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Aims: This study aims to develop a prediction tool for the overall survival of cervical cancer patients. Methods: We obtained 4116 female patients diagnosed with cervical cancer aged 25–69 during 2008–2019 from the Surveillance, Epidemiology, and End Results Program. The overall survival between groups was illustrated by the Kaplan–Meier method and compared by a log-rank test adjusted by the Bonferroni–Holm method. We first performed the multivariate Cox regression analysis to evaluate the predictive values of the variables. A prediction model was created using cox regression based on the training set, and the model was presented as a nomogram. The proposed nomogram was designed to predict the 1-year, 3-year, and 5-year overall survival of patients with cervical cancer. Besides the c-index, time-dependent receiver operating curves, and calibration curves were created to evaluate the accuracy of the nomogram at the timepoint of one year, three years, and five years. Results: With a median follow-up of 54 (28, 92) months, 1045 (25.39%) patients were deceased. Compared with alive individuals, the deceased were significantly older and the primary site was more likely to be the cervix uteri site, large tumor size, higher grade, and higher combined summary stage (all p values < 0.001). In the multivariate Cox regression, age at diagnosis, race, tumor size, grade, combined summary stage, pathology, and surgery treatment were significantly associated with the all-cause mortality for patients with cervical cancer. The proposed nomogram showed good performance with a C-index of 0.82 in the training set. The 1-year, 3-year, and 5-year areas under the curves (with 95% confidence interval) of the receiver operating curves were 0.88 (0.84, 0.91), 0.84 (0.81, 0.87), and 0.83 (0.80, 0.86), respectively. Conclusions: This study develops a prediction nomogram model for the overall survival of cervical cancer patients with a good performance. Further studies are required to validate the prediction model further. [ABSTRACT FROM AUTHOR]

Background: Additional systemic treatment for early breast cancer in elderly is challenged by increasing comorbidities with age. We aimed to examine the effect of additional chemotherapy on overall survival in patients aged 70 years or older and the impact of comorbidities on chemotherapy benefit. Methods: This retrospective monocentric cohort study includes data from all patients aged 70 years and older who underwent surgery for an early breast cancer from 1997 to 2016. A propensity score analysis allowed adjustment for chemotherapy prescription preferences based on tumour characteristics. Results: Of 15,599 patients who had surgery for an early breast cancer, 1743 (11.2%) over 70 years old were included, of whom 269 (15.4%) had received additional chemotherapy. Median follow-up was 5.3 years. Multivariate analyses on the propensity-score weighted cohort (n = 1 354) identified improved overall survival in patients with chemotherapy versus without (HR 0.54, 95% CI 0.31–0.92). Chronic obstructive pulmonary disease (HR, 2.16, 95% CI 1.40–3.34) and polypharmacy (HR 1.40, 95%CI 1.07–1.84) were associated with worse overall survival. No statistically significant interactions were identified between these comorbidities and chemotherapy prescription. Conclusion: Additional chemotherapy in elderly with early breast cancer is feasible and associated with overall survival benefit, supporting the importance of chemotherapy considerations in this population, and of avoiding undertreatment based on chronological age considerations alone. [ABSTRACT FROM AUTHOR]

Objectives: For patients with ductal carcinoma in situ (DCIS), data about the impact of breast MRI at primary diagnosis on the incidence and characteristics of contralateral breast cancers are scarce. Methods: We selected all 8486 women diagnosed with primary DCIS in the Netherlands in 2011–2015 from the Netherlands Cancer Registry. The synchronous and metachronous detection of contralateral DCIS (cDCIS) and contralateral invasive breast cancer (cIBC) was assessed for patients who received an MRI upon diagnosis (MRI group) and for an age-matched control group without MRI. Results: Nineteen percent of patients received an MRI, of which 0.8% was diagnosed with synchronous cDCIS and 1.3% with synchronous cIBC not found by mammography. The 5-year cumulative incidence of synchronous plus metachronous cDCIS was higher for the MRI versus age-matched control group (2.0% versus 0.9%, p = 0.02) and similar for cIBC (3.5% versus 2.3%, p = 0.17). The increased incidence of cDCIS was observed in patients aged < 50 years (sHR = 4.22, 95% CI: 1.19–14.99), but not in patients aged 50–74 years (sHR = 0.89, 95% CI: 0.41–1.93). Conclusions: MRI at primary DCIS diagnosis detected additional synchronous cDCIS and cIBC, and was associated with a higher rate of metachronous cDCIS without decreasing the rate of metachronous cIBC. This finding was most evident in younger patients. Key Points: • Magnetic resonance imaging at primary diagnosis of ductal carcinoma in situ detected an additional synchronous breast lesion in 2.1% of patients. • In patients aged younger than 50 years, the use of pre-operative MRI was associated with a fourfold increase in the incidence of a second contralateral DCIS without decreasing the incidence of metachronous invasive breast cancers up to 5 years after diagnosis. • In patients aged over 50 years, the use of pre-operative MRI did not result in a difference in the incidence of a second contralateral DCIS or metachronous invasive breast cancer. [ABSTRACT FROM AUTHOR]

Background: Data-generating processes are key to the design of Monte Carlo simulations. It is important for investigators to be able to simulate data with specific characteristics. Methods: We described an iterative bisection procedure that can be used to determine the numeric values of parameters of a data-generating process to produce simulated samples with specified characteristics. We illustrated the application of the procedure in four different scenarios: (i) simulating binary outcome data from a logistic model such that the prevalence of the outcome is equal to a specified value; (ii) simulating binary outcome data from a logistic model based on treatment status and baseline covariates so that the simulated outcomes have a specified treatment relative risk; (iii) simulating binary outcome data from a logistic model so that the model c-statistic has a specified value; (iv) simulating time-to-event outcome data from a Cox proportional hazards model so that treatment induces a specified marginal or population-average hazard ratio. Results: In each of the four scenarios the bisection procedure converged rapidly and identified parameter values that resulted in the simulated data having the desired characteristics. Conclusion: An iterative bisection procedure can be used to identify numeric values for parameters in data-generating processes to generate data with specified characteristics. [ABSTRACT FROM AUTHOR]

The European brown hare (Lepus europaeus) is a quite adaptable species, but populations have been decreasing for several decades in different countries, including Germany. To investigate infectious diseases as possible influences on observed population decline in the German federal state Schleswig-Holstein, 118 deceased free-ranging European brown hares were collected between 2017 and 2020 and underwent detailed postmortem examination with extended sampling. Infectious diseases were a major cause of death (34.7%). The number of juveniles found exceeded the adult ones. The main pathomorphological findings were hepatitis (32.8%), pneumonia (22.2%), nephritis (19.1%), liver necrosis (12.9%), and enteritis (40.7%). An unusual main finding was steatitis (20.9%) of unknown origin. Animals were mainly emaciated and showed high infection rates with Eimeria spp. (91.3%) and Trichostrongylus spp. (36.2%). European Brown Hare Syndrome Virus reached an epidemic status with few fatal infections (4.2%) and high seroprevalence (64.9%), whereas the prevalence of Rabbit Haemorrhagic Disease Virus 2 was very low (0.8%) in hares in Schleswig-Holstein. Pathogens such as Yersinia pseudotuberculosis (5.9%), Pasteurella multocida (0.8%), and Staphylococcus aureus (3.4%) only caused sporadic deaths. This study illustrates the wide distribution of various infectious pathogens with high mortality and even zoonotic potential. Infectious diseases need to be considered as an important influence on population dynamics in Schleswig-Holstein. [ABSTRACT FROM AUTHOR]

Background: Breast reconstruction is frequently offered to cancer patients who undergo mastectomy. Older women tend to have lower rates of reconstruction mostly due to an age-based discretion. We aimed to assess the safety of this surgery in this population. Methods: We conducted a single-center retrospective analysis of patients who underwent breast reconstruction following mastectomy between 2015 and 2020 at "Complejo Hospitalario Universitario de Albacete." Patients were classified according to age when the reconstruction process began (group A: < 65 years–group B: > 65 years). Differences in demographics and clinical data were analyzed using Student's t test and Chi-square test. Multivariable logistic regression models were used to estimate odds ratio (OR) and confidence intervals (CIs) for surgical complications according to age group. Propensity-score matching was used as a sensitivity analysis to test consistency among results. Results: We included 304 women (266: group A–38: group B). Complete reconstruction was achieved in 48.1% of patients in group A vs 10.5% in group B (P < 0.001). After adjusting for potential confounders, age was not associated with an increased risk of surgical complications, neither overall (OR 0.88, 95%CI 0.40–1.95), early (OR 1.35, 95%CI 0.58–3.13) nor late (OR 1.05, 95%CI 0.40–2.81). Radiotherapy and smoking history were significant predictors for complications in every setting. Conclusions: In our cohort, age at breast reconstruction is not associated with a higher risk of surgical complications, in contrast to radiotherapy and smoking history. Therefore, age should not be a limiting factor when considering breast reconstruction. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor-infiltrating lymphocytes (TILs) are immune cells that can be involved in the anti-tumor response and are presently viewed as a promising, inexpensive biomarker with prognostic and predictive potential. It has been demonstrated that patients with early triple-negative breast cancer and high TILs report higher responses to treatments with improved survival outcomes. Moreover, TIL expression may have a prognostic role in non-triple-negative subtypes and predict the response to immuno-oncology agents. However, the use of TILs as biomarkers in clinical practice is still limited by the lack of rigorous, prospective validation. This review summarizes the most important current issues and future challenges to assessing and validating TILs as predictive and prognostic biomarkers in patients with breast cancer. Tumor-infiltrating lymphocytes (TILs) represent a surrogate biomarker of anti-tumor, lymphocyte-mediated immunity. In early, triple-negative breast cancer, TILs have level 1B of evidence to predict clinical outcomes. TILs represent a promising biomarker to select patients who can experience a better prognosis with de-intensified cancer treatments and derive larger benefits from immune checkpoint inhibitors. However, the assessment and the validation of TILs as a biomarker require a prospective and rigorous demonstration of its clinical validity and utility, provided reproducible analytical performance. With pending data about the prospective validation of TILs' clinical validity to modulate treatments in early breast cancer, this review summarizes the most important current issues and future challenges related to the implementation of TILs assessments across all breast cancer subtypes and their potential integration into clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to estimate the extra risk of second primary cancer among breast cancer patients. Methods and materials: This is a systematic review. A comprehensive search of literature was performed in PubMed, Web of Science, Cochrane library, and Scopus. The search included all published studies up to October 2022. This systematic review included studies published in the English language that reported the risk of second primary non-breast cancer [i.e., standardized incidence ratio (SIR)] among breast cancer patients older than 15 years. After evaluating the methodological quality of the selected studies, SIRs were pooled with consideration of heterogeneity among studies. The estimates were pooled by age and time since the diagnosis of primary breast cancer for both sexes (male and female). Age was categorized based on before 50 years and after 50 years, and time was categorized as duration of less than and more than 10 years, respectively. Results: From 2,484 articles, 30 articles were eligible for inclusion in the systematic review and meta-analysis. The studies varied in terms of population, number of cases, study design, setting, and year of implementation of the research. The estimated SIR for men and women was 1.28 (95% CI: 1.18, 1.38) and 1.27 (95% CI: 1.15, 1.39), respectively. Women diagnosed with breast cancer before menopause [SIR: 1.52 (95% CI: 1.34, 1.71) vs. 1.21 (95% CI: 1.08, 1.34)] as well as women after 10 years since their breast cancer diagnosis [1.33 (95% CI: 1.22, 1.431) vs. 1.24 (95% CI: 1.10, 1.37)] were at a higher risk of developing second primary cancer. Among men, while there were no differences in risk based on age, with the increase of time, the risk of second primary cancer was reduced [SIR: 1.22 (95% CI: 1.12, 1.33) vs. 1.00 (95% CI: 0.79, 1.22)]. Conclusion: There is an extra risk of second primary cancer among breast cancer patients. The extra risk should be considered for further screening and preventive measures among this population. [ABSTRACT FROM AUTHOR]

Simple Summary: As the treatment for breast cancer continues to improve and more women survive their initial diagnosis, there is an increasingly large number of women who are at risk of a second new breast cancer in their lifetimes. However, the hereditary causes of these second breast cancers are not well understood. In this study, we used the latest genetic sequencing technologies to investigate hereditary causes for the second breast cancer in individuals who are known not to have alterations in one of the three main breast cancer genes (BRCA1, BRCA2 and PALB2). We analyzed the genetic profiles of selected participants from the WECARE study, one of the largest studies looking at second breast cancers in women. By comparing the genetic profiles of women who have had one breast cancer to similarly matched women who went on to have a second breast cancer, we found that younger women (under 50) with second breast cancers had a higher number of inherited gene alterations compared with those women with one breast cancer. We did not see the same effect in the older women. The results from this study improve our understanding of the hereditary contribution to second breast cancers. Background: Contralateral breast cancer (CBC) is associated with younger age at first diagnosis, family history and pathogenic germline variants (PGVs) in genes such as BRCA1, BRCA2 and PALB2. However, data regarding genetic factors predisposing to CBC among younger women who are BRCA1/2/PALB2-negative remain limited. Methods: In this nested case-control study, participants negative for BRCA1/2/PALB2 PGVs were selected from the WECARE Study. The burden of PGVs in established breast cancer risk genes was compared in 357 cases with CBC and 366 matched controls with unilateral breast cancer (UBC). The samples were sequenced in two phases. Whole exome sequencing was used in Group 1, 162 CBC and 172 UBC (mean age at diagnosis: 42 years). A targeted panel of genes was used in Group 2, 195 CBC and 194 UBC (mean age at diagnosis: 50 years). Comparisons of PGVs burdens between CBC and UBC were made in these groups, and additional stratified sub-analysis was performed within each group according to the age at diagnosis and the time from first breast cancer (BC). Results: The PGVs burden in Group 1 was significantly higher in CBC than in UBC (p = 0.002, OR = 2.5, 95CI: 1.2–5.6), driven mainly by variants in CHEK2 and ATM. The proportions of PGVs carriers in CBC and UBC in this group were 14.8% and 5.8%, respectively. There was no significant difference in PGVs burden between CBC and UBC in Group 2 (p = 0.4, OR = 1.4, 95CI: 0.7–2.8), with proportions of carriers being 8.7% and 8.2%, respectively. There was a significant association of PGVs in CBC with younger age. Metanalysis combining both groups confirmed the significant association between the burden of PGVs and the risk of CBC (p = 0.006) with the significance driven by the younger cases (Group 1). Conclusion: In younger BRCA1/BRCA2/PALB2-negative women, the aggregated burden of PGVs in breast cancer risk genes was associated with the increased risk of CBC and was inversely proportional to the age at onset. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the prognostic significance of clinicopathological characteristics in early-onset versus late-onset colorectal liver metastases (CRLM). Methods: The data of CRLM patients who underwent hepatectomy from September 2010 to September 2020 were retrospectively analyzed. According to the age of primary cancer diagnosis, patients were divided into early-onset CRLM (EOCRLM) and late-onset CRLM (LOCRLM) groups. Clinicopathological parameters were compared between the two groups. Cox regression model and Kaplan–Meier method were used to analyze the effect of clinicopathological parameters on overall survival (OS) and recurrence-free survival (RFS). Results: In total, 431 CRLM patients were identified, 130 with EOCRLM and 301 with LOCRLM. Compared with LOCRLM patients, EOCRLM patients had lower American Society of Anesthesia (ASA) grade and longer operation time (204 vs. 179 min). More aggressive features were presented in EOCRLM patients including synchronous liver metastases (76.9% vs. 61.1%) and bilobar involvement (43.8% vs. 33.2%). No significant difference in OS or RFS was found between the two groups. Multivariate analysis of EOCRLM group showed that preoperative CA19-9 level and RAS/BRAF status were predictive of OS, while bilobar involvement and preoperative CEA level were associated with RFS. In LOCRLM group, the number of CRLM, preoperative CA19-9 level, and BRAF status were associated with OS, while the number of CRLM was associated with RFS. Conclusions: The preoperative CA19-9 level, RAS/BRAF status, bilobar involvement, and preoperative CEA level were predictive of EOCRLM patient prognosis, while the number of CRLM, preoperative CA19-9 level, and BRAF status were predictive of LOCRLM patient prognosis. [ABSTRACT FROM AUTHOR]

