Definition and reporting of composite outcomes are often inadequate in randomized clinical trials on pharmacological interventions for coronary artery disease

OBJECTIVE: To estimate the frequency and critically appraise the use and reporting of composite outcomes in randomized clinical trials on pharmacological interventions for coronary artery disease. DESIGN: A meta-research study. A search strategy was developed to retrieve references from MEDLINE. We considered articles, published from 1st January 2020 to December 31, 2021, reporting results of clinical primary outcomes from randomized clinical trials which assessed pharmacological interventions, used alone or in combination, for the treatment or secondary prevention (previous coronary event) of coronary artery disease. RESULTS: From the 34 included studies, 28 (82.35%) had a primary composite outcome. Thirteen unique composite primary outcomes were used with the most frequent being "cardiovascular death, myocardial infarction, stroke" (12/28, 42.86%). The term MACE (major adverse cardiac events) was used for five distinct composite primary outcomes. A combination of 12 different components resulted in the 28 primary composite outcomes, with stroke being the most frequent component present in 96.43% (27/28) of the primary composite outcomes. From the included studies, 60.71% (17/28) reported the estimates for each individual component and the direction of the effect was consistent between all components and the composite outcomes in 58.82% (10/17) of them. Additionally, no included study discussed potential limitations and/or related advantages of the composite outcomes. CONCLUSIONS: In randomized clinical trials on pharmacological interventions for coronary artery disease, composite outcomes are frequently used, but the definition of their components is very heterogeneous. The estimate for individual components within the composite outcome is often not fully reported, which prevents a complete analysis of their adequacy for clinical practice. The term MACE was used inconsistently and to refer to different set of components, which can also be misleading and confusing.

Nuclear EGFR characterize still controlled proliferation retained in better differentiated clear cell RCC.

Renal cell carcinoma (RCC) is the most common solid kidney tumor representing 2-3% of all cancers, with the highest frequency occurring in Western countries. There was a worldwide and European annual increase in incidence of approximately 2% although incidence has been stabilized in last few years. One third of the patients already have metastases in the time of the diagnosis with poor prognosis because RCC are radio and chemoresistant. The prognostic value of EGFR over-expression in RCC is a controversial issue that could be explained by different histological types of study tumors and non-standardized criteria for evaluation of expression. Recent evidences points to a new mode of EGFR signaling pathway in which activated EGFR undergoes nuclear translocalization and then, as transcription factor, mediates gene expression and other cellular events required for highly proliferating activities. According to our observations, the membranous expression of EGFR associates with high nuclear grade and poor differentiated tumors. On the other hand, nuclear EGFR expression was high in low nuclear graded and well differentiated tumors with good prognosis. We hypothesize that this mode of EGFR signaling characterizes still controlled proliferation retained in well differentiated RCC with Furhman nuclear grade I or II.

[Carcinoma of the Bellini duct with an unusual clinical picture]. / Bellini-Gang-Karzinom--eine ungewöhnliche Präsentation.

A 37-year-old male patient presented with a Bellini duct carcinoma, at first as a metastatic illness of the paraaortal lymph nodes, without significant radiologic signs of a kidney tumor. Cytological diagnostics did not recognize this tumor. Macroscopically and microscopically the tumor fulfilled the major and minor criteria of Sringly et al., but immunohistochemical findings did not show cell affinity for UEA-1, which, according to the literature, typically confirms its origin from Bellini ducts. This rare neoplasm, primarily found in a younger population, still represents a diagnostic and therapeutical challenge as a result of its aggressive clinical course. In our patient, as in the majority of cases presented in the literature, tumor prognosis was very poor, in spite of aggressive surgical, radium and immune therapy.

Vascular complications after 725 kidney transplantations during 3 decades.

Among 725 renal transplantations, the most common vascular complication was arterial stenosis, which was observed in 23 patients (3.17%). The majority of 20 (6.49%) arterial stenoses appeared in our initial experiences when we routinely used end-to-end renal graft to internal iliac artery anastomoses. A significant reduction in this incidence (0.72%) was achieved by introducing end-to-side anastomoses of the renal graft artery to the external or common iliac arteries. Intractable hypertension or impaired renal function in 14 patients (60.87%) with arterial stenosis demanded treatment. Patch angioplasty was more successful than other methods. The limited possibilities of conservative treatment of arterial hypertension at that time were the main reason for this frequent surgical repair. Among other vascular complications, the most serious were 12 episodes of arterial bleeding in 10 patients. Five kidneys were lost because of ruptured arterial anastomoses. In 6 patients, the common or external iliac artery was ligated as to achieve hemostasis with acute arterial insufficiency of the lower extremity in 4 patients. One patient required leg amputation, whereas 2 underwent extra-anatomic bypass procedures and 1 died because of hepatic failure. The majority of vascular complications occurred in the initial period of our transplantation practice. However, in spite of progress in diagnostic and treatment options, vascular complications may cause considerable clinical problems.

Ultrasonography in the evaluation of hemoperitoneum in war casualties.

The aim of this study was to evaluate the sensitivity, specificity, accuracy, and positive and negative predictive values of emergent ultrasound examination in the detection of hemoperitoneum among war casualties, and to compare the results of this method in a specific war situation and civil conditions. Ninety-four wounded individuals with suspected blunt or penetrating abdominal trauma were treated at a level I war hospital (group W), and 242 civilians with multiple injuries with suspected blunt abdominal trauma were evaluated at the emergency center of a university hospital (group C). All examinations were performed in less than 5 minutes with a portable ultrasonographic scanner, and typical points were scanned (Morison's pouch, Douglas and perisplenic spaces, paracolic gutter). In group W, hemoperitoneum was identified correctly in 19 patients, with three false-negative and no false-positive findings, whereas group C presented 98 true-positive results, 13 false-negative results, and again no false-positive results. We observed that ultrasonography in specific war conditions showed sensitivity of 86%, specificity of 100%, accuracy as high as 97%, positive predictive value of 100%, and negative predictive value of 96%, whereas in civil conditions the corresponding values were 88%, 100%, 95%, 100%, and 91%, respectively. The sensitivity, specificity, accuracy, and positive and negative predictive values of emergent ultrasound examination in the diagnosis of hemoperitoneum are approximately equal in war and civil conditions.

Kidney length in postoperative acute renal failure.

PURPOSE: The aim of this study was to evaluate kidney length in patients with postoperative acute renal failure (PARF). METHODS: The effect of PARF on renal size was prospectively studied in 76 patients with PARF and 40 healthy volunteers. Sonographic measurements of kidney length and the level of serum creatinine were obtained each day patients stayed in our surgical intensive care unit. These measurements were done once in volunteers. All study subjects were divided into groups on the basis of age, those younger than 65 years and those 65 years or older. Statistical analyses on the relation of renal size, age, and degree of PARF used the kidney length:body height ratio (KBR) and the peak serum creatinine level. Follow-up kidney length and creatinine measurements were done in 24 patients 1-5 years after they recovered from PARF. RESULTS: Regardless of age, mean KBRs were significantly greater in patients than in healthy volunteers (< 65 years, p < 0.001; > or = 65 years, p = 0.008), with a negative correlation between KBR and patient age (r = -0.664; p < 0.001). A positive correlation was found between the KBR and the peak serum creatinine level in patients younger than 65 years (r = 0.543; p < 0.001); an insignificant negative correlation was found between these factors in patients 65 years or older (r = -0.264; p = 0.1). Follow-up on recovered patients showed that their KBRs were significantly lower than the values when patients had PARF (< 65 years, p < 0.001; > or = 65 years, p = 0.027). CONCLUSIONS: PARF produces a sonographically measurable increase in renal size.

Sonographic measurement of absolute and relative renal length in adults.

