GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: an observational study in patients with type 2 diabetes.

BACKGROUND: Few studies explored the effect of the combination of glucose sodium-cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on the incidence of cardiovascular events in patients with type 2 diabetes (T2D) and acute myocardial infarction (AMI). METHODS: We recruited patients with T2D and AMI undergoing percutaneous coronary intervention, treated with either SGLT-2i or GLP-1RA for at least 3 months before hospitalization. Subjects with HbA1c < 7% at admission were considered in good glycemic control and maintained the same glucose-lowering regimen, while those with poor glycemic control (HbA1c ≥ 7%), at admission or during follow-up, were prescribed either a SGLT-2i or a GLP-1RA to obtain a SGLT-2i/GLP-1RA combination therapy. The primary outcome was the incidence of major adverse cardiovascular events (MACE) defined as cardiovascular death, re-acute coronary syndrome, and heart failure related to AMI during a 2-year follow-up. After 3 months, the myocardial salvage index (MSI) was assessed by single-photon emission computed tomography. FINDINGS: Of the 537 subjects screened, 443 completed the follow-up. Of these, 99 were treated with SGLT-2i, 130 with GLP-1RA, and 214 with their combination. The incidence of MACE was lower in the combination therapy group compared with both SGLT-2i and GLP-1RA treated patients, as assessed by multivariable Cox regression analysis adjusted for cardiovascular risk factors (HR = 0.154, 95% CI 0.038-0.622, P = 0.009 vs GLP-1RA and HR = 0.170, 95% CI 0.046-0.633, P = 0.008 vs SGLT-2i). The MSI and the proportion of patients with MSI > 50% was higher in the SGLT-2i/GLP-1RA group compared with both SGLT-2i and GLP-1RA groups. INTERPRETATION: The combination of SGLT-2i and GLP-1RA is associated with a reduced incidence of cardiovascular events in patients with T2D and AMI compared with either drug used alone, with a significant effect also on peri-infarcted myocardial rescue in patients without a second event. Trial registraition ClinicalTrials.gov ID: NCT06017544.

Evolution of congenital anomalies of urinary tract in children with and without solitary kidney.

BACKGROUND: We hypothesized that children with congenital solitary functioning kidney (CSFK) present forms of congenital urinary tract anomalies (CUTA) with higher chance of spontaneous resolution compared with patients with two kidneys. METHODS: We retrospectively selected 75 consecutive children with CUTA of the CSFK and 75 matched patients with unilateral CUTA but without CSFK (controls) with prenatal suspicion of unilateral CUTA and early evaluation. We compared the spontaneous CUTA resolution and the prevalence of kidney injury between groups at last follow-up. Patients and controls were clustered under the categories of "severe" and "non-severe" CUTA. RESULTS: The mean age at first and last follow-up was 0.17 ± 0.07 and 8.5 ± 5.2 years. Compared with controls, patients with CSFK had lower prevalence of severe CUTA at first evaluation; lower prevalence of febrile urinary tract infections, need of surgical correction, and higher rate of spontaneous CUTA resolution during follow-up; and a similar prevalence of mild kidney injury at last follow-up. CSFK compared with controls presented higher cumulative proportion of spontaneous resolution from severe CUTA (100 vs 41.8%; p < 0.001) and from the single CUTA sub-categories (severe vesicoureteral reflux, non-obstructive hydronephrosis, and megaureter). CONCLUSIONS: CSFK patients had lower prevalence of severe forms and better outcomes of their CUTA compared with controls. IMPACT: One-third of patients with congenital solitary functioning kidney (CSFK) present congenital urinary tract anomalies (CUTA) and manifest poorer outcomes compared with CSFK without CUTA. CSFK patients had lower prevalence of severe forms and better outcomes of their CUTA in spite of similar prevalence of kidney injury compared with controls. This adds evidence about disturbed nephrogenesis in CSFK patients and emboldens conservative management of many of their non-obstructive CUTA.

Congenital Solitary Kidney from Birth to Adulthood.

PURPOSE: To evaluate the course of prenatally diagnosed and early-enrolled congenital solitary functioning kidney patients followed until adulthood and to identify risk factors for kidney injury. MATERIALS AND METHODS: Among all congenital solitary functioning kidney patients followed (1993-2018), we recalled 56 patients with prenatal diagnosis and congenital solitary functioning kidney confirmation at 1-3 months of life reaching at least 18 years of age. Serum uric acid, heavy smoking (≥25 cigarettes/day) and overweight/obesity were clustered as modifiable risk factors. Kidney injury was defined by estimated glomerular filtration rate <90 ml/minute/1.73 m2 and/or 24-hour ambulatory blood pressure monitoring confirmed hypertension and/or proteinuria. Modifiable risk factors and congenital anomalies of the kidney and urinary tract (CAKUT) of congenital solitary functioning kidney were evaluated as risk factors for kidney injury. RESULTS: The mean followup period was 21.1 years (range 18-33 years). Mild kidney injury was found in 15 out of 56 patients (26.8%). The mean age at proteinuria, reduced estimated glomerular filtration rate and hypertension onset was 19.7 years (1.2 SDS), 20.7 years (2.7 SDS), and 22 years (5.6 SDS), respectively. Patients with CAKUT of congenital solitary functioning kidney and with both CAKUT of congenital solitary functioning kidney and modifiable risk factors presented survival free from kidney injury of 0% at 22.2 and 24.2 years of age, respectively. Patients with modifiable risk factors presented 42.4% of survival at 30 years. Patients without CAKUT of congenital solitary functioning kidney nor modifiable risk factors presented 100% of survival at 30 years of age (p=0.002). The presence of CAKUT of congenital solitary functioning kidney was the only significant risk factor (HR 4.9; 95% CI 1.8-14.2; p=0.003). CONCLUSIONS: The outcomes of congenital solitary functioning kidney in early adulthood appear better than previously reported. Prompt diagnosis of congenital solitary functioning kidney, healthy lifestyle promotion and monitoring of serum uric acid may improve the prognosis of congenital solitary functioning kidney patients.

In children with urinary tract infection reduced kidney length and vesicoureteric reflux predict abnormal DMSA scan.

BACKGROUND: To evaluate sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of renal ultrasonography (US) in predicting renal uptake defects or reduced renal function at Tc-99m dimercaptosuccinic acid (DMSA) scan (primary outcome). We also evaluated which factors could be associated with Tc-99m DMSA renal scan anomalies. METHODS: We retrospectively included all the patients with vesico-ureteral reflux (VUR) undergoing the first Tc-99m DMSA renal scan within 3 months from the most recent renal US between 2016 and 2018. RESULTS: Sensitivity, specificity, PPV, and NPV of US in predicting abnormal Tc-99m DMSA scan were 38.9%, 91.5%, 71.9%, and 72.9%, respectively. Different length between the kidneys, expressed as standard deviation score (SDS), showed an area under the receiver operating characteristic curve of 0.70 (95% CI, 0.60-0.80; p < 0.0001) when evaluated as predictor of abnormal Tc-99m DMSA scan. A different length between the two kidneys >1.11 SDS had 91.5% sensitivity and 57.6% specificity. At multivariate analysis, the factors with significantly increased odds ratio of abnormal Tc-99m DMSA scan were difference in length between two kidneys >1.11 SDS and dilated VUR. CONCLUSIONS: The Tc-99m DMSA scan remains the gold standard to detect renal parenchymal anomalies. A different length between the kidneys >1.11 SDS and dilated VUR are predictors of abnormal Tc-99m DMSA renal scan.

Antibiotics for urethral catheterization in children undergoing cystography: retrospective evaluation of a single-center cohort of pediatric non-toilet-trained patients.

