Preprocedural prophylaxis with blood products in patients with cirrhosis: Results from a survey of the Italian Association for the Study of the Liver (AISF).

INTRODUCTION: The concept of rebalanced hemostasis in cirrhosis challenges the policy of transfusing plasma or platelets before invasive procedures in patients with prolonged PT or severe thrombocytopenia. Recent guidelines recommend against plasma transfusion and suggest avoiding/minimizing platelet transfusions. AIM: We assessed how hepato-gastroenterologists manage prolonged PT/INR or severe thrombocytopenia before invasive procedures. METHODS: On May 2021, AISF members were sent a questionnaire addressing the PT/INR and platelet thresholds required before invasive procedures, the use of other markers of bleeding risk or other hemostatic treatments and the burden of pre-emptive plasma and platelet transfusions. RESULTS: Of 62 respondents, 94% and 100% use PT/INR and platelet count to assess bleeding risk, respectively. Only 37% and 32% require less conservative PT/INR or platelet counts thresholds for low-risk procedures, respectively. As for those applying single thresholds, 68% require PT/INR <1,5 and 86% require platelet counts ≥50 × 109/L. Half respondents use additional indicators of bleeding risk and 63% other hemostatic treatments. Low-risk procedures account for 70% of procedures, and for 50% and 59% of plasma and platelets units transfused, respectively. CONCLUSIONS: the survey indicates lack of compliance with guidelines that advise against plasma and platelet transfusions before invasive procedures and the need for prospective studies and inter-society consensus workshops.

Pain-relieving properties of topically applied morphine on arterial leg ulcers: a pilot study.

OBJECTIVE: To assess whether topical morphine is pharmacologically effective in relieving pain from ulcers caused by arterial insufficiency and identify whether this effect is centrally or peripherally mediated. METHOD: The analgesic effect of a topically applied hydrogel containing 0.5% of morphine was evaluated in a double-blind, placebo-controlled, three-way crossover pilot study involving nine patients with painful arterial leg ulcers. All patients had a baseline pain intensity of at least 5 on a 10-point numeric rating scale. They received the following three treatments in random order: morphine hydrogel plus a subcutaneous (SC) placebo infusion; placebo gel plus a SC infusion of 5mg morphine over six hours and a placebo gel plus a SC placebo infusion. Each treatment lasted one day. Pain was assessed during the first 24 hours after application of the hydrogel and the start of the subcutaneous infusion. RESULTS: There was a statistically significant difference between average baseline pain scores and those reported during treatment, but this difference was not clinically relevant. The three treatments did not differ in terms of the pain relief provided. CONCLUSION: Topical morphine does not have a clinically relevant analgesic effect in patients with painful arterial leg ulcers. Further research should focus on ulcers of other aetiology.

Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot study. Energy intake was reduced by 30%, and walking for at least 30 min a day was strongly recommended. DZX treatment was started at 50 mg t.i.d. and increased by 50 mg per dose every 4 weeks to a maximum of 300 mg t.i.d., unless hyperglycaemia or other side-effects occurred. SUBJECTS AND METHODS: Eighteen obese hyperinsulinaemic men with a body mass index of 30-35 kg/m(2). Measurements included body weight, body composition, blood pressure, glycaemic control, insulin response, adiponectin and serum lipids. RESULTS: Body weight decreased by 9.4 kg (95% CI: 5.6-13.2 kg, p < 0.001), waist circumference reduced by 9.2 cm (95% CI: 5.3-12.9 cm, p < 0.001) and total body fat mass decreased by 23.3% (95% CI: 13.7-32.9%, p < 0.001), without a concomitant change in soft tissue lean body mass or bone mass. Fat loss was inversely related to fasting insulin levels achieved at 6 months (r = -0.76, p < 0.002). Diastolic blood pressure decreased by 10.9 mmHg (95% CI: 6.5-15.4 mmHg, p < 0.002). Fasting and postmeal peak insulin levels were reduced by about 65% (p < 0.001) and decreased to the normal range for non-obese men. Fasting and postmeal peak glucose levels increased by 0.8 +/- 0.3 mmol/l (p = 0.01) and 1.4 +/- 0.7 mmol/l (p = 0.06) respectively. Haemoglobin A1c rose by 0.5% to 5.9 +/- 0.2%. CONCLUSION: High-dose DZX-mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.

An international surgical collaboration: humanitarian surgery in Brazil.

