The impact of complex facial surgery provided on a short-term surgical mission.

The long-term consequences of performing facial surgery on patients living in rural Ethiopia are largely unknown. A review of 36 patients who had been treated on a short-term surgical mission (STSM) in the previous 2 years was conducted to evaluate the outcomes of the surgical interventions performed. There was a significant reduction in social isolation following a surgical intervention. Improvements in postoperative self-reported changes were found for facial appearance, facial function, and quality of life. Positive outcomes can be achieved when surgical treatment is performed on a STSM.

Clinical examination and non-invasive screening tests in the diagnosis of peripheral artery disease in people with diabetes-related foot ulceration.

AIM: Peripheral artery disease is common in people with diabetes-related foot ulceration and is a risk factor for amputation. The best method for the detection or exclusion of peripheral artery disease is unknown. This study investigated the utility of clinical examination and non-invasive bedside tests in screening for peripheral artery disease in diabetes-related foot ulceration. METHODS: Some 60 people presenting with new-onset ulceration participated. Accuracy of pulses, ankle pressure, toe pressure, toe-brachial index (TBI), ankle-brachial pressure index (ABPI), pole test at ankle, transcutaneous oxygen pressure and distal tibial waveform on ultrasound were examined. The gold standard diagnostic test used was > 50% stenosis in any artery or monophasic flow distal to calcification in any ipsilateral vessel on duplex ultrasound. RESULTS: The negative and positive likelihood ratios of pedal pulse assessment (0.75, 1.38) and the other clinical assessment tools were poor. The negative and positive likelihood ratios of ABPI (0.53, 1.69), transcutaneous oxygen pressure (1.10, 0.81) and ankle pressure (0.67, 2.25) were unsatisfactory. The lowest negative likelihood ratios were for tibial waveform assessment (0.15) and TBI (0.24). The highest positive likelihood ratios were for toe pressure (17.55) and pole test at the ankle (10.29) but the negative likelihood ratios were poor at 0.56 and 0.74. CONCLUSIONS: Pulse assessment and ABPI have limited utility in the detection of peripheral artery disease in people with diabetes foot ulceration. TBI and distal tibial waveforms are useful for selecting those needing diagnostic testing.

Brand-to-generic levetiracetam switching: a 4-year prospective observational real-life study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether switching from branded levetiracetam (Keppra® ) to a levetiracetam generic equivalent product (Matever® ) in an epilepsy cohort could provide adequate results in terms of seizure control and tolerability. METHODS: To be eligible for the study, patients had to have been taking Keppra® as monotherapy or polytherapy for at least 6 months. Between March 2013 and April 2017, patients were invited to switch to Matever® as part of their follow-up. We evaluated the number of seizures per month, drug-related adverse events and electroencephalography before the switch (T0, baseline) and 6 months after switching (T1). Furthermore, we reported the long-term follow-up of patients who continued to use Matever® after the end of the study, considering the most recent visit for each patient (T2). RESULTS: A total of 55 patients refused the switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra® as monotherapy and 66 (53%) were on Keppra® as polytherapy. All 125 patients were subjected to switching from Keppra® to Matever® . Comparing patients before (T0) and after (T1) switching, we found no statistically significant differences in terms of seizure frequency and occurrence of adverse effects. There were no significant differences (number of seizures/month and drug-related adverse events) between patients treated with Matever® as monotherapy and patients who refused the switch and continued to use Keppra® as monotherapy for a long-term follow-up of 48 months. Electroencephalography findings were also unchanged. CONCLUSION: In our sample, brand-to-generic levetiracetam switching was effective and safe in both monotherapy and polytherapy regardless of the epilepsy syndrome.

Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10(-3)), 8q24 (rs987525, P = 1.22 × 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.

CALCINOSIS CUTIS - A SERIES OF 59 CONSECUTIVE CASES CONFINED AMONG WOMEN.

BACKGROUND: Calcinosis cutis is the cutaneous deposition of calcium salts. Tumoral Calcinosis is a condition consisting of massive subcutaneous deposits of calcium salts often overlying large joints in otherwise healthy patients. OBJECTIVE: To describe the characteristics of a series of patients with Tumoral Calcinosis in the Gurage Zone of Central Ethiopia. METHODOLOGY: Data was collected from 59 patients who presented with clinical diagnosis of calcinosis cutis around hip region between January 2005 and January 2009. RESULTS: All cases were females, with a mean (standard deviation) age at diagnosis of 50.7(10.8). The duration of illness ranged from one to eighteen years. The cases were distributed in the different villages of Gurage Zone without any sign of clustering of cases. The lesions were localized around hip region on both sides. The patients did not have any related co-morbidity or any history of similar illness among close family members. None of the patients gave history of evident trauma to the site of the lesions. Significant proportion of the patients (53.4%) confirmed to carry water container and/or other goods on their side. Serum Phosphate and Calcium levels in selected patients were with in normal limit. Histo-pathological examinations of five cases revealed Calcium deposits in collagenous connective tissue. CONCLUSION: The lesion was found to be relatively common in the study area and specifically confined to females. The probable factor associated with the cases is carrying objects on their side (hip area). Further research with in-depth clinical and laboratory evaluation is of paramount importance.

[Preliminary results of the treatment of high grade (T1G3) superficial tumors of the bladder with transurethral resection]. / Resultados preliminares del tratamiento de los tumores vesicales superficiales de alto grado (T1G3) mediante resección transuretral.

OBJECTIVE: To examine the results of monotherapy with TUR in the treatment of primary T1G3 transitional cell carcinoma (TCC). METHODOLOGY: Thirty-two patients with primary TCC of the bladder were allocated into a surveillance program. Risk factors for progression to muscle-invasive disease were determined. Immediately, projections of disease-free and progression-free survival were calculated. RESULTS: Five patients (15.6%) were lost in follow-up. Twenty-three (85%) had superficial recurrences. Four patients (14.8%) progressed to muscle-invasive or metastatic disease. No independent risk-factors for progression were disclosed. Median disease-free survival was 8 months. Projection of the risk of recurrence at 79 months was 84.9%. Median time to progression has not been reached yet. Projection of progression at 79 months was 46.3%. CONCLUSIONS: The above mentioned treatment schedule is associated with very high recurrence rates. In addition, recurrences are very frequent. Nevertheless, in the medium run, projections of progression suggest that surveillance can be an alternative to other treatments in the management of T1G3 TCC of the bladder.

Resultados preliminares del tratamiento de los tumores vesicales superficiales de alto grado (T1G3) mediante resección transuretral / Monotherapy with transurethral resection in evaluating and in managing patients with bladder tumors

OBJETIVO: Analizar los resultados del tratamiento de los tumores vesicales superficiales (TVS) primarios en estadio T1G3 mediante RTU como monoterapia. METODOLOGÍA: Treinta y dos pacientes con TVS primarios estadio T1G3 fueron incluidos en un programa de vigilancia. Para este estudio se analizaron los factores clínicos para la progresión. Acto seguido, se establecieron las proyecciones de la supervivencia libre de enfermedad y libre de progresión. RESULTADOS: Cinco individuos (15,6 por ciento) resultaron perdidos en su seguimiento. Veintitrés (85 por ciento) sufrieron recidivas de carácter superficial. En cuatro pacientes (14,8 por ciento) la enfermedad progresó a infiltración mus-cular o se diseminó. No fue posible identificar factores de riesgo independientes para la progresión. La mediana de tiempo a la recidiva fue de 8 meses. La proyección del riesgo de recidivar a los 79 meses fue del 84,9 por ciento. La mediana de tiempo a la progresión todavía no se ha alcanzado. La proyección del riesgo de progresar a los 79 meses de seguimiento se situó en el 46,3 por ciento. CONCLUSIONES: Bajo el esquema de tratamiento descrito, la mayoría de los tumores recidivan, y lo hacen con gran frecuencia. Sin embargo, las proyecciones de progresión a medio plazo permiten considerar la vigilancia como una alternativa a otros tratamientos (AU)

Luteal phase support with 17alpha-hydroxyprogesterone versus unsupported cycles in in vitro fertilization: a comparative randomized study.

This study was designed to determine the efficacy of 17alpha-hydroxyprogesterone caproate (17-OHPc) for luteal phase support in in vitro fertilization (IVF). For this purpose, a total of 86 IVF patients undergoing embryo transfer were randomly allocated to two groups as follows: (1) group A, including 43 patients who received the support of luteal phase through the intramuscular administration of 17-OHPc at a dosage of 341 mg every 3 days, and (2) group B, including 43 patients who received the intramuscular administration of a saline solution as placebo every 3 days. In both groups, the treatment was started within 24 h after embryo transfer until beta-HCG evaluation. In case of positive beta-HCG, it was extended until 12 weeks. Efficacy was assessed using the pregnancy rates, which was, per transfer, statistically significantly higher in group A than in group B (32.5 vs. 18.3% respectively). On the basis of our results, we emphasize the use of 17-OHPc for luteal phase support after IVF and embryo transfer.

Intramuscular versus vaginal administration of progesterone for luteal phase support after in vitro fertilization and embryo transfer. A comparative randomized study.

A total of 156 patients were randomly treated with exogenous natural progesterone (intramuscularly, 50 mg/day) and vaginal gel (90 mg/day) P or nothing (Controls) from the day before embryo transfer (ET) for two weeks. In case of positive beta-HCG, the treatment was continued for 12 weeks. Plasma P and 17 beta-Estradiol concentrations were estimated and compared with the control not supplemented group. Both treatments were able to increase significantly the luteal plasmatic values of P versus controls. The ongoing pregnancy and the living birth rates per transfer were significantly higher in the patients supplemented with intramuscular P than in those treated with vaginal gel P. The intramuscular natural P appears the most suitable route of administration for luteal phase support in IVF-ET procedures.

17-alpha-Hydroxyprogesterone caproate and natural progesterone in assisted reproduction: a comparative study.

The use of luteal phase support has been demonstrated in patients undergoing an IVF/ET procedure. This study was designed to compare the absorption and the efficacy of two different luteal supports: 17-alpha-hydroxyprogesterone caproate (Lentogest, AMSA, Italy) and natural Progesterone (Prontogest, AMSA, Italy). A total of 80 patients received luteal supplementation with 50 mg of natural P/day intramuscularly, until beta-hCG evaluation. Then, in case of positive beta-hCG, patients were randomly divided into two groups (A and B) in order to compare two different protocols: Group A, 17-OHPc (341 mg once a week) and Group B, natural P (50 mg/day) both intramuscularly and extended for 10-12 weeks. Our study showed that the treatment with 17-OHPc results in a higher percentage of pregnancy rate compared to natural P, but the differences are not statistically significant. Thus, we emphasize that 17-OHPc preparation for better acceptance appears to be the most suitable and comfortable method for luteal phase support.

Intramuscular versus vaginal progesterone in assisted reproduction: a comparative study.

The effectiveness and the absorption of two progesterone (P) presentations have been compared for luteal phase support of patients aged < or = 37 years undergoing an in vitro fertilization (IVF) procedure for the first time, who were stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists (GnRHa). All of them had two ovaries, normal ovarian functions and normal endometrial morphology: the indication for the assisted reproductive technique was the tubal factor. Two hundred and fifty patients were randomly allocated to two groups in order to compare two treatment protocols: Group A: natural i.m. P (50 mg/day, Prontogest, AMSA, Italy); Group B: micronized vaginal P (200 mg/day Esolut, Angelini, Italy). We were able to show that the i.m. P resulted in a higher percentage of pregnancies than the vaginal preparation, with statistically significant differences. We recommend the use of injectable P, and suggest reserving intravaginal P as a second choice for patients who cannot tolerate intramuscular administration.

Efficacy and tolerability of brodimoprim at two different dosage schedules in the treatment of acute uncomplicated bacterial cystitis: comparative study vs. pefloxacin.

In an open study, 172 male and female adult patients with acute uncomplicated bacterial cystitis were randomly allocated to three treatment groups. Two groups received brodimoprim 200 mg tablets as follows: a single dose of two 200 mg tablets on day 1, followed by one tablet per day on days 2 and 3 (58 patients); or a single daily dose of two tablets, for 2 days (63 patients). The third group received a single dose of pefloxacin, as two 400 mg tablets, for 1 day (51 patients). Complete urinalysis, sediment and urine culture examinations were carried out before treatment and 10 days after the last dose. Evaluation also comprised, at the time of enrolment and 48 h after the last dose, measurement of corporal temperature and assessment of symptoms (dysuria, pollakiuria, strangury, suprapubic pain, burning sensation during urination and urgency) on a 4-point scale. The eradication rate for the pathogen concerned was 98.3% and 96.7% in the groups receiving brodimoprim for 3 and 2 days, respectively, and 92.8% in the pefloxacin group (between-group comparison n.s.). There was significant regression of symptoms (P < 0.001) in the three groups (between-groups comparison n.s.). Mainly gastrointestinal adverse events occurred in 3 patients receiving brodimoprim for 2 days and in 4 patients from each of the other two groups.

[Variations in microalbuminuria in essential hypertension treated with ACE inhibitors, calcium antagonists and their association]. / Variazione della microalbuminuria in ipertesi essenziali trattati con ACE-inibitori, calcioantagonisti e loro associazione.

OBJECTIVE: Microalbuminuria is an early and sensible marker of renal impairment; furthermore, many authors consider it an independent predictive index for cardiovascular morbidity and mortality. In our study we observed this parameter in hypertensive patients treated respectively with ACE-inhibitors, calcium channel blockers and their combination. EXPERIMENTAL DESIGN: Open comparative trial, 6 months follow-up. ENVIRONMENT: Outpatients, with no changes from usual lifestyle; office measurements. PATIENTS: Forty patients (22 men and 18 women) aged 52-78 years, with essential hypertension and microalbuminuria; diabetics and subjects with renal impairment were excluded. TREATMENT: Chronic antihypertensive drug therapy, respectively with nitrendipine 20 mg/die (Group A, n = 10), lisinopril 20 mg/die (Group B, n = 20), and lisinopril 20 mg/die+nitrendipine 20 mg/die (Group C, n = 10); all drugs were administered orally. MEASUREMENTS: Detection of urinary albumin excretion with immunochemical method (Micral Test); urine samples were taken immediately after arousal for three consecutive days; office blood pressure monitoring (sitting and standing) during the same day, with at least 2 separate readings. RESULTS: Out of 34 patients examined at follow-up, (8 from Group A, 17 from Group B and 9 from Group C) urinary albumin excretion rates were as follows: Group A: reduction (but not disappearance) in 3 patients (37%), no change in 4 patients (50%), increase in 1 patient (13%); Group B: disappearance in 11 patients (65%), reduction in 3 patients (17.5%), no changes in 3 patients (17.5%); Group C: reduction (but not disappearance) in 5 patients (55.5%), no changes in 4 patients (44.5%). CONCLUSIONS: In hypertensive patients not diabetics and not renally impaired with microalbuminuria, ACE-inhibitors appear to be a move suitable drug therapy than calcium channel blockers or the combination ACE-inhibitor+calcium channel blocker.

Pituitary testicular axis function and sex hormone binding globulin binding capacity in thalassaemia major.

Pituitary testicular function was investigated in 19 prepubertal and in 5 pubertal male thalassaemic patients. Total plasma testosterone in prepubertal and in pubertal patients was significantly lower than in controls. In the prepubertal thalassaemics, the lower total testosterone concentration correlated with the diminished sex hormone binding globulin binding capacity (SHBGcap), and the free testosterone levels were normal. The lower testosterone is probably due to the damaged liver function rather than to a diminished testicular function. In the pubertal patients, the testosterone reduction is equally due to the SHBG bound testosterone fraction and the free testosterone fraction. Basal and LHRH stimulated plasma gonadotrophin levels were also significantly decreased in the pubertal subjects. The observed hypotestosteronemia in the pubertal thalassaemics seems to depend on the impaired pituitary gonadotrophin secretion probably due to the chronic iron overload.

Gonadotropinic reserve in women affected by hyperprolactinemic amenorrhea.

The Authors have evaluated the hypophysis gonadotropic reserve after stimulation by synthetic GnRH (100 ng) in women affected by functional hyperprolactinemia and by prolactin-secreting adenoma. The LH response was significatively higher in women affected by functional hyperprolactinemia. The PRL values seem to have no influence on the gonadotropic reserve except for the cases in which The PRL levels were higher than 200 ng/ml. In all these cases a prolactinoma was present. The FSH response was similar in the two groups considered.