Antibiotics are often used to prevent post-catheterization urinary tract infections (UTIs) in patients undergoing cystography. However, there is no universally accepted protocol and the literature data are conflicting. We aimed to determine prevalence and risk factors of post-cystography UTIs in non-toilet-trained children. We retrospectively evaluated 216 non-toilet-trained children not assuming antibiotics when undergoing cystography. Only the patients with dilated vesico-ureteral reflux (VUR) assumed antibiotics just after the exam (within 15 min). One hundred eleven patients without vesico-ureteral reflux (VUR) and 29 patients with non-dilated VUR did not receive post-procedure antibiotics and did not develop UTIs. Out of the 76 patients who showed a dilated VUR and received post-procedure antibiotics, only 5 (6.6%) developed a UTI. The most significant factor associated with post-cystography UTIs was the presence of dilated VUR (p = 0.005) with the presence of bilateral VUR also being significant (p = 0.02).Conclusion: Patients without dilated VUR or bilateral VUR could not benefit from antibiotic prophylaxis for cystography. What is Known: • There is no universally accepted protocol about antibiotic administration in children undergoing cystography. • Literature data are conflicting. What is New: • Among 216 non-toilet-trained children undergoing cystography, 111 patients without vesico-ureteral reflux (VUR) and 29 patients with non-dilated VUR did not receive post-procedure antibiotics and did not develop UTIs. Out of the 76 patients who showed a dilated VUR and received post-procedure antibiotics, only 5 (6.6%) developed a UTI. • The most significant factor associated to post-cystography UTIs was the presence of dilated VUR (p = 0.005) with presence of bilateral VUR also being significant (p = 0.02).

Outcomes of a Cohort of Prenatally Diagnosed and Early Enrolled Patients with Congenital Solitary Functioning Kidney.

PURPOSE: We evaluated the clinical course of patients prenatally diagnosed and enrolled early with congenital solitary functioning kidney, and identified the risk factors for renal injury. MATERIALS AND METHODS: We retrospectively evaluated 322 patients with congenital solitary functioning kidney according to the inclusion criteria of 1) prenatal diagnosis of solitary kidney; 2) first evaluation at 1 to 3 months of life with confirmation of congenital solitary functioning kidney, and evaluation of possible associated congenital anomalies of the kidney and urinary tract by abdominal ultrasound, renal scintigraphy and cystography; and 3) absence of any condition potentially affecting renal function in the neonatal period as well as absence of renal injury at enrollment (1 to 3 months of life) confirmed by a normal estimated glomerular filtration rate, lack of proteinuria and hypertension. Followup of 306 patients was evaluated. RESULTS: Median followup was 7.2 years (range 1 to 23) and 1 or more signs of renal injury were found in 12 of 306 patients (3.9%). Considering the entire population the cumulative proportion of patients free from renal injury at 17 years old was 93.7%, vs 81.3% and 95.9% for subjects with and those without congenital anomalies of the kidney and urinary tract of congenital solitary functioning kidney (p <0.001), respectively. Of congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney resulted in significant risk factors for renal injury (HR 8.75, 95% CI 2.77-27.65). CONCLUSIONS: In an evaluation of a large cohort of patients enrolled early with congenital solitary functioning kidney with a prenatal diagnosis, excluding those with neonatal onset of renal damage, the prevalence of renal damage was 3.9%. Among congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney represented the major risk factor.

Early Renal Ultrasound in Patients with Congenital Solitary Kidney Can Guide Follow-Up Strategy Reducing Costs While Keeping Long-Term Prognostic Information.

