H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

Survey on infectious disease telephone hotlines in primary care: General practitioners' satisfaction and compliance with advice.

OBJECTIVES: Infectious disease (ID) advice is a major part of antimicrobial stewardship programs. The objective of this study was to assess general practitioners' (GPs)' opinions and compliance with advice given by ID hotlines. PATIENTS AND METHODS: This multicenter survey was based on the 7-day assessment of initial advice requested by GPs to a hotline set up by volunteer hospital ID teams to record advice for 3 years. The primary endpoint was the GPs' satisfaction with the advice given by ID specialists. RESULTS: Ten ID teams participated in the study and recorded 4138 requests for advice, of which 1325 requests included a proposal for antibiotic therapy and justified a follow-up call at seven days. Only 398 follow-up calls (30%) were carried out because many GPs were not reachable. GPs were very satisfied with ID hotlines: 58% considered them indispensable and 38% very useful. The recommendations provided by ID specialists were followed by GPs in more than 80% of cases. The two main motivations for GPs to call the hotline were to get quick advice (86%) and to receive help in managing a patient (76%). CONCLUSIONS: The ID telephone consultations and advice systems for GPs are highly appreciated and are effective in terms of following the recommendations.

[Solitary and extramedullary plasmocytoma in the head and neck region: five cases report]. / Plasmocytome solitaire extramédullaire de la tête et du cou: à propos de cinq cas.

PURPOSE: To assess the outcome and the management of solitary extramedullary plasmocytoma in the head and neck region. PATIENTS AND METHODS: From 1997 to 2008, five cases of solitary extramedullary plasmocytoma were treated in the department of radiotherapy at Salah-Azaiz Institute. Three patients had a solitary plasmocytoma of the nasal fossa; the others were ethmoidal and submandibular node. All patients received irradiation of 40 to 45 Gy in the primary site associated to surgery in four cases. Among the five patients, two had radiotherapy after recurrence. RESULTS: Four complete responses were noted with a follow-up of 12, 36, 52 and 72 months. Multiple myeloma occurred in one patient 8 years after treatment. CONCLUSION: Radiotherapy is the best effective local treatment. Local control of extramedullary plasmocytoma in the head and neck region seems to be improved when the dose is at least 45 Gy. Predictive parameters of unfavourable outcome and conversion of extramedullary plasmocytoma to multiple myeloma should be better defined.

[Prognostic value of parapharyngeal extension in nasopharyngeal carcinoma]. / Valeur pronostique de l'extension parapharyngéee dans les carcinomes nasopharyngés.

AIM: This study evaluated the prognostic value of the Para pharyngeal space involvement in nasopharyngeal carcinoma T 2 disease (UICC 1997 classification). METHODS: From January 1997 and December2001; 32 patients with nasopharyngeal carcinoma were examined by CT scan and according to the 1997 International Union Against Cancer (UICC) staging system, 15 had stage T2a M0 (G1) and 17 T2bM0(G2). The median age was 47 years. The male to female ratio was 1.81 (G1); 4.3 (G2). All patients were pathologically confirmed by biopsy from the nasopharynx as having UCNT in 100% (G1) and 94% (G2). The node involvement was 52% for the G1 (N2: 26%, N3: 26%) and 80% for the G2 (N2: 47%, N3: 41%). Both neoadjuvant chemotherapy and radiotherapy were performed for advanced N disease and only radiotherapy for NO. RESULTS: Examination and CT scan were performed for the evaluation of the treatement. The completely clinical remission after chemotherapy was 12.5% (G1) and 53% (G2), partial remission was 25% (G1) and 35% (G2). The CT scan control wasn't performed for all patients. The complete response was 69% (G1) and 53% (G2); partial response was 6% for both two groups. The median follow up was 79 months. Disease free survival rates were 70% for G1 (T2a) and 48% for G2 (T2b). Distant metastasis rates were 26% (G1) vs 6% (G2) and more likely in the presence of advanced N disease. Five years overall survival was 78% (G1) T2a vs. 55% (G2) T2b.The N disease was correlated to metastasis as overall survival was 66.7% for N3 disease vs 85.7% for N0. CONCLUSION: Parapharyngeal tumor involvement affects local and regional tumor failure. Subclassification of T2 disease into T2a/T2b should have an impact on treatment strategies.

[Sarcomatoid carcinomas of the upper airways]. / Carcinomes sarcomatoïdes des voies aéro-digestives supérieures.