Salmonella is a ubiquitous organism of public health importance that causes diarrhea and other systemic disease syndromes. The ecology and epidemiology of the organism in addition to the roles played by wild animals are important in understanding its disease. Relevant published peer-reviewed literature was obtained after imputing the study's keywords into the Google search engine. The publications were thereafter saved for the study. The study revealed the ecology of Salmonella is directly related to its epidemiology. These were found to be either positively or negatively influenced by the living and nonliving parts of the environment. Free-ranging and captive wild animals can serve as asymptomatic carriers of Salmonella, therefore, help to maintain the cycle of the disease since wildlife serves as reservoir hosts to over 70% of emerging zoonotic diseases. Cockroaches transmit Salmonella through their feces, and body parts and when ingested by birds and animals. The statistically significant over 83% of Salmonella isolation in lizards suggests the reptile could be a source of Salmonella distribution. Snakes, foxes, badgers, rodents, and raccoons have been reported to have Salmonella as a natural component of their gut with the ability to shed the organism often. The high occurrence (>45%) of diverse Salmonella serovars coupled with the fact that some of these animals were handled, kept as pets and consumed by man portends these animals as potential sources of transmission of the organism and the disease. The etiology and epidemiology of Salmonella are overtly affected by several environmental factors which also determine their survival and maintenance. The roles played by wild animals in the relationship, transmission, growth or interaction within and between Salmonella spp., the occurrence, prevalence, and distribution of the organism help maintain the organism in the environment. An understanding of the roles played by the different parts of the environment and wild animals in the ecology and epidemiology of Salmonella can help make informed decisions on the prevention and control of the diseases it causes. This review aimed to investigate the relationship between ecology, epidemiology, and environment, including the roles played by wild animals in the maintenance of the organism and its disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver metastases occur in almost half of patients with colorectal cancer, either at the time of presentation (synchronous) or eventually as a metachronous recurrence of the disease. Approximately one quarter of patients with metastasis to the liver receive surgical resection with curative intent but recurrence is frequent and related to tumor biology. Understanding cancer biology is crucial to improve outcomes. In an attempt at unveiling novel targets for treatment, this paper investigates and summarizes current knowledge of the distinct growth patterns of tumor cells at the interface with normal liver tissue, defined as the histopathological growth pattern, and their interaction with immune cells in the microenvironment. Almost half of all patients with colorectal cancer present with or eventually develop metastasis, most frequently in the liver. Understanding the histopathological growth patterns and tumor immune microenvironment of colorectal liver metastases may help determine treatment strategies and assess prognosis. A literature search was conducted to gather information on cancer biology, histopathological growth patterns, and the tumor immune microenvironment in colorectal liver metastases, including their mechanisms and their impact on clinical outcomes. A first consensus on histopathological growth patterns emerged in 2017, identifying five growth patterns. Later studies found benefits from a two-tier system, desmoplastic and non-desmoplastic, incorporated into the updated 2022 consensus. Furthermore, the tumor immune microenvironment shows additional characteristic features with relevance to cancer biology. This includes density of T-cells (CD8+), expression of claudin-2, presence of vessel co-option versus angiogenesis, as well as several other factors. The relation between histopathological growth patterns and the tumor immune microenvironment delineates distinct subtypes of cancer biology. The distinct subtypes are found to correlate with risk of metastasis or relapse, and hence to clinical outcome and long-term survival in each patient. In order to optimize personalized and precision therapy for patients with colorectal liver metastases, further investigation into the mechanisms of cancer biology and their translational aspects to novel treatment targets is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Rhabdomyosarcoma is the most frequent soft tissue sarcoma of childhood, but can occur at any age. Adolescent and young adult patients with rhabdomyosarcoma often have poorer outcomes than do children. This survival gap may be related to differences in clinical management or differences in tumor biology and intrinsic aggressiveness. Various studies have suggested that young adults may have better outcomes when treated with multidisciplinary treatment in line with the pediatric approach. However, treatment results seem to remain worse in young adults when compared with children, even when they were treated in the same way, and this suggest that part of the prognostic gap between children and adults may be attributable to biological differences in rhabdomyosarcoma arising in different age groups. A multifaced strategy is needed to further improve outcome of adults with rhabdomyosarcoma, including a trans-age academic societies and national/international cooperation, the definition of integrated biologic and genomic approach, and the development of collaborative rhabdomyosarcoma clinical trials without upper age limit. Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database. [ABSTRACT FROM AUTHOR]

Encephalitozoon cuniculi is a eukaryote, unicellular, spore-forming, obligate intracellular microorganism of the phylum Microsporidia, with domestic rabbits as its main host. Another important species in which this pathogen has been identified are humans, the infection being therefore called a "zoonosis". The transmission takes place via the horizontal route or the vertical route, and cell-mediated immunity plays the biggest role in the infected hosts' protection. Encephalitozoonosis can manifest itself as an acute infection, with neurological signs, renal signs, and ocular lesions, or as a chronic or subclinical infection, which is usually the case for asymptomatic carriers. The diagnostic techniques usually carried out are histological examination, serological tests, and molecular genetic techniques. The treatment of encephalitozoonosis is usually symptomatic, with unrewarding results, and prevention methods include periodical serological screening, prophylactic administration of fenbendazole, and maintenance of a clean environment. The purpose of this article is to review the current data regarding the pathogenesis, host immunity, clinical signs, diagnostic methods, treatment, and prevention methods of encephalitozoonosis in the domestic rabbit, as well as to analyze the prevalence of this disease in different countries of the world. [ABSTRACT FROM AUTHOR]

Malignant bowel obstruction (MBO) is one of the most severe complications in patients with advanced ovarian cancer, with an estimated incidence up to 50%. Its presence is related to poor prognosis and a life expectancy measured in weeks for inoperable cases. Symptoms are usually difficult to manage and often require hospitalization, which carries a high burden on patients, caregivers and the healthcare system. Management is complex and requires a multidisciplinary approach to improve clinical outcomes. Patients with inoperable MBO are treated medically with analgesics, antiemetics, steroids and antisecretory agents. Parenteral nutrition and gut decompression with nasogastric tube, venting gastrostomy or stenting may be used as supportive therapy. Treatment decision-making is challenging and often based on clinical expertise and local policies, with lack of high-quality evidence to optimally standardize management. The present review summarizes current literature on inoperable bowel obstruction in ovarian cancer, focusing on epidemiology, prognostic factors, clinical outcomes, medical management, multidisciplinary interventions and quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Salmonellae are enteric bacteria capable of infecting humans and both domestic and wild animals. Even if salmonellosis in humans is generally transmitted through food, the role of wildlife in the ecology of this bacteria is of increasing interest because of their potential role as reservoirs. In Italy, and in particular in the Apennines area, the interactions between wildlife and humans, pets and livestock are rising due to a growing wildlife population and this poses the problem of accidental Salmonella infections. The aim of this study was to investigate the presence of Salmonella subspecies and serotypes in wild carnivores (namely red fox, European badger and wolf) from the Emilia-Romagna Region between 2016 and 2022. Samples of the large intestine were cultured, and both serogroup and serotype identification were performed. A total of 67 strains were isolated, belonging to S. enterica subsp. enterica, S. salamae, S. diarizonae and S. houtenae. The most frequently isolated serotypes were S. veneziana and S. typhimurium. These findings highlight a prevalence of Salmonella spp. in line with other studies, showing once again the value of monitoring different possible sources of Salmonella infection. Salmonella is a pathogen of considerable health concern, given its zoonotic potential, and, in Italy, is the most frequently reported causative agent for foodborne outbreaks. Wild animals and in particular wild carnivores may be carriers of different Salmonella enterica subspecies and serotypes. Given their potential role as reservoirs, surveillance activities are necessary. This study aims to investigate the presence of different Salmonella subspecies and serotypes in wild carnivores in the Emilia-Romagna Region. A total of 718 fox (Vulpes vulpes), 182 badger (Meles meles) and 27 wolf (Canis lupus) carcasses, submitted between 2016–2022, were included for the present work. Gender and age data were collected along with geographical coordinates of carcass' discovery site. Contents of the large intestine were sampled and cultured according to ISO 6579-1 and both serogroup and serotype identification were performed according to ISO/TR 6579-3:2014. Salmonella was retrieved from 42 foxes (6%), 21 badgers (12%) and 3 wolves (12%), respectively. Isolated Salmonella enterica strains belonged to 4 different subspecies and 25 different serotypes. S. veneziana and S. typhimurium were the most frequent serotypes found (11/67 and 10/67, respectively). In conclusion, zoonotic serotypes were found in all these species of wildlife, thus confirming their potential role in the ecology of Salmonella spp. [ABSTRACT FROM AUTHOR]

