Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.

Systemic lupus erythematosus and myelofibrosis: A case report and revision of literature.

Blood cytopenia represents one of the diagnostic criteria for systemic lupus erythematosus (SLE) and may occur as the first symptom of the disease. Antibody-mediated peripheral destruction of blood cells is the main cause of cytopenia observed in patients affected by SLE, however, inflammatory anemia, nutritional deficiencies, immunosuppressive therapy and, more rarely, myelofibrosis (MF) have also been documented. In the literature, 45 cases of autoimmune MF (AIMF) and SLE have been previously reported. Here the 46 th case of a 43-year-old female with a SLE and an underhand cytopenia, with a review of the literature.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

This corrects the article DOI: 10.1038/onc.2017.75.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

Recent evidences suggest that stearoyl-CoA-desaturase 1 (SCD1), the enzyme involved in monounsaturated fatty acids synthesis, has a role in several cancers. We previously demonstrated that SCD1 is important in lung cancer stem cells survival and propagation. In this article, we first show, using primary cell cultures from human lung adenocarcinoma, that the effectors of the Hippo pathway, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are required for the generation of lung cancer three-dimensional cultures and that SCD1 knock down and pharmacological inhibition both decrease expression, nuclear localization and transcriptional activity of YAP and TAZ. Regulation of YAP/TAZ by SCD1 is at least in part dependent upon ß-catenin pathway activity, as YAP/TAZ downregulation induced by SCD1 blockade can be rescued by the addition of exogenous wnt3a ligand. In addition, SCD1 activation of nuclear YAP/TAZ requires inactivation of the ß-catenin destruction complex. In line with the in vitro findings, immunohistochemistry analysis of lung adenocarcinoma samples showed that expression levels of SCD1 co-vary with those of ß-catenin and YAP/TAZ. Mining available gene expression data sets allowed to observe that high co-expression levels of SCD1, ß-catenin, YAP/TAZ and downstream targets have a strong negative prognostic value in lung adenocarcinoma. Finally, bioinformatics analyses directed to identify which gene combinations had synergistic effects on clinical outcome in lung cancer showed that poor survival is associated with high co-expression of SCD1, ß-catenin and the YAP/TAZ downstream target birc5. In summary, our data demonstrate for the first time the involvement of SCD1 in the regulation of the Hippo pathway in lung cancer, and point to fatty acids metabolism as a key regulator of lung cancer stem cells.

Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir.

A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated.

Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells.

In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These results suggest that SCD1 is a critical target in lung cancer tumor-initiating cells.

[Epidemiology of work-related accidents in the Lazio Region of Italy]. / Epidemiologia degli infortuni sul lavoro nella Regione Lazio.

BACKGROUND: Prevention of work-related accidents requires an in-depth epidemiological assessment of the issue. In Italy the most used databases are from the national insurance (INAIL) and research (ISPESL) institutes. However, these data are only available several years after the time of accident. OBJECTIVES: To describe the characteristics of accidents and evaluate factors potentially associated with hospitalization using the Information System of Hospital Emergency Departments (SIES). METHODS: We analyzed 51.705 Emergency Department (ED) work-related accident admissions in the Lazio Region of Italy in 2008 among workers aged 16-65 years. Information on socio-demographics, diagnosis, triage codes, and outcome of ED admissions were gathered. We performed a logistic regression model to estimate association between these factors and risk of hospitalization after ED admission. RESULTS: The subjects' mean age was 39.1 (SD 11.0); 71.5% woere men, 12.7% were foreigners, 5.9% arrived by ambulance, 4.5% with triage red/yellow tags, 2.7% were hospitalized. Diagnosis was trauma in 85.1%, orthopaedic lesions in 8.3%. We found a higher risk of hospitalization in subjects with: one year of age increase (OR=1.02; 95% CIs: 1.01-1.03), males (OR=1.68; 95% CIs: 1.44-1.97), foreigners coming from countries with high emigration rates (OR=1.55; 95% CIs: 1.31-1.82), ED triage red/yellow tags (OR=84.47; 95% CIs: 47.06-151.60). CONCLUSIONS: It was confirmed that data fr-om an emergency health care information system can be a useful complement to information gathered by national insurance and research institutes, thus resolving the limit posed by the delay in availability for analysis of these data after the occurrence of accidents. We also identified some factors potentially associated with more serious accidents, which constitute a basis for planning and implementing specific public health preventive interventions.

Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF-D production by tumour cells.

The expression of NCAM was investigated in tissue sections of 61 cases of papillary carcinoma and in 14 lymph node metastases using immunohistochemistry. Tumour cells of 18 primary tumours were not stained, whereas in the remaining 43 cases, NCAM was expressed in less than 5% tumour cells. Similar results were obtained when NCAM expression was evaluated at the RNA level. Reduced expression of NCAM is an early event since 6/15 cases (40%) of micro-carcinoma were NCAM-negative. NCAM-positive tumour cells were more often located at the invasion front of the tumour. It has been reported that NCAM expression may affect lymphangiogenesis. In tissue sections immunostained for podoplanin, it was found that lymphatic vessels were extremely rare inside the body of the tumour, and were mostly associated with foci of chronic inflammation and/or of reparative fibrosis. Lymphangiogenesis is sustained by VEGF-C, VEGF-D, and FGF2. Analysis of micro-dissected samples of the tumour and of the paired normal thyroid tissue revealed that RNA transcripts for VEGF-D were significantly less numerous in the tumour tissue (p = 0.001). The potential role of NCAM in tumour cell biology was investigated by silencing the NCAM gene in the TPC1 thyroid papillary carcinoma cell line. It was found that NCAM down-regulation caused a significant reduction (p < 0.05) in the expression of both VEGF-C and VEGF-D mRNAs. In addition, NCAM-silenced TPC-1 cells were more adhesive to different extracellular matrix components, and were less efficient in cell migration (59% reduction; p < 0.05) and invasiveness (68% reduction). These latter results confirm that modifications of NCAM expression cause profound alterations in the adhesive and migratory properties of tumour cells, but are in apparent discrepancy with the observation that loss of NCAM is usually associated with increased tumour invasiveness in vivo.

Expression of autoimmune regulator gene (AIRE) and T regulatory cells in human thymomas.

Expression of the autoimmune regulator gene (AIRE) and the presence of CD25(+)/forkhead box p3 (FoxP3)(+) T regulatory (T(reg)) cells were investigated in histologically normal adult thymi and in thymomas using immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). In the normal thymus staining for AIRE was detected in the nucleus of some epithelial-like cells located in the medulla; in thymomas AIRE-positive cells were extremely rare and could be detected only in the areas of medullary differentiation of two B1 type, organoid thymomas. RNA was extracted from 36 cases of thymoma and 21 non-neoplastic thymi obtained from 11 myasthenic (MG(+)) and 10 non-myasthenic (MG(-)) patients. It was found that AIRE is 8.5-fold more expressed in non-neoplastic thymi than in thymomas (P = 0.01), and that the amount of AIRE transcripts present in the thymoma tissue are not influenced by the association with MG, nor by the histological type. A possible involvement of AIRE in the development of MG was suggested by the observation that medullary thymic epithelial cells isolated from AIRE-deficient mice contain low levels of RNA transcripts for CHRNA 1, a gene coding for acetylcholine receptor. Expression of human CHRNA 1 RNA was investigated in 34 human thymomas obtained from 20 MG(-) patients and 14 MG(+) patients. No significant difference was found in the two groups (thymoma MG(+), CHRNA1 = 0.013 +/- 0.03; thymoma MG-, CHRNA1 = 0.01 +/- 0.03). In normal and hyperplastic thymi CD25(+)/Foxp3(+) cells were located mainly in the medulla, and their number was not influenced by the presence of MG. Foxp3(+) and CD25(+) cells were significantly less numerous in thymomas. A quantitative estimate of T(reg) cells revealed that the levels of Foxp3 RNA detected in non-neoplastic thymi were significantly higher (P = 0.02) than those observed in 31 cases of thymomas. Our findings indicate that the tissue microenvironment of thymomas is defective in the expression of relevant functions that exert a crucial role in the negative selection of autoreactive lymphocytes.

[Torture survivor asylum seekers in Italy: the experience of the humanitarian association "Doctors Against Torture"]. / Vittime di tortura richiedenti asilo in Italia: l'esperienza dell'associazione umanitaria "Medici Contro la Tortura".

In recent years, the arrival in Italy of people who suffered torture in their countries led a group of volunteer doctors to set up a humanitarian association, "Doctors Against Torture", to provide care and treatment for torture survivors present in Rome. The paper describes the characteristics of 354 persons having at least one access from 1-1-1999 to 31-12-2001. About 51% of the victims came from the Middle East, 43% from Africa. Mean age was 29.6 (SD 7.0). The victims have suffered beatings and other forms of blunt trauma (64%), suspension and other positional torture (14%), psychological violence (28%), inhuman conditions of detention (10%), burns/electric shock (21%), wet asphyxiation and water jets (11%), sexual violence (15%), amputation/penetrating injuries (22%), dental torture and traumatic removal of nails (6%) and 58% suffered more than one type of torture. The types of violence observed require a thorough analysis of our knowledge in the field, in order to help victims on their way to rehabilitation, which is long and uncertain; at the same time, it is fundamental that public health begins to make itself responsible for these persons.

[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

Home breastfeeding support by health professionals: findings of a randomized controlled trial in a population of Italian women.

AIM: We conducted a randomized controlled trial to assess the effectiveness of a support intervention delivered by health professionals to increase the rate and duration of breastfeeding. METHODS: A randomized controlled intervention study was conducted in the period 2000-2001 among 605 mothers who had given birth in a public maternity ward located in the city of Rome, Italy. The intervention consisted of a home visit by a midwife from the maternity ward of the hospital. The outcome of the study was the infant's feeding habits, assessed by a 24-h recall. The effect of the intervention on the duration of breastfeeding was estimated by the Kaplan-Meier method and by the Cox multivariate regression model. RESULTS: According to intention-to-treat analysis, there was no significant difference between the intervention and the control group, after controlling for confounding factors (hazard ratio (HR) 1.04; 95% confidence interval (95% CI): 0.85-1.26). The duration of breastfeeding was shorter (HR 1.61; 95% CI: 1.13-2.31) for women in the intervention group who refused the obstetric visit. CONCLUSION: Our study shows that an early home support programme delivered by health professionals was not effective in increasing breastfeeding initiation and duration.

Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) represents the most common cause of hypothyroidism and nonendemic goiter, but its clinical and pathological heterogeneity opens the question if this disease should be more properly considered as a spectrum of different thyroid conditions rather than as a single nosological entity. In this study, we analysed 133 cases of HT for the expression of galectin-3, a lectin molecule involved in malignant transformation, apoptosis and cell cycle control. An unexpected expression of galectin-3 was demonstrated in a subset of HT together with the presence of HBME-1, c-met and cyclin-D1 that are also involved in malignant transformation and deregulated cell growth. Furthermore, a loss of allelic heterozygosity in a specific cancer-related chromosomal region was demonstrated in some HT harbouring galectin-3-positive follicular cells, by using laser capture microdissection. On the basis of the morphological and molecular findings we identified four subsets of HT: (a) HT with classic features of chronic autoimmune thyroiditis; (b) HT associated to hyperplastic/adenomatous lesions; (c) HT harbouring thyroid cancer precursors; (d) HT associated to unequivocal thyroid microcarcinomas. Our findings provide a well-substantiated morphological and molecular demonstration that HT may include a spectrum of different thyroid conditions ranging from chronic autoimmune thyroiditis to thyroiditis triggered by specific immune-response to cancer-related antigens.

Papillary carcinoma of the thyroid: methylation is not involved in the regulation of MET expression.

Hypomethylation has been reported to be responsible for the activation of several oncogenes. The possibility that hypomethylation is involved in the regulation of MET transcription was investigated through the analysis of the methylation status of one CpG island containing 43 CpGs in six cases of papillary carcinoma, in the corresponding normal thyroid tissue, and in two cases of hyperplastic goitre. Evidence of methylation was not found in any of the analysed CpG.

Molecular cloning, expression and purification of protein 2A of hepatitis A virus.

Expression of the protein 2A of Hepatitis A virus (HAV), spanning amino acids 764 through 981 of the viral polyprotein results in a strong inhibition of cap-dependent translation (Maltese et al., 2000). However, the molecular mechanism responsible has remained unclear, in part because the HAV 2A protein was not available in amounts large enough to allow biological or structural studies. To address this issue, a cDNA representation of the sequences encoding HAV 2A was generated by PCR, using primers that introduced an AUG triplet, and a sequence coding for 6 histidine residues at the 5'- and 3'-termini of the genomic sequence, respectively. The cDNA fragment was introduced by cassette exchange in the inducible expression vector pQE-60, and the construct was propagated in bacteria E. coli M15 which constitutively expresses the lac repressor. Upon induction with IPTG (1 mM), HAV 2A was visualized by SDS-PAGE of bacterial lysates as a prominent band M(r) = 21 kDa. The identity of the polypeptide was confirmed by both MALDI-TOF peptide mapping and direct amino acid sequencing. The His-tagged HAV 2A was extracted from bacterial pellets under totally denaturing conditions (6 M urea), subjected to Ni(++)-Sepharose affinity chromatography, allowed to refold while still attached to the matrix, and eluted with 250 mM Imidazole. Contaminant material was partly removed by differential ammonium sulfate precipitation. The protein was further concentrated (Vivaspin centrifugal concentrator), the insoluble material (if present) was discarded, and the homogeneity of the dispersion was ascertained by light scattering. SDS-PAGE revealed that in addition to the main protein (Mr = 21 kDa), a second one of apparent Mr = 14 kDa was always present in variable amounts. The proportion of the latter tended to increase with aging of the preparation. Edman degradation analysis proved that the 14 kDa protein resulted from the cleavage of HAV 2A at a so far undetected scissile bond Gly856/Val857 of the viral polyprotein. A first attempt to crystallize the protein by the hanging drop procedure yielded only small crystals containing exclusively the 14 kDa derivative of HAV 2A. Western blot analysis of HeLa cell extracts that had been incubated with the His-tagged HAV 2A so purified failed to reveal any change in the electrophoretic mobility of the eukaryotic initiation factor (eIF) 4G I.

Tufted hair folliculitis: complete enduring response after treatment with rifampicin.

BACKGROUND: A 47-year-old woman presented with erythematous lesions with papules and pustules on her parieto-occipital region that had been present for 8 months. Areas of sclero-atrophic alopecia were evident, whereas at different points tufted hair shafts were coming out from single dilatated follicular ostia. Before our observation, an antibiotic oral therapy with tetracyclines and local with erythromycin had been administered to the patient, with partial improvement and relapse on its suspension. METHODS: Bacterial culture from pustules showed the development of Staphylococcus aureus. A skin biopsy was done. According to clinical and histopathological findings a diagnosis of tufted hair folliculitis was made and a treatment with oral rifampicin was started at the dosage of 450 mg twice per day. RESULTS: After 3 weeks of therapy, the pustular lesions regressed completely and after a follow-up of 1 year no relapse was observed. CONCLUSIONS: Rifampicin is one of the best active antibiotics against S. aureus, which seems to play a role in the pathogenesis of tufted hair folliculitis. Our results, if further confirmed, may suggest a role for rifampicin either for the control of the pustular phase of this rare disorder or to prevent its relapses for a long time.

[Collaborative study on peritoneal dialysis (PD) as first dialysis treatment in an Italian region: 1994-2000]. / Studio collaborativo sulla dialisi peritoneale (DP) come primo trattamento nel Lazio: 1994-2000.

BACKGROUND: In Lazio, only about 5% of uremic patients are on peritoneal dialysis (PD). The present study focuses on the parameters of PD selection, the treatment schedules, and the clinical outcomes of PD patients in the nine public facilities offering a PD program. A cohort of 249 first-time PD patients, from July 1, 1994 to December 31, 2000, was retrospectively considered. METHODS: For the enrollment of the patients, the Regional Dialysis Registry databank was consulted. On December 31, 2000, a systematic review of patient charts was performed to extract the reasons for the PD choice, details of PD schedule, peritonitis episodes, reasons for drop-out, and patient survival rates. In regard to technique success-defined as the probability of having a patient alive on PD-change of modality and death were considered as final events. In regard to patient survival, only death, even in the first 2 months after a shift to hemodialysis, was considered the end point. RESULT: The main PD selection reasons were patient and/or nephrologist preference in 90% of cases. One-hundred eighty-nine patients (76%) had been started on CAPD. During the follow-up, 38.2% dialysis schedules had been modified at least once. At the end of follow-up, 41.2% patients were on APD. The peritonitis rate was one episode per 30 patient-months (1 per 27 patient-months in CAPD; 1 per 37 patient-months in APD; p = 0.08). The technique success rate was 66.3% after 2 years and 49.8% after 3 years. The patient survival rate was 81.1% after 2 years and 68.7% after 3 years. CONCLUSIONS: Patients chose PD as a first dialysis treatment mainly because of reasons unrelated to their clinical status. The technique's success, patient mortality rates, and the peritonitis rate do not explain the low PD diffusion in the region. The peritonitis rate meets the target criteria for excellence recommended by the Italian Society of Nephrology. The observed outcomes may have been favored by the selection of motivated patients and by the increased use of APD.

A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone.

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-alpha2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P =.04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P =.03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.

Short term respiratory effects of acute exposure to chlorine due to a swimming pool accident.

OBJECTIVE: Acute exposure to chlorine causes lung damage, and recovery may proceed slowly for several weeks. The short term respiratory effects of acute chlorine inhalation during a swimming pool accident were examined. METHODS: A total of 282 subjects (134 children, aged <14 years) inhaled hydrogen chloride and sodium hypochlorite during an accident caused by a malfunction of the water chlorinating system in a community pool in Rome in 1998. Most people received bronchodilators and cortisone at the emergency room; five children were admitted to hospital. A total of 260 subjects (92.2%) were interviewed about duration of exposure (<3, 3--5, >5 minutes), intensity of exposure (not at all or a little, a moderate amount, a lot), and respiratory symptoms. Lung function was measured in 184 people (82 children) after 15--30 days. The effects of exposure to chlorine were analysed through multiple linear regression, separately in adults and in children. RESULTS: Acute respiratory symptoms occurred among 66.7% of adults and 71.6% of children. The incidences were highest among those who had chronic respiratory disease and had a longer duration of exposure. In about 30% of the subjects, respiratory symptoms persisted for 15--30 days after the accident. Lung function levels were lower in those who reported a high intensity of exposure than in those who reported low exposure, both in children and in adults (mean (95% confidence interval (95% CI)) differences in forced expiratory volume in 1 second (FEV(1,)) were -109 (-310 to 93) ml, and -275 (-510 to -40) ml, respectively). CONCLUSION: Persistent symptoms and lung function impairment were found up to 1 month after the incident. Although community pool accidents happen rarely, the medical community needs to be alerted to the possible clinical and physiological sequelae, especially among susceptible people.