Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart.

SGLT2 (sodium-glucose cotransporter 2) enables glucose and sodium reabsorption in the kidney. SGLT2-inhibitors (also known as gliflozins, which include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) act by increasing glycosuria, thereby reducing glycemia. These drugs are critical to reach and keep glycemic control, a crucial feature, especially in patients with comorbidities, like frail individuals. Several studies evaluated the effects of SGLT2-inhibitors in different settings beyond diabetes, revealing that they are actually pleiotropic drugs. We recently evidenced the favorable effects of SGLT2-inhibition on physical and cognitive impairment in frail older adults with diabetes and hypertension. In the present overview, we summarize the latest clinical and preclinical studies exploring the main effects of SGLT2-inhibitors on kidney and heart, emphasizing their potential beneficial actions in frailty.

Preadmission Statin Therapy and Clinical Outcome in Hospitalized Patients With COVID-19: An Italian Multicenter Observational Study.

ABSTRACT: Statin therapy has been recently suggested as possible adjuvant treatment to improve the clinical outcome in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to describe the prevalence of preadmission statin therapy in hospitalized patients with COVID-19 and to investigate its potential association with acute distress respiratory syndrome (ARDS) at admission and in-hospital mortality. We retrospectively recruited 467 patients with laboratory-confirmed COVID-19 admitted to the emergency department of 10 Italian hospitals. The study population was divided in 2 groups according to the ARDS diagnosis at admission and in-hospital mortality. A multivariable regression analysis was performed to assess the risk of ARDS at admission and death during hospitalization among patients with COVID-19. A competing risk analysis in patients taking or not statins before admission was also performed. ARDS at admission was reported in 122 cases (26.1%). There was no statistically significant difference for clinical characteristics between patients presenting with and without ARDS. One hundred seven patients (18.5%) died during the hospitalization; they showed increased age (69.6 ± 13.1 vs. 66.1 ± 14.9; P = 0.001), coronary artery disease (23.4% vs. 12.8%; P = 0.012), and chronic kidney disease (20.6% vs. 11.1%; P = 0.018) prevalence; moreover, they presented more frequently ARDS at admission (48.6% vs. 19.4%; P < 0.001). At multivariable regression model, statin therapy was not associated neither with ARDS at admission nor with in-hospital mortality. Preadmission statin therapy does not seem to show a protective effect in severe forms of COVID-19 complicated by ARDS at presentation and rapidly evolving toward death.

Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients.

INTRODUCTION: No data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. MATERIALS AND METHODS: Data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett's formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 ms or greater (ΔQTc ≥ 60 ms) compared with baseline. RESULTS: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. Twenty patients (23%) showed extreme QTc interval prolongation; no clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke (P= 0,007). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. CONCLUSIONS: We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. Since the incidence of malignant arrhythmias seems to be not negligible, a careful electrocardiographic monitoring would be advisable.

Clinical characteristics and prognosis of hospitalized COVID-19 patients with incident sustained tachyarrhythmias: A multicenter observational study.

INTRODUCTION: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID-19. The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. MATERIALS AND METHODS: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. RESULTS: 414 hospitalized patients with COVID-19 (66.9 ± 15.0 years, 61.1% male) were included in the present study. During a median follow-up of 28 days (IQR: 12-45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new-onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in-hospital mortality (RR: 2.55; P: .003). CONCLUSIONS: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients.

Echocardiography of the pulmonary circulation and right ventricular function: exploring the physiologic spectrum in 1,480 normal subjects.

BACKGROUND: Although transthoracic echocardiography (TTE) is an excellent noninvasive screening test for pulmonary hypertension, the physiologic range of Doppler echocardiography-derived pulmonary pressures remains not completely investigated. The aim of the present study was, therefore, to explore the full spectrum of pulmonary pressures and right ventricular (RV) functional indexes by TTE in healthy subjects and to investigate clinical and echocardiographic correlates. METHODS: A random sample of 1,480 healthy individuals (mean age, 36.1 ± 15.5 years; range, 20-80 years; 905 men) underwent a comprehensive TTE. Pulmonary artery systolic pressure (PASP), mean pressure, and pulmonary vascular resistance were estimated by standard Doppler echocardiography formulas. In addition, RV diastolic (Doppler transtricuspid inflow measurements) and systolic indexes (RV fractional area change, RV tissue Doppler peak systolic velocity, tricuspid annular plane systolic excursion) were calculated. RESULTS: PASP and mean pulmonary artery pressure values were significantly higher in subjects aged > 50 years and in those with a BMI > 30 kg/m2. In particular, a PASP > 40 mm Hg was found in 118 subjects (8%) of those aged > 50 years and in 103 (7%) of those with a BMI > 30 kg/m2. No differences by age were registered in RV systolic indexes and in pulmonary vascular resistances. On multivariate analysis, in the overall study population, age, BMI, mitral E/e' ratio, and left ventricular stroke volume were the only independent predictors of PASP. CONCLUSIONS: This study delineates an estimate of pulmonary hemodynamics in a wide age range cohort of healthy subjects. Pulmonary pressures increased with age and BMI, as expected.

Right heart morphology and function in heart transplantation recipients.

BACKGROUND: The right heart is a major determinant of prognosis in cardiac transplant recipient patients. AIM: To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis. METHODS: One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ±â€Š5.8 years; 7.8 ±â€Š4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity). RESULTS: Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P < 0.01). Right ventricular diameters were significantly increased (P < 0.001), whereas TAPSE and right ventricular Sm were significantly lower in cardiac transplant recipient patients. Conversely, in cardiac transplant recipient patients, three-dimensional right ventricular ejection fraction (RVEF) was not significantly reduced (P < 0.001), whereas both PASP and PAVC were impaired. By multivariable analysis, age at transplantation (P < 0.01) and pulmonary artery mean pressure (P < 0.001) were the only independent determinants of right ventricular diameters and RVEF in cardiac transplant. Furthermore, RVEF measured by real-time three-dimensional echocardiography was a powerful independent determinant of functional capacity in cardiac transplant recipient patients. CONCLUSION: Despite the reduction of right ventricular performance along the long axis suggested by TAPSE and right ventricular Sm, the increased right ventricular diameters along with absence of a decrease in three-dimensional RVEF support the hypothesis of geometrical rather than functional changes of the right ventricle in cardiac transplant recipient patients.

Range of right heart measurements in top-level athletes: the training impact.

OBJECTIVES: To explore the full range of right heart dimensions and the impact of long-term intensive training in athletes. BACKGROUND: Although echocardiography has been widely used to distinguish the athlete's heart from pathologic left ventricular (LV) hypertrophy, only few reports have described right ventricular (RV) and right atrial (RA) adaptations to extensive physical exercise. METHODS: 650 top-level athletes [395 endurance- (ATE) and 255 strength-trained (ATS); 410 males (63.1%); mean age 28.4 ± 10.1; 18-40 years] and 230 healthy age- and sex-comparable controls underwent a transthoracic echocardiographic exam. Along with left heart parameters, right heart measurements included: RV end-diastolic diameters at the basal and mid-cavity level; RV base-to-apex length; RV proximal and distal outflow tract diameters; RA long and short diameters; and RA area. Tricuspid annular plane systolic excursion and RV tissue Doppler systolic peak velocity were assessed as indexes of RV systolic function. Pulmonary artery systolic pressure (PASP) was estimated from the peak tricuspid regurgitant velocity. RESULTS: ATS showed increased sum of wall thickness and relative wall thickness, whereas left atrial volume, LV end-diastolic volume, LV stroke volume and PASP were significantly higher in ATE. RV and RA measurements were all significantly greater in ATE than in ATS and controls. ATE also showed improved early diastolic RV function, whereas RV systolic indexes were comparable among groups. On multivariate analysis, type and duration of training (p<0.01), PASP (p<0.01) and LV stroke volume (p<0.001) were the only independent predictors of the main RV and RA dimensions in athletes. CONCLUSIONS: This study delineates the upper limits of RV and RA dimensions in highly-trained athletes. Right heart measurements were all significantly greater in elite endurance-trained athletes than in age- and sex-matched strength athletes and controls. This should be considered as a "physiologic phenomenon" when evaluating athletes for sports eligibility.

Our experience of total mesorectal excision for rectal cancers.

BACKGROUND/AIMS: The total mesorectal excision (TME) for rectal tumours was introduced in 1982 by Heald et al. and has led both to a 5% de crease of local recurrences 5 and 10 years after the operation when compared with cases treated with conventional surgery, and to an increase of survival up to five years estimated in 80% of all cases. In Italy TME was firstly introduced for distal rectal carcinomas about 20 years ago, and has shown the same rate of local recurrences reported by Heald. The aim of our work is to highlight TME advantages and demonstrate how this more demanding and longer lasting method has an acceptable risk for the surgery of rectal tumours. METHODOLOGY: We have compared two groups of patients operated for rectal carcinoma; the first, "historical control group" (no TME, including 46 patients) was treated with the standard surgery technique, while the second group (TME, 47 patients) underwent the total mesorectal excision technique. 14 of non TME patients belonged to Dukes stage A, 20 to stage B and 12 to C; whereas in the TME group 16 patients belonged to Dukes stage A, 23 to B and 8 to C. The patients of both groups undergone the exams of follow up (blood test, hepatic ultrasonography, abdominal CT, thorax Ro); the follow up pattern included periodic controls with a check-up every three and six months, from one to five years. RESULTS: Postoperative complications in both groups do not show important differences in rates, although, the first group (no TME) had 11 cases with postoperative complications confronted with the 8 cases of the second group (TME). The complications taken into consideration were: anastomotic bleeding (3 patients no TME, 6% vs 1 patients TME, 2%), intestinal obstruction (1 patient no TME, 2% vs 1 patient TME, 2%), parietal infection (4 patients no TME, 9% vs 3 patients TME, 6%), anastomotic fistulae (2 patients no TME, 4% vs 2 patients TME, 4%), retention of urine and vesicular disorder (1 patient no TME, 2% vs 1 patient TME, 2%). Tumours closer to the anus have shown more complications compared with tumours at higher levels. As a matter of fact, 9 cases of no TME and TME patients with low located tumours have undergone complications compared with the 3 cases of no TME and TME patients with tumours being more distant from the anus; the rest 7 cases belonged to the middle rectum. A higher rate of local recurrences was noticed in the no TME group: 6 (13%) compared with the TME group: 3 (6%). Other tardy complications taken into consideration were: hepatic metastasis (5 patients no TME, 11% vs 4 patients TME, 8%), pulmonary metastasis (3, 6% of the no TME vs 2, 4% of the TME), anastomotic stenosis (4, 9% of the no TME vs 2, 4% of the TME), impotence (2, 4% of the no TME vs 1, 2% of the TME). We also noticed that most of the tardy complications in the TME group belonged to Dukes stage C. CONCLUSION: From our experience, we concluded that, in TME patients, complications are lower than in no TME patients; the site of the tumour affects the appearance of complications which are more frequently in distal localizations. An important result is the minor incidence of local recurrences after TME, which brings us to the conclusion that TME can be considered a valid method with an acceptable risk for the surgery of rectal tumour.

Solid-cystic pseudopapillary tumor of pancreas: description of two cases and literature review.

The authors report the cases of two young female patients aged 17 and 27 years who underwent surgery for a rare tumor of the pancreas, Frantz's tumor or solid-cystic pseudopapillary tumor. Solid-cystic pseudopapillary tumor of the pancreas is a rare tumor, accounting for 2.7% of pancreatic exocrine tumors. About 90% of these tumors occur in young women and they can reach very large dimensions. Due to their rareness and behavior, they are often associated with diagnostic and therapeutic problems. In most cases surgical treatment is curative and neither chemotherapy nor radiotherapy should be added. In the few cases where surgery is not possible, radiotherapy can be used because these tumors appear to be radiosensitive.

Spigelian hernia: a rare lateral ventral hernia.

The authors take a treated clinical case as a starting point to consider lateral ventral hernia, generally referred to as "Spigelian hernia". Such hernias are rare (1-2% of all hernias), with a slightly higher incidence in the female sex. Obesity and multiparous status are known to be predisposing factors. Instrumental tests of great importance in terms of specificity and definition such as ultrasonography and computed tomography are available, in cases of diagnostic doubt, for a pathology that in any case has to be detected early in order to avoid possible complications. The treatment is essentially surgical. A personal variant of the surgical repair technique is described with the use of prosthetic material, which guarantees a better result in terms of strength and resistance compared to simple repair surgery.

Outcome of surgical treatment of carcinoma of the pancreas.

AIMS AND BACKGROUND: Pancreatic resections for neoplastic diseases have a high risk of severe intra- and postoperative complications and are associated with high mortality rates. They should be performed as a rule in centers specializing in this type of surgery. However, it is becoming increasingly likely that such tumors may have to be treated in surgery units which are not specifically dedicated to pancreatic surgery. The aim of this study was to assess the improvements in clinical results in a non-specialized general surgery setting in the light of the most recent progress in surgical techniques, drug treatments and nutritional support. METHODS AND STUDY DESIGN: We analyzed 48 patients with pancreatic cancer treated in our institution over the period from 1980 to 1998: 36 had cancer of the head of the pancreas, 5 of the ampulla, 1 in the second duodenal portion, and 6 of the body-tail. The operations performed consisted of 13 Whipple pancreaticoduodenectomies with cutting and stapling of the distal pancreatic stump at the level of the isthmus, 4 left pancreasectomies, 2 local resections of the ampulla, 21 palliative operations, and 2 exploratory laparotomies. RESULTS AND CONCLUSIONS: The patients were submitted to follow-up including clinical examinations, blood-chemistry tests, and instrumental investigations. The mean survival was 18 months in the cases where radical surgery was performed, compared to 11 months after palliative surgery. We conclude that an improved prognosis can obtain after pancreatic resection. This is attributable to a more accurate preoperative staging and to the aid of the various forms of nutritional support and pharmacological prophylaxis currently available.

[Peritoneal multicystic mesothelioma: unusual case of localization in the left lobe of the liver]. / Mesotelioma multicistico del peritoneo: un caso insolito localizzato al lobo sinistro del fegato.

Peritoneal multicystic mesothelioma is a very rare clinical condition. This neoplastic variant has a high incidence of recurrence after surgical resection. It usually occurs in middle-aged women with a previous history of gynaecological surgery and presents with the symptoms of an abdominal or pelvic mass. The case reported here is that of a 58-year-old woman, characterised first by a left liver-lobe tumour and then by a subsequent episode of emission of cystic matter from an abdominal fistula. The relevant literature is reviewed and the clinical aspects and treatment of this disease are discussed.