPV DNA status and clinical history of patients are supplements for accurate reporting of the cytological Pap smear

The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test.

Role of mechanical thrombectomy among large vessel stroke patients during the coronavirus disease (COVID-19) pandemic

PurposeThe aim of our study is to provide insights derived from experience at multiple centers regarding the outcomes of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in COVID-19 patients and compare them with those in non-COVID-19 patients during the coronavirus disease (COVID-19) pandemic.ResultsCOVID‐19 positive patients were younger than COVID‐19 negative patients (62.1 ± 2.69 versus 69.5 ± 2.2, P < 0.001). There was a significant difference between COVID-19 and non-COVID-19 groups in the median D-dimer levels (6 vs. 4.5; P < 0.001), median ESR levels (63 vs. 38; P < 0.001) and median CRP levels (110 vs. 48.5; P < 0.001), respectively. Median time from stroke symptoms onset to hospital admission was significantly higher among COVID-19 positive patients (366 vs. 155 min; P < 0.001). COVID‐19 positive patients with LVO presented with a higher median NIH Stroke Scale score at presentation (16 versus 8, P < 0.001) and lower median Alberta Stroke Program Early CT Score (ASPECTS) on admission (6 versus 8, P < 0.001). Patients with COVID-19 had significantly higher percentages of poor functional outcomes as scored using the mRS grades 3–5 in comparison to non-COVID-19 patients (69.2% vs. 13.6%; P = 0.002), but there was no significant difference between both groups in complications such as early cerebral re-occlusion, intracerebral hemorrhage, or in-hospital mortality (P > 0.05).ConclusionMechanical thrombectomy has effectively managed patients with LVO stroke. LVO stroke in COVID-19 patients occur at a young age, and have multi-territory vascular involvement. Poor functional outcomes post thrombectomy in COVID-19 patients, irrespective of timely, successful angiographic recanalization.

Intestinal Methanogen Overgrowth (IMO) Is Associated with Delayed Small Bowel and Colonic Transit Time (TT) on the Wireless Motility Capsule (WMC).

Methanogens are associated with gut dysmotility in animal models but have not been robustly studied in humans. The WMC assesses regional transit time (TT) and pH in the GI tract. To study the segmental TT and pH among patients with SIBO or IMO utilizing WMC. We conducted a retrospective study of 207 patients who underwent a glucose or lactulose breath test (BT) and WMC from 2010 to 2022. Diagnosis of SIBO and IMO were based on the 2017 North American consensus criteria. TT and pH were extracted from WMC recordings. We tested for differences in means of continuous variables and frequencies of categorical variables using two-sample t tests, Wilcoxon Rank Sum test, Chi-square, and Fisher exact tests. We used R version 3.3.1 (2016-06-21) for all statistical analyses. A total of 196 patients met criteria, mean age 47.4years and 155 (79.1%) females. Of the 86 (43.9%) patients with a positive BT, 42 (58.3%) had IMO only (meeting only CH4 criteria) and 30 (34.9%) met both H2 and CH4 criteria. Colonic TT was longer in patients with a positive BT compared to negative patients (40h:29min vs 28h:51min, p = 0.028). Small bowel TT and colonic TT were longer in patients with IMO compared to negative patients (SBTT: 5h:15min vs 4h:32min, p = 0.021; CTT: 44h:23min vs 28h:51min, p = 0.030). There were no significant differences in segmental pH compared to negative patients. To our knowledge, this is the largest study of patients who have undergone both BT and WMC. A positive BT was associated with delayed CTT, while having IMO only was associated with both delayed CTT and SBTT, but neither with pH. Future investigation is needed to elucidate whether changes in intestinal microbiota affect gut transit.

