Validation of the Predisposition Infection Response Organ (PIRO) dysfunction score for the prognostic stratification of patients with sepsis in the Emergency Department.

OBJECTIVE: There are many different methods for computing the Predisposition Infection Response Organ (PIRO) dysfunction score. We compared three PIRO methods (PIRO1 (Howell), PIRO2 (Rubulotta) and PIRO3 (Rathour)) for the stratification of mortality and high level of care admission in septic patients arriving at the Emergency Department (ED) of an Italian Hospital. DESIGN, SETTING AND PARTICIPANTS: We prospectively collected clinical data of 470 patients admitted due to infection in the ED to compute PIRO according to three different methods. We tested PIRO variables for the prediction of mortality in the univariate analysis. Calculation and comparison were made of the area under the receiver operating curve (AUC) for the three PIRO methods, SOFA and qSOFA. RESULTS: Most of the variables included in PIRO were related to mortality in the univariate analysis. Increased PIRO scores were related to higher mortality. In relation to mortality, PIRO 1 performed better than PIRO2 at 30 d ((AUC 0.77 (0.716-0.824) vs. AUC 0.699 (0.64-0.758) (p=0.03) and similarly at 60 d (AUC 0.767 (0.715-0.819) vs AUC 0.709 (0.656-0.763)(p=0.55)); PIRO1 performed similarly to PIRO3 (AUC 0.765 (0.71-0.82) at 30 d, AUC 0.754 (0.701-0.806) at 60 d, p=ns). Both PIRO1 and PIRO3 were as good as SOFA referred to mortality (AUC 0.758 (0.699, 0.816) at 30 d vs. AUC 0.738 (0.681, 0.795) at 60 d; p=ns). For high level of care admission, PIRO proved inferior to SOFA. CONCLUSIONS: We support the use of PIRO1, which combines ease of use and the best performance referred to mortality over the short term. PIRO2 proved to be less accurate and more complex to use, suffering from missing microbiological data in the ED setting.

False-negative real-time polymerase chain reaction tests in COVID-19 patients: an epidemiological analysis of 302 patients.

OBJECTIVES: Patients who arrive at the emergency department (ED) with COVID-19, who test negative at the first real-time polymerase chain reaction (RT-PCR), represent a clinical challenge. This study aimed to evaluate if the clinical manifestation at presentation, the laboratory and imaging results, and the prognosis of COVID-19 differ in patients who tested negative at the first RT-PCR compared with those who tested positive and also to evaluate if comorbid conditions patient-related or the period of arrival are associated with negative testing. STUDY DESIGN: We retrospectively collected clinical data of patients who accessed the ED from March 1 to May 15, 2020. METHODS: We compared clinical variables, comorbid conditions, and clinical outcomes in the two groups by univariate analysis and logistic regression. RESULTS: Patients who tested negative at the first RT-PCR showed a higher prevalence of cardiopathy, immunosuppression, and diabetes, as well as a higher leukocyte and lower lymphocyte counts compared with patients who tested positive. A bilateral interstitial syndrome and a typical pattern at computed tomography scan were prevalent in the test-negative group. Test-negative patients were more likely to be admitted to the hospital but less likely to need admission in a high level of care ward. The false-negative rate increased from March to May. CONCLUSION: False-negative RT-PCR COVID-19 patients present a similar spectrum of symptoms compared with positive cohort, but more comorbidities. Imaging helps to identify them. True positives had a higher risk of serious complications.

Validation of the Predisposition Infection Response Organ (PIRO) dysfunction score for the prognostic stratification of patients with sepsis in the Emergency Department.

OBJECTIVE: There are many different methods for computing the Predisposition Infection Response Organ (PIRO) dysfunction score. We compared three PIRO methods (PIRO1 (Howell), PIRO2 (Rubulotta) and PIRO3 (Rathour)) for the stratification of mortality and high level of care admission in septic patients arriving at the Emergency Department (ED) of an Italian Hospital. DESIGN, SETTING AND PARTICIPANTS: We prospectively collected clinical data of 470 patients admitted due to infection in the ED to compute PIRO according to three different methods. We tested PIRO variables for the prediction of mortality in the univariate analysis. Calculation and comparison were made of the area under the receiver operating curve (AUC) for the three PIRO methods, SOFA and qSOFA. RESULTS: Most of the variables included in PIRO were related to mortality in the univariate analysis. Increased PIRO scores were related to higher mortality. In relation to mortality, PIRO 1 performed better than PIRO2 at 30 d ((AUC 0.77 (0.716-0.824) vs. AUC 0.699 (0.64-0.758) (p=0.03) and similarly at 60 d (AUC 0.767 (0.715-0.819) vs AUC 0.709 (0.656-0.763)(p=0.55)); PIRO1 performed similarly to PIRO3 (AUC 0.765 (0.71-0.82) at 30 d, AUC 0.754 (0.701-0.806) at 60 d, p=ns). Both PIRO1 and PIRO3 were as good as SOFA referred to mortality (AUC 0.758 (0.699, 0.816) at 30 d vs. AUC 0.738 (0.681, 0.795) at 60 d; p=ns). For high level of care admission, PIRO proved inferior to SOFA. CONCLUSIONS: We support the use of PIRO1, which combines ease of use and the best performance referred to mortality over the short term. PIRO2 proved to be less accurate and more complex to use, suffering from missing microbiological data in the ED setting.

Why Choose the Septum-Supero-Medial (SSM)-Based Mammaplasty in Patients with Severe Breast Ptosis: An Anatomical Point of View.

Nipple-areola complex (NAC) loss is one of the most devastating complications of mastopexy or breast reduction, and it requires revisional procedures with poor aesthetic outcome. In high-risk patients, a free nipple graft could be a choice, but it is associated with the same aesthetic concerns for both patients and surgeons. We report our experience with the septum-supero-medial-based mammaplasty to treat 22 patients with severe breast ptosis (nipple-to-sternal-notch distance > 40 cm). No NAC loss was observed. The study highlights surgical technical details and discusses anatomical considerations to justify the successful result. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Immunohistochemical assessment of Ki-67 in the differential diagnosis of adrenocortical tumors.

OBJECTIVES: To evaluate the utility of Ki-67 immunohistochemical analysis in the differential diagnosis between benign and malignant adrenocortical neoplasms. METHODS: Tissue specimens were obtained from 37 patients referred to our institute from 1990 to 1999. The indications for adrenalectomy were adrenal-dependent Cushing syndrome (n = 9), hyperandrogenism (n = 1), mineralocorticoid excess (n = 8), and nonfunctioning adrenal masses (n = 19). The histologic diagnosis was cortical adenoma in 26 of 37 patients and cortical carcinoma in the remainder. Normal adrenal glands were obtained from subjects who underwent radical nephrectomy because of initial renal carcinoma. Immunohistochemical analysis was performed using the monoclonal antibody anti-Ki-67 (clone MIB-1). The Ki-67 labeling index was expressed as the number of positive cells per 1000 cells.Results. The average Ki-67 expression was 2.0 per thousand +/- 1.2 per thousand (SD) in normal adrenal glands, 11.3 per thousand +/- 16.0 per thousand in adenomas, and 185.8 per thousand +/- 60.3 per thousand in carcinomas (P <0.0001). A threshold value of the Ki-67 labeling index between 70 per thousand and 90 per thousand reliably separated adenoma from carcinoma. A significant inverse correlation was found between Ki-67 expression and overall survival in patients with adrenal carcinoma (r = -0.74, P = 0.009). CONCLUSIONS: Immunohistochemical assessment of the nuclear antigen Ki-67 can be useful in the differential diagnosis between adrenocortical adenoma and carcinoma. High levels of Ki-67 seem to indicate patients with adrenocortical cancer with a worse prognosis.

Different immunohistochemical patterns of TGF-beta1 expression in benign and malignant adrenocortical tumours.

OBJECTIVE: Transforming growth-factor beta1 (TGF-beta1) influences a number of specific functions of adrenocortical cells in several animal species. The aim of our study was to evaluate by immunohistochemical analysis the presence and distribution of TGF-beta1 in normal adrenal tissue and in different adrenal tumours. PATIENTS: We analysed 8 functioning (5 adenomas and 3 carcinomas) and 15 non functioning (6 adenomas and 9 carcinomas) adrenal tumours and 6 normal adrenal glands. RESULTS: In normal adrenal glands, the glomerulosa and the reticularis zones displayed diffuse cytoplasmic staining, while the fasciculata zone was almost completely negative. Functioning adenomas displayed cytoplasmic staining restricted to compact cells while in nonfunctioning adenomas, prevalently composed by clear cells, no staining was observed. Overall, adrenal carcinomas were characterized by the lack of cytoplasmic positivity and by sporadic positive cells around vessels both in functioning and in nonfunctioning tumours. CONCLUSIONS: TGF-beta1 expression is associated with active steroid secretion in normal adrenal tissue, as well as in benign cortical adenomas, while this relationship is lost in primary adrenal malignancies. These data provide indirect evidence for a regulatory role played by TGF-beta1 on steroid secretory pathways.

Twenty-four hour profile of blood pressure in patients with acromegaly. Correlation with demographic, clinical and hormonal features.

Cardiovascular events are frequently reported in patients with acromegaly and they are usually related to arterial hypertension. Aim of the present study was to assess the 24-hour profile of blood pressure (BP) and heart rate (HR) in patients with active acromegaly and to correlate them with clinical and hormonal data. Sixteen patients and 16 healthy, age and sex matched subjects underwent ambulatory blood pressure monitoring by means of a portable automatic device (SpaceLabs monitor 90207, Kontron) with measurements every 20 minutes for 24 hours. The presence of the nocturnal fall was assessed by the calculation of the night-day systolic and diastolic ratio. The mean 24-hour diastolic BP was significantly higher in acromegalic patients than in controls (79.1+/-11.5 mmHg vs 70.8+/-5.3 mmHg, p<0.05) and the circadian diastolic profile was flatten. In fact, 10/16 patients were defined as nondippers while this figure was 2/16 in the control group (62% vs 12%, p<0.01). Also the mean 24-hour systolic BP was higher in acromegalic patients than in controls (124.8+/-17.2 mmHg vs 114.1+/-8.6 mmHg, p<0.05). The circadian systolic profile paralleled that of diastolic and was flatten, without a significant nocturnal fall. Ten out of 16 patients were nondippers compared to 2/16 controls (62 vs 12%, p<0.01). No significant correlation was found between mean 24-hour BP, either diastolic or systolic, and demographic or hormonal characteristics of the patients. HR patterns did not differ between patients and controls and were characterized by a prominent nocturnal fall.

Cushing's syndrome due to ACTH-independent bilateral adrenocortical macronodular hyperplasia.

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is a rare cause of Cushing's syndrome in which adrenal glands become very enlarged, occupied and distorted by multiple cortical nodules. We report on such two patients, a 44-year-old man and a 40-year-old woman. Physical examination revealed in both cases a classic cushingoid habit. Laboratory studies showed overt hypercortisolism with high urinary free cortisol excretion and elevated serum cortisol with loss of the circadian rhythm. Serum cortisol levels were not modified after high dose dexamethasone. ACTH levels were undetectable both in baseline conditions and following CRH or metyrapone. In both cases, abdominal CT demonstrated bilaterally enlarged adrenal glands which were distorted by multiple bumps. 131I-Norcholesterol scintiscan showed bilateral uptake of the radionuclide. Pituitary region was normal at neuroradiologic imaging. Bilateral adrenalectomy was performed in both cases. In patient I, adrenal glands weighted 77 and 90 g, respectively, while in patient II they were of 90 and 55 g, respectively. At histological examination, the adrenal cortex was occupied by multiple nodular lesions composed mostly of clear cells. In the internodular regions, no evidence of cortical architecture was observed. At the immunohistochemical evaluation, both cases displayed KI-67 staining comparable with that of ACTH-dependent diffuse hyperplasia. Postoperative course was uneventful and signs of Cushing's syndrome resolved in about three months. At the last follow up, the patients are going well on glucocorticoid and mineralocorticoid supplementation. Plasma ACTH levels are 65 and 107 pg/ml, respectively.

High frequency of p53 expression in colo-rectal adenomatous polyps.

Previous studies on p53 protein expression in colonic adenomas showed controversial results. The present study evaluates the p53 expression in colonic adenomas, at different dysplasia degrees, by immunohistochemical analysis, using a newly introduced monoclonal anti-p53 antibody. Paraffin embedded sections of 48 colorectal adenomas, 5 colonic carcinomas and 11 normal colonic biopsies were studied by immunohistochemical analysis using a monoclonal mouse anti-p53 antibody (clone DO-1). Normal colonic mucosa specimens and 5/48 adenomas were found negative for p53 staining. p53-positive nuclei were less than 10% in 22/48 and between 10 and 40% in 15/48 adenomas. In 6/48 adenomas and in 4/5 carcinomas we found a high percentage of p53-positive nuclei (> 40%). Immunohistochemical p53-positivity is a common event in colonic adenomas, not dependent on dysplasia degree. It might be the result of p53 wild-type increase, due to the typical genomic instability of colonic adenomas.

