Epidemiology of Non-Traumatic Lower Extremities Amputations in West Africa: Nationwide Data from Togo.

OBJECTIVE: Non-traumatic lower limb amputation (NT-LLA) has consequences at individual and public health levels. Population based studies in sub-Saharan Africa are scarce and often related to single centre series. This study aimed to estimate the incidence of NT-LLA (minor and major) and to describe epidemiological, clinical, and prognostic aspects in Togo. METHODS: This was a population based observational study conducted among all patients who underwent NT-LLA. Traumatic amputations were excluded. Sociodemographic, clinical, and work up data were collected from clinical files in any Togolese health centre from 1 January 2016 to 31 December 2021. Incidence rates were adjusted for age. RESULTS: Over the six year period, 352 patients (59% males) underwent NT-LLA (mean ± standard deviation age 60 ± 15.7 years). The average age adjusted incidence rate of NT-LLA was 8.5 per million/year (95% confidence interval [CI] 7.6 - 9.4). Men were 1.7 times more likely to undergo a NT-LLA than women. The relative risk of NT-LLA was 48 times higher in patients with diabetes than in patients without diabetes. Around 61.0% of the NT-LLAs occurred within the 50 - 74 age group and 54.3% had diabetes mellitus. Among amputees, 54.5% had a diagnosis of peripheral artery disease (PAD) and 52.8% had diabetic ulcers, with co-existence of several factors. Less than 5% of participants had a history of smoking tobacco. Average length of hospital stay was 12 days. The in hospital mortality rate was 8.8% (9.0% for major, 6.7% for minor amputations). Only 18.2% had duplex ultrasound performed and 1.7% angiography prior to amputation. No patient underwent vascular intervention prior to amputation. CONCLUSION: This is the first study to report nationwide and contemporary epidemiological data on NT-LLAs in West Africa, highlighting several specificities. Large scale interventions are needed to ameliorate the care of diabetes and PAD and improve facilities for optimal management of patients at risk of amputation in Africa.

Effectiveness and safety of oral anticoagulant therapy in a real-world cohort with atrial fibrillation: The SIESTA-A study protocol.

INTRODUCTION: Oral anticoagulants (OACs) are first-line drugs for stroke prevention in patients with atrial fibrillation (AF). The introduction of new lines of therapy with direct oral anticoagulants (DOACs) has led to a decreased use of vitamin K antagonists (VKAs). Comparative analyses of DOACs in clinical trials are scarce and the comparator has mostly been warfarin. Their impact on health outcomes in observational studies has not always been consistent. The aim of this study is to evaluate the effectiveness and safety of DOACs and VKAs in patients with AF using Real-World Data (RWD). METHODS AND ANALYSIS: Population-based retrospective cohort study using RWD from actual practice. Period: January 2012-December 2020. Inclusion criteria: patients with AF who had not taken OACs in the previous 12 months. Exclusion criteria: <40 years, with severe mitral stenosis, or valvular heart disease or aortic and/or mitral valve procedures. Data source: The Andalusian Population Health Database, Spain. Outcome measures: a) Effectiveness: ischaemic stroke, transient ischaemic attack, systemic and pulmonary embolism, and death; b) Safety: gastrointestinal and intracranial haemorrhaging; Independent variables: age, sex, comorbidities, medication and health resource use, CHA2DS2-VASC, HAS-BLED, and analytical tests. Statistical analysis: crude incidence analysis, survival models, Kaplan-Meier, Cox regression analysis adjusted for possible confounding and paired analysis by propensity score matching.

Comparative Morpho-Anatomical Studies of Two Philippine Endemic Species of Amyema Tiegh. (Loranthaceae).

Amyema are epiphytic hemiparasitic plants on different types of woody host plants and are abundant in temperate, subtropical, and tropical regions. In Marilog Forest Reserve, Southern Philippines, two Philippine endemic species of Amyema were recorded, viz., Amyema curranii (Merr.) Danser and A. seriata (Merr.) Barlow. In this study, these two species were compared and examined for their morphology and anatomy. Data revealed that the two Amyema species are morphologically distinct, with A. curranii having lanceolate leaves, pink flowers, and red fruits, whereas A. seriata has obovate leaves, red flowers, and yellow fruits. For the morpho-anatomy, A. curranii has a single-layered epidermis, paracytic stomata, collateral open vascular bundles, the Eustele type of stele with pith at the center, and the inferior free central type with a hairy ovary wall. Meanwhile, A. seriata has a pinkish, single-layered epidermis, paracytic stomata, collateral open vascular bundles, a eustele type of stele with the presence of pith at the center, and an inferior free central ovary type. As a result, employing these species' gross morphology and anatomy could scrutinise future evaluations and taxonomic placements.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.

