[Intravesical adjuvant regimen of epitubicin for intermediate risk NMIBC: Feasability study from CC-AFU vessie]. / Instauration du traitement adjuvant endovésical par épirubicine des tumeurs de vessie n'infiltrant pas le muscle : premier retour national d'expérience du CC-AFU vessie.

INTRODUCTION: Mitomycin C is the gold standard intravesical adjuvant therapy for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Tensions in the supply of mitomycin have emerged in France since late 2019. The ANSM in agreement with the AFU proposed to use epirubicin, already available in other European countries in this indication. The objective of our study was to report the initial French experience with the use of epirubicin in adjuvant treatment of NMIBC. MATERIALS AND METHODS: We undertook a French multicenter retrospective descriptive study to collect, from the centers of the members of the CC-AFU bladder, the clinico-pathological data of the patients, the indications, the modalities of use (dose, indication, circuit in the pharmacy) and the tolerance data of epirubicin. The impact of the COVID-19 epidemic on treatment interruptions was also identified. Of the 20 centers contacted, 5 (25%) had implemented the epirubicin administration protocol developed by the CC-AFU bladder subcommittee. A total of 61 patients were treated with endovesical instillations of epirubicin between November 2019 and November 2020 for NMIBC at a single dose of 50mg. RESULTS: A total of 61 patients (mean age 67 years, 64-77 years) were treated with epirubicin, of which 45 (73.8%) were male. The patients had intermediate-risk NMIBC in 88.5%, the rest had high-risk disease. Induction therapy without or with maintenance was planned for 48 (78.7%) and 13 patients (21.3%), respectively. The preparation and administration of epirubicin was similar to that of mitomycin: central pharmacy preparation for same-day dispensing with immediate outpatient instillation. Unlike mitomycin, urinary alkalinization was not required. Of the 498 total instillations scheduled, 345 were performed (69.3%). The COVID-19 epidemic significantly impacted epirubicin delivery: one patient could not start treatment (1.6%), 8 patients (13.1%) had to discontinue it permanently; the rest of the patients underwent delayed instillations (18%). Other causes of discontinuation included infectious complications (9.8%). No major toxicities were reported. CONCLUSION: The implementation of an adjuvant epirubicin treatment protocol presented a good feasibility with low toxicity, without modifying the organization of the patients' care pathway. In the context of unpredictable mitomycin shortage, epirubicin represents a good therapeutic alternative in the endovesical adjuvant treatment of intermediate-risk NMIBC. LEVEL OF PROOF: 3.

Ataxia with vitamin E deficiency in the Philippines†: A case report of two siblings.

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.

[Results of active surveillance for sporadic renal angiomyolipomas greater than 4cm: A pledge for active surveillance]. / Résultats de la surveillance active des angiomyolipomes sporadiques du rein de plus de 4cm : un plaidoyer en faveur de la surveillance active.

INTRODUCTION: Active surveillance (AS) of sporadic renal angiomyolipomas (AML) is under-utilised because of an old dogma fearing a life-threatening retroperitoneal hemorrhage when tumour size exceeds 4cm. The objective of this study was to report the outcome of AS in patients with sporadic AML greater than 4cm. METHODS: The results of AS in 35 patients managed for sporadic renal AML greater than 4cm were analysed. During AS, tumour growth, occurrence of new symptoms and/or complications, discontinuation of AS protocol, reason for discontinuation as well as subsequent treatment options were reported. RESULTS: Within a median follow-up of 36 months, 16 (46 %) patients discontinued AS at the end of the study period (mean follow-up 55±66, median 36 months). Patients who discontinued AS were more symptomatic at diagnosis but had similar age, mean tumour size and sex ratio. Active treatment-free survival was 66 % at 5 years. Retroperitoneal hemorrhage was reported in 3 (8.5 %) patients. None of these bleedings required transfusion or monitoring in an intensive care unit. Other reasons for discontinuation were pain (37 %), patient preference (19), changes in the radiological appearance of the tumour (19 %), and hematuria (6 %). CONCLUSION: This study showed that AS in AML bearing patients was feasible even in the setting of tumours larger than 4cm. More than 50% of the patients were still on AS at 5 years. Discontinuation of AS was not related to bleeding complications in most cases. LEVEL OF PROOF: 3.

Care of Ebola Survivors and Factors Associated With Clinical Sequelae-Monrovia, Liberia.

BACKGROUND: The Eternal Love Winning Africa (ELWA) Clinic was the first clinic to provide free, comprehensive care to Ebola virus disease (EVD) survivors in Liberia. The objectives of this analysis were to describe the demographics and symptoms of EVD survivors at ELWA from January 2015 through March 2017 and to identify risk factors for development of sequelae. METHODS: Patients' demographic and clinical information was collected by chart review in June 2016 and March 2017. Associations with clinical sequelae were analyzed using the chi-square test, t test, and multivariate logistic regression. RESULTS: From January 2015 to March 2017, 329 EVD survivors were evaluated at ELWA. Most survivors experienced myalgia/arthralgia (73%; n = 239) and headache (53%; n = 173). The length of time from Ebola Treatment Unit (ETU) discharge to first clinic visit ranged from 0 to 30 months. Many visits (30%) occurred 24 or more months after ETU discharge. The proportion of visits for headache, weight loss, joint pain, visual problems, insomnia, fatigue, memory loss, decreased libido, depression, and uveitis decreased over time. More men than women had visits for depression; however, these differences were not significant. Symptom prevalence differed in adults and children; significantly more adults experienced myalgia/arthralgia (77% vs 44%), visual problems (41% vs 12%), post-EVD-related musculoskeletal pain (42% vs 15%), and insomnia (17% vs 2%). CONCLUSIONS: EVD survivors frequented ELWA for EVD-related symptoms many months after ETU discharge, indicating a long-term need for care. Reported symptoms changed over time, which may reflect eventual resolution of some sequelae.

Evolving epidemiology of Nipah virus infection in Bangladesh: evidence from outbreaks during 2010-2011.

Drinking raw date palm sap is the primary route of Nipah virus (NiV) transmission from bats to people in Bangladesh; subsequent person-to-person transmission is common. During December 2010 to March 2011, we investigated NiV epidemiology by interviewing cases using structured questionnaires, in-depth interviews, and group discussions to collect clinical and exposure histories. We conducted a case-control study to identify risk factors for transmission. We identified 43 cases; 23 were laboratory-confirmed and 20 probable. Thirty-eight (88%) cases died. Drinking raw date palm sap and contact with an infected person were major risk factors; one healthcare worker was infected and for another case transmission apparently occurred through contact with a corpse. In absence of these risk factors, apparent routes of transmission included drinking fermented date palm sap. For the first time, a case was detected in eastern Bangladesh. Identification of new epidemiological characteristics emphasizes the importance of continued NiV surveillance and case investigation.

Integrated cluster- and case-based surveillance for detecting stage III zoonotic pathogens: an example of Nipah virus surveillance in Bangladesh.

This paper explores the utility of cluster- and case-based surveillance established in government hospitals in Bangladesh to detect Nipah virus, a stage III zoonotic pathogen. Physicians listed meningo-encephalitis cases in the 10 surveillance hospitals and identified a cluster when ⩾2 cases who lived within 30 min walking distance of one another developed symptoms within 3 weeks of each other. Physicians collected blood samples from the clustered cases. As part of case-based surveillance, blood was collected from all listed meningo-encephalitis cases in three hospitals during the Nipah season (January-March). An investigation team visited clustered cases' communities to collect epidemiological information and blood from the living cases. We tested serum using Nipah-specific IgM ELISA. Up to September 2011, in 5887 listed cases, we identified 62 clusters comprising 176 encephalitis cases. We collected blood from 127 of these cases. In 10 clusters, we identified a total of 62 Nipah cases: 18 laboratory-confirmed and 34 probable. We identified person-to-person transmission of Nipah virus in four clusters. From case-based surveillance, we identified 23 (4%) Nipah cases. Faced with thousands of encephalitis cases, integrated cluster surveillance allows targeted deployment of investigative resources to detect outbreaks by stage III zoonotic pathogens in resource-limited settings.

Genomic analysis of filoviruses associated with four viral hemorrhagic fever outbreaks in Uganda and the Democratic Republic of the Congo in 2012.

In 2012, an unprecedented number of four distinct, partially overlapping filovirus-associated viral hemorrhagic fever outbreaks were detected in equatorial Africa. Analysis of complete virus genome sequences confirmed the reemergence of Sudan virus and Marburg virus in Uganda, and the first emergence of Bundibugyo virus in the Democratic Republic of the Congo.

Cough triggers and their pathophysiology in patients with prolonged or chronic cough.

BACKGROUND: The character or timing of chronic cough is considered to be unpredictable for diagnosing its cause. However, the associations of cough triggers with cough pathophysiology remains unknown. METHODS: We developed a closed questionnaire listing 18 triggers that were reported by ≥1% of 213 patients in a retrospective survey. Using this questionnaire, patients with cough-predominant or cough-variant asthma (n = 140) and those with non-asthmatic cough (54) were asked whether their cough was induced by the listed triggers. Associations of triggers with causes of cough, airway sensitivity to inhaled methacholine, exhaled nitric oxide (NO) levels, number of sensitizing allergens, and scores from gastroesophageal reflux (GER) questionnaires were examined. Factor analysis was used to categorize variables, including the 12 most common cough triggers, diagnosis of asthmatic cough, airway sensitivity, and exhaled NO levels. RESULTS: "Cold air" and "fatigue/stress" induced cough more often in asthmatic coughers than in non-asthmatic coughers. "Spices" and "meals" induced cough more frequently in GER-coughers (n = 19). Patients who marked "cold air" as the trigger were more sensitive to inhaled methacholine and showed higher exhaled NO levels than those who did not mark this trigger. The "post-nasal drip" trigger was associated with elevated exhaled NO levels, and this association was mainly exhibited by patients with cough-predominant asthma. The triggers "pollen" and "mold smell" were associated with a number of sensitizing allergens. The number of triggers was weakly associated with GER scores. By factor analysis, "cold air," "fatigue/stress," asthmatic cough, airway hypersensitivity, and elevated NO levels were categorized into the same factor. CONCLUSIONS: Several cough triggers may reflect the pathophysiology of prolonged or chronic cough.

Nipah virus outbreak with person-to-person transmission in a district of Bangladesh, 2007.

In February 2007 an outbreak of Nipah virus (NiV) encephalitis in Thakurgaon District of northwest Bangladesh affected seven people, three of whom died. All subsequent cases developed illness 7-14 days after close physical contact with the index case while he was ill. Cases were more likely than controls to have been in the same room (100% vs. 9.5%, OR undefined, P<0.001) and to have touched him (83% vs. 0%, OR undefined, P<0.001). Although the source of infection for the index case was not identified, 50% of Pteropus bats sampled from near the outbreak area 1 month after the outbreak had antibodies to NiV confirming the presence of the virus in the area. The outbreak was spread by person-to-person transmission. Risk of NiV infection in family caregivers highlights the need for infection control practices to limit transmission of potentially infectious body secretions.

Risk factors for Nipah virus encephalitis in Bangladesh.

Nipah virus (NiV) is a paramyxovirus that causes severe encephalitis in humans. During January 2004, twelve patients with NiV encephalitis (NiVE) were identified in west-central Bangladesh. A case-control study was conducted to identify factors associated with NiV infection. NiVE patients from the outbreak were enrolled in a matched case-control study. Exact odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using a matched analysis. Climbing trees (83% of cases vs. 51% of controls, OR 8.2, 95% CI 1.25-infinity) and contact with another NiVE patient (67% of cases vs. 9% of controls, OR 21.4, 95% CI 2.78-966.1) were associated with infection. We did not identify an increased risk for NiV infection among persons who had contact with a potential intermediate host. Although we cannot rule out person-to-person transmission, case-patients were likely infected from contact with fruit bats or their secretions.

Histopathologic and immunohistochemical characterization of Nipah virus infection in the guinea pig.

Mortality rate in humans infected with Nipah virus (NiV) has been reported as high as 92%. Humans infected with NiV show a widespread multisystemic vasculitis with most severe clinical and pathologic manifestations in the brain, lungs, and spleen. The purpose of this study was to study pathologic and immunohistochemical findings in guinea pigs infected with NiV. Of 28 animals inoculated intraperitoneally, only 2 survived the infection, and most died between 4 and 8 days postinoculation (dpi). Viral antigen with minimal pathologic changes was first detected 2 dpi in lymph nodes and spleen. More severe changes were noted in these organs 4-8 dpi, where pathologic damage had a vasocentric distribution and viral antigen was abundant in vascular endothelium, tunica media, adventitia, as well as in macrophages lining sinuses. The urinary bladder, uterus, and ovaries were also affected with necrosis and acute inflammation. In these organs, immunohistochemical positive staining was intense in blood vessels, epithelial cells, and ovarian follicles. Approximately 50% of the animals that died or were euthanized in extremis had evidence of viral antigen and histopathologic changes in brain, especially involving meninges and ependymal cells, with lesser changes in the neural parenchyma. A unifying feature of the damage for all affected tissues was necrosis and inflammation of the vasculature, chiefly in arterioles, capillaries, and venules. Inoculation of guinea pigs intraperitoneally with NiV produces a disease with considerable resemblance to the disease in humans, but with reduced pulmonary involvement and marked infection of urinary bladder and the female reproductive tract.

An unusual iatrogenic foreign body (surgical gauze) in the trachea.

We report the case of a 60-year-old male with history of surgery for tracheal stenosis 21 years prior to the onset of difficult asthma-like symptoms. Upon exploring the tracheobronchial tree using the fiberoptic bronchoscope, a surgical gauze was found. The foreign body migrated transluminally from the mediastinum into the trachea and its removal was possible with rigid bronchoscopy leading to a rapid recovery of his symptoms.

Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species.

To characterize the distribution of Zaire ebolavirus (ZEBOV) infection within the 3 bat species (Epomops franqueti, Hypsignathus monstrosus, and Myonycteris torquata) that are possible reservoirs, we collected 1390 bats during 2003-2006 in Gabon and the Republic of the Congo. Detection of ZEBOV immunoglobulin G (IgG) in 40 specimens supports the role of these bat species as the ZEBOV reservoirs. ZEBOV IgG prevalence rates (5%) were homogeneous across epidemic and nonepidemic regions during outbreaks, indicating that infected bats may well be present in nonepidemic regions of central Africa. ZEBOV IgG prevalence decreased, significantly, to 1% after the outbreaks, suggesting that the percentage of IgG-positive bats is associated with virus transmission to other animal species and outbreak appearance. The large number of ZEBOV IgG-positive adult bats and pregnant H. monstrosus females suggests virus transmission within bat populations through fighting and sexual contact. Our study, thus, helps to describe Ebola virus circulation in bats and offers some insight into the appearance of outbreaks.

Airway wall thickening in patients with cough variant asthma and nonasthmatic chronic cough.

BACKGROUND: Chronic cough, which may be of asthmatic or nonasthmatic origin, is an important clinical issue. Airway inflammation, and remodeling demonstrated by subbasement membrane thickening has been associated with cough variant asthma (CVA) as well as with nonasthmatic chronic cough (NAC). CT studies have shown airway wall thickening in patients with asthma who wheeze. We examined airway wall thickness by CT in adult patients with chronic cough and examined its pathophysiologic implication. METHODS: Nonsmoking, steroid-naïve patients with CVA (n = 27), NAC (n = 26), and healthy control subjects (n = 15) were studied. Airway dimensions were assessed by a validated CT technique, in which we measured airway wall area (WA) corrected by body surface area (BSA), the ratio of WA to outer wall area (percentage of wall area [WA%]), absolute wall thickness (T)/ square root BSA, and airway luminal area/BSA of a segmental bronchus. Correlations between CT parameters and clinical indexes such as disease duration and cough sensitivity were examined. RESULTS: In patients with CVA, WA/BSA, WA%, and T/ square root BSA were all significantly greater than those in control subjects. In patients with NAC, WA/BSA and T/ square root BSA were significantly greater than in control subjects. The increase of WA/BSA and T/ square root BSA of NAC patients was less than that of CVA patients. In a subset of patients with NAC, WA% correlated with capsaicin cough sensitivity (n = 9, r = 0.75, p = 0.034). CONCLUSIONS: Walls of central airways are thickened in patients with CVA, and also to a lesser degree in patients with NAC. Airway wall thickening in NAC may be associated with cough hypersensitivity.

[Spontaneous spinal epidural haematoma during pregnancy]. / Hématome péridural rachidien spontané au cours de la grossesse.

Spontaneous spinal epidural haematomas are quite rare. We report here the case of a 27-year-old woman, without previous history of relevant medical disorder, who presented with acute paraplegia at 36 weeks of gestation. MRI performed in emergency revealed a T8 epidural haematoma. The management consisted in an emergency Caesarean section under general anaesthesia, followed immediately by a T8 laminectomy allowing the spinal cord decompression 14 hours after the first symptoms. Neurologic recovery was rapid and complete, except for bladder dysfunction persisting one month later. Spontaneous spinal epidural haematomas require a prompt diagnosis because neurologic prognosis essentially depends on the interval of time between onset of symptoms and surgical decompression. Obstetrical management especially depends on the term of pregnancy. For the anaesthesiologist, the difficulty is the management of both pregnant condition (full stomach general anaesthesia) and spinal cord compression (maintenance of spinal cord perfusion pression and limitation of ischaemia and oedema).

[Multiple Ebola virus haemorrhagic fever outbreaks in Gabon, from October 2001 to April 2002]. / Plusieurs epidémies de fièvre hémorragique due au virus Ebola au Gabon, d'octobre 2001 a avril 2002.

Outbreaks of Ebola virus haemorrhagic fever have been reported from 1994 to 1996 in the province of Ogooué Ivindo, a forest zone situated in the Northeast of Gabon. Each time, the great primates had been identified as the initial source of human infection. End of November 2001 a new alert came from this province, rapidly confirmed as a EVHV outbreak. The response was given by the Ministry of Health with the help of an international team under the aegis of WHO. An active monitoring system was implemented in the three districts hit by the epidemic (Zadié, Ivindo and Mpassa) to organize the detection of cases and their follow-up. A case definition has been set up, the suspected cases were isolated at hospital, at home or in lazarets and serological tests were performed. These tests consisted of the detection of antigen or specific IgG and the RT-PCR. A classification of cases was made according to the results of biological tests, clinical and epidemiological data. The contact subjects were kept watch over for 21 days. 65 cases were recorded among which 53 deaths. The first human case, a hunter died on the 28th of October 2001. The epidemic spreads over through family transmission and nosocomial contamination. Four distinct primary foci have been identified together with an isolated case situated in the South East of Gabon, 580 km away from the epicenter. Deaths happened within a delay of 6 days. The last death has been recorded on the 22nd of March 2002 and the end of the outbreak was declared on the 6th of May 2002. The epidemic spreads over the Gabon just next. Unexplained deaths of animals had been mentionned in the nearby forests as soon as August 2001: great primates and cephalophus. Samples taken from their carcasses confirmed a concomitant animal epidemic.

Cell profiles of bronchoalveolar lavage fluid as prognosticators of idiopathic pulmonary fibrosis/usual interstitial pneumonia among Japanese Patients.

BACKGROUND: The role of bronchoalveolar lavage fluid (BALF) cell profiles in predicting the clinical outcome of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is still under discussion. OBJECTIVE: To determine whether BALF cell profiles affect the survival of patients with UIP diagnosed by surgical lung biopsy/autopsy at the early stage of IPF. METHODS: This hospital-based retrospective cohort study used 81 Japanese patients with histologically proven IPF/UIP who underwent BAL examination. The BALF samples were obtained from non-current smokers: NCS (n = 41) and current smokers: CS (n = 40). The Kaplan-Meier and Cox's proportional hazard methods were used to estimate the survival and evaluate the risk ratio for death in the two groups. To detect the multicollinearity, a stepwise regression was employed. RESULTS: A slight increase in the absolute numbers of BALF neutrophils tended to relate to a decrease in the relative risk for death in NCS patients and CS patients in the univariate analysis. In stepwise regression, the increase in percent vital capacity and the increase in the BALF CD4/CD8 ratio in NCS was detected as a favorable predictor, while increased BALF cells affected the results due to chronic smoking in CS. CONCLUSIONS: Based on the study bias of the biopsy-proven IPF/UIP patients at stable stages, an independent variable indicating a favorable outcome was an increased BALF CD4/CD8 ratio in NCS patients, while it was difficult to identify definite prognosticators in CS patients.

Patient characteristics and clinical features of Japanese sarcoidosis patients with low bronchoalveolar lavage CD4/CD8 ratios.

BACKGROUND: Previous studies have shown that there is an association between low BALF (bronchoalveolar lavage fluid) CD4/CD8 ratio and lower remission rates in sarcoidosis patients. AIM: To investigate the patient characteristics and clinical features of Japanese sarcoidosis patients with low BALF CD4/CD8 ratios. METHODS: 322 Japanese sarcoidosis patients were retrospectively analyzed, and 3 groups were selected according to BALF CD4/CD8 ratios as follows: patients with the BALF CD4/CD8 ratio in the lowest 5 percentile (Group 1: 0.43-1.41), median 5 percentile (Group II: 4.68-5.47), and top 5 percentile (Group III: 12.6-60.1). Each group consisted of 16 patients (5% of 322 patients). The patient characteristics, clinical features, and the short-term prognosis for at least 2 years (average 116 months) were compared among the groups. Multivariate analysis was performed for 322 patients to investigate the determinants of BALF CD4/CD8 ratios. RESULTS: The number of BALF CD8+ cells were greater in Group I than in the other two groups. In Group I, there were higher incidences of younger age, male gender, and lower number of extrathoracic lesions compared with Group III. Multivariate analysis showed that younger age and male gender were independently associated with low BALF CD4/CD8 ratios. The frequency of treatment with corticosteroid and progression to pulmonary fibrosis tended to be higher in Group I. CONCLUSIONS: Low BALF CD4/CD8 ratios were due to increased number of BALF CD8+ cells. Younger age and male gender were independently associated with low BALF CD4/CD8 ratios in sarcoidosis patients.

[Medical treatment of an important trachea injury after tracheal intubation]. / Traitement médical d'une large plaie trachéale après intubation.

Tracheal injuries are rare but life threatening complications of anaesthesia. Two therapeutic strategies are presently proposed: a non-surgical strategy for small injuries and a surgical strategy for larger ones. This case report presented the non-surgical therapeutic strategy of a large tracheal injury. This strategy was discussed according to other published reports.