PURPOSE: Brazil is the fifth most populous country in the world with widespread regional and social inequalities. Regional disparities in healthcare are unacceptably large, with the remote and poor regions of the north and northeast having reduced life expectancy compared to the south region, where life expectancy approaches that of rich countries. We report our experience of a humanitarian surgery mission to the Amazonas state, in the northwest part of Brazil. METHODS: In August 2014, a team of seven consultant surgeons, and two trainees with the charity 'International Hernia', visited three hospitals in the Amazonas state to provide hernia surgery and training. RESULTS: Eighty-nine hernias were repaired in 74 patients (female = 22, male = 52) with a median age of 44 years (range 2-83 years). Nine patients underwent more than one type of hernia repair, and there were 9 laparoscopic inguinal and ventral incisional hernia repairs. Local doctors were trained in hernia repair techniques, and an International Hernia Symposium was held at the University of the State of Amazonas, Manaus. CONCLUSION: The humanitarian mission provided hernia surgery to an underserved population in Brazil and training to local doctors, building local sustainability. Continued cooperation between host and international surgeons for future missions to Brazil will ensure continuing surgical training and technical assistance.

Potential uses of topical opioids in palliative care--report of 6 cases.

Opioids used topically may exercise several useful clinical effects. Opioids may cause immediate local analgesia and also may work indirectly through decreasing the inflammation process. In this article we describe six patients treated with topical opioids because of cutaneous pain due to tumor infiltration. skin ulcers of malignant and non-malignant origin, severe oral mucositis, pain due to knee arthrosis and severe tenesmoid pain. In all but one case, topical morphine provided rapid relief which lasted usually for 7-8 h. The side effects of topical opioids were none or minimal. Possible mechanisms of topical analgesia are discussed.

Contrast vaginography is more accurate than the radiopaque rod for localization of the vagina.

PURPOSE: To compare the radiopaque vaginal rod method with contrast vaginography in localization of the vagina. METHODS AND MATERIALS: In 25 female patients who needed pelvic radiotherapy, both our standard localization procedure using the vaginal rod and a localization procedure using contrast vaginography were performed. As a rod can change the position of the vagina, contrast vaginography was considered to display the true anatomic position of the vagina. The corresponding rod and nonrod X-rays of each patient were compared. The distance from the true vaginal apex to the displaced vaginal apex (= the top of the rod) was measured in the sagittal plane. This distance was called the inaccuracy of the rod method. Furthermore, the size of the vaginal vault was measured using the contrast vaginography. RESULTS: The median inaccuracy of the rod method was 13 mm (range 2 to 24 mm). The maximal width of the vagina ranged from 24 to 68 mm in the frontal plane (median 39 mm) and from 3 to 22 mm in the sagittal plane (median 10 mm). CONCLUSION: The rod method is not accurate to localize the vagina. Furthermore, the rod gives no information on the actual size of the vaginal vault. Contrast vaginography is the method of choice to localize the vagina.

Constitutive cyclooxygenase-1 and induced cyclooxygenase-2 in isolated human iris inhibited by S(+) flurbiprofen.

The purpose of the present study was to characterize the isoforms of cyclooxygenase (COX) in the human iris before and after stimulation with lipopolysaccharide (LPS) and to determine the selectivity of the nonsteroidal anti-inflammatory drug (NSAID), S(+) flurbiprofen, for inhibition of COX-1 and COX-2 in homogenates of this tissue. Spotblots were made of extracts of human iris in the absence and presence of LPS plus acetylsalicylic acid (aspirin). After reacting with anti-COX-1 and anti-COX-2 immunoglobulin G, the presence of both immunoreactive COX enzymes was substantiated using an indirect immunoperoxidase method. Authentic COX-1 and COX-2 were used as controls. Using an enzyme immune assay (EIA), the production of prostaglandin E2 (PGE2) was quantified in tissue homogenates of human iris under the same conditions as described above. S(+) flurbiprofen was added to tissue homogenates in order to determine the inhibitory effect on PGE2 production. Half maximal inhibitory concentrations (IC50) of S(+) flurbiprofen for the PGE2 production in the tissue homogenates were determined from concentration inhibition curves. The selectivity of S(+) flurbiprofen for inhibition of COX-1 was expressed as the ratio of IC50 for COX-2/COX-1. Spotblots of nonstimulated iris-extracts showed positive staining for COX-1 immunoreactivity (-ir) only. After incubation with LPS plus acetylsalicylic acid, positive staining was observed for both COX-1-ir and COX-2-ir. Concentrations of PGE2 released from homogenates of untreated iris varied from 1.5-4 ng/ml, and of LPS-stimulated tissue from 10-20 ng/ml of assay mixture. S(+) flurbiprofen inhibited PGE2 production of untreated tissue homogenates at an IC50 of 8 x 10(-10) M whereas, in the stimulated tissue, IC50 was found to be 3 x 10(-6) M. The selectivity of S(+) flurbiprofen for inhibition of constitutively present COX-1, relative to the inhibition of induced COX-2, was 3,600. Our results indicate that specific expression of COX isoforms in normal human iris was substantiated at the protein level by immunoreaction on spotblots. COX-1 represents the constitutively present enzyme, and COX-2 appears after stimulation with LPS. At the functional level, S(+) flurbiprofen possesses a specificity for COX-1 in inhibiting PGE2 production.

Flurbiprofen and enantiomers in ophthalmic solution tested as inhibitors of prostanoid synthesis in human blood.

The purpose of this study was to assess the selectivity and potency of the nonsteroidal anti-inflammatory drug (NSAID), flurbiprofen, and its enantiomers in their inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). An assay was used with freshly drawn, heparinized human whole blood, incubated with 25 microM calcium ionophore A23187 during 60 min to produce thromboxane B2 (TXB2) by activity of COX-1 in platelets. Incubation with E. coli lipopolysaccharide (LPS) during 24 hr produced prostaglandin E2 (PGE2) by induction of COX-2 in monocytes, suppressing any possible contribution of COX-1 activity by the addition of acetylsalicylic acid. Concentration inhibition curves were determined with racemic, S(+), and R(-) flurbiprofen in final concentrations ranging from 10(-3) to 10(-10) M. The stereoselectivity of S(+) flurbiprofen vs. R(-) flurbiprofen, expressed as the reciprocal of the ratio of the concentrations giving 50% inhibition (IC50), is 340 for COX-1 and 56 for COX-2. The selectivity for COX-1 vs. COX-2, expressed as the reciprocal ratio of the IC50, was 32 for racemic, 16 for S(+), and 5.3 for R(-) flurbiprofen. Meloxicam in the same assay showed COX-2 selectivity with a ratio of 0.19.

[Normal urinary levels of telopeptide aminoterminal (NTx) of type I collagen in healthy term newborns and infants in the first month of life]. / Livelli normali urinari di telopeptide amino terminale (NTx) del collagene di tipo I in neonati a termine e lattanti sani nei primi tre mesi di vita.

The Authors have studied urinary aminoterminal telopeptide of type I collagen (NTx), a bone catabolism marker of recent determination, by an enzyme-linked immunoassorbent assay (OSTEOMARK) in 80 urine samples of term healthy infants in the first 3 months of life. Highly significant variations have been compared in the whole period studied (P = 0.000). Levels of NTx increase significantly from 1 to 7 days of life, reaching a plateau that is kept until 45th day and then significantly decrease until 90th day, when, however, they result higher than the values reported in literature concerning older ages. The Authors conclude that even this bone catabolism marker is influenced, in the first week of life, by the particular phenomenology linked to the neonatal adaptation, and that, subsequently, shows a trend strictly linked to the bone turnover modifications throughout the faster stage of the growth.

Outcome and quality of screening in a nationwide survey on retinopathy of prematurity in The Netherlands.

PURPOSE: Provide insight in natural history, screening and treatment policy of retinopathy of prematurity (ROP) in The Netherlands. METHODS: A multicentre, prospective, population-based study (NEDROP) included all preterm infants born in 2009 in The Netherlands fulfilling the inclusion criteria for ROP screening. Anonymised data from ophthalmologists, neonatologists and paediatricians were merged on identification number. RESULTS: Of 2033 reported infants, 1688 (83%) were screened for ROP. ROP stage was reported in 100%, zone in 94.4% and plus disease in 83%. ROP developed in 324 (19.2%), mild ROP (stage 1-2) in 294 (17.4%), severe ROP (stage 3 or more) in 30 (1.8%) and 17 (1%) were treated. The initial screening examination was not performed within the required 42 days in 641 (38%). Date for follow-up was recorded 1973 times and accomplished within 3 days from the planned date in 1957 (99.2%). The chance of not being screened increased from 12.9% without transfer to another hospital to 23.5, 18.5 and 25% after 1, 2, or 3 transfers, respectively. CONCLUSIONS: The incidence of severe ROP and infants treated was low. NEDROP emphasises that timing of initial examination and transfer to another hospital are issues of concern within the screening process.

Reduction in screening for retinopathy of prematurity through risk factor adjusted inclusion criteria.