We aimed to evaluate the prognostic value of renal length (RL) > 2 standard deviation scores (SDS) measured by renal ultrasound (RUS), across infancy, childhood and adolescence, in identifying which patients with congenital solitary functioning kidney (CSFK) are at lower risk of developing kidney injury (KI). We also estimated the cost saving of integrating the current follow-up protocols with an early RUS algorithm (ERUSA). Fifty-six CSFK adult patients who were 1-3 months old at first observation of undergoing RUS were enrolled. KI was defined by hypertension and/or proteinuria and/or declined renal function. ERUSA was assessed by early (at 1-3 months of life) RUS and was retrospectively tested in our patients. ERUSA establishes that patients with RL > 2SDS at early RUS do not undergo further follow-ups. The others undergo another RUS at 1 year of age along with follow-ups according with current protocols, with the exception of RUS which could be no longer performed. Direct and indirect costs were calculated for each analysed protocol and the cost saving of applying ERUSA was calculated. None of the patients with early RL > 2SDS presented KI in adulthood. A RL > 2SDS was predictive of absence of KI only at 1-3 months (OR = infinity) and 1 year of age (OR = 0.13; 95%CI: 0.03-0.66; p = 0.01). ERUSA provided a total cost-sparing ranging from 38.6% to 55.3% among the analysed follow-up protocols. With ERUSA, no patients developing KI in adulthood were missed. In conclusion, only a RL > 2SDS at 1-3 months and 1 year of age predicted good prognosis in young adulthood. ERUSA can guide a cost-sparing follow-up strategy in CSFK patients while maintaining important long-term information.

Inflammatory bowel disease: value in diagnosis and management of MDCT-enteroclysis and 99mTc-HMPAO labeled leukocyte scintigraphy.

OBJECTIVES: The aims of this study are: (a) to evaluate the reliability of Multidetector Computed Tomography Enteroclysis (MDCT-E) and (99m)Tc-HMPAO labeled leukocyte scintigraphy (TLLS), in inflammatory bowel disease, (b) to test the accuracy of the two techniques with regard to their histological results, (c) to define how each technique can influence the natural course of inflammatory bowel disease (IBD), (d) to assess the potential value of the two techniques combined. MATERIALS AND METHODS: Thirty-seven patients with suspected IBD underwent MDCT-E and TLLS. We made a separate assessment of the results shown by the two methods and then compared and contrasted the histological results of the two. The latter, however, were either disappointing or not available in 15 patients who, for this reason, had to be dismissed from the study. As result, the number of participants eventually dropped to 22 subjects: 12 women, 10 men with an average age of 44 years. RESULTS: MDCT-E and TLLS were successful in all patients. Sensitivity, specificity, and efficiency values have been reported as follows: MDCT-E: 62%, 100%, 64%,100%, 11%, respectively. TLLS: 90%, 100%, 91%, 100%, 33%, respectively. The two methods combined: 95%, 100%, 95%, 100%, 50%, respectively. CONCLUSIONS: The two techniques can be employed in different stages of the natural course of the disease. In our experience, TLLS proved itself to be useful in the diagnosis of the disease and the assessment of its development. Conversely, MDCT-E proved itself to be more reliable in identifying the seat and the extent of the disease inside and outside the bowel wall as well as potential intra-peritoneal and extra-intestinal complications. The combined use of the two methods represents the Criterion Standard for diagnosing IBD with imaging.

Early Renal Ultrasound in Congenital Solitary Kidney May Help to Select Patients at Lower Risk of Associated Vesicoureteral Reflux.

BACKGROUND: Vesicoureteral reflux (VUR) may be associated with renal dysplasia and reduced renal length (RL). The diagnosis of VUR in children with congenital solitary functioning kidney (CSFK) identifies patients at risk of kidney injury but exposes to invasive procedures. OBJECTIVE: We aimed to test the hypothesis that an RL >2 standard deviation score (SDS) in the first months of life - reflecting renal hyperplasia - could identify CSFK patients with lower probability of presenting VUR. METHOD: We retrospectively selected 207 CSFK patients with prenatal diagnosis of CSFK and having undergone renal ultrasound (RUS) both at 0-3 and 10-13 months of life, renal scintigraphy, and cystourethrography/cysto-scintigraphy. We compared the cumulative proportion of an RL >2 SDS by Kaplan-Meier analysis and evaluated the odds to present VUR of patients with an RL >2 SDS both at the first and second RUS. RESULTS: Overall, 3.3% of patients with VUR and 22.0% of patients without VUR presented an RL >2 SDS at the first RUS (p = 0.02). At the second RUS, 53.3% of patients with VUR and 52.5% of patients without VUR presented an RL >2 SDS (p = 0.93). Patients without VUR presented higher cumulative proportion of an RL >2 SDS at 3 months of life than those with VUR (p = 0.02). This difference however disappeared at 11 and 13 months of age (p = 0.17 and p = 0.54, respectively). An RL >2 SDS within 3 months of life presented an OR for VUR of 0.12 (95% CI: 0.02-0.92; p = 0.005), while an RL >2 SDS at 12 months of life presented an OR for VUR of 0.96 (95% CI: 0.45-2.1; p = 0.93). CONCLUSION: Only an RUS made in the first months of life could identify CSFK patients at lower risk of presenting an associated VUR.