Urinary volatile Organic compounds in non-alcoholic fatty liver disease (NAFLD), type two diabetes mellitus (T2DM) and NAFLD-T2DM coexistence.

INTRODUCTION: Accumulating evidence have shown a significant correlation between urinary volatile organic compounds (VOCs) profile and the manifestation of several physiological and pathological states, including liver diseases. Previous studies have investigated the urinary metabolic signature as a non-invasive tool for the early discrimination between non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), which nowadays represents one of the most important challenges in this context, feasible only by carrying out liver biopsy. OBJECTIVES: The aim of the study was to investigate the differences in the urinary VOCs profiles of non-alcoholic fatty liver disease (NAFLD) patients, diabetes mellitus (T2DM) subjects and NAFLD/T2DM patients. METHODS: Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) was applied to profile the urinary VOCs. Urine samples were analysed both under acid and alkaline conditions, to obtain a range of urinary volatiles with different physicochemical properties. RESULTS: Urinary VOCs profiles of 13 NAFLD patients, 13 T2DM subjects and 13 NAFLD/T2DM patients were investigated by multivariate and univariate data analysis techniques which allowed to identify 21 volatiles under alkaline conditions able to describe the NAFLD/T2DM group concerning the other two groups. CONCLUSION: Our results suggest that VOCs signatures can improve the knowledge of the pathological condition where NAFLD coexists with T2DM and discovering new features that are not simply the sum of the two diseases. These preliminary findings may be considered as hypothesis-generating, to be clearly confirmed by larger prospective investigations.

Are insulin resistance and non-alcoholic fatty liver disease associated with Peyronie's disease? A pilot study.

Risk factors for Peyronie's disease (PD) are serum lipid abnormalities, hypertension and type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation are key-players in the pathogenesis of arterial diseases, leading to insulin resistance (IR), which is a major determinant of non-alcoholic fatty liver disease (NAFLD). We studied the potential relationship between PD, IR, and NAFLD. Forty-nine male patients were enrolled, fulfilling the well-accepted diagnostic criteria of stable PD. Fifty male individuals without PD, well-matched for age and BMI, were selected as the control group. Comorbidities (T2DM and hypertension), as well as the lipid profile and the glucometabolic asset, were evaluated. The triglycerides/HDL ratio (TG/HDL-C ratio) with a cut-off of ≥3 and the triglycerides-glucose index (TyG) with an optimal cut-point of 8.5 were used for diagnosis of IR and NAFLD, respectively. NAFLD diagnosis was confirmed by the presence of bright liver at ultrasonography. Hypertension was found more frequently in PD patients than in no-PD subjects (P=0.017), independently of age (P=0.99). Both IR and NAFLD were significantly associated with the presence of PD in our population of men (P=0.043 and 0.0001, respectively), no matter how old (P=0.11 and 0.74, respectively). At logistic regression, NAFLD was the only predictor of the PD presence (p=0.021). The AUROC of TyG to predict PD was 0.7437 (sensitivity 67.35% and specificity 80%) with a percentage of correctly classified patients of 73.74%. Oxidative stress markers were significantly associated with NAFLD. Testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses. Both factors, i.e., oxidative stress and hypogonadism, are central to PD pathogenesis. In conclusion, NAFLD and IR are strongly associated with PD. The pathogenic link between these conditions and the underlying mechanisms are only hypothetical and thoroughly summarized in the discussion.

Intestinal microbiota, intestinal permeability and the urogenital tract: is there a pathophysiological link?

Human gut microbiome is related to different clinical conditions and diseases. Recently several hypotheses have been theorized about a link between gut microbiota and genitourinary disease including urinary tract infections, and benign prostatic hyperplasia. Despite several data, underlying mechanisms still remain unclear. The aim of this review is to report the current state of knowledge in relation to urinary tract infections, benign prostatic hyperplasia and intestinal microbiota with a focus on its role in the development of disease and the underlying pathophysiologic mechanisms.

May chronic cough in chronic obstructive pulmonary disease be a contraindication of Percutaneous Endoscopic Gastrostomy placement: a case report.

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. CONCLUSION: We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

Impact of COVID-19 on hand surgery in Italy: A comparison between the Northern and the Southern regions.

The aims of this study were to evaluate the impact of the COVID-19 pandemic on emergency and elective hand surgery in four Italian regions that had either a high (Lombardy and Piemonte) or a low (Sicilia and Puglia) COVID-19 case load to discuss problems and to elaborate strategies to improve treatment pathways. A panel of hand surgeons from these different regions compared and discussed data from the centers they work in. The COVID-19 pandemic had an enormous impact on both elective and emergency surgery in Italy, not only in highly affected regions but also - and paradoxically even at a higher extent - in regions with a low COVID-19 case load. A durable and flexible redesign of hand surgery activities should be promoted, while changing and hopefully increasing human resources and enhancing administrative support. Telematics must also be implemented, especially for delivering rehabilitation therapy.