INTRODUCTION: The sarcomatoid carcinoma of the superior aerodigestive tracts is a rare malignant tumour which presents diagnostic and therapeutic challenges. MATERIAL AND METHOD: We report 11 cases of spindle cell carcinomas of the upper airways. RESULTS: Sex-ratio was 10:1 and the mean age was 57.3 years (30 - 75 years). Nine patients were smokers and 4 presented with a history of radiation exposure. Tumoral locations were as follows: larynx: 6, hypopharynx: 1, oropharynx: 1, nasopharynx: 1, oral cavity: 2. Histological diagnosis in 3 cases required the use of immunohistochemical studies. Four patients were first seen at an advanced stage. This left 9 patients and among them 7 received a curative treatment: 5 by surgery alone, 1 by surgery and radiotherapy, 1 by radiotherapy, 1 by chemo-radiotherapy for the nasopharyngeal lesion and 1 by chemotherapy alone. Two patients died from their disease before treatment. With an average delay of 15.4 months, the rates of global survival and disease-free were 5/9 and 4/9 respectively. CONCLUSION: The sarcomatoid carcinoma of the upper airways is rare, but not unusual. Its diagnosis benefits from progresses in immunohistochemistry, but also from advances in the field of molecular biology. Its treatment and natural evolution remain controversial.

[Epidemiology of nasal and paranasal sinus cancer in Tunisia]. / Epidémiologie des cancers du massif facial en Tunisie.

OBJECTIVE: To report the epidemiological and clinical features of nasal and paranasal sinus cancers collected during a period of 35 years at the Salah Azaiez Institute of Tunis. MATERIAL AND METHODS: This retrospective study concerned patients with histologically confirmed nasal and paranasal sinus cancers treated at our institute from 1969 to 2004. We collected the following data: age, sex, residence (rural or urban), site, occupation and professional exposure, histological type and tumor extension. RESULTS: We identified 265 cases (163 M; 102 F; Sex-ratio=1.65) with a mean age of 60 years (3 months - 91 years). Epidermoid carcinoma (47%) and adenocarcinoma (16%) predominated followed by sarcoma (14%) and melanoma (6%). We observed only 2 cases (0.7%) of ethmoidal adenocarcinoma. CONCLUSION: Nasal and paranasal cancers in Tunisia are linked more to chronic rhino-sinusal inflammation than professional exposition (wood).

[Hodgkin disease of the nasopharynx: report of three cases]. / Maladie de Hodgkin du cavum: à propos de trois cas.

We report three cases of Hodgkin's disease (HD) involving the nasopharynx. Their clinical presentations, morphological and immunohistochimical features and their therapy modalities are discussed. The patients were aged 36, 41 and 77, presenting with increasing bilateral nasal obstruction in one case and a cervical mass in the two others. Histological study showed mixed cellularity type of HD in all cases. The Reed Sternberg cells expressed both of CD15 and CD30 in one case, and only one of them in the other cases. In one case, LMP1 was detected, CD20 and CD3 were not. HD of nasopharynx should be differentiated from EBV-associated lymphoproliferations. The treatment is based on radiotherapy that can be associated to neoadjuvant chemotherapy if nodes are involved.

[Regional failure of hypopharyngeal squamous cell carcinoma]. / Echecs ganglionnaires du carcinome épidermoïde de l'hypopharynx.

PURPOSE: Lymph nodes and distant metastases contribute to the poor prognosis of hypopharyngeal squamous cell carcinoma. The purpose of this study is to estimate the frequency, mode and prognosis factors related to regional and distant metastasis. PATIENTS AND METHOD: The authors' report is based on a retrospective study concerning 271 hypopharyngeal squamous cell carcinoma, compiled in the service of Surgery of Head and Neck Cancers of the Salah-Azaïz Institute (1977-2002). Frequency and histoclinical characters of cervical and distant metastases have been assessed, as well as their prognosis factors among 155 patients treated in a curative purpose. RESULTS: 39.1% of the tumours were classified N0, 24.4% N1, 10.7% N2 and 25.8% N3 (UICC 2002). The cervical nodal invasion was significantly more frequent for the classified tumors T3T4 than for the T1T2 (for pyriform sinus, postcricoid esophagus, posterior wall, and total hypopharynx, respectively : P =0.001, P =0.007, P =0.047 and P =0.0005). A cervical lymphatic evidement was preferred in thirty two patients. Among N0, 46.9% were N+; The frequencies of the capsular effraction were not significantly different for the N0N1 from for the N2N3 (P =0.11). The two and five years survival rates were respectively 32.5 and 20.5% for N0, and 10.9% and zero for N3. The survival differences after two and five years between the N0N1 and the N2N3 were significant (P =0.04). A regional failure was noticed for 18.5% of the patients. The tumoral site did not influence significantly the rate of nodal failure (P =0.98), neither the clinical status N (P =0.34). Capsular effraction was a significant factor for the regional failure (P =0.007). Distant metastasis significantly occurred more frequently among the patients initially classified N2N3 than those classified N0N1 (P =0.03), and in case of capsular effraction (P =0.0009). CONCLUSION: Hypopharyngeal squamous cell carcinoma has a high rate of lymph nodes metastasis, correlated to the local extension, and a high rate of occult nodal metastasis. Lymph node clinical status does not seem to have influenced the patients survival; however, capsular effraction constitutes a major prognosis factor of regional failure and distant metastasis. Distant metastases are frequent, particularly in case of wide local and regional tumoral extension.

[Hypopharyngeal squamous cell carcinoma: retrospective study of 149 patients]. / Carcinome épidermoïde de l'hypopharynx: étude rétrospective de 149 traitements à visée curative.

PURPOSE: Hypopharyngeal squamous cell carcinoma is associated to one of the most unfavorable prognosis among the cancers of the head and neck. The purpose of this study is to analyze its therapeutic modalities in the Salah-Azaïz Institute (Tunis) and to compare their results. PATIENTS AND METHOD: This retrospective study concerns 271 hypopharyngeal squamous cell carcinomas, compiled in the Carcinologic Surgery Department of Head and Neck of the Salah-Azaïz Institute over a period of 25 years (from 1977 to 2002). The average age of the patients was of 56 years; sex-ratio was on average of 1.2 (man/woman). The indication of a curative treatment was initially retained for 149 (55%) patients, who were the only ones retained for the analysis of results. RESULTS: We retained the indication of a protocol including surgery and postoperating radiotherapy for 26.2% of the patients. Postoperation mortality rate was 5.1%; the operating rate of morbidity was 46.2%. For 13.5% of the patients, postoperating radiotherapy was permanently interrupted because of a gradual deterioration of the patients' health in the course of treatment. We retained the indication of exclusive radiotherapy for 59.7% of the patients. The average age was of 56 years and the sex-ratio of 1.2. The external radiotherapy was conventional. Radiotherapy had to be permanently interrupted in progress in 32.6% of cases on account of an deterioration of the patients' health; the rate of morbidity of the radiotherapy was 33.3%. We indicated a protocol of conservation of organ with induction chemotherapy for 21 patients (14.1%). The average age was of 53 years (28-65 years) and sex-ratio (man/woman) of 0.5. The global survival was 25.5% at one year, 18.1% at two years, 11.4% at three years and 7.4% at five years. All the patients selected for chemotherapy died in the course of treatment. The rates of survival in two and five years according to protocols surgery-radiotherapy and exclusive radiotherapy were respectively: 21.5 and 12%, and 18.3 and 10%. The difference between the rates of survival of this two protocols is not significant (P =0.08). CONCLUSION: Although the induction chemotherapy entails a particularly high death rate in our series, the association surgery-radiotherapy and the exclusive radiotherapy seem to be similarly efficient for the treatment of the hypopharyngeal carcinoma.

[Morbidity diagnosed in the general medicine public structures in Tunisia]. / La morbidité diagnostiquée dans les structures publiques de médecine générale en Tunisie.

The study of morbidity in general medicine is very useful in order to adapt training curricula to the reality of medical practice in the first degree. The objective of this work was to describe the morbidity charted in general medicine in Tunisia's Sousse region. It consisted of a prospective and descriptive study involving six basic health centres in Sousse and was conducted over the course of 30 randomly selected days during the year 2000. There were 4022 consultations included in the study which were described according to the SOAP plan. The coding of the charted diagnoses was carried out according to the International Classification of Primary Care (CISP). There were 98% of the consultants who were self-referred and 84% of the consultations corresponded to new cases. The consultants' sex-ratio was 0.5 in favour of females with an average age of 27 years. There were 4,597 diagnoses noted utilising 336 codes from the CISP classification system. The "Respiratory" chapter took the first place on the list (39.6%) followed by the "Circulatory" chapter. The "Top 30" list of the most often charted diagnoses totaled 72% of the consultations among which the three most frequent health problems were pharyngitis (14.4%), acute bronchitis (8.3%) and arterial hypertension (7.4%). This study demonstrates that the practice of general medicine is characterised by instinctive first solutions and versatility. The predominance of cardiovascular and respiratory illnesses illustrates the double burden of morbidity which is faced by Tunisian general medicine practitioners. The "Top 30" list should serve as basis for planning pregraduate and continuing medical training.