F-18-2-fluoro-2-deoxyglucose positron emission tomography compared to technetium-99m hexakis-2-methoxyisobutyl isonitrile single photon emission chest tomography in the diagnosis of indeterminate lung lesions.

BACKGROUND: (18)FDG-PET plays a significant role in diagnosing malignancy of lung lesions but remains an expensive test available at a limited number of sites in Italy. OBJECTIVE: We prospectively compare the diagnostic accuracy of (99m)Tc-MIBI- SPECT and (18)FDG-PET in patients with indeterminate lung lesions to demonstrate that (99m)Tc-MIBI-SPECT may be considered as a valid alternative when (18)FDG-PET is not available. METHODS: 52 patients with indeterminate lung lesion were examined by (18)FDG-PET and (99m)Tc-MIBI-SPECT before surgery. The scintigraphic findings were analyzed visually and semiquantitatively and then correlated to the definitive diagnosis. RESULTS: 38 were malignant lesions while 14 were benign. At visual analysis, the sensitivities of (18)FDG-PET and (99m)Tc-MIBI-SPECT were 92 and 84%, respectively (McNemar test p = 0.4), whereas the specificities were 78.6 and of 93% (p = 1.0), respectively. At semiquantitative analysis, (18)FDG-PET showed a sensitivity and specificity of 92 and 71.4%, respectively, while (99m)Tc-MIBI-SPECT produced a sensitivity and specificity of 86 and 100%, respectively (p = 0.194). For lymph node staging, (18)FDG-PET and (99m)Tc-MIBI-SPECT have a sensitivity and specificity of 88 and 92 of 77 and 100%, respectively. CONCLUSION: (99m)Tc-MIBI-SPECT is similar to (18)FDG-PET in the detection of lung malignancies and represents an alternative when PET is not available. Yet, the combination of both techniques may improve patient selection for surgery.

ROBO2 gene variants are associated with familial vesicoureteral reflux.

The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted.

Congenital solitary kidney size at birth could predict reduced eGFR levels later in life.

OBJECTIVES: To evaluate the impact of congenital solitary functioning kidney (CSFK) length, measured early in life, on the eGFR levels during the follow-up. STUDY DESIGN: We retrospectively selected 162 CSFK patients undergoing, within 60 days of life, renal length (RL) measurement by ultrasound. We divided the population in: Group 1 = RL ≥ 2 standard deviation score (SDS). Group 2 = RL < 2 SDS and showing RL ≥ 2 SDS during the follow-up. Group 3 = RL < 2 SDS and showing RL < 2 SDS during the follow-up. PRIMARY OUTCOME: development of eGFR below the range of normality. RESULTS: The median follow-up period of the overall population was 6.2 years (range 2-21.5 years). The cumulative proportion of patients free of primary outcome at 15 years of age was 96.4% in group 1, 64.6% in group 2, and 45.6% in group 3 (p = 0.03). The RL > 2 SDS within 60 days of life was a significant protective factor (hazard ratio = 0.13; 95% C.I. 0.02-0.97) against development of primary outcome. CONCLUSION: RL ≥ 2 SDS within 60 days of life could identify a population of CSFK with reduced risk of presenting reduced eGFR levels later in life.

Continuous monitoring of left ventricle function by VEST in hemodialyzed patients.

