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.

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.

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.

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.

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.

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).

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.

[Effects of using an information leaflet in reducing perioperative anxiety and pain in patients undergoing urological surgery]. / Efectos del uso de un tríptico informativo en la reducción de la ansiedad y el dolor perioperatorios en pacientes intervenidos de patología urológica.

INTRODUCTION: The preoperative anxiety state is mainly caused by the fear of the circumstances surrounding the intervention. Anxiety causes increased postoperative pain, and a prolonged length of stay in hospital, which directly affect the cost of care. OBJECTIVE: To evaluate the effects of providing an anaesthesia information leaflet on postoperative anxiety and pain in patients undergoing urological surgery in the Miguel Servet Hospital. MATERIAL AND METHODS: A prospective quasi-experimental study of 100 cases, 51 of whom made up the intervention group who received the information leaflet, with the remaining 49 cases being in the control group. The Hospital Anxiety and Depression Scale and the visual analogue scale for pain were assessed in both groups, before and after surgery. RESULTS: Of the 100 patients, 72% were male and 28% female, with an average age of 67.3 years (standard deviation, 9.7). In the intervention group, 21.6% showed anxiety before surgery and 0% in the postoperative period. In the control group 30.6% presented anxiety during the preoperative period and 4% in the postoperative period (χ(2) Pearson 5.20, P=.023). The study showed a direct relationship between preoperative anxiety and postoperative pain (χ(2) Pearson 10.519, P=.001). CONCLUSIONS: Good information about the surgical process reduces anxiety levels in the postoperative period.

[A not very essential obesity: the Rohhad syndrome. Description of two cases and review of the literature]. / Un'obesità poco essenziale: la sindrome ROHHAD. Due casi clinici e review della letteratura.

UNLABELLED: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Children typically show ROHHAD after the first years of life with rapid weight gain and subsequently autonomic nervous system dysregulation (altered pain perception, pupillary dysfunction, hypothermia and bradycardia); alveolar hypoventilation with risk of cardiorespiratory arrest and hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, growth hormone and corticotrophin deficiency). Tumours of neural crest origin, such as ganglioneuroblastoma and ganglioneuronoma, are reported in 33% of the patients and may be found in the chest or abdomen. Here we describe two girls who presented with rapid weight gain, at the age of 5 and 9 years respectively. The first was admitted due to obesity and central hypothyroidism. After two months she rapidly developed a clinical picture characterized by thermal dysregulation, hypodipsia and severe hypernatriemia, hypertrigliceridemia, alveolar hypoventilation supported by mechanical ventilation. The second presented with rapid-onset obesity and a mild hyperprolactinemia. After three months of follow-up she was admitted due to a clinical picture of hypothermia, seizures and hyponatremia. Subsequentely she developed altered water balance (severe hypernatremia) and severe hypoventilation. Chest CT and MR imaging showed a posterior mediastinal mass. Endocrinological investigation showed corticotrophin deficiency and central hypothyroidism treated with specific replacement therapies. CONCLUSIONS: On the basis of our experiences we can infer that it is necessary perform specific further investigations of hypothalamic function in all the children with rapid onset obesity in order to early prevent the catastrophic consequences that may occur in this syndrome.

Clinical and MRI predictors of response to interferon-beta and glatiramer acetate in relapsing-remitting multiple sclerosis patients.

BACKGROUND AND PURPOSE: It is still unclear which patients benefit more from available disease-modifying treatments (DMTs) in multiple sclerosis (MS). Our objective is to identify the baseline clinical and magnetic resonance imaging (MRI) predictors of response to first-line DMTs in a cohort of relapsing-remitting (RR) MS patients in a real-world clinical setting. METHODS: Consecutive naïve RRMS patients treated with interferon-beta or glatiramer acetate have been included and followed for 2 years. Patients were grouped into responders (R) in case of absence of clinical and MRI activity, and non-responders (NR) if the on-treatment annualized relapse rate (ARR) reduction was < 50% of the ARR in the 2 years before treatment or in the presence of MRI activity (≥ 2 active lesions at 1-year MRI or ≥ 4 active lesions at 1 + 2-year MRI). RESULTS: At 2-year follow-up, 272 patients were R (34.6%) and 322 NR (40.9%), and multivariate analysis revealed that a later age at onset of the disease (P < 0.0001), a lower disability (P < 0.0001) and a lower number of gadolinium-enhancing lesions at baseline MRI (P = 0.002) were predictors of efficacy of DMTs. Moreover, the first year response had a good predictive power on the second year, as 73.7% of 1-year R had no evidence of clinical and MRI activity within the ensuing year. CONCLUSION: A lower baseline MRI and clinical activity have been identified as predictors of DMT efficacy in patients with RRMS in routine clinical practice. Evaluation of clinical and MRI activity at 1 year is recommended to monitor patients over time.

