Complications and predictors associated with moderate to severe obstructive sleep apnoea in bariatric surgery: Evaluation of routine obstructive sleep apnoea screening.

PURPOSE: Obstructive sleep apnoea (OSA) is a breathing disorder resulting in blockage of airflow and hypo-oxygenation. The incidence of OSA in patients with class 2 or 3 obesity (Body Mass index, BMI >35) is 60-70%. Unfortunately, most bariatric patients are unaware they suffer from OSA. Untreated OSA can lead to perioperative cardiopulmonary complications. The aim of this study was to identify predictors associated with moderate to severe OSA and asses the incidence of OSA-related complications in a large cohort of patients who underwent OSA-screening and treatment if indicated before bariatric surgery. METHODS: All consecutive patients who underwent primary bariatric surgery between September 2013 and September 2019 were included. Univariable and multivariable logistic regression analysis was performed to identify potential predictors for moderate to severe OSA using sleep studies. RESULTS: A total of 2872 patients who underwent bariatric surgery were included for analysis. Overall, OSA was identified in 62.5% of all patients and moderate to severe OSA (AHI ≥15) in 28.6%. Independent predictors for moderate to severe OSA were male gender (p < 0.001), age (p < 0.001), preoperative BMI (p < 0.001), preoperative waist circumference (p < 0.001), hypertension (p < 0.001), and dyslipidaemia (p = 0.046). The incidence of OSA-related complications was low (0.8%) and not significantly different among the different OSA severity classes. CONCLUSION: This is the largest study to assess OSA presence and OSA-related complications in patients undergoing bariatric surgery. The incidence of potential OSA-related complications was low (0.8%). We believe focus could be shifted towards more cost-efficient strategies where OSA screening is omitted such as perioperative continuous monitoring.

Evaluation of CPAP adherence in bariatric patients diagnosed with obstructive sleep apnea: outcomes of a multicenter cohort study.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent but mostly undiagnosed in obese patients scheduled for bariatric surgery. To prevent cardiopulmonary complications, many clinics perform preoperative OSA screening. Consequently, adequate adherence to continuous positive airway pressure (CPAP) therapy is essential but challenging. We aimed to evaluate CPAP adherence and its influence on postoperative outcomes. METHODS: In a prospective multicenter cohort study, we compared different perioperative strategies for handling undiagnosed OSA in bariatric patients. In this subgroup analysis, patients newly diagnosed with OSA were compared to those with pre-existing OSA. We assessed inadequate CPAP adherence, defined as < 4 h/night, between the preoperative period and 6 months postoperative. Cardiopulmonary complications and (un)scheduled ICU admissions were also evaluated. RESULTS: In total, 272 patients with newly diagnosed OSA (67.4%) and 132 patients with pre-existing OSA (32.6%) were included. Before surgery, 41 newly diagnosed patients used CPAP inadequately, compared to 5 patients with pre-existing OSA (15% vs. 4%, p = 0.049). Six months after surgery, inadequate CPAP use increased to 73% for newly diagnosed patients and 39% for patients with pre-existing OSA, respectively (p < 0.001). Incidences of cardiopulmonary complications, scheduled, and unscheduled ICU admissions were similar in the two study groups (p = 0.600, p = 0.972, and p = 0.980, respectively). CONCLUSION: Inadequate CPAP adherence is higher in bariatric patients newly diagnosed with OSA when compared to patients with pre-existing OSA. Strategies to increase CPAP adherence may be valuable when considering routine OSA screening and CPAP therapy in patients undergoing bariatric surgery. Further studies are needed to improve current guidelines on perioperative OSA management of obese patients. TRIAL REGISTRATION: POPCORN study, registered at Netherlands Trial Register, https://www.trialregister.nl/trial/6805 . ID no: 6805.

Validation of a Scoring System to Distinguish Uncomplicated From Complicated Appendicitis.