Cardiovascular disease is a major cause of morbidity and mortality in chronic kidney disease. Radionuclide-based methods can be used for analyses on the perfusion of coronary arteries and ventricular function. The present study reports the use of a new procedure for continuous measurements of left ventricle function during a dialytic session with the use of a recently developed portable gamma radiation detector (ventricular function study system). On average, left ventricle ejection fraction and stroke volume progressively and continuously decreased throughout the session (end session versus baseline: -13.8% for ejection fraction, -25.9% for stroke volume, P<.02). A biphasic response was found for heart rate: a transient modest decrease (at session midpoint, -4.2%) followed by an increase up to values higher than baseline (end session, +4.7%). Cardiac output decreased by 10.4% at session midpoint (P=.023 versus baseline) without further reduction in the following hours. Mean changes in systolic pressure paralleled data for cardiac output. Individual changes in indices of left ventricle function were scattered and strongly were correlated with thickness of interventricular septum and telediastolic left ventricular volume measured by standard echocardiogram in the interdialytic period (R>.75, P<.05). Data indicate that the ventricular function study system could be a powerful tool for characterization of the profile of left ventricular function in hemodialyzed patients.

Fever of unknown origin, infection of subcutaneous devices, brain abscesses and endocarditis.

The term 'fever of unknown origin' includes a wide range of conditions that often remain undiagnosed. The possibility of an infection must be promptly diagnosed in order to begin appropriate therapy. Imaging with radiopharmaceuticals, computed tomography, magnetic resonance imaging and ultrasound are the most commonly applied techniques, usually performed in addition to blood tests, biopsies or tissue cultures when required. The lack of comparative studies investigating the accuracy of each radiopharmaceutical for the study of fever of unknown origin was the incentive to perform a meta-analysis of peer articles published between 1981 and 2004 (33 papers) describing the use of nuclear medicine imaging for this purpose. Furthermore, infection of subcutaneous devices, brain abscesses and endocarditis must be considered amongst the causes of fevers of unknown origin. Reviews of 23, 10 and 10 papers, respectively (from 1976 to 2005), were performed on these specific topics. The results may be a useful guide for the choice of the optimal radiopharmaceutical(s) and diagnostic strategy to be applied in each clinical condition and for different aims.

Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review.

Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of 'acute abdomen', an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM.

Effects of α-lipoic acid therapy on sympathetic heart innervation in patients with previous experience of transient takotsubo cardiomyopathy.

BACKGROUND: Takotsubo syndrome is a stress cardiomyopathy, characterized by reversible left ventricle (LV) apical ballooning in the absence of significant angiographic coronary artery stenosis. The frequent association with emotional stress suggests in this disease an autonomic nervous system involvement. We could think that a therapeutic treatment targeting heart sympathetic dysfunction could be of crucial importance. METHODS: From January 2010 to June 2012, 886 patients were consecutively evaluated at Cardarelli Hospital, Naples, Italy. Among these, 48 patients met takotsubo cardiomyopathy (TCM) criteria. Each patient was assessed with history and physical examination, 12-lead electrocardiogram, serum troponin, coronary arteriography, and left ventricular angiogram, perfusion myocardial scintigraphy with technetium 99m, with echocardiography and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. At discharge, the surviving patients were randomly assigned to α-lipoic acid (ALA) treatment (600mg once daily) or placebo. Following discharge, after the initial TCM event, patients returned to our outpatient clinic at Internal Medicine of the Second University Naples for the follow-up evaluation quarterly until 12 months. Routine analysis, myocardial damage serum markers, oxidative stress serum markers, pro-inflammatory cytokines, and sympathetic tone activity were evaluated in all patients. RESULTS: ALA administration improved MIBG defect size at 12 months compared to placebo. CONCLUSIONS: Adrenergic cardiac innervation dysfunction in TCM patients persists after previous experience of transient stress-induced cardiac dysfunction. ALA treatment improves the adrenergic cardiac innervation. This study evaluates whether sympatho-vagal alterations are TCM event-related.

Peri-procedural tight glycemic control during early percutaneous coronary intervention up-regulates endothelial progenitor cell level and differentiation during acute ST-elevation myocardial infarction: effects on myocardial salvage.

