Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical-cytological grading: a precision medicine-based approach.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder that strongly impacts patients' quality of life. CRSwNP is still a challenge for ENT specialists due to its unknown pathogenesis, difficult control and frequent relapse. We tested the hypothesis that a new standardised therapeutic approach based on individual clinical-cytological grading (CCG), may improve control of the disease and prevent the needing for surgery. We analysed 204 patients suffering from bilateral CRSwNP, 145 patients of whom regularly assumed therapy, respecting the planned check-up, and were considered cases; 59 patients were not assuming therapy as indicated and were considered as controls. After five years of standardised treatment, 15 of 145 (10.5%) improved endoscopic staging, 61 of 145 (42%) did not change their endoscopic staging, and 69 of 145 (47.5%) were worse. In the control group, 49 of 59 (83%) were worse by at least two stages (p < 0.05). Patients and controls were stratified basing on clinical and cytological grading as mild, moderate and severe. After patient stratification, in the mild group (n = 27) 92% patients had a constant trend, with no worsening and no need for surgery over a 5-year period, whereas in the mild CCG control group 1 of 59 (1.6%) required surgery (p < 0.05). In moderate GCC (n = 83), 44% of patients did not modify or improve endoscopic staging and 3.6% needed surgery, compared to 13.6% of controls with moderate GCC (p < 0.05). In severe CCG (n = 35), even though no patients achieved significant amelioration of endoscopic grading, 40% of patients were considered as "clinically controlled" and 5.7% of patients underwent surgery, but the percentage was significantly higher (49%) in the control group significant (p = 0.0000). Finally, statistical analyses revealed a clear trend that polyp size increased at a faster rate in the control group than in the treatment group and for each subgroup (low, moderate and severe). The present study suggests a new approach in the management of CRS according to clinical cytological grading that allows defining the grade of CRSwNP severity and to adapt the intensity of treatment. This approach limited the use of systemic corticosteroids to only moderate-severe CRSwNP with a low corticosteroid dosage in comparison with those previously suggested. Our protocol seems to improve the adherence by patients, control of disease and the need for surgery in the long-term.

Intranasal T-LysYal® as adjunctive therapy for patients after functional endoscopic sinus surgery.

Functional Endoscopic Sinus Surgery (FESS) is a common day surgery technique for upper airway disorders. Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert reparative, anti-inflammatory and immune-modulating activities. Recently, a new intranasal HA formulation has been proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (RinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 83 patients (49 males and 34 females mean age 45.4±6.2 years) treated with FESS. All patients were treated with isotonic saline solution for 4 weeks, and a sub-group (active group) was also treated with intranasal T-LysYal®. Patients were visited at baseline, after treatment, and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells in comparison to isotonic solution. In conclusion, the present study demonstrates that intranasal T-LysYal® is able to significantly improve patients after FESS and its effect is long lasting.

Effect of sodium hyaluronate on mucociliary clearance after functional endoscopic sinus surgery.

BACKGROUND: To determine the effect of intranasal sodium hyaluronate on mucociliary clearance time following functional endoscopic sinus surgery in patients with nasal polyposis. STUDY DESIGN: Randomized, controlled, blinded study. METHODS: Thirty-six patients with grade II nasal polyposis undergoing functional endoscopic sinus surgery received intranasal sodium hyaluronate 9 mg twice daily or saline for 30 days commencing on the second day after surgery. Ciliary mucous transport time was assessed using charcoal powder and saccharin administered during rhinoscopy. Other outcomes included changes in symptoms, endoscopic appearance of the nasal mucosa, and tolerability. RESULTS: Patients receiving sodium hyaluronate had a significantly faster mucociliary clearance time at 1 month compared with controls (14.3 +/- 2.5 vs. 23.6 +/- 3.3 minutes; p = 0.000). Furthermore, sodium hyaluronate recipients experienced a lower incidence of rhinorrhea, less nasal obstruction and a lower incidence of exudate on endoscopy than control subjects at 1 month (all p < 0.05). Sodium hyaluronate was well tolerated in patients following functional endoscopic sinus surgery. CONCLUSION: The use of intranasal sodium hyaluronate in patients undergoing functional endoscopic sinus surgery for nasal polyposis augmented the improvement in mucociliary clearance observed following this procedure and improved several clinical and endoscopic parameters. These data provide encouraging evidence of the beneficial effects of sodium hyaluronate in the care of patients undergoing functional endoscopic sinus surgery with which to continue the development of the product for this indication.

Implementación y evaluación de un sistema localmente sustentable de diagnostico prenatal que permite detectar casos de transmisión congénita de la enfermedad de Chagas en zonas endémicas del Paraguay / Implementation and evaluation of a locally sustainable system of prenatal diagnosis to detect cases of congenital Chagas disease in endemic areas of Paraguay

A locally sustainable system of prenatal screening of Trypanosoma cruzi infection has been implemented in rural health care centers of endemic areas in Paraguay A total of 61.091 women from Paraguari and Cordillera Departments were serologically evaluated, where 7.802 (12,7%) resulted to be anti-T. cruzi IgG positive. A total of 1,865 infants born to seropositive mothers were examined by parasitological techniques, such as direct microscopic observation and polymerase chain reaction, and serologically by ELISA, ELISA-SAPA and IFI. 104 infected babies were detected and treated with benznidazole. The recovery of babies born to seropositive mothers performing a single examination at the age of 6 months was significantly higher, as compared with the recommended method involving two examinations, both at birth and after 6 months of age. Although at 6 months of age in 7% of the infants maternal IgG was still detected. PCR was the most sensitive technique for early detection of T. cruzi infection in babies, but we do not recommend it use for diagnosis in high endemic areas, considering that for the screening of 815 babies, 2000 reactions were needed. We propose a strategy to detect congenital transmission of Chagas disease, based on a large-scale study, where the shortcomings of the different serological and parasitological techniques are discussed.

Acute diarrhea in Paraguayan children population: detection of rotavirus electropherotypes.

Group A rotavirus infections were detected in 93 of 410 fecal samples from children with acute diarrhea, admitted in three main hospitals of Asunción, Paraguay, from August 1998 to August 2000. Most of the rotavirus-infected patients were admitted during the winter season in the three epidemic years. The rotavirus infection rate was highest in infants from 6 to 23 months of age. In the 93 samples examined, 10 different rotavirus electropherotypes were recognized, but two of them largely predominated. Only one sample showed a short electropherotype pattern, thus indicating a minor involvement of the rotavirus subgroup I in rotaviral acute diarrhea in the area and the time during which the survey was carried out.

trans-sialidase inhibition assay, a highly sensitive and specific diagnostic test for Chagas' disease.

For the diagnosis of Chagas' disease, the trans-sialidase inhibition assay was able to resolve the results for samples with borderline results, to detect as positive 60% of samples that were negative by conventional serology, and to discriminate idiopathic from chagasic megaviscera or cardiopathy. No cross-reaction with sera from patients with other diseases was observed.

Clínica y laboratorio de la diarrea aguda por rotavirus en niños menores de 5 años

Presenta un estudio alos niños menores de 5 años de edad, de ambo sexos, que consultan al servicio de urgencias de la cátedra de pediatría del hospital de clínicas e internados en la sala de lactantes, por cuadros de diarrea aguda siendo la causa más importante los los rotavirus

Treatment of congenital Chagas' disease diagnosed and followed up by the polymerase chain reaction.

In 1991 and 1992, a prenatal screening of Trypanosoma cruzi infection was carried out using ELISA and indirect immunofluorescence techniques. A total of 840 blood samples from pregnant women, obtained at the Maternity Ward of the Hospital de Clínicas, National University of Asunción (Asunción, Paraguay), and 1,022 samples from the Regional Hospital of the San Pedro Department of Paraguay were examined. It was observed that 7.7% and 10.5%, respectively, of the pregnant women were serologically positive for infection with T. cruzi. When blood samples obtained from newborns on the day of birth or, at the most, on the first few days afterwards were examined by direct microscopic observation, an incidence of congenital transmission of 3% was found. These results are consistent with those of neighboring countries. When a serologic follow-up was conducted on the newborns until six months of age, the incidence of congenital transmission reached 10%. The same incidence rate was obtained when the samples collected during the first days after birth were examined by the polymerase chain reaction (PCR). Fifty-eight infants born to seropositive mothers were followed-up, two of which were positive by direct microscopic observation at birth, and four who were PCR-positive, but microscopy-negative at birth. None of the infants were positive for IgM at birth. The infected babies were treated with benznidazole and were followed-up by serology and PCR for four years. We conclude that the PCR has a clear advantage over conventional techniques for the early detection of congenital transmission of T. cruzi infection, and for monitoring infants undergoing chemotherapy.

[Bilateral semicircular canal pathology]. / La cupulolitiasi bilaterale.

The authors report 12 cases of bilateral cupulolithiasis found in 142 subjects diagnosed as having benign paroxysmal positional vertigo. A case history was taken for these patients (4 males, 8 females; average age 28 years) and 10 reported a previous cranial trauma while the remainder did not refer any previous condition of note. All patients had normal cochleovestibular test results and showed no signs of concomitant internal and/or central pathologies. The Hallpike maneuver was able to evoke an intense symmetrical paroxysmal vertigo and this was often accompanied by neurovegetative phenomena while paroxysmal nystagmus always appeared. The patients were treated with a rehabilitative technique: the Brandt-Daroff was preferred as it is better tolerated. Within 15 days all patients had full remission of symptoms and at 6 months after treatment there have been no signs of recurrence. The conclusion is, thus, drawn that while the technical characteristics of the Sémont maneuver make it suitable only for use as rehabilitation in unilateral benign paroxysmal positional vertigo, this experience indicates that the Brandt-Daroff technique is better suited for the bilateral forms of this disorder.

Fibrin polymerization defect in HIV-infected patients--evidence for a critical role of albumin in the prolongation of thrombin and reptilase clotting times.

Thrombin clotting time (TCT) and reptilase clotting time (RCT) were found significantly prolonged in a series of 72 HIV-infected patients drawn for routine coagulation testing. Both TCT and RCT were highly significantly correlated with albumin (r = -0.64, and r = -0.73 respectively, p < 0.0001). TCT and RCT were significantly higher (p < 0.0001) in a series of 30 other HIV-infected patients selected on their albumin level below 30.0 g/l (group 1) than in 30 HIV-infected patients with albumin level above 40.0 g/l or in 30 HIV-negative controls; the two latter groups were not different. In vitro supplementation of plasma from group 1 patients with purified human albumin up to 45.0 g/l (final concentration) lead to a dramatic shortening effect on both TCT and RCT, which reached normal values. The TCT and RCT of the purified fibrinogen solutions (2.0 g/l final concentration) were not different in the three groups, and normal polymerization curves were obtained in all cases. This further ruled out the presence of any dysfibrinogenemia in the plasma from group 1 patients. Using purified proteins, highly significant correlations were demonstrated between the albumin concentration and the prolongations of both TCT and RCT, which were of the same magnitude order than those found in the patients plasma. These results suggest that hypoalbuminemia is responsible for the acquired fibrin polymerization defect reported in HIV-infected patients. The pathophysiological defect reported in HIV-infected patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Muco-ciliary transport in chronic inflammatory pathology of the middle ear]. / Il trasporto mucociliare nella patologia flogistica cronica dell'orecchio medio.

The Authors have studied the behaviour of nasal mucociliary transport (MCT) in the chronic phlogistic pathology of the middle ear, in subjects suffering from simple and cholesteatomatous otitis. In both groups the duration of MCT was longer than a control group of normal subjects; instead no significant difference was observed either between the two kind of pathologies nor between the two different phases of the otitis (quiescence and breakthrough). The Authors conclude therefore that, in the recurrent phlogistic pathology of the middle ear, the function of MCT must be carefully studied, possibly corrected if damaged, to prevent the evolution in the breakthrough.

[Effect of physical exercise on nasal resistance in normal subjects and in patients with vasomotor rhinopathy]. / Effetto dell'esercizio fisico sulle resistenze nasali in soggetti normali e rinopatici vasomotori.

The study has evaluated the behaviour of the nasal resistances, studied using Anterior Active Rhinomanometry, after physical exercise, in normal subjects and in allergic and non allergic vasomotor rhinopathics. The results, in accordance with the literature, show a reduction of nasal resistances in all subjects, particularly in the rhinopathics, immediately after the effort and a return to the starting values after a rest period of 30 minutes. Among vasomotor patients, only the non-allergic group has shown very significant variations in the resistances, because in these subjects there is almost always an exaltation of the neurovegetative system, which we did not observe in the allergic subjects in the intercritical phase. The effort test is therefore, among the aspecific tests of nasal reactivity useful, perhaps, more to therapy than to diagnostic aims.

[Herpetic vestibular neuronitis: a hypothesis]. / Neuronite vestibolare erpetica: un'ipotesi.

Abundant experimental research has shown the potentially damaging effects that the herpes simplex virus (HSV) may have on peripheral or central nervous pathways. Fifty subjects (ages 20-45) with labial herpes virus (HSV-1) and 15 (ages 25-35) with genital herpes virus (HSV-2) were studied through recording spontaneous and optokinetic nystagmus (OKN) and using the eye-tracking-test (ETT) by means of electronystagmography (ENG). Recording was carried out during the first two days after vesicular eruption and seven days later, when cutaneous manifestations had disappeared. Thirty-five of the 50 subjects with HSV-1 showed spontaneous nystagmus, frequently with a vertical component, which in most cases had disappeared by the seventh control day. We recorded qualitative alterations of OKN as well as ETT in 19 patients while in 3 subjects only ETT was abnormal. All the subjects were normal on the seventh control day. At no time did any of the patients with HSV-2 show objective signs involving the peripheral or central vestibular system. Our research shows that HSV infection, especially HSV-1 infection, determines subclinical alterations of the vestibular function, probably due to the involvement of the brainstem. Therefore the virus is to be taken into account in establishing the etiology of "unknown" vertigo.

[Visual inhibition of the ampullar rotational-acceleratory excitation]. / Inibizione visiva dell'eccitamento rotoacceleratorio ampollare.

We have studied in normal subjects, the monocular and binocular influence on the nystagmus provoked by angular acceleration. The results show that the fixation determines a reduction of all quantitative parameters of the nystagmic response that, in the binocular fixation condition, is nearly 80% and halves with monocular fixation. The data shows activity conditions in a simple summation report of the values of visual input and demonstrate not only that the quality of the visual inhibition is, in normal subjects, perfectly equivalent between the two eyes but also that the stimulations evoked in the two labyrinths, convergent to the equilibrium centres, integrate in a perfectly complementary way. We have to study how this complex and harmonious polysensorial activity deteriorates with pathologic alterations of the visual and ampullar systems.

[Interaction between vision and vestibular nystagmus]. / Ricerche sull'interazione visiva del nistagmo vestibolare.

In order to assess the visuo-vestibular interaction and its behaviour in connection with the age, we have submitted 20 healthy subjects from two age groups ranging between 21-30 and 65-75 years of age to two rotation tests (with closed eyes and with opened eyes with fixation of a light). The results show a variation of the nystagmic response with fixation of about 60% in the young people and of about 40% in the elderly. These results demonstrate that the extent of the inhibition is dependent upon age and is less effective in the elderly.

[Experimental research on vestibular compensation using posturography]. / Richerche sperimentali sul compenso vestibolare mediante posturografia.

Vestibular compensation is a representation of nervous system plasticity which manifests as a gradual recovery of equilibrium function both in vestibulo-spinal system and vestibulo-oculomotor system. In order to assess whether the vestibular compensation is a homogeneous process among the different reflexes, the Authors have studied two groups of subjects affected by peripheral or central lesion. The development of the vestibular compensation has been evaluated by the rotation and posturographic tests. The results demonstrate a constant correlation between rotation and stabilometric parameters in the patients suffering from peripheral dizziness while there isn't any correlation between acceleratory and posturographic tests in patients affected by central vertigo. These results demonstrate that the compensation develops at the different levels of the balance function in a very different and independent way and that comparison of the rotation and posturographic patterns may be useful to establish the peripheral or central site of the lesions.

[Effect of aging on posture]. / Effetti della senescenza sulla postura.

In order to assess the postural behaviour of the elderly, we have submitted twenty subjects of more than seventy years old to posturography. In all cases, compared to young people, significant variations of the posturographic parameters regarding in a particular way the total tracing length, the ellipse surface and the mean speed have been recorded. The conclusion is that the values obtained should always be compared with the standard values for each age group.

[Experimental research on sensitized posturography: importance of the neck reflexes]. / Ricerche sperimentali sulla posturografia sensibilizzata: importanza dei riflessi cervicali.

In order to assess the influence of the cervical structures on the vestibulo-spinal reflex, and so on the posture, we have studied twenty subjects undergoing stimulation of the neck's proprioceptor structures. Each subject, by means of computerized stabilometric platform, has been submitted to the sensitized test with head retroflexed. In all cases significant variations of the posturographic parameters regarding in a particular way the total tracing length, the ellipse surface and the mean speed have been recorded. The results show that there are in man too stimulations of cervical origin which serve the purpose of maintaining posture; we can't exclude the possibility of the interference of an otolithic stimulation.

[Effect of the cervical reflex on the posture of normal subjects. Balance measurement study]. / Effetti dei riflessi cervicali sulla postura del soggetto normale. Ricerche stabilometriche.

The little we know about the existence and the meaning of the cervical component on the vestibulo-spinal reflex, led us to carry out a study on normal subjects examined by computerized stabilometry with the head turned 75 degrees left and right, in order to check the postural alterations during the stimulation of the neck proprioceptors. The results show a significant increase of the values of the LTT, SE and Vm with the head turned to the left; the increases were not significant with the head turned to the right. The difference is difficult to explain. The results show that in man too the posture is affected by reflex of cervical origin.