Nivolumab plus chemotherapy or ipilimumab versus chemotherapy in patients with advanced esophageal squamous cell carcinoma (CheckMate 648): 29-month follow-up from a randomized, open-label, phase III trial.

BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.

LEAP-014: first-line lenvatinib + pembrolizumab + chemotherapy in advanced/metastatic esophageal squamous cell carcinoma.

Treatment options for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) are improving. Current guidelines recommend first-line pembrolizumab plus chemotherapy for patients with unresectable or metastatic ESCC, which has led to improvements in survival outcomes. Antiangiogenic therapy combined with immune checkpoint inhibitors can act synergistically to convert the immunosuppressive tumor microenvironment to an immune supportive microenvironment, thus enhancing antitumor immune responses. In preclinical models, the antiangiogenic agent lenvatinib combined with an anti-PD-1 agent showed synergistic antitumor activity. We describe the design and rationale for the randomized, open-label, phase III LEAP-014 study of lenvatinib in combination with pembrolizumab plus chemotherapy in patients with advanced or metastatic ESCC. Overall survival and progression-free survival are the dual primary end points. Clinical Trial Registration: NCT04949256 (ClinicalTrials.gov).

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4).

INTRODUCTION: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). METHODS: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. RESULTS: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DISCUSSION: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

Epidemiologic analysis and mortality outcome of firearm injuries in French Guiana (2016-2019).

BACKGROUND: French Guiana (FG) is a French territory located in South America with the highest rate of armed assaults. FG presents a poorly developed road system and a young and precarious population that makes the geographical and socio-demographic characteristics specific. No data concerning the firearm injury management are available in this country. Studying thesis trauma could permit to improve the management of victims. The objective of this study is to investigate the epidemiology of firearm injuries in FG, to define characteristics of the victims, and to assess factors associated with death. These identified factors could enable target primary prevention and intensification of medical management. METHODS: From January 2016 to December 2019, we conducted a retrospective study at the Cayenne General Hospital (CGH), including all patients admitted for firearm injuries in the emergency department, the medical emergency and resuscitation service, and the forensic service. A bivariate analysis was performed to assess relevant clinical data that were entered into a logistic regression model to assess factors associated with death. RESULTS: A total of 871 files were analyzed concerning 340 patients included after cross-checking. Victims were mainly males (90%) and young (30 ± 11 years old). The injury occurred mainly at night (60%), in a context of assaults (83%) and with long-barreled guns (82%). Among the 290 patients managed at the CGH, 60% were hospitalized including 12% that were in the intensive care unit, 41% that required surgical treatment, and 7% that died in hospital. The overall average length of stay was 10 ± 18 days. Overall mortality (n = 71, 21%) is statistically associated with male gender (p = 0.007) and suicide context (p < 0.001). In multivariate analysis, the sites of wounds (head and neck, thorax; p < 0.001) as well as induced organ injuries (neurological, respiratory, and vascular; p < 0.005) were independent factors associated to mortality. CONCLUSIONS: This work underlines the high incidence of ballistic trauma in FG. This mainly involves a young and male population linked to the use of long arms and assaults. Despite the geographical difficulties of the territory and the technical platform deficits (no neurosurgery, no cardiothoracic surgery, no interventional radiology), the mortality is comparable to other studies, but remains more than twice as high as in mainland France. Finally, despite a change in legislation restricting access to firearms, our results show that gunshot firearm injuries remain a major public health concern requiring greater political actions.

Triplet chemotherapy plus cetuximab as first-line treatment in extended RAS wild-type metastatic colorectal cancer patients.

