Relazione tra Ossitocina ed attaccamento romantico

E’ noto da tempo che l’ossitocina gioca un ruolo chiave durante il parto, l’allattamento e le corrispondenti attività nell’ipotalamo, adenoipofisi e sistema nervoso autonomo. Negli ultimi anni, a queste funzioni “classiche”, si sono aggiunti numerosi dati che hanno evidenziato un suo spettro di azioni più ampie che riguardano principalmente la modulazione del cosiddetto comportamento sociale. In particolare, sembra che l’ossitocina sia uno dei mediatori principali dei meccanismi neurobiologici che sottendono ogni tipologia di attaccamento, da quello materno-infantile a quello tra due partner adulti. Obiettivi: Dato che l’attaccamento romantico è uno dei prototipi delle relazioni sociali umane, scopo del presente studio è stato quello di valutare le possibili relazioni tra i livelli plasmatici di ossitocina e l’attaccamento romantico in un gruppo di soggetti sani. Soggetti e Metodi: Sono stati inseriti nello studio quarantacinque soggetti fisicamente sani e con anamnesi negativa per disturbi psichiatrici, di cui dodici di sesso maschile e trentatré di sesso femminile, di età compresa tra i 31.5 +/- 6.2 anni, selezionati tra gli specializzandi della Clinica Psichiatrica dell’ospedale S.Chiara di Pisa. Tali soggetti hanno compilato il questionario “Experiences in Close Relationships” (ECR), per valutare l’attaccamento romantico. L’ECR permette di classificare ciascun partecipante secondo uno dei quattro stili di attaccamento romantico identificati, vale a dire “preoccupato”, “timoroso”, “distanziante” o “sicuro”. Ai soggetti sono stati prelevati 20 cc di sangue, da cui si è ottenuto il plasma trattato con aprotinina e conservato a –70°C. Per l’estrazione del peptide ogni campione è stato acidificato con eguale quantità di soluzione A (1% acido trifluoracetico in H2O ) e poi centrifugato. Il sopranatante ottenuto è stato poi caricato su colonna cromatografica C18, al fine di ottenere un eluato contenente il peptide. Quest’ultimo è stato poi sottoposto a dosaggio radioimmunologico (RIA). Risultati: I livelli plasmatici di ossitocina ottenuti erano compresi in un intervallo tra 0.13 e 4.59 pg/ml, senza differenze legate al sesso o tra soggetti che avevano o non avevano una relazione affettiva. E’ stata osservata una correlazione significativa e positiva tra la scala “ansietà” dell’ ECR e i livelli plasmatici di ossitocina (r = 0.30, p = 0.045). Per quanto riguarda gli stili di attaccamento individuati, è stata osservata la tendenza a maggiori concentrazioni di ossitocina nel plasma dei soggetti “preoccupati”. Conclusione: In accordo con la maggior parte dei dati attualmente disponibili, è possibile avanzare l’ipotesi che la relazione positiva tra i livelli di ossitocina e la scala “ansietà” dell’ ECR possa rappresentare un meccanismo compensatorio per favorire l’attaccamento verso un partner, ossia un estraneo che istintivamente genera timore e paura. L’ossitocina, quindi, modulando l’ansia e riducendola, promuoverebbe l’accettazione da parte dell’ individuo del rischio implicito nei legami sociali e, come tale, può essere considerata un elemento essenziale nell’assicurare il piacere ed i benefici insiti nell’incontro degli altri

Dermoscopic and reflectance confocal microscopy features of two cases of vulvar basal cell carcinoma

Basal cell carcinoma (BCC) is the most common malignant skin cancer. Its genital localization is rare, and the diagnosis in this site could be challenging. Here, we report two patients with vulvar BCC and describe their clinical, dermoscopic and in vivo and ex vivo reflectance confocal microscopic (RCM) features. Dermoscopy and RCM can be useful tools for helping the clinical diagnosis of vulvar BCC and for identifying the correct surgical margins

Deregulation of Ion Channel and Transporter Encoding Genes in Pediatric Gliomas

Brain tumors, including the majority gliomas, are the leading cause of cancer-related death in children. World Health Organization has divided pediatric brain tumors into different grades and, based upon cDNA microarray data identifying gene expression profiles (GEPs), it has become evident in the last decade that the various grades involve different types of genetic alterations. However, it is not known whether ion channel and transporter genes, intimately involved in brain functioning, are associated with such GEPs. We determined the GEPs in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures. The correspondence between the two types of samples was statistically significant. We then performed bioinformatic analyses on those samples (a total of nine) which corresponded to tumors of glial origin, either tissues or cell cultures, depending on the best “RNA integrity number.” We used R software to evaluate the genes which were differentially expressed (DE) in gliomas compared with normal brain. Applying a p-value below 0.01 and fold change ≥4, led to identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport. We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results. From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters

Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment

Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity

Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An exploratory analysis

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their associ-ation with clinical outcome.A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits.A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk.Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger pro-spective studies, it would identify a new class of skeletal-related irAEs

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

Биологическое и клиническое действие абиратерона на антирезорбтивную и анаболическую активность микроокружения костной ткани

Применение абиратерона ацетата (АА) сопровождается не только значимым увеличением выживаемости пациентов с метастатическим кастрационно-резистентным раком предстательной железы (мКРРПЖ), но также отдалением времени до развития рентгенологического прогрессирования заболевания. Эти преимущества относительно костных метастатических очагов могут быть связаны с непосредственным воздействием на метастатические клетки рака предстательной железы в костях или со специфическими механизмами, направленными на костное микроокружение. Чтобы проверить эти гипотезы, мы прове- ли исследование in vitro, направленное на оценку потенциального действия AA на первичные остеокласты (ОКЛ) / остеобласты (ОБЛ); in vivo оценивали изменения уровней маркеров костного метаболизма, С-концевых телопептидов коллагена 1-го типа (CTX, маркер костной резорбции) и щелочной фосфатазы (ЩФ) у 49 пациентов с мКРРПЖ, получавших AA.Наши результаты показали, что AA оказывает статистически значимое ингибирующее действие на дифференцировку и активность ОКЛ, уменьшая экспрессию ОКЛ-маркерных генов TRAP (тартратрезистентная кислая фосфатаза), образование катепсина К и матриксной металлопротеиназы-9. Кроме того, AA способствовал дифференцировке ОБЛ и отложению костной матрицы, увеличивая экспрессию специфичных для ОБЛ генов RUNX2 (фактор транскрипции-2, содержащий домен Runt), образование ЩФ и остеокальцина. Также мы наблюдали in vivo значимое снижение уровня CTX в сыворотке и повышение уровня ЩФ у пациентов, получавших AA.Эти данные позволяют предполагать новый биологический механизм действия AA, состоящий в прямом анаболическом и антирезорбтивном влиянии на костную ткань.Применение абиратерона ацетата (АА) сопровождается не только значимым увеличением выживаемости пациентов с метастатическим кастрационно-резистентным раком предстательной железы (мКРРПЖ), но также отдалением времени до развития рентгенологического прогрессирования заболевания. Эти преимущества относительно костных метастатических очагов могут быть связаны с непосредственным воздействием на метастатические клетки рака предстательной железы в костях или со специфическими механизмами, направленными на костное микроокружение. Чтобы проверить эти гипотезы, мы провели исследование in vitro, направленное на оценку потенциального действия AA на первичные остеокласты (ОКЛ) / остеобласты (ОБЛ); in vivo оценивали изменения уровней маркеров костного метаболизма, С-концевых телопептидов коллагена 1-го типа (CTX, маркер костной резорбции) и щелочной фосфатазы (ЩФ) у 49 пациентов с мКРРПЖ, получавших AA.Наши результаты показали, что AA оказывает статистически значимое ингибирующее действие на дифференцировку и активность ОКЛ, уменьшая экспрессию ОКЛ-маркерных генов TRAP (тартратрезистентная кислая фосфатаза), образование катепсина К и матриксной металлопротеиназы-9. Кроме того, AA способствовал дифференцировке ОБЛ и отложению костной матрицы, увеличивая экспрессию специфичных для ОБЛ генов RUNX2 (фактор транскрипции-2, содержащий домен Runt), образование ЩФ и остеокальцина. Также мы наблюдали in vivo значимое снижение уровня CTX в сыворотке и повышение уровня ЩФ у пациентов, получавших AA.Эти данные позволяют предполагать новый биологический механизм действия AA, состоящий в прямом анаболическом и антирезорбтивном влиянии на костную ткань

Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

We analyzed data from 738 HER2\u2010positive metastatic breast cancer (mbc) patients treated with pertuzumab\u2010based regimens and/or T\u2010DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression free survival at first\u2010line (mPFS1) was 12 months. Pertuzumab as first\u2010line conferred longer mPFS1 compared to other first\u2010line treatments (16 vs 9 months, p=0.0001), regardless of IHC subtype. Median PFS in second\u2010line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T\u2010DM1 compared to other agents (7 vs 6 months, p=0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs) (p=0.17), while a trend emerged for tumors with one HR (p=0.05). Conversely, PFS2 gain was significant in HRs\u2010negative tumors (p=0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T\u2010DM1 in second\u2010line following pertuzumab were significantly lower compared to pertuzumab\u2010na\uefve patients(p=0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p=0.02 and p=0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment\u2010related outcomes of HER2\u2010positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor (ER) pathways in HER2\u2010positive (mbc) patients

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide