Normal reference ranges of antithrombin,protein C and protein S: Effect of sex,age and hormonal status

Introduction

Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, age, menopause and hormone therapy on natural anticoagulant plasma levels in a large group of healthy individuals, and to evaluate the need of separate reference ranges.

Materials and Methods

AT and PC were measured with a chromogenic assay, antigenic free PS with an ELISA test. To evaluate the effect of sex, age, oral contraception, hormonal status (and their interaction) on AT, PC and PS levels, linear regression models were used. Biological relevance and the value of the normal deviate z were chosen as rules to decide for separate reference ranges.

Results

The study population consisted of 1837 healthy adult individuals (741 men, 1096 women), aged 18-85 years (median age: 44 years). In men AT levels decreased after the age of 50 years. Men had higher levels of PS than women, particularly at young ages. In women, after correction for menopause, only PC levels increased with age. Menopause affected AT and PS, but not PC levels. Oral contraceptive intake was associated with a decrease of AT and PS, and an increase of PC levels.

Conclusions

For AT, PC and PS, sex- and age-specific normal reference ranges can be useful, in order to better discriminate true carriers of a natural anticoagulant deficiency.     

Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection

Objective

To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Materials and methods

Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N?=?0) or with one (N?=?1) or more than one metastatic node (N?>?1). The risk of multiple pelvic lymph node metastasis (N?>?1, mPLNM) was assessed by comparing it to the other two groups (N?>?1 vs. N?=?0 and N?>?1 vs. N?=?1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT?>?1) and tumor grade group greater than two (ISUP?>?2).

Results

Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N?=?1 and 31 (5%) with N?>?1. On multivariate analysis, ET was inversely associated with the risk of N?>?1 when compared to both N?=?0 (odds ratio, OR 0.997; CI 0.994–1; p?=?0.027) as well as with N?=?1 cases (OR 0.994; 95% CI 0.989–1.000; p?=?0.015).

Conclusions

In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

     

Monomeric (7S) IgM found in the serum of rheumatoid arthritis patients share idiotypes with pentameric (19S) monoclonal rheumatoid factors

Serum from some seropositive (RF+) rheumatoid arthritis (RA) patients contains relatively high concentrations of monomeric (7S) IgM molecules. Seven S IgM molecules fail to bind the Fc portion of IgG, unlike 19S IgM RFs that bind aggregated IgG in classical RF assays. Some pentameric IgM RFs are marked by crossreactive idiotypes (RCRI) defined by prototypic monoclonal RFs. In previous studies, we observed that a proportion of pokeweed mitogen (PWM) induced plasma cells from RA patients' blood lymphocytes express the major RCRI as assayed by indirect immunofluorescence with polyclonal anti-RCRI antibodies. In this study, 7S IgM obtained from three different RF+ RA patients inhibits specific anti-RCRI intracytoplasmic staining of PWM induced RF+ RA-derived plasma cells. These 7S molecules also block polyclonal anti-RCRI antibodies from reacting with red blood cells bearing 7S IgM molecules from RF+ patients with RA or Waldenstrom's macroglobulinemia. We conclude that some 7S IgM molecules in the serum of RF+ RA patients are marked by the major RCRI idiotype and are related to 19S monoclonal and polyclonal RFs.     

Tumor–parenchyma interface and long-term oncologic outcomes after robotic tumor enucleation for sporadic renal cell carcinoma

Objective

Tumor enucleation has been shown to be oncologically safe for elective treatment of renal cell carcinoma (RCC); yet, evidence on long-term oncologic outcomes after robotic tumor enucleation is lacking.In this study we provide a detailed histopathological analysis of tumor–parenchyma interface and the long-term oncologic outcomes after robotic tumor enucleation for sporadic RCC in a high-volume referral center.

Acute Vs. Elective Paraesophageal Hernia Repair: Endoscopic Gastric Decompression Allows Semi-Elective Surgery in a Majority of Acute Patients

Background

Historically, patients presenting acutely with paraesophageal hernia and requiring urgent operation demonstrated inferior outcomes compared to patients undergoing elective repair.

Methods

A prospective IRB-approved database was used to retrospectively review 570 consecutive patients undergoing paraesophageal hernia repair between 2000 and 2016.

Results

Thirty-eight patients presented acutely (6.7%) and 532 electively. Acute presentation was associated with increased age (74 vs. 69 years) but similar age-adjusted Charlson comorbidity scores. A history of chest pain, intrathoracic stomach ≥75%, and mesoaxial rotation were more common in acute presentations. Emergency surgery was required in three patients (8%), and 35 patients were managed in a staged approach with guided decompression prior to semi-elective surgery. Acute presentation was associated with an increased hospital stay (5 (2–13) days vs. 4 (1–27) days, p = 0.001). There was no difference in postoperative Clavien-Dindo severity scores. One patient in the elective group died, and the overall mortality was 0.2%.

Conclusion

Our findings suggest that a majority of patients presenting with acute paraesophageal hernia can undergo a staged approach instead of urgent surgery with comparable outcomes to elective operations in high-volume centers. We suggest elective repair for patients presenting with a history of chest pain, intrathoracic stomach ≥75%, and a mesoaxial rotation.

     

Carbon dioxide elimination during laparoscopy in children is age dependent

The absorption of carbon dioxide (CO₂) used for positive pressure pneumoperitoneum may lead to an increased CO₂ load. CO₂ elimination during laparoscopy has not been investigated previously in paediatrics. The aim of this study was to characterise the pattern of CO₂ elimination during laparoscopic surgery in infants and children. Methods: Twenty children undergoing laparoscopy and 19 children undergoing laparotomy for elective abdominal operations were studied. Pneumoperitoneum was achieved using insufflation of unheated CO₂. CO₂ elimination (metabolically produced + absorbed; milliliters per kilogram per minute) was measured minute by minute during the operation by indirect calorimetry. End-tidal CO₂ (kPa) was recorded every 10 minutes. The above variables were assessed before CO₂ insufflation, during pneumoperitoneum, and after desufflation. Results: Before insufflation, CO₂ elimination was 4.6 [plusmn] 0.3 ml/kg/min and increased after 15 minutes of pneumoperitoneum to 5.2 [plusmn] 0.3 (P [lt ] .001). Post desufflation, CO₂ elimination decreased toward preinsufflation values, but did not return to baseline by the end of operation (5.8 [plusmn] 0.3; P [lt ] .001). End-tidal CO₂ was 4.7 [plusmn] 0.2 preinsufflation, peaked at 1 hour (5.3 [plusmn] 0.2; P [lt ] .001) and subsequently decreased in response to ventilatory adjustments. The total amount of CO₂ insufflated was positively correlated with patient age (r² = 0.27; P [lt ] .01). CO₂ elimination was age related, as indicated by multilevel model analysis and by negative correlations between maximum increase in CO₂ elimination and both age (r² = 0.27; P [lt ] .01) and weight (r² = 0.29; P [lt ] .01). These data suggest that the younger or smaller the child, the larger the increase in CO₂ elimination. Seven patients (35%) responded to desufflation with a sharp transient increase in CO₂ elimination, which did not appear to be related to patient age, length of pneumoperitoneum, abdominal pressure, or type of operation. Conclusions: During pneumoperitoneum, younger children absorb proportionately more CO₂ than older individuals. The short-lived increase in CO₂ elimination postdesufflation may be related to an increase in venous return from the lower limbs after release of the abdominal pressure. These findings suggest that small children warrant close monitoring during laparoscopy and during the immediate postoperative period. J Pediatr Surg 38:105-110.     

The role of epsilon phenotype in brain glucose consumption in Alzheimer’s disease

The aim of our study was to investigate the impact of the epsilon phenotype in brain glucose consumption in a population with Alzheimer’s disease. Statistical Parametric Mapping (SPM8) was used to investigate differences in brain glucose consumption (as detectable by means of 18F FDG-PET/CT) in the population examined. A total of 129 patients (72 females and 57 males) with a diagnosis of probable AD according to the NINCDS-ADRDA criteria underwent the PET/CT examination. The mean (SD) age of the patients was 70 (± 7) years; the mean Mini-Mental State Examination was 19(± 5.6). 59 expressed epsilon 4 phenotype (E4) and 70 expressed the epsilon 3 phenotype (E3). Cerebral spinal fluid amyloid, tau, and t-tau have been measured resulting equal to 367.4 (± 149.1), 584.7 (± 312.1), and 79.2(± 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered as high risk of AD, were classified as IAD. Age, sex, MMSE, scholarship, and CSF parameters were used as a covariate in the SPM analyses. We did not find significant differences in age, gender, and MMSE and CSF parameters among groups. In the analysis of the AD group as compared to AD-E3, AD-E4 subjects show a significant reduction of brain glucose consumption in inferior frontal gyrus bilaterally (BA 45, BA 47). In the analysis of the IAD group as compared to IAD-E3, IAD-E4 subjects show a significant reduction of brain glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and between IAD-E4 and AD-E4 (and vice versa analysis) resulted not significant. APO-e4 is related to a major involvement of the frontal cortex confirming its role of risk factor in AD, while APO-3 seems not related to a specific pattern, supporting the hypothesis of neutral/protective role in AD.     

Cytological aspects of the nasal respiratory epithelium in reproductive-age women taking oral contraceptives

Objective To determine the effects of monophasic oral contraceptives on the nasal respiratory epithelium in premenopausal women.

Design Prospective open clinical trial.

Setting Outpatient Family Planning Centre.

Patient(s) Eighty-eight premenopausal women, with ovulatory cycle, who were planning to take oral contraceptives.

Intervention(s) Baseline endovaginal ultrasound examination and blood test to measure serum progesterone to confirm ovulatory cycle. Thirty-eight women on pill containing 30 μg ethinylestradiol (EE) plus 75 μg gestodene, and 35 women on pill containing 15 μg ethinylestradiol plus 60 μg gestodene.

Main outcomes/Measure(s) Cytological changes on the nasal respiratory epithelium evaluated with the maturation index performed during the follicular, periovular, and luteal phases of the menstrual cycle, and on the sixth cycle of pill intake.

Result(s) Hematoxylin-eosin staining for the maturation index showed similar trophic cytological aspects between the nasal and vaginal epithelium during the menstrual cycle and pill usage. Both the nasal and vaginal cytological samples showed higher maturation indexes during both the follicular and the periovular phases than during the luteal phase. Women on pill containing 15 μg EE showed lower trophic aspects in the nasal cytological samples compared with those on pill with 30 μg EE.

Conclusion(s) Along with the vaginal cells, the nasal respiratory epithelium is an ovarian steroid target. The maturation index of the nasal respiratory epithelium seems to depend on the variation of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives.