First episode psychosis during the Covid-19 pandemic in Milan, Italy: Diagnostic outcomes at 1-year follow-up.

An influence of the Covid-19 pandemic on First Episode Psychosis (FEP) has been hypothesized. We previously reported an increase of FEP during the early stages of the pandemic in Milan, Italy. Here we report a 1-year follow-up of the same cohort and comparison with a FEP cohort from 2019. The higher proportion of non-chronic psychoses observed during the pandemic (58.62% in 2020 vs 43,75% in 2019) should be confirmed in larger cohorts over a longer follow-up period.

Do exist differences in kinematics and EMG of the hip and knee between male runners with and without patellofemoral pain in different running speeds?

OBJECTIVE: Patellofemoral pain (PFP) presents a higher prevalence in female runners, while PFP in male is somehow neglected. Moreover, the effects of progressive greater running speed have not been reported. This study investigates the influence of progressive greater running speed on lower limb tridimensional kinematics and muscle activation (EMG) in male runners with PFP while compared with controls. DESIGN: Cross-Sectional Design. METHODS: Thirteen runners with PFP and 18 controls ran in a treadmill under three different speeds: 9, 11, and 13 km/h. Principal component scores from kinematic data and EMG onset and amplitude were used to compare groups through the Mann-Whitney test at each running speed. RESULTS: Male PFP subjects presented increased hip internal rotation at 11 km/h and increased hip and knee internal at 13 km/h, as well as reduced knee adduction at all speeds. PFP subjects also ran with delayed and shorter vastus medialis oblique pre-activation compared with normal subjects. CONCLUSIONS: This study demonstrated that PFP increased knee and hip internal rotation at higher demand running, therefore, it is important to evaluate the transverse plane of the hip and knee biomechanics in male runners with PFP to optimize the rehabilitation and reconditioning method of these subjects.

Primary dental care treatment in primary Sjögren's syndrome: a possible role in improving salivary flow rate.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. METHODS: Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. RESULTS: At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p≥0.05). CONCLUSIONS: PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. CLINICALTRIALS: gov (Identifier: NCT03711214).

SARS-CoV-2 vaccine in patients with systemic sclerosis: impact of disease subtype and therapy.

OBJECTIVE: To analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) vaccination in patients with SSc. METHODS: This is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the second dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants. RESULTS: Patients and controls had comparable median ages [48(38.5-57) vs 48(38-57) years, P =0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly MMF (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, P < 0.001) and NAb positivity (53.8% vs 76.9%; P =0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both seroconvertion rates (SC) (P =0.958) and NAb positivity (P =0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC: 31.3% vs 90%, P < 0.001) and NAb(18.8% vs 85%, P < 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95% CI: 0.009, 0.034), P =0.002] and NAb positivity [OR = 0.047(95% CI: 0.007, 0.036), P =0.002]. No moderate/severe side-effects were observed. CONCLUSION: CoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04754698.

Human-SARS-CoV-2 interactome and human genetic diversity: TMPRSS2-rs2070788, associated with severe influenza, and its population genetics caveats in Native Americans.

For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population genetics and of sequencing data in the design of genetic association studies in different human populations: the high linkage disequilibrium (LD) between rs2070788 and rs383510 is Asian-specific. Leveraging on a combination of genotyping and sequencing data for Native Americans (neglected in genetic studies), we show that while their frequencies of the Asian tag-SNP rs2070788 is, surprisingly, the highest worldwide, it is not in LD with the eQTL rs383510, that therefore, should be directly genotyped in genetic association studies of SARS in populations with Native American ancestry.

Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial.

CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.

Impact of the first Covid-19 pandemic wave on first episode psychosis in Milan, italy.

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic appears to increase risk for mental illness, either directly due to inflammation caused by the virus or indirectly due to related psychosocial stress, resulting in the development of both anxious-depressive and psychotic symptoms. The purpose of the present study was to assess the frequency and characteristics of all patients with First Episodes Psychosis (FEP) without COVID-19 infection hospitalized in the first four months since lockdown in Milan. We recruited sixty-two patients hospitalized between March 8 to July 8, 2020 versus those first  hospitalized in the same period in 2019. The two subgroups were compared for sociodemographic variables and clinical characteristics of the episodes. Patients with FEP in 2020 were significantly older than patients with FEP in 2021, and presented with significantly less substances abuse. Interestingly, patients presenting with FEP in 2020 were significantly older than patients with FEP in 2019. These data are compatible with the greater vulnerability to stressful factors during the pandemic, as well as with the greater concern regarding a possible COVID-19 infection producing brain damage causing the FEP.

The genetic structure and adaptation of Andean highlanders and Amazonians are influenced by the interplay between geography and culture.

Western South America was one of the worldwide cradles of civilization. The well-known Inca Empire was the tip of the iceberg of an evolutionary process that started 11,000 to 14,000 years ago. Genetic data from 18 Peruvian populations reveal the following: 1) The between-population homogenization of the central southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes, and Amazonia accompanied cultural and socioeconomic interactions revealed by archeology. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower, and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia. 2) The genetic homogenization between the populations of the arid Andes is not only due to migrations during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the Wari Empire (600 to 1,000 years before present). 3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, a putative enhancer in HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, a noncoding gene related to cardiovascular function) and rs269868-C/Ser1067 in DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes and, in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T and B lymphocytes in viral-host interaction.

Discovery of an Aedes (Stegomyia) albopictus population and first records of Aedes (Stegomyia) aegypti in Canada.

A population of Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), a vector of chikungunya, dengue, yellow fever, and Zika and West Nile viruses, has been detected in Windsor, Ontario, Canada from 2016 onwards. Here, we describe its seasonal distribution, as well as the various aquatic habitats from which this species was collected and its larval co-habitation. We collected immatures from tires, treeholes, extruded polystyrene foam containers, discarded plastic cups, old recycling bins and oviposition traps. Aedes albopictus larvae were collected with Aedes japonicus (Theobald), Anopheles punctipennis (Say), Culex pipiens Linnaeus, Ochlerotatus hendersoni (Cockerell), Ochlerotatus triseriatus (Say) and Orthopodomyia signifera (Coquillett). Adult female and male specimens were collected from Biogents sentinel traps (Biogents AG, Regensburg, Germany), as well as Centers for Disease Control and Prevention miniature light traps (CDC, Atlanta, GA, U.S.A.), and also as they alighted on the investigators. Peak adult collections occurred in September during epidemiological week 37. We also collected Aedes (Stegomyia) aegypti (Linnaeus), a new record for Canada, in 2016 and from two new collection sites in 2017. The 2017 collections were 3.5 km north and 19.4 km south of the index site. The present study adds to the increasing number of studies reporting range expansions of these mosquito species.

Genetics of cognitive trajectory in Brazilians: 15 years of follow-up from the Bambuí-Epigen Cohort Study of Aging.

Age-related cognitive decline (ACD) is the gradual process of decreasing of cognitive function over age. Most genetic risk factors for ACD have been identified in European populations and there are no reports in admixed Latin American individuals. We performed admixture mapping, genome-wide association analysis (GWAS), and fine-mapping to examine genetic factors associated with 15-year cognitive trajectory in 1,407 Brazilian older adults, comprising 14,956 Mini-Mental State Examination measures. Participants were enrolled as part of the Bambuí-Epigen Cohort Study of Aging. Our admixture mapping analysis identified a genomic region (3p24.2) in which increased Native American ancestry was significantly associated with faster ACD. Fine-mapping of this region identified a single nucleotide polymorphism (SNP) rs142380904 (ß = -0.044, SE = 0.01, p = 7.5 × 10-5) associated with ACD. In addition, our GWAS identified 24 associated SNPs, most in genes previously reported to influence cognitive function. The top six associated SNPs accounted for 18.5% of the ACD variance in our data. Furthermore, our longitudinal study replicated previous GWAS hits for cognitive decline and Alzheimer's disease. Our 15-year longitudinal study identified both ancestry-specific and cosmopolitan genetic variants associated with ACD in Brazilians, highlighting the need for more trans-ancestry genomic studies, especially in underrepresented ethnic groups.

Mate choice strategies in a spatially-explicit model environment.

Decisions about the choice of a mate can greatly impact both individual fitness and selection processes. We developed a novel agent-based model to investigate two common mate choice rules that may be used by female gray treefrogs (Hyla versicolor). In this model environment, female agents using the minimum-threshold strategy found higher quality mates and traveled shorter distances on average, compared with female agents using the best-of-n strategy. Females using the minimum-threshold strategy, however, incur significant lost opportunity costs, depending on the male population quality average. The best-of-n strategy leads to significant female:female competition that limits their ability to find high quality mates. Thus, when the sex ratio is 0.8, best-of-5 and best-of-2 strategies yield mates of nearly identical quality. Although the distance traveled by females in the mating task varied depending on male spatial distribution in the environment, this did not interact with female choice for the best-of-n or minimum-threshold strategies. By incorporating empirical data from the frogs in this temporally- and spatially-explicit model, we thus show the emergence of novel interactions of common decision-making rules with realistic environmental variables.

Population genetics of immune-related multilocus copy number variation in Native Americans.

While multiallelic copy number variation (mCNV) loci are a major component of genomic variation, quantifying the individual copy number of a locus and defining genotypes is challenging. Few methods exist to study how mCNV genetic diversity is apportioned within and between populations (i.e. to define the population genetic structure of mCNV). These inferences are critical in populations with a small effective size, such as Amerindians, that may not fit the Hardy-Weinberg model due to inbreeding, assortative mating, population subdivision, natural selection or a combination of these evolutionary factors. We propose a likelihood-based method that simultaneously infers mCNV allele frequencies and the population structure parameter f, which quantifies the departure of homozygosity from the Hardy-Weinberg expectation. This method is implemented in the freely available software CNVice, which also infers individual genotypes using information from both the population and from trios, if available. We studied the population genetics of five immune-related mCNV loci associated with complex diseases (beta-defensins, CCL3L1/CCL4L1, FCGR3A, FCGR3B and FCGR2C) in 12 traditional Native American populations and found that the population structure parameters inferred for these mCNVs are comparable to but lower than those for single nucleotide polymorphisms studied in the same populations.

Adjuvant Hormonal Therapy in Women with Early-stage Breast Cancer.

For decades, adjuvant hormonal therapy has become the standard treatment of patients with estrogen receptor-positive breast cancer. Currently, the drugs available are GnRH agonists, selective estrogen receptor modulators, and aromatase inhibitors. The use of GnRH agonists represents a potentially reversible treatment that can restore ovarian function after chemotherapy. In premenopausal women, systemic therapy based on selective estrogen receptor modulators administration (e.g., tamoxifen) usually represents the standard adjuvant treatment. There are not sufficient data to recommend the routine addition of GnRH agonists to other endocrine therapies. In postmenopausal women, the disease-free survival was significantly prolonged in patients treated with aromatase inhibitor compared with those treated with tamoxifen, but the survival benefit was modest. Better results were obtained when the two drugs were administered sequentially. According to the ASCO guidelines, after 5 years of tamoxifen treatment, either tamoxifen or aromatase inhibitors therapy should be suggested for an additional 5 years. Unfortunately, most adverse events are consistent with estrogen deprivation and are common to all therapies, and the cumulative toxicity causes discontinuation and nonadherence to therapy in up to 50% of patients. Switching tamoxifen to an aromatase inhibitor may reduce adverse event incidence. Molecular-targeted therapy is useful in patients with advanced, relapsed or hormonal therapy-resistant tumors, usually as second- or third-line treatment. These drugs are usually added to aromatase inhibitors; however, currently, they have not yet been used in patients with early breast cancer.

Factors Affecting Survival in Patients with Lung Metastases from Colorectal Cancer. A Short Meta-analysis.

Liver and pulmonary metastases (PMs) are relatively common in patients with colorectal cancer. The majority of metastases are suitable for surgical resection, and the effectiveness of metastasectomy is usually assessed based on overall survival (OS). Metastasectomy provides a mean 5-year OS rate of approximately 50%, but the results are better in patients with liver metastases compared to those with PMs. Unfortunately, the presence of bilateral or multiple PMs represents a relative contraindication to surgical metastasectomy. Unresectable PMs can be safely treated with percutaneous radiofrequency ablation or radiotherapy, but the reported results vary widely. Several clinical prognostic factors affecting OS after metastasectomy have been reported, such as number of PMs, hilar or mediastinal lymph node involvement, disease-free interval, age and gender, resection margins, size of the metastases, neoadjuvant chemotherapy administration, and histological type of the primary cancer. The accurate evaluation of all clinical prognostic factors, circulating and immunohistochemical markers, and the study of gene mutational status will lead to a more accurate selection of patients scheduled to metastasectomy, with the aim of improving outcome.

Sentinel Node Biopsy in Early Breast Cancer.

The approach to the axilla is an evolving paradigm, and recognition of the complexity of breast cancer (BC) biology is changing treatment options. The sentinel lymph node biopsy (SLNB) technique is based on the excision and histological examination of the axillary lymph nodes(s), which is assumed to be the first one draining from the primary tumor. SLNB can accurately stage the axilla, and several trials have shown that there are no significant differences in local recurrence and overall survival between patients treated with or without axillary node dissection (ALND) after a negative SLNB. Surgical morbidity was significantly reduced in terms of rates of lymphedema and neuropathy, with reduced hospital stay and better quality of life after the SLNB procedure. ALND can safely be omitted in patients with ≥2 positive nodes who received conservative surgery and radiotherapy, while ALND is still recommended in clinically N1 BCs, in case of ≥3 positive nodes, and when the number of positive nodes would be crucial for the choice of chemotherapy. Micrometastatic disease can be safely managed with SLNB alone, and additional identification of micrometastases with immunohistochemistry does not affect disease-free survival or overall survival. An appropriate management of the axilla is crucial for the outcome of patients with early BC, and SLNB introduction into the clinical practice dramatically changed the surgical treatment, reducing morbidity without decreasing survival. A tailored approach should be suggested in each patient with BC, considering the biology of the tumor rather than nodal involvement.

Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer.

Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low-risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high-risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents.

Establishment of Culex (Melanoconion) erraticus (Diptera: Culicidae) in Southern Ontario, Canada.

Culex (Melanoconion) erraticus (Dyar and Knab) is now established in southern Ontario, Canada. This species was first discovered in 2002 during a province-wide adult mosquito surveillance program for West Nile virus. Using CO2-baited CDC miniature light traps, a few Cx. erraticus were collected from 2002 to 2011, but the total number increased during the 2012 and 2013 seasons. The number of Ontario Public Health Units with records for Cx. erraticus has also increased since 2002, demonstrating that the geographic distribution of this species is expanding northward. Cx. erraticus is a potential arboviral bridge vector for a number of pathogens and its establishment in Ontario should be considered a potential public health concern.

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

Short-term Survival of Patients with Lung Metastases from Colorectal and Non-colorectal Cancer Who Underwent Pulmonary Metastasectomy.

The lung is a common site of metastases, whose prevalence varies as a function of the primary tumor site, which is usually colorectal cancer (CRC), breast carcinoma, or genitourinary cancers, such as ovary, urinary bladder and renal cell carcinomas. The aim of the present study was to analyze whether the site of primitive tumor affects overall survival (OS) of patients with lung metastases (LMs) who underwent pulmonary metastasectomy. The data of 41 patients with surgically treated CRC (Group A=22 patients) and non-colorectal carcinomas (Group B=19 patients), who developed matachronous LMs and underwent pulmonary metastasectomy with curative intent, were analyzed. The origin of non-colorectal LMs was genitourinary cancer in nine and breast cancer in 10 patients. Overall, there were 22 men and 19 women, with a median age of 65 years (range=31-80); 18 patients had a solitary metastatic tumor, while 23 had two or more LMs. Twenty-nine patients underwent wedge resection, through thoracotomy or video-assisted thoracic surgery, while 12 underwent pulmonary lobectomy. Seventy-five LMs were resected with a 5-tear OS of 48.8%. No difference was found between elderly (≥65 year-old) and younger patients (p=0.26), and between those with solitary or multiple LMs (p=0.62) in terms of survival rate. The female patients had a worse OS (31.6% vs. 63.6%; odds ratio (OR)=3.79, 95% confidence interval (CI)=1.03-13.91, p=0.003) compared to males, independent of the origin of primary cancer. There was no difference in the cumulative survival rates (OR=1.65, 95%CI=0.48-5.69, p=0.42) between Groups and the log-rank test (p=0.75) was not significant. In conclusion, the main pathological characteristics of metastatic lesions and advanced age do not appear to be associated with a poor prognosis in patients with LMs, while the female gender is a negative prognostic factor. Thus, the primary tumor site should not be considered a major criterion in selecting patients for pulmonary metastasectomy.

Preoperative serum C-reactive protein and its prognostic significance in patients with stage III-IV colorectal cancer.

The molecular mechanism underlying the development of colorectal cancer (CRC) is not yet fully-understood, but there is evidence that inflammation plays a key role. Several circulating tumor and inflammatory markers can be useful for studying patients with CRC. It has been suggested that high serum levels of C-reactive protein (CRP) are associated with elevated risk of various malignancies and that CRP may affect survival of patients with CRC. We analyzed the relationship existing between the stage of the disease and baseline CRP serum levels in a group of 91 patients undergoing surgery for stage III (N=72, 79.1%) and IVa (N=19, 20.9%) CRC. There were 51 (56%) men and 40 (44%) women, with a median age of 66 years. Prior to surgery, all patients underwent quantitative serum CRP measurement. The overall 5-year survival was 37.1 ± 13.0 months. Patients with stage III disease and the sub-group with CRP<3 mg/l (N=43, 47.3%) had a longer survival (p<0.01) than patients with stage IVa and the sub-group with CRP ≥ 3 mg/l (N=48, 52.7%). No relationship between the age of the patients and CRP levels was found (R=-0.005, p=0.96), whilst there was a significant inverse relationship between survival and CRP level (R=-0.37, y=37.5343-0.5868x, p=0.0003). Using multivariate Cox model analysis (forward stepwise method), adjusted for age, CRP and CRC stage were independent parameters related to survival, with a relative risk of 3.5 (95% confidence interval=1.5-8.2) and 8.1 (95% confidence interval=3.0-21.3), respectively. In conclusion, CRP is a sensitive and easily detectable serum marker that can be useful in patients with CRC, allowing their better clinical stratification.