Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

OBJECTIVES: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. METHODS: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. RESULTS: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. CONCLUSIONS: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.

The road ahead for cervical cancer prevention and control.

Since the early 1950s, Papanicolaou ("Pap") cytology screening has dramatically reduced cervical cancer mortality in most high-income settings. Currently, human papillomavirus (hpv) vaccination has the greatest potential to reduce the global burden of cervical cancer and precancerous lesions. However, as the prevalence of precancerous lesions declines, maintaining cytology as the primary screening test in settings with established programs might become less efficient. A reduction in test performance (sensitivity, specificity, and positive predictive value) would lead to an increase in unnecessary colposcopy referrals. Fortunately, hpv dna testing has emerged as a suitable candidate to replace cytology. Compared with the Pap test, hpv testing is less specific but much more sensitive in detecting high-grade precancerous lesions, less prone to human error, and more reproducible across settings. Linkage of hpv vaccination and screening registries could serve the added role of monitoring vaccine efficacy. As a triage test, cytology is expected to perform with sufficient accuracy because most hpv-positive smears would contain relevant abnormalities. This approach and others-for example, hpv testing followed by genotyping-are being evaluated in large population studies and have already been recommended in some settings. Other specific biomarkers that might perform well for screening and triage include hpv E6/E7 messenger rna testing, methylation of host or viral genes, and p16(INK4a) staining. Considering the rapid pace of major discoveries and the anticipated arrival of a nonavalent hpv vaccine (currently in phase iii trials), the evidence base in this field has become an elusive target and will continue to be an obstacle for policymakers.

[Esophageal anastomosis--based on the experience with 1460 operations]. / Nyelócsó anasztomózisokról: 1460 mútét tapasztalata alapján.

The authors reviewed the clinical records of 1460 patients with esophageal anastomoses, the operations performed in their institute between 1973 and 2000. Surgical outcome was assessed with incidence of anastomotic leaks and overall mortality. Hand-sewn anastomoses were performed by inserting single layer interrupted monofil steel wire (507), PDS (232) or Vicryl (65) sutures and circular stapler (EEA, Ethicon) was used in 656 patients. 453 (65 cervical, 293 thoracic, and 95 abdominal) anastomoses performed between 1995 and 2000 were analyzed separately. During this 6-year period, the majority of operations (88%) were performed because of esophageal malignancy (squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia). Surgery was performed for benign disease (e.g. stricture, perforation, and stage IV achalasia) in 12%. The incidence of anastomotic leak was the highest (20%) after cervical anastomosis, compared to a 4.4% or 1% associated with thoracic or abdominal anastomoses. These differences are statistically significant (p < 0.001). The rate of anastomotic leakage was strongly connected to surgical technique: it was 15% in hand-sewn anastomoses and only 4.4% with stapled anastomosis. During the 6-year period overall mortality was 6.6%t.

[Method for the determination of the functional degree of esophageal stricture and the effectiveness of dilatation]. / Módszer a nyelöcsöszükületek funkcionális mértékének és a nyelöcsötágítás hatékonyságának megítélésére.

Based on their experiences of 494 oesophagus dilatation in 98 patients, authors developed a stadium system for defining the severity of dysphagia caused by oesophagus stenosis of stricture. This system is usable for follow-up the course of the disease, for the establishing the necessity of the dilatation, and for the comparison of results achieved by different dilatation methods, as well. The method is based on simple, well-defined clinical parameters, special skills or instrumentations not required, and fits the clinical experiences of many years of the authors. For this reasons it is useful both general practitioners and for the specialists performing the esophagus dilatation, as well.

Dilation of strictures after esophageal resection and reconstruction.

Dilation has remained an indispensable method of therapy for postoperative esophageal stricture even nowadays. Dilation with proper equipment and instruments of esophageal stricture after resection is a safe procedure. It can be performed most effectively and with reduced danger by Savary-Gilliard instrument or balloon. If it is only scar and there is no relapse, dysphagia starts mostly within 2-3 months after the operation. In the case of local relapse the postoperation stenosis gives rise to dysphagia later. The possible presence of postoperative fistula does not contraindicate stricture dilation. In fact, the dilation of narrow anastomosis helps the closure of the fistula.

Role of ultrasonography in the differential diagnostics of neck masses.

Ultrasonography of 70 cases of palpable neck masses are analyzed. On the basis of histological diagnoses the cases are put into groups of cysts, tumors and other lesions of the neck. According to this grouping the aetiological factors are also discussed (congenital lesions: mainly cysts, lesions of the salivary glands and the parotid gland, thyroid and parathyroid diseases, vascular lesions). The diagnostic value of ultrasonography is calculated in view of the morphological signs of a given lesion. The specificity, sensitivity and the accuracy of ultrasonography in our material supports the view that in the differential diagnostics of neck masses ultrasonography is a useful, simple and effective tool.

[Disorders of acid-base equilibrium in the cerebrospinal fluid after intracranial operations]. / Dynamika zaburzen równowagi kwasowo-zasadowej w plynie mózgowo-rdzeniowym u chorych po zabiegach sródczaszkowych.

The authors collected 27 patients after intracranial operations in whom the cerebrospinal fluid was investigated at least 3 times during 10 days. The patients were divided into 2 groups--a group of 16 patients with favourable outcome, and a group of 11 patients who died. On the basis of arithmetical means of pCO2 and HCO3 values hypothetical curves of the course of acid-base equilibrium in the blood and cerebrospinal fluid were plotted in both groups during 10 days. In the initial period metabolic acidosis was found in the cerebrospinal fluid and respiratory alkalosis in the blood in both groups. After several days metabolic alkalosis developed in the group of patients with favourable outcome while the metabolic acidosis in the cerebrospinal fluid was balanced. In the group with unfavourable outcome metabolic alkalosis in the blood was less evident and metabolic acidosis in the cerebrospinal fluid was increased. The authors think that metabolic alkalosis in the blood has a compensatory effect on metabolic acidosis in the cerebrospinal fluid and brain.

Histological findings in infantile otoantritis.

The histopathological findings in the granulation tissue removed at mastoidectomy from 34 infants between 1971 and 1974 are described. Granulation tissue was present in every case, characterized by the histological features of chronic inflammation and fibrosis (sclerosis), although the process was of short duration. The great number of thick fibers was a surprising finding. To prevent fibrosis (sclerosis) to develop later on, it is advisable to operate as early as indicated.

[Acid-base equilibrium in cerebrospinal fluid following intracranial surgery]. / Równowage kwasowo-zasadowa w plynie mózgowo-rdzeniowym u chorych po zabiegach sródczaszkowych

In 48 patients the acid-base equilibrium in the CSF and blood was determined on the 2nd day after intracranial operation. In the postopertive period various disturbances of this equilibrium were found which were probably various stages of metabolic acidosis compensation in the CSF which was a reflection of metabolic (lactate) acidosis developing primarily in the damaged brain area. On the basis of determinations it was found that changes in the CSF of the type of metabolic acidosis (21 cases) corresponded most frequently to respiratory alkalosis in the blood (11 cases). Changes of the type of respiratory acidosis in the CSF(13 cases) corresponded usually to metabolic alkalosis in the blood (7 cases). The development of metabolic acidosis in patients in severe and moderately severe condition (19 cases) was associated with poor prognosis as to survival since the mortality in this group was 10 (about 53%). The favourable effect of dehydrating treatment may be due also to facilitation of passage of bicarbonates from the blood into the cerebral tissue and CSF since their level is increased in the blood during metabolic alkalosis (during a decrease in the extracellular space) resulting from dehydration.