Testing asymptomatic mental health patients for COVID-19 overburdens hospital resources

BackgroundInpatient mental health facilities required COVID-19 testing for all patients, including asymptomatic ones, due to perceived high susceptibility.AimThis study examined how the policy affected patient care and hospital resources.MethodA retrospective review was conducted on asymptomatic psychiatric patients admitted to the psychiatric emergency room between July and December 2020, analyzing COVID-19 test results, conversion rate, length of stay (LOS), and demographic variables.ResultsAmong asymptomatic patients (N = 2020), 2.5% (n = 51) tested positive, with 7.8% (n = 4) experiencing mild symptoms. The average hospital length of stay was 8 days, with 90.2% discharged home and 9.8% transferred to outside mental health inpatient facilities. Chi-square testing found no significant differences in age, gender, or housing status between positive and negative patients (p’s > 0.05), except for a significant difference in positivity rates among Hispanic patients (p < 0.05).ConclusionThe positivity rate among asymptomatic mental health patients was low. The policy of universal testing increased hospital spending and resource utilization, including unnecessary testing and hospital admissions, leading to longer stays. These findings underscore the need to assess the efficacy of COVID-19 testing policies and reconsider resource allocation based on evidence.

Revealing the clinical impact of MTOR and ARID2 gene mutations on MALT lymphoma of the alimentary canal using targeted sequencing

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are a group of diseases with marked heterogeneity, including clinical, immunohistochemical, and molecular heterogeneity. The disease remains unspecified in the genetic landscape with only a few sequencing studies to date; however, systematic studies of alimentary canal MALT lymphoma have not been reported. To better understand the genetics of this tumor, targeted sequencing in a group of 31 cases (including 2 esophageal, 2 colonic, 4 small intestinal, and 23 gastric cases) and two cases of lymph node hyperplasiawere performed. We found epigenetic regulation (DNMT3A, KMT2D, KMT2A, EP300, TET2, etc.), signaling pathways (APC, CHD8, TNFAIP3, TNFRSF14, ZAP70, NF1,), and tumor suppressor genes (TP53, BCORL1, FOXO1, ATM, etc.) involved. Moreover, we found MTOR gene mutations in 16% of the cases that made these patients more prone to recurrence and metastasis than those with MTOR wild type genes. More interestingly, ARID2 mutations were detected in 32% of all the cases, and the mutation rate was higher and statistically significant in Helicobacter pylori (Hp)-negative patients in the gastric group. Therefore, this study found that MTOR and ARID2 gene mutations have pathogenic and prognostic implications.

TME-analyzer: a new interactive and dynamic image analysis tool that identified immune cell distances as predictors for survival of triple negative breast cancer patients

Spatial distribution of intra-tumoral immune cell populations is considered a critical determinant of tumor evolution and response to therapy. The accurate and systemic search for contexture-based predictors would be accelerated by methods that allow interactive visualization and interrogation of tumor micro-environments (TME), independent of image acquisition platforms. To this end, we have developed the TME-Analyzer, a new image analysis tool, which we have benchmarked against 2 software tools regarding densities and networks of immune effector cells using multiplexed immune-fluorescent images of triple negative breast cancer (TNBC). With the TME-Analyzer we have identified a 10-parameter classifier, predominantly featuring cellular distances, that significantly predicted overall survival, and which was validated using multiplexed ion beam time of flight images from an independent cohort. In conclusion, the TME-Analyzer enabled accurate interactive analysis of the spatial immune phenotype from different imaging platforms as well as enhanced utility and aided the discovery of contextual predictors towards the survival of TNBC patients.

Small Fiber Neuropathy Associated with Post-COVID-19 and Post-COVID-19 Vaccination Arthritis: A Rare Post-Infective Syndrome or a New-Onset Disease?

Post-COVID-19 (PC) and post-COVID-19 vaccination (PCV) syndromes are considered emergent multidisciplinary disorders. PC/PCV small fiber neuropathy (SFN) was rarely described and its association with undifferentiated arthritis (UA) was never defined. We aimed to evaluate PC/PCV-UA associated with the recent onset of severe lower limb paresthesia, compare SFN positive (+) to negative (-) patients, and evaluate changes in biomarkers in SFN+ during treatments. Nineteen PC/PCV-UA-patients with possible SFN underwent skin biopsy at the Usl Tuscany Center (Florence) early arthritis outpatient clinic from September 2021 to March 2024. Eight selected SFN+ were compared to ten SFN- patients. In SFN+ patients, baseline joint ultrasound (US), electromyography (EMG), optical coherence tomography (OCT), and skin biopsy were repeated at six months. Moreover, SFN+ patients were clinically assessed by a 0-10 numeric rating scale for neurological symptoms and DAS28/ESR up to 12 months follow-up. SFN+ patients showed a lower intraepidermal nerve fiber density at histopathological examination of skin biopsies and a higher frequency of OCT and EMG abnormalities in comparison to SFN- patients. In SFN+ patients, US and DAS28/ESR significantly improved, while intraepidermal nerve fiber density did not significantly change at the six-month follow-up. Fatigue, motor impairment, burning pain, brain fog, and sensitivity disorders decreased at long-term follow-up (12 months).

Host urinary biomarkers in HIV positive and HIV negative patients with tubercular uveitis and other uveitic diseases

PurposeTo determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection. MethodsConcentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection. ResultsOne-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&-II, IP-10, MIP-1β, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+. ConclusionDecreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.

Estimating Impacts of p16 Status on Tumor Radiosensitivity in Head and Neck Cancer using Predictive Models.

The intrinsic radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) were reported to be able to predict the surviving fraction at 2 Gy and therapeutic effect when delivering actual treatment doses using the gene expression profiles of clinical cases. Given the impact of p16 status, a surrogate marker of the human papillomavirus (HPV) infection, on radiosensitivity, we attempted to apply the RSI and GARD to estimate p16-associated radiosensitivity in head and neck squamous cell carcinoma (HNSC). For this purpose, The Cancer Genome Atlas (TCGA) dataset was employed. In the GARD calculation, we assumed that p16-positive patients received 60 Gy in 30 fractions, while p16-negative patients received 70 Gy in 35 fractions. p16 positivity was associated with favorable characteristics compared to negative patients. The RSI and GARD analyses demonstrated increased radiosensitivity and high therapeutic effect in p16-positive patients, compared to p16-negative patients. Additionally, tumor microenvironmental conditions predicted by other models were also significantly affected by p16 status. Collectively, the models used in this study could be a promising tool for estimating p16-associated radiosensitivity in HNSC.

Genetic mutations in Parkinson's disease: screening of a selected population from North-Eastern Italy.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a multifactorial pathogenesis. Several genetic variants increase the risk of PD and about 5-10% of cases are monogenic. This study aims to define the genetic bases and clinical features of PD in a cohort of patients from Northeastern Italy, a peculiar geographical area previously not included in genetic screenings. Using an NGS multigenic panel, 218 PD patients were tested based on age at onset, family history and development of atypical features. A total of 133 genetic variants were found in 103 patients. Monogenic PD was diagnosed in 43 patients (20% of the cohort); 28 (12.8%) carried mutations in GBA1, 10 in LRRK2 (4.6%) and 5 in PRKN (2.3%). In 17% of patients the genetic defect remained of uncertain interpretation. The selection criterion "age of onset < 55years" was a significant predictor of a positive genetic test (OR 3.8, p 0.0037). GBA1 patients showed more severe symptoms and a higher burden of motor and non-motor complications compared to negative patients (dyskinesias OR 3, sleep disturbances OR 2.8, cognitive deficits OR 3.6; p < 0.05), with greater autonomic dysfunction (COMPASS-31 score 34.1 vs 20.2, p 0.03). Applying simple clinical criteria for genetic testing allows to increase the probability to identify patients with monogenic PD and better allocate resources. This process is critical to widen the understanding of disease mechanisms and to increase the individuation of patients potentially benefitting from future disease-modifying therapies.

Frequency and clinical significance of Herpes simplex virus type 1/2 reactivation in adult patients with mild to moderately severe community-acquired pneumonia: a multicentre cohort study.