AIMS: To develop a new national screening guideline for retinopathy of prematurity (ROP). METHODS: Included were infants of the 2009 prospective ROP inventory in The Netherlands with gestational age (GA) <32 weeks and/or birth weight (BW) <1500 g. Five models were studied, based on GA and BW in combination with no, one or a set of five risk factors for ROP. Risk factors were determined by logistic regression. In MEDLINE and EMBASE, additional risk factors were searched. A precondition was that no infants with severe ROP would be missed. Receiver operating characteristic curves or classical measures were used to determine diagnostic accuracy. RESULTS: The model including all infants with severe ROP comprised screening of infants with GA <30 weeks and/or BW <1250 g and a selection of infants with GA 30-32 weeks and/or BW 1250-1500 g, with at least one of the following risk factors: artificial ventilation (AV), sepsis, necrotising enterocolitis (NEC), postnatal glucocorticoids or cardiotonica. This model would not detect 4.8% (95% CI 2.5% to 8.0%) of infants with mild ROP and would reduce infants eligible for screening by 29%. CONCLUSIONS: In The Netherlands, screening may be safely reduced using a new guideline based on GA, BW, AV, sepsis, NEC, postnatal glucocorticoids and cardiotonica.

The incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant disabilities in the Netherlands: a 30 year overview.

AIM: To determine the incidence of visual impairment (VI) caused by retinopathy of prematurity (ROP) and concomitant disabilities in preterm neonates born between 2000 and 2009 in the Netherlands. METHODS: Data were retrieved from the Dutch institutes for the visually impaired. They were compared with similar Dutch studies conducted in 1975-1987, 1986-1994 and 1994-2000. RESULTS: Records of 42 infants with VI due to ROP were included. A gradual decrease of gestational age and birthweight but an increase of duration of artificial ventilation, supplemental oxygen administration, bronchopulmonary dysplasia, developmental delay and behavioural abnormalities was found. Compared with the previous study (1994-2000), significantly fewer children were visually impaired due to ROP (1.84 per 100,000 live births/year vs 3.93 per 100,000 live births/year, p=0.000), the incidence of complete blindness decreased from 27.5% to 7.1% (p < 0.05) and more children were treated (66.7% vs 56.9%, NS). The incidence of concomitant disabilities was high and did not differ greatly from the previous study. CONCLUSION: This was a retrospective study showing a significant decrease in VI due to ROP in the Netherlands. Changes in neonatal care practices did not result in a decrease in the incidence of concomitant disabilities. More children were treated for ROP, but 33% were not treated.

Randomized clinical trial of surgical technique and local antibiotics for ingrowing toenail.

BACKGROUND: The aim of this study was to investigate different surgical techniques for treating ingrowing toenails (IGTNs) and to determine the value of a locally applied antibiotic after intervention. METHODS: One hundred and twenty-three patients with IGTN were assigned randomly to one of four groups. All patients had partial nail avulsion. This was combined with excision of the matrix or application of phenol, with or without local application of gentamicin afterwards. All procedures were performed by one physician. The primary outcome measure was symptomatic recurrence of IGTN. RESULTS: One hundred and seventeen patients were available for follow-up. Phenol gave significantly better results than matrix excision with respect to recurrence (including regrowth and spike formation) after 1 year (P < 0.001). In terms of signs of infection, there was no significant difference between phenol and matrix excision after 2 days (P = 0.224) or 1 week (P = 0.501). Antibiotics had no effect in reducing the risk of infection after 2 days (P = 0.989) or 1 week (P = 0.676), or in reducing the rate of recurrent IGTN at 1 year (P = 0.187). If regrowth or spike formation is included, the effect is even less significant (P = 0.876). CONCLUSION: Partial nail avulsion with phenolization gave better results than partial avulsion with matrix excision. Local antibiotics did not reduce signs of infection or recurrence. Use of phenol did not produce more signs of infection than matrix excision.

[Multiple arterial ischemic strokes in a child with moyamoya disease and Mycoplasma pneumoniae infection]. / Infarti cerebrali multipli in una paziente pediatrica con malattia di moyamoya e infezione da Micoplasma pneumoniae.

Moyamoya disease is a rare disorder characterised by a progressive occlusion or stenosis of the distal portions of bilateral internal carotid arteries with the development of a network of collateral vessels. Pediatric patients show transient ischemic attacks or strokes; diagnosis is made on the basis of clinical and radiographic findings. The case of a 2-year-old female, which after a Mycoplasma pneumoniae infection presented multiple cerebral strokes is reported. A diagnosis of moyamoya disease was made on the basis of neuroradiological findings; neurological complications due to Mycoplasma infection are reported and the relationship between disease and infection are discussed.