BACKGROUND: Triplet chemotherapy plus cetuximab showed promising results in phase II trials in unsystematically selected RAS population. We evaluated FOLFIRINOX+cetuximab efficacy as first-line treatment in extended RAS wild-type metastatic colorectal cancer (mCRC) patients. METHODS: We retrospectively analyzed patients treated with FOLFIRINOX+cetuximab, using data from clinical trials and real-life practice. Extended mutation analysis was performed when RAS/BRAF status was unavailable. The primary endpoint was progression-free survival (PFS). RESULTS: Seventy patients (61.4 % male, median age 58.7 years) were analyzed. Eighty percent had left-sided mCRC and 97.1 % had liver metastases. Median PFS and overall survival (OS) were 13.3 and 48.5 months, respectively. The objective response rate was 85.7 %, with 20 % complete response. Primary tumor location did not affect OS and PFS. BRAF wild-type patients (n = 65) had longer PFS (13.3 vs. 6.0 months; p = 0.005) and OS (50.1 vs. 21.2 months; p = 0.007) than BRAF mutated patients (n = 5, including four BRAFV600E). Median OS was significantly longer in resected patients (n = 39, 55.1 vs. 30.7 months; p = 0.030). Main toxicities were diarrhea (31.4 %) and neutropenia (21.4 %). CONCLUSION: FOLFIRINOX+cetuximab provides good PFS, high response rate and prolonged disease control in initially unresectable extended RAS wild-type mCRC. This combination is particularly interesting for selected patients with liver-limited disease eligible to secondary resection.

Migration in French Guiana: Implications in health and infectious diseases.

In French Guiana, more than a third of the population, and nearly half of the adults, are of foreign origin. This immigration is explained by the French standard of living, which is attractive to nationals of surrounding countries. Infectious diseases remain in the top 10 causes of premature death, often in the most precarious populations. In this context we aimed to synthesize the state of the knowledge regarding immigration and infectious diseases in French Guiana and the general implications that follow this diagnosis. For HIV, although the majority of patients are of foreign origin, estimates of the presumed date of infection based on CD4 erosion modelling and from molecular analyses suggest that the majority of transmissions in foreign-born individuals occur in French Guiana and that the Guiana shield has been a crossroad between Latin America and the Caribbean. Among key populations bridging these regions illegal gold miners are very mobile and have the greatest proportion B Caribbean HIV viruses. Gold miners have been a key vulnerable population for falciparum malaria and other tropical diseases such as leishmaniasis, leprosy, or leptospirosis. The complex history of migrations in French Guiana and on the Guiana Shield is also reflected in the fingerprinting of mycobacterium tuberculosis and the high incidence of tuberculosis in French Guiana, notably in immigrants, reflects the incidences in the countries of origin of patients. The high burden of infectious diseases in immigrants in French Guiana is first and foremost a reflection of the precarious living conditions within French Guiana and suggests that community-based proactive interventions are crucial to reduce transmission, morbidity, and mortality from infectious diseases.

Social determinants of health among people working on informal gold mines in French Guiana: a multicentre cross-sectional survey.

INTRODUCTION: Social determinants of health, such as living and working conditions, economical and environmental context and access to care, combine to impact the health of individuals and communities. In French Guiana (FG), the persons working in informal artisanal and small-scale gold mining in the rainforest are a particularly vulnerable population which lives in precarious conditions and far from the health system. Previous studies have demonstrated their high morbidity due to infectious diseases. This study aims to describe the social determinants of health in this specific population. METHODS: This international multicentre cross-sectional survey included people working on the informal FG gold mines at the crossing points located at both borders with Suriname and Brazil. After collecting written informed consent, a structured questionnaire was administered. RESULTS: From September to December 2022, 539 gold miners were included. These poorly educated migrants, mainly from Brazil (99.1%) did not have access to drinkable water (95.4%), lived in close contact with wild fauna by hunting, eating bushmeat or being bitten and were exposed to mercury by inhalation (58.8%) or ingestion (80.5%). They report frequent accidents (13.5%) and chronic treatment interruptions (26.6% of the 11.9% reporting chronic treatment). Half of them considered themselves in good health (56.4%). CONCLUSION: This study shows a singular combination of adverse exposures of gold miners working in FG such as zoonoses, heavy metal poisoning, aggression of wild fauna. For ethical as well as public health reasons, actions towards health equity must be considered at different levels: individual, community, environmental, systemic and global level. As end users of minerals, we must assume our responsibilities for the well-being of the extractors by including health in political decisions to engage together in global health. TRIAL REGISTRATION NUMBER: NCT05540470.