Background: Currently, the proportion of standard chemotherapy for elderly patients is much lower than that for young patients, with little evidence from clinical trials supporting the use of chemotherapy for elderly patients. The effectiveness of chemotherapy for the elderly suffering from breast cancer remains to be further verified. Methods: A total of 75,525 female breast cancer patients aged 70 years or older were hereby identified, all from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010 to December 31, 2016. Kaplan–Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of chemotherapy on overall survival (OS) and breast cancer‐specific survival (BCSS). Propensity score matching (PSM) (PSM ratio: 1:1, caliper: 0.2 standard deviation of propensity score) was applied to construct balanced cohorts with or without chemotherapy based on demographic and pathophysiological characteristics. Results: A total of 33,177 eligible patients were included, with 5273 (15.89%) receiving chemotherapy. Through PSM, 8360 patients were successfully matched, and balances between groups were almost reached. In the matched data set, multivariable Cox analysis reveals that chemotherapy was associated with a 36% and 21% risk reduction on OS (HR = 0.64, 95% CI 0.58 to 0.71) and BCSS (HR = 0.79, 95% CI 0.69 to 0.91), respectively. Furthermore, subgroups with more adjacent lymph nodes involved by tumor, or nonluminal A, were inclined to benefit more from chemotherapy. Moreover, chemotherapy did not increase the chances of dying from heart disease. Conclusions: The present study provided evidence that chemotherapy may improve the prognosis of elderly breast cancer, especially for those subpopulations that benefit more from chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Background: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB., Methods: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)., Results: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02)., Conclusions: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848., (© 2024. The Author(s).)

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI COG ) that maximized discrimination of the predictive model. Patients with higher PI COG have higher predicted relapse risk. The PI COG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PI COG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PI COG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PI COG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PI COG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure., (© 2024. The Author(s).)

Background: Malignant bowel obstruction (MBO) affects 3% to 15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction., Aims: This retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO., Results: In a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023)., Conclusions: The use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

When modeling competing risks (CR) survival data, several techniques have been proposed in both the statistical and machine learning literature. State-of-the-art methods have extended classical approaches with more flexible assumptions that can improve predictive performance, allow high-dimensional data and missing values, among others. Despite this, modern approaches have not been widely employed in applied settings. This article aims to aid the uptake of such methods by providing a condensed compendium of CR survival methods with a unified notation and interpretation across approaches. We highlight available software and, when possible, demonstrate their usage via reproducible R vignettes. Moreover, we discuss two major concerns that can affect benchmark studies in this context: the choice of performance metrics and reproducibility., (© 2024 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

European brown hare syndrome (EBHS) is one of the main causes of mortality in brown hares (Lepus europaeus) and mountain hares (Lepus timidus) in Europe. Since the mid-1990s, this highly lethal and contagious plague has been widespread in many European countries, contributing to a drastic decline in the number of free-living and farmed hares. A second lagovirus, able to infect some species of hares is rabbit haemorrhagic disease virus 2 (RHDV2; GI.2) recognised in 2010, a new viral emergence of RHDV (GI.1) which is known to be responsible for haemorrhagic disease in rabbits—RHD. The aim of this study was to evaluate the current EBHS epidemiological situation on the basis of the presence of antibodies to European brown hare syndrome virus (EBHSV) and anti-RHDV2 antibodies in sera collected from free-ranging hares in Central and Southeastern Poland in 2020–2021. Additionally, studies on the presence of EBHSV and RHDV2 antigens or their genetic material in the blood and internal organs taken from brown hares between 2014–2021 have been carried out. The results of the serological examination showed nearly 88% of tested blood samples were positive for EBHSV antibodies. No EBHSV was identified in the examined hares using virological and molecular tests. The positive results of EBHS serological studies confirmed the circulation and maintenance of EBHSV in free-living brown hares in Poland. However, no serological, virological or molecular evidence was obtained indicating that the brown hares tested had been in contact with RHDV2. [ABSTRACT FROM AUTHOR]

Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g., coronary artery disease or breast cancer. Polygenic risk scores (PRS) are subsets of individual genotypes designed to capture heritability of common traits, and hence to allow the stratification of risk of the trait in a population. We systematically reviewed the PubMed database for unequivocal evidence of clinical utility of polygenic risk scores, using stringent inclusion and exclusion criteria. While we identified studies demonstrating clinical validity in conditions where medical intervention based on a PRS is likely to benefit patient outcome, we did not identify a single study demonstrating unequivocally such a benefit, i.e. clinical utility. We conclude that while the routine use of PRSs hold great promise, translational research is still needed before they should enter mainstream clinical practice. [ABSTRACT FROM AUTHOR]

Background: Women with history of chest irradiation for Hodgkin lymphoma are at increased risk of developing bilateral breast cancer, although contralateral breast cancer risk estimates in this population remain undefined. Methods: We queried the SEER database for women treated with radiation therapy for Hodgkin lymphoma prior to age 30 years and were diagnosed with a subsequent breast cancer between 1990–2016. Trends in surgical management and the 5- and 10-year cumulative incidence of contralateral breast cancer were evaluated. Results: The cohort included 295 women with a median age of 22 years (range 8–30 years) at Hodgkin lymphoma diagnosis, and 42 years (range 22–65 years) at breast cancer diagnosis. Overall, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Breast-conserving surgery was performed in 17.3% of patients, while mastectomy was performed in 82.7%. In 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent breast-conserving surgery and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients demonstrated a 40.5% bilateral mastectomy rate. The 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% [95% confidence interval (CI), 5.6–15.4%], increasing to 20.2% (95% CI, 13.7–29.2%) at 10-year and 29.9% (95% CI, 20.8–41.9%) at 15-year follow-up. Conclusions: Women with a history of prior chest radiation for Hodgkin lymphoma with a diagnosis of breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making for management of this high-risk patient population. [ABSTRACT FROM AUTHOR]

Simple Summary: Red foxes (Vulpes vulpes) are largely present in Italian wooded areas and often reach urban environments. These animals are susceptible to several bacterial and protozoan pathogens that are able to affect dogs and humans. Foxes may harbor arthropod-borne microorganisms, enteropathogens and leptospirae, and thus represent a potential source of infections for other animals. Previous surveys in fox populations have usually focused on few of these pathogens, whereas in the present investigation, the occurrence of several bacterial and protozoan pathogens have been investigated: Salmonella spp., Yersinia spp., Listeria monocytogenes, Brucella spp., Ehrlichia canis, Anaplasma phagocytophilum, Coxiella burnetii, Leptospira spp., Neospora caninum, Hepatozoon canis, Babesia spp. and microsporidia. Even though the survey was based on a small number of animals, the results suggested that red foxes in Central Italy are involved in the epidemiology of some infections. Most surveys of pathogens in red foxes (Vulpes vulpes) have focused on particular agents. The aim of this study was to verify, with bacteriological and molecular analyses, the occurrence of the main bacterial and protozoan pathogens that are able to infect canids, in red foxes regularly hunted in Central Italy. Spleen, brain, kidney and fecal samples from red foxes were submitted to bacteriological and/or molecular analyses to detect Salmonella spp., Yersinia spp., Listeria monocytogenes, Brucella spp., Ehrlichia canis, Anaplasma phagocytophilum, Coxiella burnetii, Leptospira spp., Neospora caninum, Hepatozoon canis, Babesia spp. and microsporidia. Two (9.1%) strains of Yersinia enterocolitica biotype 1 and 2 (9.1%) of Yersinia frederiksenii were isolated from 22 fecal samples. Among the 22 spleen samples, seven (31.8%) were PCR-positive for H. canis and 3 (13.6%) for Babesia vulpes. Kidneys from two (2.9%) foxes, among 71 tested, were PCR-positive for L. interrogans. Even though the analyses were carried out on a small number of animals, the results suggested that red foxes from the selected geographic area may act as reservoirs of some investigated pathogens. [ABSTRACT FROM AUTHOR]

The histopathological growth patterns (HGPs) of liver metastases (LMs) are independently associated with the long-term prognosis of the primary tumor, with different HGPs predicting different patient outcomes and clinical treatment decisions. Non-invasive imaging biomarkers for stratification of HGPs are beneficial for treatment monitoring, evaluation of efficacy, and prognosis prediction of LMs. This review describes the state of research regarding computed tomography (CT), magnetic resonance imaging (MRI), and radiomics imaging biomarkers for LM-HGPs; discusses the advantages of CT, MRI, and radiomics for classification of LM-HGPs; and provides a reference for the stratification of LM-HGPs. Finally, the difficulties and deficiencies of CT, MRI, and radiomics in LM-HGP research are summarized along with the proposed directions for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Several elements that are composed of, or related to, neutrophils, have been shown to inhibit strong immune responses to cancer and promote cancers' growth. This paper presents the collected data showing these elements and how their coordinated actions as an ensemble facilitate growth in the common cancers. The paper goes on to present a drug regimen, TICO, designed to reduce the cancer growth enhancing effects of the neutrophil related elements. TICO uses four already marketed, readily available generic drugs, repurposed to inhibit neutrophil centered growth facilitation of cancer. This paper presents remarkably uniform data showing that higher NLR is a robust prognostic indicator of shorter overall survival across the common metastatic cancers. Myeloid derived suppressor cells, the NLRP3 inflammasome, neutrophil extracellular traps, and absolute neutrophil count tend to all be directly related to the NLR. They, individually and as an ensemble, contribute to cancer growth and metastasis. The multidrug regimen presented in this paper, TICO, was designed to decrease the NLR with potential to also reduce the other neutrophil related elements favoring malignant growth. TICO is comprised of already marketed generic drugs: the phosphodiesterase 5 inhibitor tadalafil, used to treat inadequate erections; isotretinoin, the retinoid used for acne treatment; colchicine, a standard gout (podagra) treatment; and the common fish oil supplement omega-3 polyunsaturated fatty acids. These individually impose low side effect burdens. The drugs of TICO are old, cheap, well known, and available worldwide. They all have evidence of lowering the NLR or the growth contributing elements related to the NLR when clinically used in general medicine as reviewed in this paper. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) aim to re-establish cancer immune control by modulating immune-inhibitory signaling pathways. ICIs are currently approved in breast cancer treatment act by blocking cell anti-PD-1/PD-L1 interactions. Nonetheless, as many mechanisms of immune escape can underlie the insurgence of cancer cells, most patients progress to ICIs, even when combined with chemotherapy. Multiplexed single-cell spatially resolved tissue analysis, by combining monoclonal antibodies with different reporters, can obtain precise single-cell epitope colocalization and thus allow to infer cellular functional states, while conserving their spatial coordinates. In this review, we highlight the potential of this technology in the context of breast cancer by selecting relevant prognostic and predictive markers through the lens of the cancer-immunity cycle. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many solid tumors. In breast cancer (BC), immunotherapy is currently approved in combination with chemotherapy, albeit only in triple-negative breast cancer. Unfortunately, most patients only derive limited benefit from ICIs, progressing either upfront or after an initial response. Therapeutics must engage with a heterogeneous network of complex stromal–cancer interactions that can fail at imposing cancer immune control in multiple domains, such as in the genomic, epigenomic, transcriptomic, proteomic, and metabolomic domains. To overcome these types of heterogeneous resistance phenotypes, several combinatorial strategies are underway. Still, they can be predicted to be effective only in the subgroups of patients in which those specific resistance mechanisms are effectively in place. As single biomarker predictive performances are necessarily suboptimal at capturing the complexity of this articulate network, precision immune-oncology calls for multi-omics tumor microenvironment profiling in order to identify unique predictive patterns and to proactively tailor combinatorial treatments. Multiplexed single-cell spatially resolved tissue analysis, through precise epitope colocalization, allows one to infer cellular functional states in view of their spatial organization. In this review, we discuss—through the lens of the cancer-immunity cycle—selected, established, and emerging markers that may be evaluated in multiplexed spatial protein panels to help identify prognostic and predictive patterns in BC. [ABSTRACT FROM AUTHOR]

Simple Summary: The presence of immune cells within the tumor (TILs) indicates good prognosis for some aggressive breast cancer subtypes. However, less is known about TILs role within the hormone-responsive breast cancer (ER+/HER2−). These tumors represent up to 70% of all breast cancers and often exhibit long-term metastasis. TILs were quantified in tumor section samples from 763 postmenopausal women who received tamoxifen vs. no treatment and categorized into low, intermediate, or high. Among the ER+/HER2−, TILs were associated with poor prognostic variables but did not have prognostic value. High TILs indicate less benefit from tamoxifen. Interestingly, high gene expression of some TIL markers did indicate good prognosis even after adjusting for other clinical variables or were associated with less tamoxifen benefit. These results suggest that TIL markers could be used as prognostic, predictive indicators, and potential candidates for immunotherapy interventions after tamoxifen failure. The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with H&E and divided into low (<10%), intermediate (10–39%), or high (≥40%). High TILs were associated with poor prognostic variables and good prognoses for all patients, but not within the ER+/HER2− group. Within the ER+/HER2− group, high gene expression of CD19 and PD-L1 and high IMMUNE1 score indicated good prognosis in multivariable analysis while high CD8 and CD19 gene expression and high IMMUNE1 score were associated with less tamoxifen benefit. These results indicate that within the ER+/HER2− subtype there could be subsets of patients where expression of specific TIL markers might be used to reveal candidates for immune therapy interventions upon failure of the endocrine therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer remains one of the most significant sources of cancer-related morbidity and mortality worldwide. The liver is the most common site of metastatic spread. Multiple modalities exist to manage and potentially cure patients with metastatic colorectal cancer. However, reliable biomarkers to assist with clinical decision-making are limited. Recent advances in genomic sequencing technology have greatly expanded our knowledge of colorectal cancer carcinogenesis and significantly reduced the cost and timing of the investigation. In this article, we discuss the current utility of biomarkers in the management of colorectal cancer liver metastases. Surgical management combined with improved systemic therapies have extended 5-year overall survival beyond 50% among patients with colorectal liver metastases (CRLM). Furthermore, a multitude of liver-directed therapies has improved local disease control for patients with unresectable CRLM. Unfortunately, a significant portion of patients treated with curative-intent hepatectomy develops disease recurrence. Traditional markers fail to risk-stratify and prognosticate patients with CRLM appropriately. Over the last few decades, advances in molecular sequencing technology have greatly expanded our knowledge of the pathophysiology and tumor microenvironment characteristics of CRLM. These investigations have revealed biomarkers with the potential to better inform management decisions in patients with CRLM. Actionable biomarkers such as RAS and BRAF mutations, microsatellite instability/mismatch repair status, and tumor mutational burden have been incorporated into national and societal guidelines. Other biomarkers, including circulating tumor DNA and radiomic features, are under active investigation to evaluate their clinical utility. Given the plethora of therapeutic modalities and lack of evidence on timing and sequence, reliable biomarkers are needed to assist clinicians with the development of patient-tailored management plans. In this review, we discuss the current evidence regarding biomarkers for patients with CRLM. [ABSTRACT FROM AUTHOR]