[Thyroid papillary microcarcinoma. Salah Azaiz Institute experience]. / Microcarcinomes papillaires de la thyroïde. Expérience de l'Institut Salah Azaiz.

The incidence of thyroid papillary microcarcinoma appears to be increasing and therapeutic modalities remain controversial. This retrospective study concerns 25 cases, from 1978 to 1999. The circumstances of diagnosis were: a cervicotomy for thyroid nodule (88% of cases), cervical node metastases (8%), and osseous metastases (4%). The sensitivity of ultrasounds was 22.2%, that of scintigraphy was 9.1% and that of extemporaneous histological examination was 18.2%. Multifocality was found in 16% of cases and bilaterality in 16.6%. Treatment modalities were guided by histological examination. Adjunctive radioiodine ablation was used for 20% of the patients. The treatment of the osseous metastases was completed with external irradiation. The average follow up was 4.8 years (4 months to 19 years), with a rate of survival without disease of 100%.

[Cervical lymph node involvement in carcinomas of the mobile tongue in Tunisia. Retrospective study of 135 cases]. / Envahissement ganglionnaire dans les carcinomes épidermoïdes de la langue mobile (CELM) en Tunisie.

OBJECTIVE: To report the profile of histologic cervical nodes involvement associated with mobile tongue squamous cell carcinoma. PATIENTS AND METHODS: Our retrospective study concerned patients treated from 1978 to 1998 by cervical neck dissection for mobile tongue carcinoma. RESULTS: A population of 135 patients (90 M/45 F, sex-ratio 2) with a 53.5 mean age (19 to 75) is analyzed. Clinical palpable nodes were present in 68 cases (50%) mainly submental-submaxillar (54). Histologic examination showed a node involvement in 54 cases without (32 cases) or with capsular rupture (22 cases) mainly in the jugulo-carotidian chain (46/54). Among the 67 clinically N0 patients collected after 1990, 22 patients (33%) exhibited an histological involvement vs 32/68 (47%) for the group presenting palpable cervical nodes for the whole period. Histologic node involvement seemed to be linked to the clinical status, node size and TNM stage. CONCLUSION: Cervical lymph node treatment needs to be systematic in mobile tongue carcinoma. The probability of histologic involvement is linked to the loco-regional extent of disease and influences the prognosis. In N0 patients, neck dissection is required because of the frequency of histological involvement, particularly when loss to follow-up may be expected.

[Thyroid oncocytomas]. / Les oncocytomes thyroidiens.

OBJECTIVE: Thyroid oncocytomas are rare tumors. They put problems of differential diagnosis enter malignant and benign forms. The modalities of the surgical treatment are controversial, in form as benign as malignant. Their prognosis is also debated. MATERIAL AND METHOD: Our retrospective study concerns 111 thyroid oncocytomas, so 6.5% of thyroid operated in our centre between 1981 and 2001. The sex-ratio of the patients was 0.16 with an average age of 41 years (15 to 72 years). RESULTS: All the fixed nodules, those associated to a recurrential paralysis, to tangible nodes or/and to microcalcifications on the radiography of the neck was malignant. Histological extemporaneous exam was not decisive in 16% of cases, among which 33% showed themselves malignant in the definitive exam, which put in evidence 9 carcinomas (8%). We treated benign oncocytomas by a loboisthmectomy for the isolated nodules, and the subtotal or total thyroidectomy for multinodular glands. For oncocytic carcinomas, we realized a total thyroidectomy with ganglionic taking and histological extemporaneous exam, followed by evidment in case of invasion (2 patients). For the 5 patients having presented a residual fixation, we obtained a white cartography after radioactive iodine administration. For the benign oncocytoma, we did ot notice any recurrences with an average drop of 28 months (2 months to 7 years). For carcinoma, 8 patients on 9 presented an actuarial survival without disease with an average drop of 44 months (18 months to 8 years). CONCLUSION: The diagnosis of malignancy of thyroid oncocytomas can be strongly evoked on however fickle clinical and radiological criteria; it can be eliminated only after definitive anatomo-pathological exam.

[Primary sino-nasal lymphomas. Apropos of 25 cases]. / Lymphomes primitifs nasosinusiens. A propos de 25 cas.

PURPOSE: To report on the epidemiological and therapeutic features of a series of Tunisian patients treated for primitive sinonasal lymphoma. PATIENTS AND METHODS: Our retrospective study concerns patients with histologically proven primitive sinonasal lymphoma diagnosed and treated at our institution from 1975 to 1997. Initial work-up included: clinical plus ENT examination, WBC, ESR, LDH, abdominal ultrasonography, bone marrow biopsy and facial CT-scan taken since 1985. All slides are reviewed and reclassified using the Kiel system. Treatment is based on radiotherapy with or without chemotherapy (mainly with the CHOP protocol). RESULTS: We collected 25 patients (22 males and three females, sex-ratio = 7) with a mean age of 48 years (18 to 78). Mean delay of consultation is 4 months and patients consulted mainly for nasal obstruction (65%), more rarely epistaxis (40%) or rhinorrhea. ENT examination showed a fungating nasal fossa tumor in 20% of cases, predominantly unilateral (80%), associated to cervical nodes in 25% of cases. High-grade lymphomas represented 60% of the cases, and 60% of the patients were stage IE. All stage IEs have been treated by exclusive radiotherapy while more advanced stages received combined chemo- and radiotherapy (eight patients). The five-year actuarial survival rate was 69% for the whole population, with a better prognosis for localized stage and low-grade lymphomas. DISCUSSION: Radiotherapy remains a standard treatment for sinonasal lymphomas, permitting us to cure localized stages. In extended stages (more than IE), combined chemoradiotherapy seems to be a good option, especially in case of bulky tumors as observed for the other nodal and extra-nodal head and neck lymphomas.

[Mucous malignant melanoma of the neck and face. Experience at the Salah Azaiz Institute (Tunis)]. / Mélanomes malins muqueux cervico-faciaux. Expérience de l'Institut Salah Azaiz (Tunis).

The mucosal melanoma of the head and neck is rare and of late diagnosis. This retrospective study concerns 17 cases brought together in 30 years. Sex-ratio was of 1.1, the average age of 58 years. Tumoral seats were the following ones: nasal cavity and paranasal sinus (n = 10), nasopharyngeal cavity (n = 2), gingival seat (n = 2), palate (n = 1), laryngeal seat (n = 1), middle ear (n = 1). Tumoral extension was classified an follows: stage I: 52.9%, stage II: 17.6%, stage III: 29.4%. Melanomas were achromic in 23.5% of cases. On the therapeutic plan, 47.1% of the patients were treated in a purpose palliative because of the importance of the tumoral extension. Seven patients (41.2%) were treated surgically; three among them received an additional radiotherapy for an insufficient tumoral excision or adenopathy in break capsular. Two patients (11.8%) were treated by exclusive radiotherapy. The rates of survival were 17.6% in 2 years, and 5.9% in 5 years. The average duration of survival was of 18.1 months. The causes of failure were essentially local and metastatic.

[Contraceptive use prevalence in a suburban zone around Sousse (Tunisia)]. / La prévalence contraceptive dans une zone périurbaine de la ville de Sousse (Tunisie).

A contraceptive prevalence survey was conducted among 1277 women of reproductive age, to explore knowledge of and attitudes to contraceptive use and study factors influencing contraceptive use. We found that family planning methods were generally well known. The prevalence of modern contraceptive use was 53.6%, IUDs being the most commonly used followed by sterilization and pills. The public sector was the main source for obtaining contraceptives although pills and condoms tended to be obtained from the private sector. There was a significant correlation between contraceptive use and urban residence.

[Dermatomyositis and nasopharyngeal carcinoma: 3 cases]. / Dermatomyosite et cancer du cavum : 3 observations.

BACKGROUND: Nasopharyngeal carcinoma is a common cancer in Tunisia with an estimated incidence of 1.8/100,000. The tumor shows a characteristic association with paraneoplastic syndromes. CASE REPORTS: We report three cases of histologically proven dermatomyositis associated with nasopharyngeal carcinoma in patients aged 40, 24 and 65 years. In all cases, the course of the paraneoplastic syndrome ran parallel to the nasopharyngeal carcinoma. DISCUSSION: Dermatomyositis is one of the numerous paraneoplastic syndromes associated with nasopharyngeal carcinoma. Systematic examination of the nasopharynx is required in case of dermatomyositis.

[Secondary head and neck osteosarcoma following treatment of undifferentiated nasopharyngeal neoplasms (UCNT)]. / Ostéosarcome secondaire de la tête et du cou après traitement de carcinome indifférencié du nasopharynx (UCNT).

Secondary tumours after radio and/or chemotherapy are mainly of hematopoietic (acute non lymphoblastic leukemia, non-Hodgkin lymphoma) or soft tissue lineage previously described most frequently after breast cancer and Hodgkin disease treatment with radio and/or chemotherapy. We report two cases of classical osteosarcoma's observed 9 and 3 years after treatment for UCNT with combined radiotherapy and alkylant-based adjuvant chemotherapy in one case and exclusive loco-regional irradiation in the second case.