Misdiagnosis of Cushing's syndrome in a patient receiving rifampicin therapy for tuberculosis.

We hereby describe a patient in whom chronic rifampicin treatment led to a misdiagnosis of Cushing's syndrome. He had long-standing insulin-dependent diabetes mellitus and active tuberculosis resistant to conventional treatment. The course was complicated by muscle weakness, lower limb atrophy, unstable glycemic control and hypokalemia. Ectopic Cushing's syndrome was suspected on the basis of high urinary free cortisol excretion (UFC) with a blunted circadian profile of serum cortisol and measurable plasma ACTH concentrations. Dynamic endocrine tests and imaging studies were compatible with occult ectopic ACTH syndrome. After substitution of rifampicin UFC excretion returned to normal within two weeks, as well as the 24-h cortisol profile and dynamic tests. The present case provides a practical example of the possibility to incorrectly suspecting Cushing's syndrome in patients treated with rifampicin, as previously envisaged by pharmacological studies.

High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age.

BACKGROUND: An association between acromegaly and colonic polyps has been reported, although risk factors are still uncertain. METHODS: Full colonoscopy was performed with a fiberoptic colonoscopy on 31 acromegalic patients, 11 men and 20 women aged 27 to 85 years (mean, 52.2 years), and on 236 subjects, 127 men and 109 women aged 23 to 84 years (mean, 50.1 years), referred for hemorrhoids, who were considered controls. The colonoscopic findings were evaluated in relation to demographic, clinical, and hormonal data pertaining to the two groups. RESULTS: The prevalence of either adenomatous or hyperplastic polyps was higher in acromegalic patients than in controls (38% vs 14% and 26% vs 10%, respectively; P < .001, respectively). Acromegalics with and without colonic adenomas did not differ significantly in growth hormone and insulinlike growth factor I levels or duration of acromegalic disease and its status (activity or remission); however, patients with adenoma were younger (median age, 50.5 vs 59 years; range, 27 to 85 years vs 39 to 66 years; P < .05). An opposite age pattern was observed in the control group. Indeed, the prevalence of adenoma in acromegalic patients was much higher than that in controls among those less than 50 years of age (46% vs 7%, P < .001); the difference was less remarkable at older ages. Adenomatous polyps were more frequently found in male subjects, in both patients and controls (45% vs 33% [not significant] and 19% vs 9% [P < .05], respectively). CONCLUSIONS: Acromegaly may carry an increased risk of colonic adenoma, especially in younger patients, who usually display more aggressive disease. A smaller increase in risk was observed in elderly patients, in whom disease is reportedly milder. We suggest that acromegalic patients should undergo screening colonoscopy.

Biochemical markers of bone and collagen turnover in acromegaly or Cushing's syndrome.

We evaluated serum bone Gla-protein (osteocalcin, BGP), carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) in 15 patients with active acromegaly (6M aged 27-54, 4 PMF aged 39-51, 5MP aged 54-65 years), 12 with active Cushing's syndrome [(CS) 2M of 32 and 42 years; 4PMF aged 25-40; 6MF aged 50-64)] and controls evenly matched for age, sex and menstrual status. Patients with acromegaly were evaluated before and at regular intervals on octreotide treatment (50-150 micrograms t.i.d., s.c.); the duration of the follow-up was 5-49 months (median 28). Endocrine evaluation included measurements of serum GH, IGF-I, BGP, PICP and PIINP. In a case-control analysis, acromegalic patients showed increased BGP (14.3 +/- 2.1 vs 8.3 +/- 2.1 ng/ml p < 0.001) and PIIINP concentrations (4.8 +/- 1.4 vs 3.1 +/- 0.7 micrograms/l, p < 0.02). During octreotide treatment we observed a roughly parallel decline of GH, IGF-I and BGP. BGP and log-transformed 24-h mean GH concentrations were positively correlated (r = 0.48, p < 0.001) as was the case for BGP and IGF-I (r = 0.43, p < 0.001). Also PIIINP correlated with log-transformed GH (r = 0.58, p < 0.001) and IGF-I (r = 0.35, p < 0.05). Serum PICP did not differ in the two groups (152 +/- 55 vs 120 +/- 55 micrograms/l, NS) and did not correlate either with GH or IGF-I. Patients with CS were evaluated measuring serum and urinary cortisol (UFC), ACTH, BGP, PICP, PIIINP.(ABSTRACT TRUNCATED AT 250 WORDS)