Factors associated with chronic kidney disease in patients with diabetes in French Guiana.

Introduction: With over half of the population living under the poverty threshold, the social and health context in French Guiana is more difficult than in mainland France. The prevalence of diabetes is twice as great and end-stage renal failure is 45% higher than in mainland France. Objective: Our objective was to describe the profile of diabetic patients with chronic kidney disease in French Guiana and search for possible risk factors. Method: We conducted a multicenter cross-sectional observational study based on the CODIAM cohort (Cohort of Diabetes in French Amazonia). We analyzed 1,287 patients followed up between May 2019 and June 2021 at Cayenne Hospital, Saint Laurent Hospital, and delocalized health centers. Results: In our cohort, chronic kidney disease was present after an average of 12 years of diabetes. Compared with the French population, 41% of diabetic patients had chronic kidney disease (i.e., 12% more), and had an average age of 56 years (i.e., 10 years younger). Forty-eight per cent of these patients were obese (i.e., 7% more). Seventy-four per cent of patients were precarious and 45% were foreigners but neither was associated with chronic kidney disease, contrary to countries where the health system is not universal. Conclusion: Screening of patients with chronic kidney disease among diabetics in French Guiana remains a real challenge. Patients were younger and more obese than in other French territories. In this cohort, precariousness and immigration were not associated with the presence of chronic kidney disease. However, particular attention should be paid to hypertensive patients and those over 65 years of age, which are, with diabetes itself, the two most obvious risk factors for developing chronic kidney disease among diabetic patients in our territory.

Access to health care for migrants in French Guiana in 2022: a qualitative study of health care system actors.

Background: Access to health care is a major public health issue. The social determinants of health have a role in accessing health care and in meeting the health needs of populations. With 281 million international migrants around the world, population movements are another major issue. Migrants are particularly exposed to precariousness during their migratory journey and after their settlement. These vulnerabilities may have deleterious effects on their health status and on their social conditions. In French Guiana, 36% of the population is of foreign origin. The objective of this study is to explore the barriers and the facilitators to accessing health care for migrants in French Guiana in 2022, from the perspective of health care professionals, social workers and local NGO actors. Methods: This research is an exploratory qualitative study based on the experiential knowledge of health care professionals, social workers and local NGO actors in French Guiana. 25 semi-structured interviews were conducted with these professionals and actors between April and June 2022, using an interview guide to explore their practices, representations and beliefs of access to health care and accompaniment of migrants in their patient journey. The interviews were transcribed and analyzed using the thematic analysis method. Results: A total of 25 health care professionals, social workers and local NGO actors were included in the study. Participants highlighted that migrants are exposed to many factors hindering their access to health care in French Guiana (administrative complexity, language barriers, financial barriers, mobility issues, etc.). With the situations of great precariousness and the inadequacies of the public authorities, associative support (social, health and legal accompaniment process provided by NGOs and associations) has an important role in providing close support to migrants. Moreover, health mediation supports migrants in their social and health care journey to lead them toward empowerment. Health mediators contribute to promote a better understanding between professionals and migrants. Conclusion: In French Guiana, associative support and health mediation promote access to health care and social accompaniment for migrants. This article highlights the issues surrounding access to health care, associative support and health mediation in the Guianese context, which is marked by significant socio-cultural diversity and precariousness. Considering the benefits of associative support and health mediation, as well as social inequalities in health, is essential for health care professionals, social workers, local NGO actors, associations, public health authorities and political decision-makers to initiate concrete and suitable actions in favor of access to health care and social support for migrants in French Guiana.

Pulmonary Histoplasmosis in People Living with Human Immunodeficiency Virus in French Guiana: Clinical Epidemiology, Medical Imaging and Prognostic.

BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care. METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded. RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%. CONCLUSION: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.

From an interventional study to a national scale-up: lessons learned from the Malakit strategy at the French Guiana-Suriname border.

Scaling-up an experimental intervention is always a challenge. On the border between French Guiana, Brazil and Suriname, an interventional study demonstrated the effectiveness of distributing self-diagnosis and self-treatment kits (Malakits) to control malaria in mobile and hard-to-reach populations. Its integration into the Suriname's National Malaria Elimination Plan after a 2-year experiment faced numerous challenges, including human resources to cope with the additional workload of coordinators and to maintain the motivation of community health workers. The economic recession in Suriname, the Covid pandemic, and logistical issues also hampered the scale-up. Finally, thanks to the commitment of stakeholders in Suriname and French Guiana, the integration of Malakit distribution into the Surinamese national programme was proved possible.

Diabetes in a hospital cohort of persons living with HIV: a descriptive and comparative study in French Guiana.

BACKGROUND: In French Guiana (population 294,000) the prevalence of type 2 diabetes (10%) and of HIV(1.1%) are very high. Our objective was to determine the prevalence of diabetes and its complications in a HIV cohort. MATERIALS AND METHODS: We enrolled HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals between January 1, 1992 and December 31, 2021 in the French Hospital Database for HIV (FHDH) a national database compiling data from all French regions. RESULTS: There was no difference of diabetes prevalence between men (8.2%) and women (8.8%), P = 0.4. Patients with diabetes were older (56 years ± 13.4) than those without diabetes (44.7 years ± 13.6) and prevalence increased with age. The proportion of persons with diabetes was greater among virologically suppressed persons (10%) than those with a detectable viral load under antiretroviral treatment (5.8%). Persons with diabetes had substantially greater CD4 counts at diagnosis than persons without diabetes. The majority of macro and microvascular complications were observed in people with diabetes. Persons with diabetes and HIV were significantly less likely to have had AIDS (1.6 versus 2.2 per 100 person-years, respectively). Overall, 374 persons living with HIV of 4167 had died (9%) the proportion of persons with diabetes among the dead was greater than those who did not die 11.7% versus 8.1%, respectively, p = 0.017. However, persons with diabetes were older and hence died older, 62.3 years (SD = 1.9) for deceased persons with diabetes versus 50.4 years (SD = 0.8), P < 0.0001. However, using Cox regression to adjust for age, initial CD4 count, country of birth there was no significant difference in the Hazard for death between persons with diabetes and persons without diabetes (aHR = 0.99, 95%CI = 0.65-1.5), P = 0.9. CONCLUSIONS: The prevalence of diabetes in our HIV cohort was high. Persons with diabetes had greater CD4 counts, earlier care, and greater virological suppression than persons without diabetes. There were no significant differences between persons with diabetes and without diabetes in terms of survival.

Complex Sex Differences in Life Expectancy in French Guiana.

In the complex context of French Guiana, different vulnerabilities and different risk factors between genders may lead to complex differences in health outcomes, mortality, and life expectancy. Our aim was, thus, to compare male and female mortality and life expectancy, to compare it between French Guiana and mainland France, and to look at temporal trends and the main specific causes of death in order to identify actionable singularities. National databases were used to obtain life expectancy at birth, at 20, 40, and 60 years, and mortality statistics. Standardized death rates and causes of death for French Guiana and mainland France were obtained through the CEPIDC, which analyzes information from death certificates. When comparing with mainland France, life expectancy at birth was significantly shorter both in males and females (mean = -2.9 years); life expectancy at 20 years, which allows to remove the effect of the greater child mortality in French Guiana, was also shorter in French Guiana for males (mean = -1.8 years) and females (mean = -2 years). The differences between mainland France and French Guiana regarding life expectancy at 40 and 60 years (mean = -1.5 and -1.3 years) was mainly found among females, males in French Guiana life expectancy at 40 and 60 years was closer to that in mainland France (mean = -0.8 and -0.6 years). Although they have a greater life expectancy at birth than men, women in French Guiana are substantially more affected by overweight/obesity and type 2 diabetes. The observed patterns of life expectancy at different ages presumably reflect the burden of external causes and AIDS in males and perhaps metabolic diseases in women.

[Overview of infectious and non-infectious diseases in French Guiana in 2022]. / Panorama des pathologies infectieuses et non infectieuses de Guyane en 2022.

Source of many myths, French Guiana represents an exceptional territory due to the richness of its biodiversity and the variety of its communities. The only European territory in Amazonia, surrounded by the Brazilian giant and the little-known Suriname, Ariane 6 rockets are launched from Kourou while 50% of the population lives below the poverty line. This paradoxical situation is a source of health problems specific to this territory, whether they be infectious diseases with unknown germs, intoxications or chronic pathologies.Some infectious diseases such as Q fever, toxoplasmosis, cryptococcosis or HIV infection are in common with temperate countries, but present specificities leading to sometimes different management and medical reasoning. In addition to these pathologies, many tropical diseases are present in an endemic and / or epidemic mode such as malaria, leishmaniasis, Chagas disease, histoplasmosis or dengue. Besides, Amazonian dermatology is extremely varied, ranging from rare but serious pathologies (Buruli ulcer, leprosy) to others which are frequent and benign such as agouti lice (mites of the family Trombiculidae) or papillonitis. Envenomations by wild fauna are not rare, and deserve an appropriate management of the incriminated taxon. Obstetrical, cardiovascular and metabolic cosmopolitan pathologies sometimes take on a particular dimension in French Guiana that must be taken into account in the management of patients. Finally, different types of intoxication are to be known by practitioners, especially due to heavy metals.European-level resources offer diagnostic and therapeutic possibilities that do not exist in the surrounding countries and regions, thus allowing the management of diseases that are not well known elsewhere.Thanks to these same European-level resources, research in Guyana occupies a key place within the Amazon region, despite a smaller population than in the surrounding countries. Thus, certain pathologies such as histoplasmosis of the immunocompromised patient, Amazonian toxoplasmosis or Q fever are hardly described in neighboring countries, probably due to under-diagnosis linked to more limited resources. French Guiana plays a leading role in the study of these diseases.The objective of this overview is to guide health care providers coming to or practicing in French Guiana in their daily practice, but also practitioners taking care of people returning from French Guiana.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

The Epidemiologic Transition in French Guiana: Secular Trends and Setbacks, and Comparisons with Continental France and South American Countries.

There are great variations between population subgroups, notably in poorer countries, leading to substantial inconsistencies with those predicted by the classical epidemiologic transition theory. In this context, using public data, we aimed to determine how the singular case of French Guiana fit and transitioned in the epidemiologic transition framework. The data show a gradual decline in infant mortality to values above 8 per 1000 live births. Premature mortality rates were greater but declined more rapidly in French Guiana than in mainland France until 2017 when they reascended in a context of political turmoil followed by the COVID-19 pandemic and strong reluctance to get vaccinated. Although infections were a more frequent cause of death in French Guiana, there is a marked decline and circulatory and metabolic causes are major causes of premature death. Fertility rates remain high (>3 live births per woman), and the age structure of the population is still pyramid-shaped. The singularities of French Guiana (rich country, universal health system, widespread poverty) explain why its transition does not fit neatly within the usual stages of transition. Beyond gradual improvements in secular trends, the data also suggest that political turmoil and fake news may have detrimentally affected mortality in French Guiana and reversed improving trends.

Development of a case fatality prognostic score for HIV-associated histoplasmosis.

OBJECTIVES: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality. METHODS: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods. RESULTS: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin <9 g/dl and/or a platelet <100000/ml, and an interstitial lung pattern on chest X-ray. We constructed a 12-point prognostic score. A threshold ≥5 classified patients as alive or dead at 30 days with a sensitivity of 84%, a specificity of 81%, a positive predicted value of 40%, and a negative predicted value of 97%. The area under the curve of the receiver operating characteristic curves from the different resamples were stable between 0.88 and 0.93. CONCLUSION: The histoplasmosis case fatality score, which is easy and inexpensive to perform, is a good tool for assessing severity and helping in the choice of induction therapy. An external validation remains necessary to generalize these results.

Definition, diagnosis and treatment of oligometastatic oesophagogastric cancer: A Delphi consensus study in Europe.

BACKGROUND: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. METHODS: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%). RESULTS: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). CONCLUSION: The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.