Cardiovascular Structural and Functional Parameters in Idiopathic Pulmonary Fibrosis at Disease Diagnosis.

INTRODUCTION: Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated. AIM: In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done. METHODS: We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD - endothelial function) and Pulse Wave Velocity (PWV-arterial stiffness) RESULTS: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF. CONCLUSIONS: Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects.

Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors.

BACKGROUND: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. METHODS: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. RESULTS: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). CONCLUSIONS: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments.

FOLFIRINOX or nab-paclitaxel plus gemcitabine in metastatic pancreatic adenocarcinoma: an observational study.

Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n = 43) or NabGem (n = 117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28 weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86 weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p < 0.0001). In the FFN → NabGem and NabGem → FFN groups, median overall survival was 51.2 and 71.6 weeks (HR: 0.69; p = 0.15). In patients receiving NabGem, second-line FFN, compared with FOLFOX/CAPOX or FOLFIRI, improved median progression-free survival 2 (25.6 vs 12.1 weeks; HR: 0.47; p = 0.0067) and median overall survival 2 (39.0 vs 19.14 weeks; HR: 0.49; p = 0.032). Conclusion: First-line FFN and NabGem promote similar clinical outcomes. Second-line FFN should be considered after NabGem.

The Male Reproductive System and Endocrine Disruptors.

The male reproductive system is exposed to a great number of chemical substances which can interfere with the normal hormonal milieu and reproductive function; these are called endocrine disruptors (EDs). Despite a growing number of studies evaluating the negative effects of EDs, their production is continuously growing although some of them have been prohibited. The prevalence of poor semen quality, hypospadias, cryptorchidism, and testicular cancer has increased in the last decades, and recently, it has been postulated that these could all be part of a unique syndrome called testicular dysgenesis syndrome. This syndrome could be related to exposure to a number of EDs which cause imbalances in the hormonal milieu and oestrogenic over-exposure during the foetal stage. The same EDs can also impair spermatogenesis in offspring and have epigenetic effects. Although studies on animal and in vitro models have raised concerns, data are conflicting. However, these studies must be considered as the basis for future research to promote male reproductive health.

Use of FOLFIRINOX or Nab-Paclitaxel Plus Gemcitabine for the Treatment of Locally Advanced Pancreatic Adenocarcinoma: A Single Institution Observational Study.

Patients with locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) do not present distant metastases but are not eligible for surgery upfront. Chemotherapy regimens, such as FOLFIRINOX (FFN) or nab-paclitaxel plus gemcitabine (GemNab) in combination with loco-regional treatments are generally used in this setting. However, the best treatment choice is unknown. We retrospectively analyzed the information of 225 patients with stage II-III PDAC treated at our institution between October 2011 and December 2020. A total of 94 patients with LA PDAC who are non-eligible for surgery upfront received neoadjuvant FFN or GemNab. Of the 67 patients receiving FFN, 28 (41.8%) underwent surgery after neoadjuvant therapy. Of the 27 patients treated with GemNab, 6 (22.2%) became eligible for resection. The median overall survival (OS) was 85.1 weeks and 54.3 weeks in the FFN and GemNab groups, respectively (HR = 0.54, p = 0.0109). The median OS was 189.7 weeks and 76.4 weeks in the resected and unresected cohorts, respectively (HR = 0.25, p < 0.0001). Neutropenia (37.3%), anemia (6.0%), and diarrhea (6.0%) in the FFN group and neutropenia (22.2%) and thrombocytopenia (18.5%) in the GemNab groups were the most frequent grade 3-4 side effects. Higher rates of thrombocytosis (p < 0.0001) and peripheral edema (p < 0.0001) were observed in the GemNab group. Our results suggest that the use of FFN is associated with more favorable clinical outcomes than GemNab for patients with LA PDAC. Future randomized and controlled clinical trials are needed to further elucidate the role of these regimens and loco-regional treatments in this setting.

Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor.

BACKGROUND AND AIMS: Continuous glucose monitoring improves glycemic control in diabetes. This study compared the accuracy of the Dexcom G5 Mobile (Dexcom, San Diego, CA) transcutaneous sensor (DG5) and the first version of Eversense (Senseonics,Inc., Germantown, MD) implantable sensor (EVS). METHODS AND RESULTS: Subjects with type 1 diabetes (T1D) and using EVS wore simultaneously DG5 for seven days. At day 3, patients were admitted to a clinical research center (CRC) to receive breakfast with delayed and increased insulin bolus to induce glucose excursions. At CRC, venous glucose was monitored every 15 min (or 5 min during hypoglycemia) for 6 h by YSI 2300 STAT PLUS™ glucose and lactate analyzer. At home patients were requested to perform 4 fingerstick glucose measurements per day. Eleven patients (9 males, age 47.4 ± 11.3 years, M±SD) were enrolled. During home-stay the median [25th-75th percentile] absolute relative difference (ARD) over all CGM-fingerstick matched-pairs was 11.64% [5.38-20.65]% for the DG5 and 10.75% [5.15-19.74]% for the EVS (p-value = 0.58). At CRC, considering all the CGM-YSI matched-pairs, the DG5 showed overall smaller median ARD than EVS, 7.91% [4.14-14.30]% vs 11.4% [5.04-18.54]% (p-value<0.001). Considering accuracy during blood glucose swings, DG5 performed better than EVS when glucose rate-of-change was -0.5 to -1.5 mg/dL/min, with median ARD of 7.34% [3.71-12.76]% vs 13.59% [4.53-20.78]% (p-value<0.001), and for rate-of-change < -1.5 mg/dl/min, with median ARD of 5.23% [2.09-15.29]% vs 12.73% [4.14-20.82]% (p-value = 0.02). CONCLUSIONS: DG5 was more accurate than EVS at CRC, especially when glucose decreased. No differences were found at home.

Performance of the Steno type 1 risk engine for cardiovascular disease prediction in Italian patients with type 1 diabetes.

BACKGROUND AND AIMS: Premature cardiovascular disease cause excess mortality in type 1 diabetes (T1D). The Steno T1D Risk Engine was developed and validated in northern European countries but its validity in other populations is unknown. We evaluated the performance of the Steno T1D Risk Engine in Italian patients with T1D. MATERIALS AND METHODS: We included patients with T1D with a baseline visit between July 2013 and April 2014, who were free of cardiovascular disease and had complete information to estimate risk. The estimated cardiovascular risk score was compared with the 5-year rate of cardiovascular events by means of logistic regression. RESULTS: Among 223 patients (mean age 43 ± 13 years, 34.5% male, mean duration of diabetes 22 ± 12 years) the mean estimated cardiovascular risk at 5 years was 5.9% (95% C.I. 5.2-6.5%). At baseline, high estimated risk discriminated the presence of asymptomatic atherosclerosis better than microangiopathy, and was not associated with markers of inflammation or endothelial activation. After a mean follow-up of 4.7 ± 0.5 years, only 3 cardiovascular events were observed and nonetheless the risk score was significantly associated with their incidence (OR 1.22; 95% C.I. 1.08-1.39, p = 0.001). However, the observed event rate was significantly lower than the estimated one (3 vs 13; 95% C.I. 12-14; p < 0.001). CONCLUSION: The Steno T1D Risk Score identified subjects with subclinical atherosclerosis and high cardiovascular risk in an Italian T1D population. However, the absolute risk was significantly overestimated. Further studies in larger population are needed to confirm these results.

Cross-Sex Hormone Treatment and Psychobiological Changes in Transsexual Persons: Two-Year Follow-Up Data.

CONTEXT: To date, there are few studies investigating the impact of body changes induced by cross-sex hormonal treatment (CHT) on psychobiological well-being in gender-dysphoric persons (GDs). OBJECTIVE: The objective of the study was to assess whether CHT-related body changes affect psychobiological well-being in GDs. METHODS: A consecutive series of 359 GDs was considered for a cross-sectional section of the study. In addition, 54 GDs were studied in a 2-year follow-up. A physical examination was performed, including body mass index, waist circumference, and hair distribution. We also evaluated breast development and testis volume in male to female subjects and clitoris length in female to male. Subjects were asked to complete several psychometric measures for the assessment of body uneasiness, GD, and psychopathology levels. The evaluation was repeated 2 years prospectively. RESULTS: The following results were found: 1) GDs undergoing CHT reported significantly lower subjective levels of GD, body uneasiness, and depressive symptoms as compared with those without; 2) CHT-induced body modifications were significantly associated with a better psychological adjustment; 3) during CHT, GDs reported a significant reduction of general psychopathology, depressive symptoms, and subjective GD, whereas social and legal indicators of GD showed a significant increase across time; and 4) among body changes induced by CHT, only breast development and increased body mass index had a significant impact on psychopathology reduction across time in male to female subjects and female to male subjects, respectively. CONCLUSIONS: The aforementioned results support the efficacy of CHT intervention in improving subjective perception of one's own body, which was partially associated with objective changes.

Carbon dioxide: Global warning for nephrologists.

The large prevalence of respiratory acid-base disorders overlapping metabolic acidosis in hemodialysis population should prompt nephrologists to deal with the partial pressure of carbon dioxide (pCO2) complying with the reduced bicarbonate concentration. What the most suitable formula to compute pCO2 is reviewed. Then, the neglected issue of CO2 content in the dialysis fluid is under the spotlight. In fact, a considerable amount of CO2 comes to patients' bloodstream every hemodialysis treatment and "acidosis by dialysate" may occur if lungs do not properly clear away this burden of CO2. Moreover, vascular access recirculation may be easy diagnosed by detecting CO2 in the arterial line of extracorporeal circuit if CO2-enriched blood from the filter reenters arterial needle.

The First Report of Bayés Syndrome in Hemodialysis Patient.

A chronic hemodialysis patient-known to have advanced interatrial block (IAB)-had reported symptoms suggesting arrhythmias, hence she underwent hemodialysis treatment while on the cardiac monitor. This allowed us to recognize the occurrence of paroxysmal atrial fibrillation and, in turn, disclose the first case of Bayés syndrome. Even though atrial fibrillation and IAB are very frequent in hemodialysis patients, Bayés syndrome, that comprehends both, has never been described, likely because the IAB is often overlooked and undiagnosed. This case could improve the awareness of IAB and of the Bayés syndrome in hemodialysis population.

Carbon Dioxide and Acetate-Free Biofiltration: A Relationship to be Investigated.

As the name reveals, acetate-free biofiltration (AFB) is featured by lack of acetate and this would seem to allow better hemodynamic stability. However, AFB also has a unique characteristic of carbon dioxide (CO2 )-free dialysate, whereas all other modern dialysis techniques imply an overload of CO2 from dialysate to the patient. This notwithstanding the role of CO2 in tolerance to dialysis treatment, both AFB and all other dialysis techniques seem not investigated in due depth. Specifically, the amount of CO2 coming back to the patient's bloodstream during AFB and bicarbonate dialysis (BD) is unknown. We measured partial pressure of CO2 (pCO2 ) in blood samples withdrawn from the venous line of the extracorporeal circuit during BD and subsequently during AFB in 22 stable chronic hemodialysis outpatients. The amount of CO2 coming back to the patient's bloodstream is higher in BD (59.1 ± 4.0 mmol/L) than in AFB (42.8 ± 4.5 mmol/L, P < 0.0001). Such difference exceeds 30%. Moreover, shifting from BD to AFB shows, notably for each patient, the reduction of pCO2 toward physiological values. BD implies CO2 overload from dialysate, whereas AFB does not. Further studies are required to evaluate if AFB would be the most appropriate dialysis technique in patients affected by chronic, but especially acute, lung diseases.

[Central venous blood gas analysis]. / Emogasanalisi dal catetere venoso centrale: una finestra sulla perfusione.

The hemodialysis might interfere with patients hemodynamic, as the technique allows a sophisticated game with extra and intravascular fluids. As the cardiocirculatory response could sometimes be unpredictable, it is interesting to collect valuable information by reaching a deep understanding of the tissue metabolism which is mirrored by the blood gas analysis of variations in arterial and central venous blood samples. Particularly interesting are the time course variations of the central venous hemoglobin saturation (ScvO2), which are directly related to the patient with O2-demand as well as to the O2-Delivery (DO2). The ScvO2 is determined by four parameters (cardiac output, Hb concentration, arterial Hb saturation and O2 consumption): If the fluids subtraction during dialysis was about to determine an occult hypoperfusion, the ScvO2 reduction would be a timely warning sign to be considered. Moreover, while the normal veno-arterial PCO2 difference is 2-4 mmHg, whenever a mismatch between O2-demand and DO2arise, a larger v-aPCO2 difference should be observed.

Second-degree interatrial block in hemodialysis patients.

Interatrial conduction delays manifest as a prolonged P-wave duration on surface ECG and the term interatrial block (IAB) has been coined. They are usually fixed, but cases of intermittent IAB have been described, suggesting functional conduction block at the Bachmann bundle region. We report 2 cases of patients on chronic hemodialysis therapy presenting with intermittent IAB.

A very simple formula to compute pCO2 in hemodialysis patients.

PURPOSE: To identify mixed acid-base disorders, clinicians must estimate the value of partial pressure of carbonic dioxide (pCO2), complying with the reduced plasma bicarbonate concentration (HCO3). What is the most appropriate equation relating the two quantities in chronic hemodialysis patients remains unknown. Chronic hemodialysis patients remains unknown, which motivates our study. METHODS: Among a large database of blood gas analysis from chronic hemodialysis patients, we selected 291 blood samples showing HCO3 < 24 mmol/L and, among these, we further selected a subset of samples claimed for pure metabolic acidosis. A linear approximation based upon the least-square criterion was adopted to derive the best-fit equation. The differences between this and other commonly used formulas were computed in terms of root mean square (RMS) errors. RESULTS: In chronic hemodialysis patients, the reduction in pCO2 due to metabolic acidosis is better predicted multiplying by 1.2 the reduction in HCO3, or by using the expression pCO2 = HCO3 + 15; the two approaches lead to almost the same results. In contrast, the equation pCO2 = 1.5 × HCO3 + 8, known as Winters' formula, exhibits larger errors. CONCLUSIONS: The easy-to-use expression pCO2 = HCO3 + 15 seems suitable for the daily clinical practice in hemodialysis patients. However, if HCO3 value is lower than 12 mmol/L, a threshold at which different formulas return almost the same value, also Winters' formula, derived in the 60's from patients with low values of HCO3, could be used.