Liver Resection vs Nonsurgical Treatments for Patients With Early Multinodular Hepatocellular Carcinoma.

Importance: The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. Objective: To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. Design, Setting, and Participants: This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. Interventions: LR, PRFA, or TACE. Main Outcomes and Measures: Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. Results: A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. Conclusions and Relevance: For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Laparoscopic versus open parenchymal sparing liver resections for high tumour burden colorectal liver metastases: a propensity score matched analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM. METHODS: Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors. RESULTS: 277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR). CONCLUSION: Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach.

Colorectal metastases with intrabiliary growth: incidence, treatment, and outcomes.

Intrabiliary growth (IG) is an unusual modality for colorectal metastases to spread. Relatively little is known about this condition because large series are lacking. The aim of the study was to compare the surgical and oncological outcomes of patients with or without IG. From 01/2010 to 12/2020, 999 patients underwent hepatectomy for colorectal metastases. Clinicopathological variables were retrospectively analyzed from a prospective-collected database of patients with or without IG. A propensity score matched (PSM) analysis to compare OS and DFS was performed. At first hepatectomy, 29 patients (2.9%) had IG: 7 isolated IG and 22 mixed-type (mass-forming lesion with IG). 4 patients presented IG at repeat hepatectomy for recurrence, of whom 3 had no biliary invasion at initial surgery. IG resulted to be more common in older patients (median age 70 in IG vs 60 years of no-IG, p = 0.004). Mean time from colorectal tumor was longer in IG (20.4 months) than no-IG (12.9 months), p = 0.038. Major hepatectomies (55.2% IG vs 29.7% no-IG, p = 0.003) and anatomic resections (89.7% vs 58.2%, p = 0.001) were more frequently required to treat IG. In 5 (17%) of IG, a resection of main bile duct was performed. Overall postoperative mortality and complications were similar in the two groups, while bile leak was 17.2% IG vs 5.6% no-IG (p = 0.024). Median margin width was comparable in IG (1.4 mm) and no-IG (2 mm). Five-year overall survival (IG 45.9% vs no-IG 44.5%) and Disease-Free Survival (IG 35.9% vs no-IG 36.6%) were similar in the two groups. According to PSM, 145 patients with no-IG were compared to 29 of IG group. After PSM, OS and DFS did not show any statistically significant difference. IG has similar oncological outcomes of resected colorectal metastases without IG, although it affects surgical management.

Laparoscopic Liver Tunnel for Tumors at the Hepatocaval Confluence.

BACKGROUND: Tumors at the hepatocaval confluence can be treated with parenchyma-sparing surgery, also with minimally invasive approach.1,2 The "Liver Tunnel" was described for tumors involving the paracaval portion of Sg1 in contact or infiltrating the middle hepatic vein (MHV).3 A "Liver Tunnel" with laparoscopic approach is proposed. METHODS: A 48-year-old woman was referred for three synchronous colorectal liver metastases in the paracaval portion of Sg1 in contact with the inferior vena cava and the MHV, in Sg8 ventral and in Sg6, after an urgent left laparoscopic hemicolectomy for an obstructing carcinoma. A laparoscopic Sg1 resection extended to Sg8 ventral were planned after neoadjuvant chemotherapy. Estimated future liver remnant (FLR) was 75% (840 ml) of healthy liver (Fig. 1). In case of right hepatectomy extended to Sg1, estimated FLR was 25% (280 ml) of healthy liver. Fig. 1 3D reconstruction and intraoperative images of Liver Tunnel (A) and Sg6 resection (B). Total liver volume: 1110 ml. Total resected liver volume 270 ml: Liver Tunnel 93 ml; Sg6 177 ml. Liver volumes were measured with HA3D™ technology with Medics3D software (Medics3D, Turin, Italy) RESULTS: Pneumoperitoneum is established, and four operative ports are placed. Sg1 is approached from the left, dividing the Glissonean pedicles and short hepatic veins. MHV is approached cranio-caudally from the dorsal side. The resection continues on the ventral side, according to our "Ultrasound Liver Map technique" with a cranio-caudal approach to the MHV.4 Sg8 ventral pedicles are divided and the resection completed with aid of indocyanine green negative staining. A Sg6 resection is then performed. Operative time was 480 min. Blood loss was 100 ml. The postoperative course was uneventful, and the patient was discharged on fourth postoperative day. The two parenchyma-sparing resections saved an estimated volume of 75% (840 ml) of healthy liver (Fig. 1). The estimated remnant liver volume after a right hepatectomy extended to Sg1 would have been only 25%. CONCLUSIONS: Tumors at the hepatocaval confluence involving Sg1 can be removed with the "Liver Tunnel," which can be performed with minimally invasive approach. The "Laparoscopic Liver Tunnel" pushes further the limit of minimally invasive parenchyma-sparing surgery for ill-located tumors with complex vascular relationship.

Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis.

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.

Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis.

Objective: Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years. Methods: The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. Results: After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Conclusion: Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.

Real-world ANASTASE study of atezolizumab+nab-paclitaxel as first-line treatment of PD-L1-positive metastatic triple-negative breast cancer.

The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, 'real-world' data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program. A retrospective analysis was conducted in 29 Italian oncology centers among patients who completed at least one cycle of treatment. Data from 52 patients were gathered. Among them, 21.1% presented de novo stage IV; 78.8% previously received (neo)adjuvant treatment; 55.8% patients had only one site of metastasis; median number of treatment cycles was five (IQR: 3-8); objective response rate was 42.3% (95% CI: 28.9-55.7%). The median time-to-treatment discontinuation was 5 months (95% CI: 2.8-7.1); clinical benefit at 12 months was 45.8%. The median duration of response was 12.7 months (95% CI: 4.1-21.4). At a median follow-up of 20 months, the median progression-free survival was 6.3 months (95% CI: 3.9-8.7) and the median time to next treatment or death was 8.1 months (95% CI: 5.5-10.7). At 12 months and 24 months, the overall survival rates were 66.3% and 49.1%, respectively. The most common immune-related adverse events included rash (23.1%), hepatitis (11.5%), thyroiditis (11.5%) and pneumonia (9.6%). Within the ANASTASE study, patients with PD-L1-positive mTNBC treated with first-line atezolizumab plus nab-paclitaxel achieved PFS and ORR similar to those reported in the IMpassion130 study, with no unexpected adverse events.

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study.

AIMS: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. METHODS: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. RESULTS: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and,  of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. CONCLUSIONS: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged.

Inverse probability of treatment weighting analysis of laparoscopic versus open Sg4b-5 bi-segmentectomy in patients with gallbladder cancer.

Sg4b-5 anatomical bi-segmentectomy with regional lymphadenectomy (Sg4b5) is a surgical option for gallbladder cancer (GBC) treatment. The laparoscopic approach to this challenging operation is still controversial. Aim of this study was to compare short- and long-term outcomes of laparoscopic versus open Sg4b5 in a single institution series of patients. All consecutive patients who underwent Sg4b5 for GBC from January 2000 to September 2021 were retrospectively reviewed. Inverse probability of treatment weighting (IPTW) analysis was performed. 75 patients were analyzed, 18 in the laparoscopic and 57 in the open group. After IPTW, laparoscopic approach was associated with a significantly decreased median intraoperative blood loss (100 vs 237.09 ml, p = 0.001), shorter median length of hospital stay (4 vs 8 days, p = < 0.001) and a higher median number of harvested nodes (9 vs 7, p = 0.026). Operation time was shorter in the open group (355 vs 259 min, p < 0.001). No significant differences were found regarding clear resection margins, overall and major (Clavien-Dindo ≥ 3) morbidity, bile leakage rate, 90 days post-operative mortality, overall and disease-free survival. Laparoscopic Sg4b-5 anatomical bi-segmentectomy and regional lymphadenectomy is feasible and safe with long term outcome comparable to open approach at least in early stages. Laparoscopic approach confirms its well-known short-term benefits with less intraoperative bleeding and shorter length of stay. Moreover, it might allow a better lymphadenectomy.

Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia.

Several studies have shown that downregulation of GALNT2 (Polypeptide N-Acetylgalactosaminyltransferase 2), encoding polypeptide N-acetylgalactosaminyltransferase 2, decreases high-density lipoprotein cholesterol (HDL-C) and increases triglycerides levels by glycosylating key enzymes of lipid metabolism, such as angiopoietin like 3, apolipoprotein C-III, and phospholipid transfer protein. GALNT2 is also a positive modulator of insulin signaling and action, associated with in vivo insulin sensitivity and during adipogenesis strongly upregulates adiponectin. Thus, the hypothesis that GALNT2 affects HDL-C and triglycerides levels also through insulin sensitivity and/or circulating adiponectin, is tested. In 881 normoglycemic individuals the G allele of rs4846914 SNP at the GALNT2 locus, known to associate with GALNT2 downregulation, is associated with low HDL-C and high values of triglycerides, triglycerides/HDL-C ratio, and theHomeostatic Model Assessment of insulin resistance HOMAIR (p-values = 0.01, 0.027, 0.002, and 0.016, respectively). Conversely, no association is observed with serum adiponectin levels (p = 0.091). Importantly, HOMAIR significantly mediates a proportion of the genetic association with HDL-C (21%, 95% CI: 7-35%, p = 0.004) and triglyceride levels (32%, 95% CI: 4-59%, p = 0.023). The results are compatible with the hypothesis that, besides the effect on key lipid metabolism enzymes, GALNT2 alters HDL-C and triglyceride levels also indirectly through a positive effect on insulin sensitivity.

Artificial Intelligence in Brain Tumor Imaging: A Step toward Personalized Medicine.

The application of artificial intelligence (AI) is accelerating the paradigm shift towards patient-tailored brain tumor management, achieving optimal onco-functional balance for each individual. AI-based models can positively impact different stages of the diagnostic and therapeutic process. Although the histological investigation will remain difficult to replace, in the near future the radiomic approach will allow a complementary, repeatable and non-invasive characterization of the lesion, assisting oncologists and neurosurgeons in selecting the best therapeutic option and the correct molecular target in chemotherapy. AI-driven tools are already playing an important role in surgical planning, delimiting the extent of the lesion (segmentation) and its relationships with the brain structures, thus allowing precision brain surgery as radical as reasonably acceptable to preserve the quality of life. Finally, AI-assisted models allow the prediction of complications, recurrences and therapeutic response, suggesting the most appropriate follow-up. Looking to the future, AI-powered models promise to integrate biochemical and clinical data to stratify risk and direct patients to personalized screening protocols.

CDK4/6 Inhibitors Overcome Endocrine ESR1 Mutation-Related Resistance in Metastatic Breast Cancer Patients.

ESR1 mutations contribute to endocrine resistance and occur in a high percentage of hormone-receptor-positive (HR+) metastatic breast cancer (mBC) cases. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) changed the treatment landscape of HR+ mBC, as they are able to overcome estrogen resistance. The present retrospective study investigates the clinical benefit of CDK4/6i in ESR1 mutant HR+ mBC patients treated with a CDK4/6i as first- or second-line therapy. Plasma was collected at baseline prior to CDK4/6i plus hormone therapy as a first- or second-line treatment. Circulating free DNA (cfDNA) was extracted from plasma, and ESR1 mutation analysis was performed on a ddPCR. Statistical analyses were performed to investigate the predictive power of ESR1 mutations and any association with clinical factors. A total of 42 patients with mBC treated with CDK4/6i plus endocrine therapy as first- (n = 35) or second-line (n = 7) were enrolled. Twenty-eight patients received hormonal therapy (AI or tamoxifen) in the adjuvant setting. ESR1 mutation status in blood was associated with shorter median disease-free survival (DFS) (30 vs. 110 months; p = 0.006). Multivariate analysis confirmed ESR1 mutations as independent factors of resistance in adjuvant hormone therapy. On the contrary, no difference in progression-free survival (PFS) was observed in the presence or absence of an ESR1 mutation in patients treated with CDK4/6i as first-line treatment (p = 0.29). No statistically significant correlation between the best response to CDK4/6i and ESR1 mutation was found (p = 0.46). This study indicates that the ESR1 mutation detected in cfDNA is an independent predictive factor of clinical recurrence in the adjuvant setting and that CDK4/6i can overcome ESR1-dependent resistance.