Validation of the Glasgow Facial Palsy Scale for the assessment of smile reanimation surgery in facial paralysis.

OBJECTIVES: To evaluate the Glasgow Facial Palsy Scale as a tool to assess facial reanimation surgery in facial palsy. Software analysis of digital video data is used to measure facial movements, comparing the affected to the normal side. We present the first use of the Glasgow Facial Palsy Scale following facial re-animation surgery. DESIGN: A comparison of the Glasgow Facial Palsy Scale against the Nottingham scoring system. Subjects undergoing unilateral surgical smile reanimation procedures were selected. Comparison was made with the Nottingham facial palsy scale and the House-Brackmann Scale pre- and postoperatively. SETTING: Patients were recruited in the facial palsy clinic of Canniesburn Plastic Surgery Unit, Glasgow. PARTICIPANTS: Seven consecutive patients were selected who were due to undergo unilateral facial reanimation. MAIN OUTCOME MEASURES: The difference in pre- and post-surgical facial movement as measured using the Glasgow Facial Palsy Scale with this value being compared to that obtained using the Nottingham scoring system. Note was also taken of the correlation with House-Brackmann system and clinical correlation. RESULTS AND CONCLUSIONS: Statistical analysis indicated a linear relationship between the Glasgow Facial Palsy Scale and the Nottingham System. The Pearson correlation test was used to confirm the relationship between the two methods giving a result of -0.587, which indicates significant correlation between the two methods. We conclude that the Glasgow Facial Palsy Scale is a standardised objective method of assessing the change in facial movement following smile reanimation surgery. We commend it as a useful tool to objectively assess surgical results in this challenging field.

Prognostic value of CD34+ peak in peripheral blood during mobilization in intermediate-risk AML patients treated in first CR by autologous or allogeneic transplantation.

Ninety-six AML patients in 1st CR were evaluated for peak CD34+ cell levels in peripheral blood (PB) during PBSC mobilization and harvest. Distribution of CD34+ cell peaks was determined and cases were grouped on the basis of 50th and 75th percentile: group A, those having a CD34+ cell peak ≤70 × 10(9)/L (n=48); group B, those having a CD34+ cell peak between 70 and 183 × 10(9)/L (n=24); group C, those having a CD34+ cell peak >183 × 10(9)/L (n=24). Irrespective of post-remission treatment received, group A had a disease free survival (DFS) of 73%, group B a DFS of 51% and group C of 30% (P=0.0003). In intermediate cytogenetic risk patients, those treated by autologous transplantation had a DFS of 68, 33 and 14% in the groups A, B and C, respectively, (P=0.01) whereas after allogeneic transplantation DFS was 87% in group A+B vs 50% in group C (P=0.009). The peak of CD34+ cells in PB, was an independent predictor for DFS in multivariate analysis.

Reduction mammaplasty and related impact on psychosexual function.

INTRODUCTION: Reduction mammaplasty brings an effective improvement, both from the physical and psychological points of view. However, psychosexual consequences are as yet poorly studied, although scars, impairment of sensibility, change in shape and asymmetry can have a negative effect on sexual life. AIM: These authors retrospectively reviewed 55 patients to verify the existence of a close relationship between this popular surgical procedure and psychosexual function. MATERIAL AND METHODS: All patients were compared to a group (51 healthy women) chosen from the hospital personnel. Both groups answered four psychological questionnaires (Short Form (SF)-36, Hamilton Anxiety Rating Scale (Ham-A), Hamilton Rating Scale for Depression (Ham-D), Female Sexual Function Index (FSFI)) anonymously, in addition to the scar-assessment test as a single physical test. Psychological tests aim to evaluate self-esteem, quality of life (SF-36) and sexual function in women (FSFI, a test based on Erectile Function Index of Male). High levels of anxiety and depression were used as exclusion criteria in our study (Ham-D and Ham-A). Statistical analysis was based on non-parametric correlation test adjusted for small groups and Spearman's rho test to verify the associations among sub-items scales. RESULTS: Almost all patients (98%) fulfilled the inclusion criteria for our study. Sexual function index was equal in both groups, but it still showed a higher quality of life in the control group. Nevertheless, the SF-36 value of the patients' group is still enough to allow for acceptable self-esteem. CONCLUSIONS: We can confirm that reduction mammaplasty does not impair sexual satisfaction or quality of life; moreover, we believe that this procedure can improve such indices. Further investigation will compare patient's values prior to and following surgery to put in evidence a stronger relationship between mammary reduction and sexual function.