BACKGROUND: Studies have shown that uncomplicated appendicitis can be treated conservatively with antibiotics. It is important to select only those patients with uncomplicated appendicitis when considering conservative management. Recently, a scoring system based on clinical evaluation and ultrasound was developed to improve this selection and aid in shared decision making when considering an antibiotics-first strategy. The aim of this study was to externally validate the scoring system. MATERIALS AND METHODS: A retrospective cohort study of all adult patients presenting to the emergency department between January 2014 and January 2017 with suspected acute appendicitis based on clinical evaluation and ultrasound was performed. For every patient, a score was calculated using the previously described scoring system. A final diagnosis, subdivided into complicated appendicitis, uncomplicated appendicitis, complicated alternative disease, and uncomplicated alternative disease, was assigned to every patient based on operative findings. RESULTS: A total of 678 patients with suspected acute appendicitis based on clinical and ultrasonography findings were identified, of whom 175 (25.8%) had complicated appendicitis, 491 (72.4%) had uncomplicated appendicitis, and 12 (1.8%) had an alternative disease. Of the 678 patients, 272 had a score of five points or less, of whom 17 (6.2%) had complicated appendicitis, giving a negative predictive value of 93.8%. CONCLUSIONS: With the scoring system based on clinical and ultrasonography features, 93.8% of patients predicted to have uncomplicated appendicitis were correctly identified. The scoring system could help identify patients suitable for conservative management in future studies.

Rapid TB diagnostic service and community action to FIND.TREAT.ALL#EndTB, Maputo, Mozambique, 2013-2018.

Finding and treating all tuberculosis (TB) patients is crucial for ending TB. We investigated whether rapid diagnostic turnaround time (TAT) and patient tracking could increase TB treatment initiation in Maputo, Mozambique. Among 3329 TB patients newly diagnosed by the University Eduardo Mondlane-Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling/Anti-Personnel Landmines Detection Product Development (APOPO) Laboratory between 2013 and 2018, on average 61% were verifiably linked to care. This proportion increased from 54% (first half 2013) to 79% (second half 2018) after introducing a 24-hour TAT in 2015 and patient tracking conducted by a community-based partner, Associação Kenguelekezé, in 2017. Rapid, well-connected TB diagnostic services can reduce pre-treatment loss to follow-up and support the joint initiative of WHO, Stop TB and Global Fund to 'FIND.TREAT.ALL.#EndTB'.

Identifier et traiter tous les patients atteints de tuberculose (TB) est crucial pour mettre fin à la TB. Nous avons vérifié si un délai plus court de diagnostic (TAT) et un système de recherche des patients augmentait la mise en œuvre du traitement de la TB à Maputo, Mozambique. Parmi 3329 patients TB nouvellement diagnostiqués par le laboratoire UEM-APOPO (2013­2018), en moyenne 61% ont été réellement connectés à la prise en charge. Le pourcentage a augmenté de 54% (première moitié de 2013) à 79% (deuxième moitié de 2018) après l'introduction du TAT en 24h en 2015 et la surveillance des patients effectuée par notre partenaire l'association à base communautaire Kenguelekezé en 2017. Notre expérience suggère que des services de diagnostic de TB rapides, bien connectés peuvent réduire les abandons avant le traitement et soutenir les tentatives mondiales « FIND.TREAT.ALL.#EndTB ¼.

La búsqueda y el tratamiento de todos los pacientes con tuberculosis (TB) son primordiales para poner fin a esta enfermedad. Se investigó si con un lapso corto de obtención del diagnóstico y el seguimiento de los pacientes aumentaría el inicio del tratamiento antituberculoso en Maputo, Mozambique. En promedio, en 61% de los 3329 casos nuevos de TB diagnosticados en el laboratorio UEM-APOPO (2013­2018) se confirmó la vinculación de los pacientes con los servicios de atención. El porcentaje aumentó de 54% (primer semestre del 2013) a 79% (segundo semestre del 2018), después de haber introducido un plazo de obtención del diagnóstico de 24 horas en el 2015 y la localización de los pacientes por parte de la asociación comunitaria Kenguelekezé en el 2017. Esta experiencia indica que los servicios diagnósticos de la TB que son rápidos y mantienen vínculos adecuados disminuyen la pérdida durante el seguimiento antes de comenzar el tratamiento y fortalecen los esfuerzos de la iniciativa 'FIND.TREAT.ALL.#EndTB'.

Feasibility of Postoperative Home Monitoring Using Video Consultation and Vital Sign Monitoring of Bariatric Patients.