Kawasaki disease and cardiac involvement: an update on the state of the art.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It has a self-limiting course and so far, represents the most common cause of coronary heart disease acquired in children aged between 6 months and 5 years. The inflammatory process can involve the coronary arteries with the formation of aneurysms and thrombotic occlusions with the risk of sudden death, especially in infants. Myocardial inflammation and abnormalities of cardiac contractility can occur acutely or many years after the disease onset. Therapy must be started within 10 days after the onset of symptoms to reduce the risk of heart complications. Immunoglobulin and aspirin treatment are effective in reducing heart complications. Recent studies have shown new therapeutic strategies (corticosteroids, immunosuppressive and biological drugs) in case of ineffectiveness of treatment with immunoglobulins.

Assessment of neurocognitive decline in cancer patients, except brain cancer, under long-term treatment with bevacizumab.

PURPOSE: We performed a cross-sectional study of neurocognitive function in non-brain cancer patients treated with long-term bevacizumab. METHODS/PATIENTS: From 2015 to 2017, we included patients with different types of cancer treated with bevacizumab with or without chemotherapy (BEV; N = 20) or only chemotherapy (ChT; N = 19) for at least 34 weeks, patients who received non-brain radiotherapy (RxT; N = 19), and healthy controls (HC; N = 19) were assessed once at week 34 of treatment (BEV and ChT) or at completion of radiotherapy. Neurocognition was evaluated with the Hopkins Verbal Learning Test-Revised (HVLT-R) total and delayed recall, the Trail Making Test A and B, and the Controlled Oral Word Association Test in the four groups. Non-parametric tests were used to assess differences between groups. RESULTS: The BEV, ChT, and RxT groups scored significantly lower than the HC group on all tests and especially on the HVLT-R total recall. In no case were the mean scores of the BEV group significantly lower than those of the ChT or RxT groups. CONCLUSIONS: Neurocognitive impairment was seen even in patients treated with local non-brain radiotherapy. Treatment with bevacizumab for a long period of time does not seem to worsen neurocognitive function to a greater extent than chemotherapy.

Wearable, Fiber-less, Multi-Channel System for Continuous Wave Functional Near Infrared Spectroscopy Based on Silicon Photomultipliers Detectors and Lock-In Amplification.

Development and in-vivo validation of a Continuous Wave (CW) functional Near Infrared Spectroscopy (fNIRS) system is presented. The system is wearable, fiber-less, multi-channel (16×16, 256 channels) and expandable and it relies on silicon photomultipliers (SiPMs) for light detection. SiPMs are inexpensive, low voltage and resilient semiconductor light detectors, whose performances are analogous to photomultiplier tubes (PMTs). The advantage of SiPMs with respect to PMTs is that they allow direct contact with the scalp and avoidance of optical fibers. In fact, the coupling of SiPMs and light emitting diodes (LEDs) allows the transfer of the analog signals to and from the scalp through thin electric cables that greatly increase the system flexibility. Moreover, the optical probes, mechanically resembling electroencephalographic electrodes, are robust against motion artifacts. In order to increase the signal-to-noise-ratio (SNR) of the fNIRS acquisition and to decrease ambient noise contamination, a digital lock-in technique was implemented through LEDs modulation and SiPMs signal processing chain. In-vivo validation proved the system capabilities of detecting functional brain activity in the sensorimotor cortices. When compared to other state-of-the-art wearable fNIRS systems, the single photon sensitivity and dynamic range of SiPMs can exploit the long and variable interoptode distances needed for estimation of brain functional hemodynamics using CW-fNIRS.

Chemotherapy and PARP inhibitors in heavily pretreated BRCA1/2 mutation ovarian cancer (BMOC) patients.

OBJECTIVES: The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients. METHODS: g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models. RESULTS: 135 g/sBMOC patients were identified (6% sBRCA1/2 mutations). The median number of chemotherapy lines was 2 (1-7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p = 0.98). A total of 57 (42%) patients had ≥3 CT lines (3-7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2 months (CI 95% 8.4-11.9 months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1 m), PCT (12.6 m) or PARPi (12.4 m) versus non-PCT (4.9 m; p < 0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI) > 12 months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse. CONCLUSIONS: Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12 months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients.

Digital epidemiology confirms a latitude gradient of MS in France.