PURPOSE: The aim of this study was to evaluate sonographically measured absolute and relative lengths of normal kidneys according to subject height, sex, and age. METHODS: Real-time sonography was performed on 202 subjects. Measurements of longitudinal renal diameter represented absolute renal length. Relative renal length was calculated using the kidney length: body height ratio (KBR). RESULTS: Statistical analyses were done on findings in 175 subjects without renal impairment (104 men and 71 women) whose ages ranged from 17 to 85 years (mean +/- SD, 46.3 +/- 17.1). The mean heights of the subjects were 176 +/- 7 cm for men and 167 +/- 6 cm for women. The left kidney was absolutely (mean +/-SD, 112 +/- 9 mm) and relatively (mean KBR +/- SD, 0.655 +/- 0.042) longer than the right kidney (absolute length, 110 +/- 8 mm; KBR, 0.641 +/- 0.038), regardless of sex (p < 0.01). The absolute renal length was significantly greater in men than in women for both kidneys (p < 0.01), but there was no significant difference between KBRs (p > 0.05). Renal length decreased with age, and the rate of decrease seemed to accelerate at 60 years and older. When height and age were included in the multivariate regression analysis, sex was not a significant predictor of kidney length. CONCLUSIONS: Relative renal length better represents kidney size than absolute renal length because it eliminates sex and height differences.

Resistance and pulsatility indices in acute renal obstruction.

PURPOSE: The aim of this study was to evaluate the reliability of Doppler waveform alterations in diagnosing acute unilateral renal obstruction. METHODS: From December 1993 to January 1996, 54 patients with unilateral renal obstruction were prospectively examined by conventional and duplex Doppler sonography. Seventy-eight patients with nonrenal abdominal problems comprised the control group. Doppler signals were obtained from interlobar arteries and arcuate arteries at the corticomedullary junction. From the waveform analysis, we calculated resistance (RI) and pulsatility (PI) indices. We also used the differences in RI and PI between the 2 kidneys in the same examinee (delta RI and delta PI) for further statistical analysis. RESULTS: The mean RI and PI (+/- standard deviation) in the patients without renal impairment were 0.64 +/- 0.04 and 1.14 +/- 0.14, respectively. The mean delta RI and delta PI were 0.02 +/- 0.01 and 0.07 +/- 0.05, respectively. Both the RI and PI were significantly correlated with age (r = 0.74 and 0.69, respectively; p < 0.01). Acute renal obstruction significantly (p < 0.01) elevated the mean RI (0.72 +/- 0.04), delta RI (0.09 +/- 0.04), PI (1.42 +/- 0.17), and delta PI (0.33 +/- 0.18). Significant decreases in RI and delta RI were noted after relief of the obstruction. The best accuracy in diagnosing acute unilateral renal obstruction was achieved with the combination of delta RI > or = 0.06 and/or delta PI > or = 0.20, which had a sensitivity of 94% and specificity of 99%. CONCLUSIONS: Renal Doppler indices are reliable parameters in the sonographic diagnosis of acute unilateral obstructive uropathy.

Inguinal hernia incarceration as a form of intestinal tuberculosis.

We report the case of a 41 year-old male who came to the emergency room with a complaint of abdominal pain, and was diagnosed to have an acute obstructive abdomen due to a right inguinal hernia incarceration. During surgery, an intestinal granulomatous inflammation was observed adhered to the hernial sac. The histopathologic study confirmed the diagnosis of tuberculosis. We present a review of the different clinical forms of intestinal tuberculosis and the difficulties encountered in the differential diagnosis of such, emphasizing the uncommon presentation described in our patient.

Management and complications of urolithiasis during pregnancy.

OBJECTIVE: To identify all pregnant women with urolithiasis, and to determine the mode of diagnosis and treatment with reference to obstetric outcome. METHOD: From January 1, 1986 to December 31, 1991, relevant medical records were retrospectively analyzed. RESULTS: Among 21,597 deliveries 10 pregnant women were diagnosed as having urolithiasis. They constituted 0.04% of all women who delivered at the Department of Obstetrics and Gynecology in Rijeka during this period. Conservative treatment was successful in 5 patients. Ureteral stents were inserted in 3 patients, nephrostomy was performed in 1 patient and a nephrectomy was necessary in 1 patient because of a nonfunctional kidney and chronic pyelonephritis. CONCLUSION: In our series all applied procedures in diagnosis and treatment of urolithiasis resulted in favorable maternal and perinatal outcome.