RATIONALE: The length of hospital stay after bariatric surgery has decreased rapidly in recent years to an average of 1 day (one midnight). The transition from a controlled hospital environment to home environment may be a big step for patients. For these patients, home monitoring can be a substitute. METHODS: A pilot study of 84 morbidly obese patients undergoing either laparoscopic Roux-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LGS) was performed. Home monitoring consisted of daily contact via video consultation and measurement of vital signs at home. The primary outcome was feasibility of home monitoring. Secondary outcomes were complications and patient satisfaction measured with a questionnaire (PSQ-18). RESULTS: In 77 of the 84 patients (92%), videoconference was possible on day 1, 74 patients (88%) on day 2 and 76 patients (90%) on day 3. Four patients (5%) were never reached. On day 1, 52 patients (62%) performed all instructed measurements, on day 2, 49 patients (58%) and on day 3, 63 patients (75%). Only 47 out of 84 patients (56%) measured the instructed amount of times on all 3 days. High satisfaction rates were reported in the patients receiving home monitoring. CONCLUSION: Our first experience with home monitoring was disappointing since home monitoring of vital signs had poor compliance and not all patients were able to use the application. Further refinement of the home monitoring tool is needed to increase compliance and utility of the tool.

Risk Factors Associated with Prolonged Hospital Stay and Readmission in Patients After Primary Bariatric Surgery.

INTRODUCTION: The introduction of enhanced recovery after surgery (ERAS) has resulted in a decrease in length of hospital stay of patients after bariatric surgery. The general length of hospital stay is 1 day. Some bariatric patients stay longer after an uncomplicated procedure or are readmitted for varying reasons. OBJECTIVES: The aim of the present study is to identify risk factors associated with prolonged hospital stay and readmissions. METHODS: A retrospective study of all patients who underwent a primary procedure (i.e. Roux-en-Y gastric bypass or sleeve gastrectomy) between January 2016 and January 2019 was performed. RESULTS: A total of 1669 patients who underwent primary laparoscopic Roux-en-Y gastric bypass (70.7%) or sleeve gastrectomy (29.3%) were included. The median length of stay was 1 day (range 1-69 days). In 138 patients (8.3%), a postoperative complication was diagnosed and 89 patients were readmitted (5.3%) within 30 days after discharge. Overall, 348 patients (20.9%) stayed longer than 1 day. Univariable analysis showed that depression, ASA III, sleeve gastrectomy and a perioperative and/or postoperative complication were significantly (p value < 0.05) associated with a prolonged stay. In the multivariable model depression, sleeve gastrectomy and postoperative complication were independent risk factors for prolonged stay. Univariable analysis of risk factors associated with readmission identified depression and perioperative and postoperative complications. Multivariable analysis for readmission demonstrated only presence of a postoperative complication was an independent risk factor. CONCLUSION: Depression, sleeve gastrectomy and postoperative complications were independent risk factors for prolonged stay. Postoperative complication was an independent risk factor for readmission.

The Influence of Body Contouring Surgery on Weight Control and Comorbidities in Patients After Bariatric Surgery.

INTRODUCTION: A considerable number of patients experience some long-term weight regain after bariatric surgery. Body contouring surgery (BCS) is thought to strengthen post-bariatric surgery patients in their weight control and maintenance of achieved improvements in comorbidities. OBJECTIVES: To examine the impact of BCS on long-term weight control and comorbidities after bariatric surgery. METHODS: We performed a retrospective study in a prospective database. All patients who underwent primary Roux-en-Y gastric bypass (RYGB) and presented for preoperative consultation of BCS in the same hospital were included in the study. Linear and logistic mixed-effect model analyses were used to evaluate the longitudinal relationships between patients who were accepted or rejected for BCS and their weight loss outcomes or changes in comorbidities. RESULTS: Of the 1150 patients who underwent primary RYGB between January 2010 and December 2014, 258 patients (22.4%) presented for preoperative consultation of BCS. Of these patients, 126 patients eventually underwent BCS (48.8%). Patients who were accepted for BCS demonstrated significant better ∆body mass index (BMI) on average over time (- 1.31 kg/m2/year, 95% confidence interval (CI) -2.52 - -0.10, p = 0.034) and percent total weight loss (%TWL) was significantly different at 36 months (5.79, 95%CI 1.22 - 10.37, p = 0.013) and 48 months (6.78, 95%CI 0.93 - 12.63, p = 0.023) after body contouring consultation. Patients who were accepted or rejected did not differ significantly in the maintenance of achieved improvements in comorbidities. CONCLUSION: BCS could not be associated with the maintenance of achieved improvements in comorbidities after bariatric surgery, whereas it could be associated with improved weight loss maintenance at 36 and 48 months after body contouring consultation. This association should be further explored in a large longitudinal study.

Extrinsic mechanical forces mediate retrograde axon extension in a developing neuronal circuit.

To form functional neural circuits, neurons migrate to their final destination and extend axons towards their targets. Whether and how these two processes are coordinated in vivo remains elusive. We use the zebrafish olfactory placode as a system to address the underlying mechanisms. Quantitative live imaging uncovers a choreography of directed cell movements that shapes the placode neuronal cluster: convergence of cells towards the centre of the placodal domain and lateral cell movements away from the brain. Axon formation is concomitant with lateral movements and occurs through an unexpected, retrograde mode of extension, where cell bodies move away from axon tips attached to the brain surface. Convergence movements are active, whereas cell body lateral displacements are of mainly passive nature, likely triggered by compression forces from converging neighbouring cells. These findings unravel a previously unknown mechanism of neuronal circuit formation, whereby extrinsic mechanical forces drive the retrograde extension of axons.How neuronal migration and axon growth coordinate during development is only partially understood. Here the authors use quantitative imaging to characterise the morphogenesis of the zebrafish olfactory placode and report an unexpected phenomenon, whereby axons extend through the passive movement of neuron cell bodies away from tethered axon tips.

Do Complications Alter Postoperative Weight Loss 1 Year After Primary and Revisional Roux-en-Y Gastric Bypass?

BACKGROUND: Around 10 % of the bariatric surgery patients experience postoperative complications (<30 days). It could be hypothesized that complications influence postoperative weight loss, which is one of the most important endpoints of bariatric surgery. Therefore, this study inventoried the effect of complications on postoperative weight loss. METHODS: A consecutive database including patients who were operated from November 2007 onwards was retrospectively reviewed. All short-term complications were classified according to the Clavien-Dindo classification. Weight loss was assessed at 6 and 12 months postoperatively. RESULTS: A total of 1130 patients underwent either primary (n = 907, 80.3 %) or revisional (n = 233, 19.7 %) surgery till October 2013. Short-term complications occurred in 115 (10.2 %) patients, of whom 48 (41.7 %) had a severe (Clavien-Dindo ≥ 3) complication. One year post surgery, 184 patients (16.3 %) were lost to follow-up. Patients with a short-term complication had a higher percentage of excess weight loss (%EWL) at 6 months (58.6 (SD 16.6) versus 52.9 (SD 17.6), p = 0.003) and 1 year (71.9 (SD 22.3) versus 65.9 (SD 21.3), p = 0.017) of follow-up. Although a trend was seen toward higher BMI loss and total weight loss (TWL) after 6 months, no effect was seen 1 year postoperatively. In multivariable linear regression analysis, complications were not a significant predictor for 1-year %EWL. CONCLUSIONS: Although short-term complications alter 1-year %EWL, no effect was seen on BMI loss and TWL. In addition, complications were not a predictor in a multivariable linear regression model for 1-year %EWL. It can be concluded that short-term complications do not impair weight loss after Roux-en-Y gastric bypass.

Comparison of Two Types of Liquid Biopsies in Patients With Hepatocellular Carcinoma Awaiting Orthotopic Liver Transplantation.

INTRODUCTION: Orthotopic liver transplantation (OLT) is considered one of the few curative treatments available for early stages of hepatocellular carcinoma (HCC). It has been shown that more than 10% of transplanted individuals suffer relapse during the first year after surgery and most of them die because of the tumor. The circulating tumor cells (CTCs) are the main source of recurrences as they disseminate from a primary or metastatic tumor lesion through peripheral blood. We aimed to determine the concentration of CTCs in peripheral blood in these patients by 2 different approaches: the CellSearch and the IsoFlux systems to assess their applicability to this disease monitoring. PATIENTS AND METHODS: A comparative study was conducted in 21 patients with HCC eligible for liver transplantation according to the Milan criteria, whose peripheral blood was processed by the CellSearch and the IsoFlux systems. RESULTS: CTCs were isolated in 1 of the 21 patients (4.7%) by the CellSearch system and in 19 of the 21 patients (90.5%) by the IsoFlux method. The comparison of both methods using Bland-Altman plot shows that there is not consistency in the determination of CTCs in our patients, finding a proportional bias between them. CONCLUSION: The results obtained by both CTCs isolation systems are not interchangeable nor transferable. The CellSearch system does not seem to be the ideal approach for studying CTCs in patients with HCC. The IsoFlux system displays greater sensitivity in the identification of CTCs and might become an important tool in patient management.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

BACKGROUND: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. DISCUSSION: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. TRIAL REGISTRATION: ClincalTrials.gov: NCT02243735 .

Treatment strategies in elderly breast cancer patients: Is there a need for surgery?

BACKGROUND: The aim of this study was to determine the role of surgery in elderly patients with breast cancer. METHODS: Between 1999 and 2009, 153 consecutive women, ≥80 years old with breast cancer were treated at our hospital. Surgically and non-surgically treated patients were compared with respect to characteristics and survival. RESULTS: Treatment was surgical in 102 patients (67%). The non-surgically treated patients were older than surgically treated patients, had more co-morbidity and were more often diagnosed with a clinically T3/T4 tumour and distant metastasis. Patients not receiving surgery, had an 11% overall survival rate at 5-year versus 48% in surgically treated patients (P < 0.001). Independent factors for survival were clinical N0 status, M0 status at presentation and surgery. CONCLUSION: One in three patients of 80 years and older did not have surgical treatment for breast cancer. Patient not treated surgically are older, have more severe co-morbidity and are diagnosed with more advanced disease than patients who underwent surgery.The selection of patients, who have a poor prognosis, is made on clinical grounds not measurable with a common co-morbidity survey. Better and evidence-based selection criteria for surgical and non-surgical treatment in these patients are needed.

Incidental findings on total-body CT scans in trauma patients.

INTRODUCTION: Total-body Computed Tomography (CT) scans are increasingly used in trauma care. Herewith the observation of incidental findings, trauma unrelated findings, is also increased. The aim of this study was to evaluate the number of incidental findings in adult trauma patients. PATIENTS AND METHODS: All consecutive trauma patients that underwent total-body CT scanning between January 2009 and December 2011 were analysed. Incidental findings were divided in three categories: category I (potentially severe condition, further diagnostic work-up is required), category II (diagnostic work-up dependent on patients' symptoms) and category III (findings of minor concern, no diagnostic work-up required). RESULTS: There were 2248 trauma room presentations; 321 patients underwent a total-body CT scan (14.3%). In 143 patients (44.5%), 186 incidental findings were reported. There were 13 category I findings (7.0%), 45 category II findings (24.2%) and 128 category III incidental findings (68.8%). Overall, 18 patients (5.6%) required additional diagnostic work-up. Four patients underwent work-up by additional radiologic imaging. Three patients required further invasive work-up or treatment. Three patients were transferred to another hospital, no extended follow-up was performed. In three patients, there was no documentation of follow-up. Five patients deceased before diagnostic work-up of the incidental finding could start. CONCLUSION: Total-body CT scanning as part of the evaluation of trauma patients leads to a substantial amount of incidental findings. Documentation of incidental findings and their clinical consequences was incomplete. Therefore, the findings of this study have prompted us to add an item to our electronic trauma room report that obliges residents to report whether or not incidental findings are found during trauma imaging.

Co-assembly of tetrapeptides into complex pH-responsive molecular hydrogel networks.

Here we prepare pH-responsive complex molecular hydrogels from oppositely charged tetrapeptidic components that can be pH-tuned resulting in interconversion between different networks. Two different systems are described based on tetrapeptides with an alternating sequence of non-polar (F) and polar (D or K) residues. Co-aggregated hydrogels are easily formed in situ at neutral pH whereas one-component networks are maintained after changing into acidic or basic pH. These systems have been applied for the pH selective release of two hydrophobic dyes - Methylene Blue and Bromothymol Blue - as drug models. Different release profiles have been observed depending on the characteristics of the network as well as the pH of the media. These materials offer great potential as multidrug carriers.

Henoch-Schönlein disease localized in the appendix.

A 16-y-old boy presented with complaints of acute abdomen. Ultrasonography showed an enlarged and tender appendix suggestive of acute appendicitis. The patient underwent surgery and during surgery the appendix was found with a red vasculitis-like distal end, not typical for acute appendicitis. Further per operative examination of the intestines revealed a circular, vasculitis-like red band in terminal ileum. Four days after surgery, the patient developed skin purpura and complained of joint pain classical of Henoch-Schönlein disease. Pathological evaluation of the appendix and a skin biopsy confirmed the diagnosis and the patient was managed accordingly.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I.

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.