BACKGROUND: A gradient of prevalence of MS has been previously reported, and this may be due to different environmental and genetic features of the different populations, but also to methodological issues. In France, for example, three studies analysed the presence of such a gradient with conflicting results. The aim of this study was to assess whether digital epidemiology could confirm the presence of such a gradient. METHODS: through Google Trends, we analysed the relative search volume (RSV) for 'multiple sclerosis' in France, from 2004 to 2017, and assessed if an association with the decimal degree of latitude existed. RESULTS: Latitude was correlated with crude RSV (r2 0.39, p 0.04) in the 21 regions considered, with a southwest/northeast gradient. A multiple linear regression model adjusted for sex and age confirmed the existence of such a latitudinal effect, with an increase of 2.43 RSV units for each unit increase in latitude (95% CIs 0.62-4.24, p < 0.01, adjusted r2 0.61). CONCLUSIONS: our study provides additional evidence for the existence of a latitude gradient in MS, and the value of Internet-acquired data as real-time surveillance tools and alerts for healthcare systems.

Electrochemotherapy for the Treatment of Unresectable Locoregionally Advanced Cutaneous Melanoma: A Systematic Review. / Electroquimioterapia para el tratamiento del melanoma cutáneo locorregionalmente avanzado irresecable. Revisión sistemática.

Electrochemotherapy is a therapeutic option for the treatment of cutaneous and subcutaneous metastases from melanoma and other tumors. The procedure consists of the administration of anticancer drugs followed by locally applied electrical impulses to achieve an effect known as electroporation, which facilitates entry into the cytosol of drugs that cannot cross the cell membrane. The aim of this review is to evaluate the evidence that supports the use of electrochemotherapy as a therapeutic strategy in melanoma. We conducted a qualitative systematic review of the literature using advanced searches of bibliographic databases and full text reviews. Seven studies (3 systematic reviews and 4 cases series) were selected. The quality of the evidence was not good, but the coincidence of results for certain variables supports their consistency. Results of the meta-analyses favored electrochemotherapy over chemotherapy. Electrochemotherapy appears to be an effective procedure for the local treatment of malignant tumor nodules (evidence of intermediate or low quality). This inexpensive method is simple to apply, well tolerated, and achieves objective responses under certain circumstances. There is no evidence that electrochemotherapy alters the natural course of the disease and it should therefore be considered a palliative treatment. With an evidence level of 1- (minus), electrochemotherapy can be recommended for the palliative treatment of unresectable, locoregionally advanced melanoma (grade B recommendation).

Validation of 1-year predictive score of long-term response to interferon-ß in everyday clinical practice multiple sclerosis patients.

BACKGROUND AND PURPOSE: The Rio score (RS) and the modified Rio score (MRS) are two scoring systems that can identify the early predictive factors of disability progression in relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-ß (IFN-ß). The objective of the study was to validate the usefulness of the RS and MRS in a large cohort of multiple sclerosis patients treated with IFN-ß in daily clinical practice. METHODS: The analysis included a cohort of RRMS patients treated with different formulations of IFN-ß for at least 1 year. The RS and MRS were used to classify the patients after 1 year of treatment. Multivariate analysis was performed to identify predictive variables of suboptimal response at 5 years, defined as Expanded Disability Status Scale confirmed progression or switching to a second-line therapy. RESULTS: Sixty-nine of 416 included patients were considered as suboptimal responders at 5-year evaluation. The possible score range was 0-3. A higher risk of suboptimal response was found for RS and MRS in the presence of ≥2 scores (hazard ratio 3.0, P = 0.002, and hazard ratio 5.0, P < 0.0001, respectively). CONCLUSIONS: Our study confirmed, in a daily clinical setting, that MRS had a better specificity and accuracy than RS in identifying the patients who will have a poor response to long-term IFN-ß treatment.

Cut-off proposal for the detection of ketamine in hair.

Ketamine is a powerful anesthetic drug used in both human and veterinary surgery, but it is also commonly misused because of its psychotropic properties. Since the abuse of this drug has been reported in many countries worldwide, its determination in hair samples is offered as a specialist test by hundreds of laboratories. However, unlike other common drugs of abuse, a cut-off level for ketamine in hair has not been fixed yet. Therefore, aim of this study is to propose a concentration value for ketamine in hair analysis, in order to discriminate between chronic and occasional use, and between active use and external contamination. After considering the chemical properties of this molecule, and the experimental data collected in our laboratory or reported in several other published studies, we propose a cut-off level of 0.5ng/mg, as indicative of repeated exposure to ketamine. Additionally, we suggest that the detection of the metabolite norketamine should be mandatory to prove active intake and exclude false positive result from external contamination. Thus, a reasonable cut-off value for norketamine could be fixed at 0.1ng/mg, while the minimal concentration ratio norketamine/ketamine may be positively established at 0.05.