BACKGROUND: We examined the effects of peri-procedural intensive glycemic control during early percutaneous coronary intervention (PCI) on the number and differentiation of endothelial progenitor cells (EPCs) and myocardial salvage (MS) in hyperglycemic patients with first ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: We conducted a randomized, prospective, open label study on 194 patients with STEMI undergoing PCI: 88 normoglycemic patients (glucose < 140 mg/dl) served as the control group. Hyperglycemic patients (glucose ≥140 mg/dl) were randomized to intensive glycemic control (IGC) for almost 24 h after PCI (n = 54; 80-140 mg/dl) or conventional glycemic control (CGC, n = 52; 180-200 mg/dl). EPC number, differentiation, and SIRT1expression were assessed immediately before, 24 h, 7, 30 and 180 days after PCI. The primary end point of the study was salvage index, measured as the proportion of initial perfusion defect (acute technetium-99m sestamibi scintigraphy, performed 5 to 7 days after STEMI) and myocardium salvaged by therapy (6 months after STEMI). Hyperglycemic patients had lower EPC number and differentiation and lower SIRT1 levels than normoglycemic patients (P < 0.01). After the insulin infusion, mean plasma glucose during peri-procedural period was greater in CGC group than in IGC group (P < 0.001). The EPC number, their capability to differentiate, and SIRT1 levels were significantly higher in IGC group than in CGC, peaking after 24 h (P < 0.01). In the IGC group, the salvage index was greater than in patients treated with CGC (P < 0.001). CONCLUSIONS: Optimal peri-procedural glycemic control, by increasing EPC number and their capability to differentiate, may improve the myocardial salvage.

The role of technetium-99m hexakis-2-methoxyisobutyl isonitrile in the detection of neoplastic lung lesions.

OBJECTIVE: Our goal was to determine the role of technetium-99m hexakis-2-methoxyisobutyl isonitrile ((99m)Tc-MIBI) in the detection of neoplastic lung lesions. MATERIALS AND METHODS: We prospectively studied 79 consecutive patients with indeterminate lung lesion between January 2006 and September 2007. All patients were submitted to (99m)Tc-MIBI single-photon emission chest tomography (SPECT) before invasive diagnostic procedure. Qualitative analysis was performed to evaluate SPECT images in order to localize abnormal activity in the radiologically demonstrated lesion. In addition, semiquantitative analysis was made by calculating tumor/contralateral normal lung ratio (T/N). Finally, the scintigraphic findings were correlated to the histopathological diagnosis obtained by invasive procedure or confirmation of instrumental exams. RESULTS: Sixty patients had a malignant lesion: 44 squamous cell carcinoma, 7 adenocarcinomas, 4 large cell carcinoma, 1 small cell lung cancer, and 4 metastases. The mean size+/-standard deviation of malignant nodules was 3.9+/-1.61 cm (range 1.5-5.5 cm). Nineteen patients had a benign disease. The mean size+/-standard deviation of benign nodules was 3.3+/-1.71 cm (range 2-6 cm). (99m)Tc-MIBI SPECT delineated focal lesions with an increase in tracer accumulation in 55/60 malignant lesions; in 5/60 malignant lesions was negative. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91%, 73%, 91%, and 73%, respectively. In patients with neoplastic lesion, the mean T/N ratio value+/-standard deviation was 1.72+/-0.35 whereas in patients with benign lesions was 1.14+/-0.25. Semiquantitative analysis showed that for a T/N value >1.23, the value of sensitivity, specificity, PPV, and PNV were 91%, 84%, 94%, and 76%, respectively (ROC curve). Metastatic mediastinal lymph nodes were found in 3/57 patients. (99m)Tc-MIBI SPECT showed a specificity and PPV of 100% in the detection of mediastinal lymph nodes with sensitivity, and PNV of 66% and 97%, respectively. Age, sex, histological type, and size of lesion did not affect the SPECT results. CONCLUSION: Our experiences seem to confirm that (99m)Tc-MIBI SPECT is a reliable diagnostic tool in the finding of lung cancer particularly cases in which radiological evaluation is indeterminate.

A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity.

Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder.