From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

[Guide for management of patients with possible respiratory sequelae after a SARS-CoV-2 pneumonia. Support proposals developed by the French-speaking Respiratory Medicine Society. Version of 10 November 2020]. / Guide de prise en charge des séquelles respiratoires post infection à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de Pneumologie de Langue Française. Version du 10 novembre 2020.

The French-speaking Respiratory Medicine Society (SPLF) proposes a guide for the management of possible respiratory sequelae in patients who have presented with SARS-CoV-2 pneumonia (COVID-19). The proposals are based on known data from previous epidemics, preliminary published data on post COVID-19 follow-up and on expert opinion. The proposals were developed by a group of experts and then submitted, using the Delphi method, to a panel of 22 pulmonologists. Seventeen proposals were validated ranging from additional examinations after the minimum assessment proposed in the SPLF monitoring guide, to inhaled or systemic corticosteroid therapy and antifibrotic agents. These proposals may evolve over time as knowledge accumulates. This guide emphasizes the importance of multidisciplinary discussion.

[Guide for follow-up of patients with SARS-CoV-2 pneumonia. Management proposals developed by the French-language Respiratory Medicine Society. Version of 10 May 2020]. / Guide pour le suivi respiratoire des patients ayant présenté une pneumonie à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de pneumologie de langue française. Version du 10 mai 2020.

The French-language Respiratory Medicine Society (SPLF) proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: (1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea; (2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit; (3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome…). These proposals may evolve over time as more knowledge becomes available.

A phase II study evaluating the cisplatin and epirubicin combination in patients with unresectable malignant pleural mesothelioma.

Few chemotherapeutic agents have demonstrated their efficacy in malignant mesothelioma. The cisplatin plus doxorubicin combination has one of the highest response rates. Epirubicin is an anthracyclin, analogous to doxorubicin, with a different toxicologic pattern. As there are no data on the activity of the combination cisplatin plus epirubicin in malignant mesothelioma, the European Lung Cancer Working Party (ELCWP) designed a phase II study with response rate as primary objective. Sixty-nine eligible patients with malignant pleural mesothelioma were centrally registered. The majority of the patients were male (n=59), had a Karnofsky performance status of 80 or more (n=62) and presented with an epithelial histologic subtype (n=43). Median age was 62 years. In nine patients, metastases were documented at the initial work-up, mainly in bone, lung and skin. Three hundred and twenty-four cycles of chemotherapy were administered. The main toxicities were nausea and vomiting, neutropenia and alopecia. Among 63 assessable patients, response rate was 19.0% (95% confidence interval [CI] 9-29%). Median survival was 13.3 months. In multivariate analysis, poor prognostic factors for survival were neutrophil count and CALGB groups 4-6. In conclusion, cisplatin plus epirubicin appears as an effective regimen in malignant mesothelioma, with a favourable toxicity profile. However, it does not demonstrate superior activity to other active regimens in this disease.

Identification of stapedius muscle motoneurons in squirrel monkey and bush baby.

The location of brainstem neurons which mediate the stapedius reflex was identified by injecting horseradish peroxidase into the stapedius muscle of squirrel monkeys and bush babies. Retrogradely labeled neurons, arranged in a one- to three-cell column, were found medial to the main facial motor nucleus in squirrel monkeys and ventral to it in bush babies. Nissl, protargol, and acetylcholinesterase stains were subsequently used to identify and describe this unique column of cells. It was found that staining characteristics, as well as shape, size, and location, distinguish stapedius muscle motoneurons from closely associated cell groups. Furthermore, stapedius muscle motoneurons are morphologically similar to periolivary cells and morphologically dissimilar to cells within the facial motor nucleus.

Earliest prevention of endemic goiter by iodine supplementation during pregnancy.

During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. It has been demonstrated that with decreasing iodine supply maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. Therefore iodine supplementation during pregnancy is now strongly recommended also in areas of moderate iodine deficiency. To monitor the success of iodine supplementation and its theoretical risk of increasing the frequency of thyroid autoantibodies, we have investigated the thyroid volume, thyroid function, urinary iodine excretion and antibodies to thyroid peroxidase at 10-12 weeks of gestation and postpartum in 38 mothers receiving 300 micrograms potassium iodide/day and in 70 mothers without iodine supplementation. In all of their newborns thyroid volume was determined by ultrasound. The thyrotropin (TSH) levels and antibodies to thyroid peroxidase (TPO-ab) in the neonates were measured in dried blood spots on filter paper from their newborn screening. Urinary iodine excretion was increased significantly after iodine supplementation in mothers (p < 0.001) and their newborns (< 0.05). No hypo- or hyperthyroidism was observed in the mothers or newborns. Interestingly, no difference of maternal thyroid volumes was observed between the two groups after pregnancy, but the volumes of the thyroid glands in newborns of mothers who received iodine were significantly (p < 0.004) lower (0.7 +/- 0.4 ml) than in the control group (1.5 +/- 1.1 ml). There was no change in the frequency of TPO-ab in either group after pregnancy. In four mothers transplacental passage of these antibodies was documented by positive measurement in the blood sample of the newborn. This study documents that iodine supplementation during pregnancy in an area of moderate iodine deficiency results in a lower size of neonatal thyroid volume and that this supplementation was not accompanied by an increase in the frequency of TPO-ab.

The prevalence of anti-thyroid peroxidase antibodies and autoimmune thyroiditis in children and adolescents in an iodine replete area.

BACKGROUND: The iodine supply of the population in Berlin has normalized during the last 5 Years. Therefore autoimmune thyroiditis has become the most important differential diagnosis in children and adolescents with goiter. OBJECTIVE: The aim of the present study was to define the prevalence of anti-thyroid peroxidase (TPO) antibodies and autoimmune thyroiditis in children and adolescents with a normalized iodine intake. DESIGN: To enable the measurement of antibodies to thyroid peroxidase (anti-TPO-Ab) in a large cohort, a method to determine anti-TPO-Ab in dried filter paper blood spots was established. In co-operation with pediatricians the antibody prevalence was assessed and data regarding thyroid size, echostructure and the medical history concerning iodine intake and familial thyroid diseases were collected. METHODS: 660 children and adolescents participated in the study; urinary iodine, TSH and TPO-Ab were measured and an ultrasound of the thyroid gland was performed. RESULTS: The sensitivity of the newly established filter paper assay was 91.8% and specificity was 100%. The results confirmed the improved iodine supply, with a median urinary iodine concentration of 139 microg iodine/g creatinine. The prevalence of anti-TPO-Ab was 3.4% with a female to male ratio of 2.7:1. CONCLUSION: The prevalence of anti-TPO-Ab is lower or equal to data reported from other iodine sufficient areas. Data from a moderate iodine deficiency in schoolchildren range from 0.0 to 7.3%. Using the new filter paper method field studies can be implemented to monitor the effect of changes in iodine nutrition on thyroid autoimmunity. Furthermore, this study on the prevalence of anti-TPO-Ab in a cohort of healthy children and adolescents in an iodine replete area can serve as reference data for future investigations and for the comparison with other groups of patients with increased risks for thyroid autoimmunity.

The status of iodine nutrition in newborn infants, schoolchildren, adolescents and adults in former East Germany.

In the former East Germany (GDR) like in the former West Germany (FRG) iodine deficiency and endemic goiter have been described since more than 2 decades. After a program of salt iodization which was started in East Germany in 1985 the urinary iodine excretion of the population increased significantly. The thyroid gland of the newborn is much more sensible to changes of the iodine supply than the thyroid of older children. A total of 1732 subjects was enrolled in the study. After the implementation of the mandatory salt iodization the goiter prevalence in newborns decreased markedly to less than 1%. After the reunification of Germany in 1990 the mandatory prophylaxis was stopped and the urinary iodine excretion in newborns, school-children, adolescents and adults diminished markedly. So in newborns the renal iodine excretion decreased to 2.82 micrograms I/dl in 1992. Since 1994 a reasonable improvement of the iodine supply is observed in the region of Leipzig. In school-children, adolescents and adults the mean value of the urinary iodine excretion is now above 10.0 micrograms I/dl. This value may be considered as an indicator for a normal iodine supply. In a small cohort (n = 28) of newborns infants we found a renal iodine excretion of 18.74 micrograms/dl in 1997. That value also means a significant increase since 1992 and a normal iodine supply in the fetal period. The present results from the region of Leipzig/Saxonia are not representative for the whole of East Germany. To provide an optimal iodine nutrition the use of iodized salt for food manufacturing must be significantly increased.

Small thyroid volumes and normal iodine excretion in Berlin schoolchildren indicate full normalization of iodine supply.

Iodine deficiency is the major cause of an increase in thyroid gland volume in infants and children. In this field study we monitored the iodine supply and its effect on the thyroid gland volume in prepubertal and pubertal children in the eastern and western parts of the city of Berlin, so far considered as an area with borderline iodine deficiency. The thyroid gland volume was determined by ultrasound in 1080 (f = 552, m = 528) children aged 3-15 years, and was correlated to age, body-surface area and iodine excretion, which was measured in a first-morning spot urine. The mean iodine concentration was 115.8 micrograms iodine/g creatinine (12.2 micrograms iodine/dl urine), with no significant differences between eastern parts with 114.5 micrograms iodine/g creatinine (12.3 micrograms iodine/dl urine) vs 116.7 micrograms iodine/g creatinine (12.0 micrograms iodine/dl urine) in the western parts of the city. This good iodine supply of the children was surprising compared to former studies in children and adults. Moreover this normalization of the iodine excretion was reflected by smaller thyroid gland volumes in the children. The volume was found to increase with age and was 2.4 +/- 1.1 ml in prepubertal (Prader and Largo: f < or = 10.9 ys, m < or = 11.5 ys) children, compared to 4.3 +/- 1.7 ml in pubertal children. The goiter prevalence, calculated on this data was below 5%. Among all children there were only 11 (aged 8-13 ys) with abnormal findings of the thyroid gland on ultrasound: 6 with small nodules, 1 girl with a thyroid-cyst, 2 girls had an inhomogenous echo structure and 2 girls presented with a hemithyroidea. This study shows that the iodine supply of the children in Berlin has improved, resulting in smaller sized thyroid glands, compared to those which have been previously published for Germany (Müller-Leisse 1988; Klingmüller, 1991; Menken, 1992), but they correspond well to volumes described in countries with sufficient iodine supply.

Cyclic steroid replacement alters auditory brainstem responses in young women with premature ovarian failure.

To determine the independent contributions of estradiol and progesterone to the auditory brainstem response (ABR) latency changes associated with the menstrual cycle, we obtained ABRs on young women with premature ovarian failure who were undergoing cyclic hormone replacement therapy (HRT). We evaluated the influence of cyclic HRT on the ABRs of young women in three controlled phases of the same replacement cycles: 1) no steroid replacement, 2) estrogen-only replacement (E2-only), and 3) estrogen-plus-progesterone replacement (E2-plus-P). A significantly lengthening of wave V peak latency and I-V interpeak interval was found during E2-only replacement. Despite equivalent circulating estradiol levels, both wave V peak latencies and wave I-V interpeak intervals significantly decreased during the E2-plus-P replacement phase as compared to the E2-only replacement phase. These findings are compatible with the hypothesis that estradiol potentiates secretion of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA) at auditory nerve synapses, leading to delayed synaptic conduction time. Progesterone is known to blunt E2-potentiated GABA release and may antagonize its prolongation of wave V latency.

Estrogen influences auditory brainstem responses during the normal menstrual cycle.

We evaluated the impact of the menstrual cycle on auditory brainstem response (ABR) latency in nine normally cycling women. Subjects (age 23-40 years) using no hormonal therapy were recruited and underwent ABR testing during four different phases of the same menstrual cycle: early follicular (cycle days 1 to 3); mid-cycle (cycle days 12 to 15); mid-luteal (cycle days 17 to 22), and premenstrual (cycle days 25-27). Cycles were verified by basal body temperature, and serum estrogen (E2), progesterone (P), and gonadotropin levels. A control group of nine women (age 23-40 years) on oral contraceptives (Nordette-28) was also studied four times during a pill cycle. Results show a significant increase in the latency of wave III and wave V peak latencies and in the I-V interpeak interval associated with a high estrogen state at the mid-cycle phase. No statistically significant variations in latency were found in the birth control pill group. These data suggest the existence of brainstem auditory neural pathways that are sensitive to fluctuations in E2 levels during the menstrual cycle.

Hearing aids. I. Conventional hearing devices.

State-of-the-art hearing aids incorporate advances in signal processing, miniaturization, and programmability. This technological progress has been accompanied by parallel enhancements in evaluating and fitting strategies. In addition, in the past several years, knowledge has increased about the influences of amplification on hearing ability and about the influences of hearing ability on benefit from amplification.

Sudden hearing loss in multiple sclerosis: case report.

This case illustrates the occurrence of a sudden hearing sensitivity loss that, in all likelihood, was the result of brainstem disorder resulting from multiple sclerosis (MS). Subject LD is a young woman who developed a sudden hearing loss while hospitalized for exacerbation of symptoms related to multiple sclerosis. By her own report, she had normal hearing in her left ear at the time of hospitalization. Four days after admission, she developed a hearing loss in her left ear, accompanied by roaring tinnitus and fullness. An audiologic evaluation revealed a substantial high-frequency sensitivity loss in the left ear. The combination of absent acoustic reflexes, depressed speech understanding, abnormal Bekesy audiometry, and an abnormal auditory brainstem response (ABR) was consistent with brainstem site of disorder. Over the next 2 weeks, hearing sensitivity recovered to within normal limits. This change in hearing sensitivity coincided with the recovery of acoustic reflexes, improvement in speech understanding, and partial recovery of the ABR.

The prevalence of central presbyacusis in a clinical population.

To evaluate the prevalence of central auditory disorder as a function of aging, we analyzed speech audiometric test results on 700 patients, 100 patients from each of seven half-decades beginning at age 50 years. In addition, we evaluated the extent to which prevalence estimates could be explained by the effect of hearing loss on measures of central auditory processing and the difference in prevalence of central presbyacusis between a clinical sample and a nonclinical sample. Results showed that the prevalence of central presbyacusis increased with age and that the highest prevalence was a striking 95 percent in the 80+ year age group. Results also showed that, even when degree of hearing loss and ability to perform the speech audiometric task were equated, the prevalence of central presbyacusis increased systematically with age. Finally, results showed that the prevalence was lower in the nonclinical sample than in the clinical sample at all ages, but that a substantial amount of central presbyacusis existed in the nonclinical subjects, especially in the oldest age groups.

Otoacoustic emissions as a cross-check in pediatric hearing assessment: case report.

Audiologic assessment of infants and young children can be confounded by neurologic disorders or neuromaturational delays. In some cases, this results in an inability to assess hearing sensitivity by behavioral measures or by auditory evoked potentials. This case illustrates such an audiologic challenge. Subject DF was born with hydrocephaly, which was treated with repeated shunt surgeries and resulted in seizures and pervasive developmental delays. At 9 months of age, the child was tested by auditory brainstem response (ABR) measurement and found to have no response to sound. Believing that her child had hearing, DF's mother sought a second opinion. Results of an audiologic evaluation at 11 months of age showed no measurable behavioral responses in the sound field and an ABR abnormality that prevented prediction of hearing sensitivity. In contrast, sensitivity prediction by the acoustic reflex and results of both transient-evoked and distortion-product otoacoustic emissions predicted normal peripheral hearing sensitivity. This case illustrates the usefulness of otoacoustic emissions as an additional cross-check measure in pediatric hearing assessment.

Gender affects audiometric shape in presbyacusis.

A review of large-scale surveys of hearing over the past 50 years reveals a "gender-reversal" phenomenon in the average audiograms of the elderly. Above 1 kHz males show greater average loss than females, but below 1 kHz females show greater average loss than males. The effect increases with both age and degree of hearing loss. The difference is present whether or not the elderly persons complain of a hearing problem and remains after persons with a history of noise exposure are excluded from the analysis. A possible explanation, based on the greater likelihood of cardiovascular disease in the elderly female, is considered.

Auditory disorder in central nervous system miliary tuberculosis: case report.

We evaluated a 28-year-old female with a unilateral hearing loss of unusual pathogenesis, that of central nervous system miliary tuberculosis. Audiologic and otologic findings were consistent with left retrocochlear disorder, characterized by a profound hearing sensitivity loss, absent acoustic reflexes, normal otoacoustic emissions, and the presence of only wave I of the auditory brainstem response. Imaging studies revealed the presence of multiple punctate lesions, one of which was extra-axial and located at the left cerebellopontine angle. The pattern of audiometric test results, particularly the combination of normal otoacoustic emissions and profound hearing sensitivity loss, contributed importantly to the investigative sequence leading to the final diagnosis.

Improving the efficiency of speech audiometry: computer-based approach.

Speech audiometric measures were carried out on 981 patients using a computer-based system that permitted a comparison between two modes of signal presentation, manual and automatic. The manual mode, designed to simulate the pace of live-voice testing, allowed the presentation of speech signals at a rate dictated by the patient's response. The automatic mode, designed to simulate tape-player testing, fixed the interstimulus interval. A comparison of elapsed time for the completion of word recognition testing with phonetically balanced (PB) word lists showed that use of the manual mode resulted in increased efficiency. Testing time was reduced by an average of 22 percent. These results suggest that the clinical efficiency of speech audiometric testing can be enhanced by using a computer-based manual approach. The combination of digitally recorded speech stimuli with a computer-based manual approach may provide a useful compromise between the efficiency of live-voice testing and the signal consistency of magnetic-tape or compact-disc recordings.

Auditory evoked potentials in Rett syndrome.

This study was designed to assess auditory function in subjects with Rett syndrome, a rare neurologic disorder that is characterized by progressive symptoms of dementia, ataxia, respiratory disorder, and communication disorder. Auditory evoked potentials, including the auditory brainstem response (ABR), middle latency response (MLR), and late vertex response (LVR), were recorded in 36 subjects with Rett syndrome. Results showed a systematic decline in auditory function from the peripheral to the central auditory system, with normal ABR in all subjects, normal MLR in 50 percent of subjects, and normal LVR in 36 percent of subjects. Results suggest that hearing sensitivity and the functional integrity of eighth nerve and auditory brainstem pathways are not affected in subjects with Rett syndrome. However, abnormality of both the MLR and LVR suggest the presence of central auditory disorder.

[Adenocarcinomatous pleural lesion associated with hypoglycemia]. / Lésion pleurale adénocarcinomateuse associée à une hypoglycémie.

We report the case of a patient suffering from a glandular pleural lesion. The evolution of the disease was punctuated by periods of hypoglycaemia, which caused a coma. There was no clinically evident explanation for these hypoglycaemic episodes. Investigations revealed adrenal failure, but this adrenal failure was unrelated to the neoplastic process in the patient. This case is a reminder that the cause of hypoglycaemia associated with tumours can really have a paraneoplastic origin and justifies an in depth study to achieve an aetiological diagnosis.