Evaluation of inherited germline mutations in cancer susceptibility genes among pancreatic cancer patients: a single-center study.

BACKGROUND: Germline mutations in cancer susceptibility genes were identified in pancreatic cancer (PanC) patients with a sporadic disease and in those unselected for family cancer history. METHODS: With the aim to determine the prevalence of germline predisposition genes mutations in PanC, and to evaluate whether they were associated with the presence of PanC, we profiled a custom AmpliSeq panel of 27 cancer susceptibility genes in 47 PanC patients and 51 control subjects by using the Ion Torrent PGM system. RESULTS: Multigene panel testing identified a total of 31 variants in 27 PanC (57.4%), including variants with pathogenic/likely pathogenic effect, those of uncertain significance, and variants whose clinical significance remains currently undefined. Five patients carried more than one variant in the same gene or in different genes. Eight patients (17.0%) had at least one pathogenic/likely pathogenic variant in four main genes: CFTR (10.6%), BRCA2 (8.5%), ATM and CHEK2 (2.1%). Pathogenic/likely pathogenic mutation were identified in patients with positive PanC family history (20%) or in patients without first-degree relatives affected by PanC (13.6%). All the BRCA2 mutation carriers were unselected PanC patients. The presence of mutations in BRCA2 was significantly associated with an increased occurrence of PanC and with positive family history for endometrial cancer (p = 0.018). CONCLUSIONS: This study confirmed the potential remarkable contribution of BRCA2 in assessing the presence of PanC. Overall our findings supported the recommendation of offering the germline testing to all the PanC patients with the intent to reduce the number of underdiagnosed carriers of mutations in predisposition genes, and not to preclude their relatives from the opportunity to benefit from surveillance programs.

Cultural adaptation and validation of the Brazilian Portuguese version of the PROactive Physical Activity in COPD-clinical visit instrument for individuals with COPD / Adaptação cultural e validação da versão brasileira do instrumento PROactive Physical Activity in COPD-clinical visit para indivíduos com DPOC

ABSTRACT Objective: To adapt the PROactive Physical Activity in COPD-clinical visit (C-PPAC) instrument to the cultural setting in Brazil and to determine the criterion validity, test-retest reliability agreement, and internal consistency of this version. Methods: A protocol for cultural adaptation and validation was provided by the authors of the original instrument and, together with another guideline, was applied in a Portuguese-language version developed by a partner research group from Portugal. The adapted Brazilian Portuguese version was then cross-sectionally administered twice within a seven-day interval to 30 individuals with COPD (57% were men; mean age was 69 ± 6 years; and mean FEV1 was 53 ± 18% of predicted) to evaluate internal consistency and test-retest reliability. Participants also completed the International Physical Activity Questionnaire (IPAQ), the modified Medical Research Council scale, the COPD Assessment Test, and Saint George's Respiratory Questionnaire to evaluate criterion validity. Results: The C-PPAC instrument showed good internal consistency and excellent test-retest reliability: "amount" domain = 0.87 (95% CI, 0.73-0.94) and "difficulty" domain = 0.90 (95% CI, 0.76-0.96). Bland & Altman plots, together with high Lin's concordance correlation coefficients, reinforced that agreement. Criterion validity showed moderate-to-strong correlations of the C-PPAC with all of the other instruments evaluated, especially with the IPAQ (rho = −0.63). Conclusions: The Brazilian Portuguese version of the C-PPAC is a reliable and valid instrument for evaluating the experience of Brazilian individuals with COPD with their physical activity in daily life.