Encephalitozoon cuniculi is a microsporidian parasite mostly associated with its natural host, the rabbit (Oryctolagus cuniculus). However, other animals can be infected, like other mammals, birds, and even humans. Although it usually causes subclinical infection, it can also lead to encephalitozoonosis, a clinical disease characterized by neurological, ocular, and/or renal signs that can be even fatal, especially in immunocompromised individuals. Therefore, this multidisciplinary review contributes with updated information about the E. cuniculi, deepening in its molecular and genetic characterization, its mechanisms of infection and transmission, and its prevalence among different species and geographic locations, in a One Health perspective. Recent information about the diagnostic and therapeutic approach in the main host species and the prophylaxis and infection control measures currently suggested are also discussed. [ABSTRACT FROM AUTHOR]

Background: The histopathological growth patterns (HGPs) are a prognostic and predictive biomarker in colorectal cancer liver metastasis (CRLM). This study evaluates the relationship between the HGP and primary colorectal cancer (CRC) histopathology.Methods: A total of 183 treatment-naive patients with resected CRC and CRLM were included. Thirteen CRC histopathology markers were determined and compared between the desmoplastic and non-desmoplastic HGP; tumour sidedness, pT&pN stage, tumour grade, tumour deposits, perineural- (lympho-)vascular- and extramural venous invasion, peritumoural budding, stroma type, CRC growth pattern, Crohn's-like lymphoid reaction, and tumour-infiltrating lymphocyte (TIL) density. Logistic regression analysis was performed using both CRC and CRLM characteristics.Results: Unfavourable CRC histopathology was more frequent in non-desmoplastic CRLM for all markers evaluated, and significantly so for a lower TIL density, absent Crohn's-like lymphoid reaction, and a "non-mature" stroma (all p < 0.03). The cumulative prevalence of unfavourable CRC histopathology was significantly higher in patients with non-desmoplastic compared to desmoplastic CRLM, with a median (IQR) of 4 (3-6) vs 2 (1-3.5) unfavourable characteristics observed, respectively (p < 0.001). Multivariable regression with 9 CRC histopathology markers and 2 CRLM characteristics achieved good discriminatory performance (AUC = 0.83).Conclusions: The results of this study associates primary CRC histopathology with the HGP of corresponding liver metastases. [ABSTRACT FROM AUTHOR]

Background: The rate of childhood cancer death has dropped steadily over the past 50 years. The pediatric cancer risk has remained under investigation. Objectives: This study aims at investigating the associated factors with the survival of pediatric patients with retinoblastoma, sarcoma, brain tumor, and leukemia cancer. Methods: The cohort study of 1879 children with retinoblastoma, sarcoma, brain tumor, and leukemia aged < 1, 1 - 5, 6 - 10, 11 - 15, and > 15 years in Mahak Hospital and Rehabilitation Complex from 2007 to 2016 were enrolled in the study. Median survival time was reported for each cancer. Parametric survival models including Gompertz, Weibull, lognormal, and log-logistic models were fitted. Then, the model with almost minimum Akaike information criterion (AIC) was chosen. The hazard ratio (HR) and the analysis were performed by R3.5.1. Results: Totally, 270 (14.37%) patients with Retinoblastoma, 667 (35.5%) with leukemia, 625 (33.26%) with a Brain tumor, and317 (16.87%) with Sarcoma were included in this study; 815 (43.37%) patients were female. Gompertz's model was chosen to fit the data due to the minimum AIC. The associated factors with the survival of childhood cancers were as follows: age < 1 year, parental relation, locoregional relapse and chemotherapy alone (HR: 7.63, 1.56, 4.61, 1.12) in leukemia, other nationalities, metastasis or metastasis and loco-regional relapse and chemotherapy alone (HR = 3.74, 5.75, 2.12) in retinoblastoma, loco-regional relapse and metastasis (HR = 2.40, 3.71) in brain tumor, other ages except for 5 - 10 years, parental relation, chemotherapy alone, and metastasis (HR = 33.3, 1.80, 3.57, 3.8) in sarcoma. Conclusions: Age, parental familial relationships, combination therapy, and metastasis of primary cancer were the risk factors for survival of children with 4 common cancers of leukemia, retinoblastoma, brain tumors, and sarcoma, using the Gompertz model. [ABSTRACT FROM AUTHOR]

Purpose: Genetic testing (GT) can identify individuals with pathogenic/likely pathogenic variants (PV/LPVs) in breast cancer (BC) predisposition genes, who may consider contralateral risk-reducing mastectomy (CRRM). We report on CRRM rates in young women newly diagnosed with BC who received GT through a multidisciplinary clinic. Methods: Clinical data were reviewed for patients seen between November 2014 and June 2019. Patients with non-metastatic, unilateral BC diagnosed at age ≤ 45 and completed GT prior to surgery were included. Associations between surgical intervention and age, BC stage, family history, and GT results were evaluated. Results: Of the 194 patients, 30 (15.5%) had a PV/LPV in a BC predisposition gene (ATM, BRCA1, BRCA2, CHEK2, NBN, NF1), with 66.7% in BRCA1 or BRCA2. Of 164 (84.5%) uninformative results, 132 (68%) were negative and 32 (16.5%) were variants of uncertain significance (VUS). Overall, 67 (34.5%) had CRRM, including 25/30 (83.3%) PV/LPV carriers and 42/164 (25.6%) non-carriers. A positive test result (p < 0.01) and significant family history were associated with CRRM (p = 0.02). For the 164 with uninformative results, multivariate analysis showed that CRRM was not associated with age (p = 0.23), a VUS, (p = 0.08), family history (p = 0.10), or BC stage (p = 0.11). Conclusion: In this cohort of young women with BC, the identification of a PV/LPV in a BC predisposition gene and a significant family history were associated with the decision to pursue CRRM. Thus, incorporation of genetic services in the initial evaluation of young patients with a new BC could contribute to the surgical decision-making process. [ABSTRACT FROM AUTHOR]

Background: Cachexia is one of the most common complications affecting lung cancer patients that seriously affects their quality-of-life and survival time. This study aimed to analyze the predictors and prognostic factors of lung cancer cachexia as well as to develop a convenient and accurate clinical prediction tool for oncologists. Methods: In this multicenter cohort study, 4022 patients with lung cancer were retrospectively analyzed. The patients were randomly categorized into training and verification sets (7:3 ratio). Univariate and multivariate logistic regression analyses were performed to determine the risk factors of cachexia in patients with lung cancer. Cox regression analysis was applied to determine independent prognostic factors in the patients with lung cancer cachexia. Meanwhile, two nomograms were established and evaluated by time-dependent receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Results: Stage, serum albumin, ALI, anemia, and surgery were independent risk factors for cachexia in patients with lung cancer. Patients with lung cancer cachexia have a shorter survival time. Sex, stage, serum albumin, ALI, KPS score, and surgery served as independent prognostic factors for patients with lung cancer cachexia. The area under the curves (AUCs) of diagnostic nomogram in the training and validation sets were 0.702 and 0.688, respectively, the AUCs of prognostic nomogram in the training set for 1-, 3-, and 5-year were 0.70, 0.72, and 0.75, respectively, while in the validation set the AUCs were 0.71, 0.75, and 0.79, respectively. The calibration curves and DCA of the two nomograms were consistent and the clinical benefit rate was high. Conclusion: Cachexia brings an additional economic burden and worsens the prognosis of lung cancer patients. The two nomograms can accurately screen and predict the probability of occurrence of cachexia in lung cancer and the prognosis of patients with lung cancer cachexia, and guide clinical work. [ABSTRACT FROM AUTHOR]

Purpose: Black breast cancer (BC) survivors have a higher risk of developing contralateral breast cancer (CBC) than Whites. Existing CBC risk prediction tools are developed based on mostly White women. To address this racial disparity, it is crucial to develop tools tailored for Black women to help them inform about their actual risk of CBC. Methods: We propose an absolute risk prediction model, CBCRisk-Black, specifically for Black BC patients. It uses data on Black women from two sources: Breast Cancer Surveillance Consortium (BCSC) and Surveillance, Epidemiology, and End Results (SEER). First, a matched lasso logistic regression model for estimating relative risks (RR) is developed. Then, it is combined with relevant hazard rates and attributable risks to obtain absolute risks. Six-fold cross-validation is used to internally validate CBCRisk-Black. We also compare CBCRisk-Black with CBCRisk, an existing CBC risk prediction model. Results: The RR model uses data from BCSC on 744 Black women (186 cases). CBCRisk-Black has four risk factors (RR compared to baseline): breast density (2.13 for heterogeneous/extremely dense), family history of BC (2.28 for yes), first BC tumor size (2.14 for T3/T4, 1.56 for TIS), and age at first diagnosis of BC (1.41 for < 40). The area under the receiver operating characteristic curve (AUC) for 3- and 5-year predictions are 0.72 and 0.65 for CBCRisk-Black while those are 0.65 and 0.60 for CBCRisk. Conclusion: CBCRisk-Black may serve as a useful tool to clinicians in counseling Black BC patients by providing a more accurate and personalized CBC risk estimate. [ABSTRACT FROM AUTHOR]

Simple Summary: Ductal carcinoma in situ (DCIS) is a potential precursor to invasive breast cancer (IBC). Although in many women DCIS will never become breast cancer, almost all women diagnosed with DCIS undergo surgery with/without radiotherapy. Several studies are ongoing to de-escalate treatment for DCIS. Multiple decision support tools have been developed to aid women with DCIS in selecting the best treatment option for their specific goals. The aim of this study was to identify these decision support tools and evaluate their quality and clinical utility. Thirty-three studies were reviewed, in which four decision aids and six prediction models were described. While some of these models might be promising, most lacked important qualities such as tools to help women discuss their options or good quality validation studies. Therefore, the need for good quality, well validated decision support tools remains unmet. Even though Ductal Carcinoma in Situ (DCIS) can potentially be an invasive breast cancer (IBC) precursor, most DCIS lesions never will progress to IBC if left untreated. Because we cannot predict yet which DCIS lesions will and which will not progress, almost all women with DCIS are treated by breast-conserving surgery +/− radiotherapy, or even mastectomy. As a consequence, many women with non-progressive DCIS carry the burden of intensive treatment without any benefit. Multiple decision support tools have been developed to optimize DCIS management, aiming to find the balance between over- and undertreatment. In this systematic review, we evaluated the quality and added value of such tools. A systematic literature search was performed in Medline(ovid), Embase(ovid), Scopus and TRIP. Following the PRISMA guidelines, publications were selected. The CHARMS (prediction models) or IPDAS (decision aids) checklist were used to evaluate the tools' methodological quality. Thirty-three publications describing four decision aids and six prediction models were included. The decision aids met at least 50% of the IPDAS criteria. However, most lacked tools to facilitate discussion of the information with healthcare providers. Five prediction models quantify the risk of an ipsilateral breast event after a primary DCIS, one estimates the risk of contralateral breast cancer, and none included active surveillance. Good quality and external validations were lacking for all prediction models. There remains an unmet clinical need for well-validated, good-quality DCIS risk prediction models and decision aids in which active surveillance is included as a management option for low-risk DCIS. [ABSTRACT FROM AUTHOR]

Recurrence and survival vary widely among patients who undergo curative-intent resection of colorectal liver metastases (CRLM). Prognostic models provide estimated probabilities of these outcomes and allow the effects of multiple potentially interacting variables to be adjusted and assessed simultaneously. Although many prognostic models based on clinicopathologic factors have been developed since the 1990s to predict survival after resection of CRLM, these models vary in their predictive performance when applied to contemporary cohorts. Rat sarcoma viral oncogene homolog (RAS) mutation status is routinely tested in patients with metastatic colorectal cancer to predict response to anti-epidermal growth factor therapy. In addition, mutations in RAS predict survival and recurrence in patients undergoing hepatectomy for CRLM. Several recent prognostic models have incorporated RAS mutation status as a surrogate of tumor biology and combined revised clinicopathologic variables to improve the prediction of recurrence and survival. This narrative review aims to evaluate the differences between contemporary prognostic models incorporating RAS mutation status and their clinical applicability in patients considered for curative-intent resection of CRLM. [ABSTRACT FROM AUTHOR]

Background: Although the global prevalence of colorectal cancer (CRC) is decreasing, there has been an increase in incidence among young-onset individuals, in whom the disease is associated with specific pathological characteristics, liver metastases, and a poor prognosis. Methods: From 2010 to 2016, 1874 young-onset patients with colorectal cancer liver metastases (CRLM) from the Surveillance, Epidemiology, and End Results (SEER) database were randomly allocated to training and validation cohorts. Multivariate Cox analysis was used to identify independent prognostic variables, and a nomogram was created to predict cancer-specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curve, C-index, area under the curve (AUC), and calibration curve analyses were used to determine nomogram accuracy and reliability. Results: Factors independently associated with young-onset CRLM CSS included primary tumor location, the degree of differentiation, histology, M stage, N stage, preoperative carcinoembryonic antigen level, and surgery (all p < 0.05). The C-indices of the CSS nomogram for the training and validation sets (compared to TNM stage) were 0.709 and 0.635, and 0.735 and 0.663, respectively. The AUC values for 1-, 3-, and 5-year OS were 0.707, 0.708, and 0.755 in the training cohort and 0.765, 0.735, and 0.737 in the validation cohort, respectively; therefore, the nomogram had high sensitivity, and was superior to TNM staging. The calibration curves for the training and validation sets were relatively consistent. In addition, a similar result was observed with OS. Conclusions: We developed a unique nomogram incorporating clinical and pathological characteristics to predict the survival of young-onset patients with CRLM. This may serve as an early warning system allowing doctors to devise more effective treatment regimens. [ABSTRACT FROM AUTHOR]

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Simple Summary: Epstein–Barr virus (EBV) is a very ubiquitous and persistent virus present in ~90% of the world population. The infection is generally asymptomatic during the lifetime, though it can cause lymphoid tumors and carcinomas in some subjects. The role of EBV in breast cancer (BC) has yet to be determined. In this review, we present the historical background and scientific evidence regarding the presence and potential role of EBV in this malignancy and we propose possible molecular mechanisms. Knowledge of EBV´s role in BC will contribute to establishing prevention strategies, early detection, and control of this highly aggressive and prevalent malignancy. Epstein–Barr virus (EBV) is an enveloped DNA virus that belongs to the gamma Herpesviridae family. The virus establishes a latent/lytic persistent infection, though it can be involved in cancer development in some subjects. Indeed, evidence supports an etiological role of EBV in undifferentiated nasopharyngeal carcinoma (NPC), a subset of gastric carcinomas and lymphomas. Additionally, EBV has been detected in breast carcinomas (BCs) although its role has not been established. In this review, we summarize epidemiological information regarding the presence of EBV in BC and we propose mechanistic models. However, additional epidemiological and experimental evidence is warranted to confirm these models. [ABSTRACT FROM AUTHOR]

Worldwide, the coronavirus 19 disease pandemic caused a worse chance of a timely diagnosis for cancer patients. We conducted a retrospective analysis of new diagnoses registered in the national pediatric oncology database, comparing the first lockdown period (March–May 2020) with the same period of 2015–2019. The total number of cases (0–19 years) dropped by 20.8% (from 441 between 2015 and 2019 to 349 in 2020). A major reduction was observed for adolescents (15–19 years) (−32.9%) and for adolescents with solid tumors (−56.4%, p = 0.03). Our data suggest that the enforced lockdown reduced the possibility for these already vulnerable patients to access the referral centers. [ABSTRACT FROM AUTHOR]

Simple Summary: Emerging diseases (EIDs) represent a constant challenge in public health. With the recent emergence of new pathogens, some questions about the mechanisms and sites where they are generated have aroused interest. Natural environments could be the sites where pathogenic microorganisms find the conditions to generate new variants. It has been established that approximately 60.3% of EIDs are caused by potentially zoonotic pathogens, of which more than half are thought to have originated from wild individuals. In this aspect, carnivores can play an important role in the dynamics of various diseases, since there are species that are widely distributed, roam large areas, and can be carriers of a wide range of microorganisms, some of which are zoonotic. The results obtained in this work show that different species of wild carnivores can be carriers of atypical strains of pathogenic microorganisms, which shows that natural environments can represent important sites for the study of EIDs. Enterobacteriaceae are considered one the most important zoonotic pathogens. In this study, we analyzed the characteristics of E. coli and Salmonella spp. strains present in carnivores from Janos Biosphere Reserve, Mexico. These microorganisms had been isolated from a wide range of domestic and free-range animals, including wild carnivores. Fifty-five individuals were sampled, and the presence of Salmonella and E. coli was determined by bacteriological standard methods. Strains isolated were characterized by molecular methods and in vitro infection assays. Eight different species of carnivores were captured, including coyotes (Canis latrans), gray fox (Urocyon cinereoargenteus), desert foxes (Vulpes macrotis), striped skunks (Mephitis mephitis), hooded skunks (Mephitis macroura), lynxes (Lynx rufus), raccoons (Procyon lotor), and badgers (Taxidea taxus). Salmonella spp. and E. coli were isolated from four species of carnivores. Five Salmonella spp. strains were isolated, and their molecular characterization revealed in three of them the presence of fimbrial and virulence genes associated with cell invasion. In vitro evaluation of these strains showed their capability to invade human Hep2 cells. Sixty-one E. coli strains were isolated; different serotypes and phylogroups were observed from these strains. Additionally, the presence of virulence genes showed differently. [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein-negative (<20 ng/mL) hepatocellular carcinoma (AFP-NHCC) cannot be easily diagnosed in clinical practice, which may affect early treatment and prognosis. Furthermore, there are no reliable tools for the prediction of AFP-NHCC early recurrence that have been developed currently. The objective of this study was to identify the independent risk factors for AFP-NHCC and construct an individual prediction nomogram of early recurrence of these patients who underwent curative resection. Methods: A retrospective study of 199 patients with AFP-NHCC who had undergone curative resection and another 231 patients with AFP-positive HCC were included in case-controlled analyses. All AFP-NHCC patients were randomly divided into training and validation datasets at a ratio of 7:3. The univariate and multivariate Cox proportional hazards regression analyses were applied to identify the risk factors, based on which the predictive nomogram of early recurrence was constructed in the training dataset. The area under the curve (AUC), calibration curve, and decision curve was used to evaluate the predictive performance and discriminative ability of the nomogram, and the results were validated in the validation dataset. Results: Compared to AFP-positive patients, the AFP-negative group with lower values of laboratory parameters, lower tumor aggressiveness, and less malignant magnetic resonance (MR) imaging features. AST (HR = 2.200, p = 0.009), tumor capsule (HR = 0.392, p = 0.017), rim enhancement (HR = 2.825, p = 0.002) and TTPVI (HR = 5.511, p < 0.001) were independent predictors for early recurrence of AFP-NHCC patients. The nomogram integrated these independent predictors and achieved better predictive performance with AUCs of 0.89 and 0.85 in the training and validation datasets, respectively. The calibration curve and decision curve analysis both demonstrated better predictive efficacy and discriminative ability of the nomogram. Conclusions: The nomogram based on the multivariable Cox proportional hazards regression analysis presented accurate individual prediction for early recurrence of AFP-NHCC patients after surgery. This nomogram could assist physicians in personalized treatment decision-making for patients with AFP-NHCC. [ABSTRACT FROM AUTHOR]

A healthy, immunocompetent South Asian man in his mid-20s, with a medical history of gastric ulcer, presented to Accident & Emergency with pleuritic chest pain, shortness of breath, fever, night sweats, weight loss, dry cough and asymptomatic iron deficiency anaemia. Following his initial assessment and investigations (chest X-ray, CT and blood tests), a diagnosis of miliary tuberculosis (TB) was made and empirical antimicrobial treatment started. However, subsequent microbiological testing, including urine, blood, induced sputum and lymph node sampling, was negative. Being interpreted as non-diagnostic, the antimicrobial therapy was continued. Following a clinical deterioration while on treatment, the patient’s case was re-evaluated and further investigations, including a repeat CT and a liver biopsy, confirmed a diagnosis of stage IV (T1aN3bM1) gastric carcinoma. Our case highlights the diagnostic challenges in differentiating metastatic cancer from miliary TB. We also focus on possible cognitive biases that may have influenced the initial management decisions. [ABSTRACT FROM AUTHOR]

Background: Due to the lack of clinical trials on the efficacy of chemotherapy in older patients, an optimal treatment strategy has not been developed. We investigated whether adjuvant chemotherapy could improve the survival of older patients with breast cancer in Japan. Methods: We retrospectively analyzed data of patients with breast cancer aged ≥ 70 years who underwent breast cancer surgery in eight hospitals between 2008 and 2013. Clinical treatment and follow-up data were obtained from the patients' medical electric records. Results: A total of 1095 patients were enrolled, of which 905 were included in the initial non-matched analysis. The median age and follow-up period were 75 (range 70–93) and 6.3 years, respectively. Of these patients, 127 (14%) received adjuvant chemotherapy (Chemo group) while the remaining 778 (86%) did not (Control group). The Chemo group was younger (mean age in years 73 vs 76; P < 0.0001), had a larger pathological tumor size (mean mm 25.9 vs 19.9; P < 0.0001), and more metastatic axillary lymph nodes (mean numbers 2.7 vs 0.7; P < 0.0001) than the Control group. The disease-free survival (DFS) and overall survival (OS) did not differ significantly between the two groups (P = 0.783 and P = 0.558). After matched analyses, DFS was found to be significantly prolonged with adjuvant chemotherapy (P = 0.037); however, OS difference in the matched cohort was not statistically significant (P = 0.333). Conclusion: The results showed that adjuvant chemotherapy was associated with a reduced risk of recurrence, but survival benefits were limited. [ABSTRACT FROM AUTHOR]

Malnutrition has a multifactorial origin and can be caused by cancer. This study determined the consensus of a panel of experts on the nutritional approach for cancer patients in Spain using a multidisciplinary approach. Using the Delphi methodology, a 74-question questionnaire was prepared and sent to 46 experts. The areas of knowledge addressed were the nutritional status of the cancer patient, nutritional screening, nutritional therapy, patient referral, and multidisciplinary care. A total of 91.7% of the experts agreed with the questions posed on nutritional status, 60.0% with those on nutritional screening, 76.7% with those on nutritional therapy, and the entire panel of experts agreed with the questions posed on patient referral and multidisciplinary care. The experts agreed upon a high prevalence of malnutrition among cancer patients in Spain. Unlike medical and radiation oncologists, medical nutrition specialists believe that body composition assessment should not be carried out in all types of cancer patients during nutritional screening and that interventions can be conducted outside the oncology clinic. In general, it is recommended that nursing staff routinely perform nutritional screening before starting cancer treatment. It is necessary to develop a multidisciplinary action protocol that includes nutritional and/or sarcopenia screening. [ABSTRACT FROM AUTHOR]