This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP). The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death). Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7-16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0-2 and survived the first 28day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS. Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course.

Implementation of Choosing Wisely® Recommendations for Lymph Node Surgery in Male Breast Cancer

BackgroundThe Choosing Wisely® (CW) campaign recommended de-implementation of surgical management of axillary nodes in specified patients. This study aimed to assess trends in the application of CW guidelines for lymph node (LN) surgery in males with breast cancer.MethodsThe National Cancer Database was queried for males diagnosed with breast cancer from 2017 to 2020. Patients were categorized into two cohorts based on CW criteria. Cohort 1 included all T1-2, clinically node-negative patients who underwent breast-conserving therapy and with ≤ 2 positive nodes, and Cohort 2 included all T1-2, node-negative, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative patients aged ≥ 70 years. In Cohort 1, patients who underwent sentinel LN biopsy (SLNB) alone were compared with axillary LN dissection (ALND) or no LN surgery, while in Cohort 2, patients who underwent LN surgery were compared with those with no LN surgery.ResultsOf 617 patients who met the criteria for Cohort 1, 73.1% underwent SLNB alone compared with ALND (11.8%) or no LN surgery (15.1%). Those who received SLNB alone were younger (65 vs. 68 vs. 73 years; p < 0.001). The annual proportion of males who underwent SLNB alone remained stable from 2017 to 2020. Overall, 1565 patients met the criteria for Cohort 2, and 84.9% received LN surgery. LN surgery was omitted in older patients (81 vs. 77; p < 0.001). The proportion of elderly males with early-stage breast cancer who underwent LN surgery increased from 2017 to 2020.ConclusionThis study demonstrates that CW recommendations are not being routinely applied to males. These findings reinforce the need for additional studies and subsequent recommendations for optimal application of axillary surgery de-implementation for males diagnosed with breast cancer.

Effect of PR status on the prognosis of advanced ER-high HER2-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy

BackgroundThis study was designed to evaluate the effect of progesterone receptor (PR) status on the prognosis of advanced estrogen receptor (ER)-high human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy.MethodsAdvanced ER-high HER2-negative breast cancer patients who were admitted to Harbin Medical University Cancer Hospital and received cyclin-dependent kinase (CDK)4/6 inhibitor combined with endocrine as first-line therapy were included for analysis. Patients were divided into PR-high group (11-100%), PR-low group (1-10%), and PR-negative group (< 1%) according to the expression of PR. Chi-square test was used to analyze the correlation of variables between groups. COX regression analysis were used to analyze the risk factors of survival. Kaplan-Meier survival curve was used to analyze the differences of progression-free survival (PFS) and overall survival (OS) between groups.ResultsAmong the 152 patients, 72 were PR-high, 32 were PR-low, and 48 were PR-negative. Compared with PR-negative group, the proportions of disease-free survival (DFS) ≥ 5 years and Ki-67 index ≤ 30% in PR-low group and PR-high group were significant higher. PR-negative patients were more likely to occur first-line progression of disease within 24 months (POD24) than PR-high(P = 0.026). Univariate and multivariate analysis showed that PR-negative and first-line POD24 occurrence were risk factors for survival. Survival curve analysis showed that compared with PR-high group, the PFS and OS were significantly lower in PR-negative group (P = 0.001, P = 0.036, respectively). Patients with first-line POD24 had shorter OS in the overall population as well as in subgroups stratified by PR status.ConclusionsPR-negative and first-line POD24 occurrence were risk factors of advanced ER-high HER2-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. PR-negative patients had shortest PFS and OS. Regardless of PR status, first-line POD24 occurrence predicted shorter OS.

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P=0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P=0.007], serum creatinine [60 μmol/L (IQR 50-70) versus 70 (54-114); P=0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P=0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P=0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P=0.668 and P=0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8%vs. 8.1%, P=0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P=0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.

To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC). Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS. Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03). Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.