RESUMO Objetivo: Adaptar o instrumento PROactive Physical Activity in COPD - clinical visit (C-PPAC) ao contexto cultural brasileiro e determinar a validade de critério, concordância da confiabilidade teste-reteste e consistência interna dessa versão. Métodos: Um protocolo de adaptação cultural e validação foi fornecido pelos autores do instrumento original e, juntamente com outra diretriz, foi aplicado em uma versão em português desenvolvida por um grupo de pesquisa parceiro de Portugal. A versão brasileira adaptada foi então aplicada transversalmente duas vezes, com intervalo de sete dias, em 30 indivíduos com DPOC (57% de homens; média de idade de 69 ± 6 anos; e média do VEF1 de 53 ± 18% do previsto) para avaliação da consistência interna e da confiabilidade teste-reteste. Os participantes também responderam ao International Physical Activity Questionnaire (IPAQ), à escala modificada do Medical Research Council, ao COPD Assessment Test e ao Saint George's Respiratory Questionnaire para avaliação da validade de critério. Resultados: O instrumento C-PPAC apresentou boa consistência interna e excelente confiabilidade teste-reteste: domínio "quantidade" = 0,87 (IC95%: 0,73-0,94) e domínio "dificuldade" = 0,90 (IC95%: 0,76-0,96). As disposições gráficas de Bland-Altman, juntamente com os altos coeficientes de correlação de concordância de Lin, reforçaram essa concordância. A validade de critério mostrou correlações moderadas a fortes do instrumento C-PPAC com todos os outros instrumentos avaliados, principalmente com o IPAQ (rho = −0,63). Conclusões: A versão brasileira do instrumento C-PPAC é uma ferramenta confiável e válida para avaliar a experiência de indivíduos brasileiros com DPOC em relação à sua atividade física na vida diária.

Concomitant administration of proton pump inhibitors does not significantly affect clinical outcomes in metastatic breast cancer patients treated with ribociclib.

BACKGROUND: Gastric pH changes by proton-pump-inhibitors (PPIs) were found to affect progression-free survival (PFS) in metastatic breast cancer (mBC) patients treated with palbociclib. The current study was aimed at investigating whether the same effect could occur in patients treated with ribociclib. PATIENTS AND METHODS: Patients with hormone-positive/HER-2-negative mBC candidates for first-line treatment with ribociclib were enrolled in this retrospective-cohort study. Patients were classified as "no concomitant PPIs" or "concomitant PPIs"; PPI administration covered the entire or not less than 2/3 of treatment with ribociclib. All clinical interventions were made according to clinical practice. RESULTS: A total of 128 patients were consecutively enrolled in the study; 78 belonged to the "no concomitant PPIs" group and 50 to the "concomitant PPIs" group. One hundred and six patients were endocrine-sensitive and received ribociclib and letrozole, while 22 were endocrine-resistant and were treated with ribociclib and fulvestrant. The most prescribed PPI was lansoprazole. According to PFS, patients taking PPIs had a PFS almost superimposable to those assuming ribociclib and endocrine therapy alone (35.3 vs. 49.2 months, p = 0.594). No difference in PFS was observed in estrogen-sensitive or estrogen-resistant mBC in the presence or absence of concomitant PPI treatment (p = 0.852). No correlation with adverse events was found including grade>2 hematological toxicities. CONCLUSIONS: The present study supports the hypothesis that the concomitant use of PPIs does not compromise the efficacy of ribociclib in a real-life setting.

Development and testing of diagnostic algorithms to identify patients with acromegaly in Southern Italian claims databases.

Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist's visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4-9.8) to 13.8 (95% CI 11.7-16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1-8.6) to 16.4 (95% CI 15.3-17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1-84.6%) to 84.2% (95% CI 68.8-94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6-41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms.