Ibrexafungerp: A narrative overview.

Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the ß-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including Candida and Aspergillus spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the FKS genes, primarily FKS2 mutations in Nakaseomyces glabrata. In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating Pneumocystis jirovecii infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in C. auris infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.

Importance of consultations using mobile teams in the screening and treatment of neglected tropical skin diseases in Benin.

CONTEXT: Since 2013, the World Health Organization has recommended integrated control strategies for neglected tropical diseases (NTDs) with skin manifestations. We evaluated the implementation of an integrated approach to the early detection and rapid treatment of skin NTDs based on mobile clinics in the Ouémé and Plateau areas of Benin. METHODS: This descriptive cross-sectional study was performed in Ouémé and Plateau in Benin from 2018 to 2020. Consultations using mobile teams were performed at various sites selected by reasoned choice based on the epidemiological data of the National Program for the Control of Leprosy and Buruli Ulcer. All individuals presenting with a dermatological lesion who voluntarily approached the multidisciplinary management team on the day of consultation were included. The information collected was kept strictly anonymous and was entered into an Excel 2013 spreadsheet and analyzed with Stata 11 software. RESULTS: In total, 5,267 patients with various skin conditions consulted the medical team. The median age of these patients was 14 years (IQR: 7-34 years). We saw 646 (12.3%) patients presenting NTDs with skin manifestations, principally scabies, in 88.4% (571/646), followed by 37 cases of Buruli ulcer (5.8%), 22 cases of leprosy (3.4%), 15 cases of lymphatic filariasis (2.3%) and one case of mycetoma (0.2%). We detected no cases of yaws. CONCLUSION: This sustainable approach could help to decrease the burden of skin NTDs in resource-limited countries.

An Overview of 10 Years of Activity of a Molecular Laboratory for Buruli Ulcer Diagnosis at a Field Hospital in Benin.

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. Early diagnosis is crucial to prevent morbidity. In November 2012, a field laboratory fully equipped for the rapid on-site quantitative PCR (qPCR) diagnosis of M. ulcerans was established at the Buruli ulcer treatment center (CDTLUB) center in Pobè Benin, a region where BU is endemic. We describe its first 10 years of activity and its gradual evolution into an expert laboratory for BU diagnosis. From 2012 to 2022, the laboratory analyzed 3,018 samples from patients attending consultations for suspected BU at the CDTLUB in Pobè. Ziehl-Neelsen staining and qPCR targeting the IS2404 sequence were performed. Since 2019, the laboratory has also received and analyzed 570 samples from other centers. The laboratory confirmed the diagnosis of BU by qPCR for 39.7% samples: M. ulcerans DNA was detected in 34.7% of swabs, 47.2% of all fine needle aspiration samples (FNA) and 44.6% of all skin biopsy specimens. Positive Ziehl-Neelsen staining results were obtained for 19.0% samples. Bacterial load, estimated by qPCR, was significantly greater for the Ziehl-Neelsen-positive samples than for Ziehl-Neelsen-negative samples, and detection rates were highest for FNA samples. Overall, 26.3% of the samples received from other centers were positive for BU. Most of these samples were sent by the CDTLUBs of Lalo, Allada, and Zagnanado, Benin. The establishment of the laboratory in the CDTLUB of Pobè has been a huge success. Optimal patient care depends on the close proximity of a molecular biology structure to BU treatment centers. Finally, FNA should be promoted among caregivers. IMPORTANCE Here, we describe the first 10 years of activity at a field laboratory established at the Buruli ulcer treatment center (CDTLUB) in Pobè, Benin, a country in which Mycobacterium ulcerans is endemic. Between 2012 and 2022, the laboratory analyzed 3,018 samples from patients consulting the CDTLUB of Pobè with a suspected clinical BU. Ziehl-Neelsen staining and qPCR targeting the IS2404 sequence were performed. In total, 39.7% of samples tested positive by qPCR and 19.0% tested positive by Ziehl-Neelsen staining. Detection rates were highest for FNA samples, and the bacterial loads estimated by qPCR were significantly higher for Ziehl-Neelsen-positive samples than for Ziehl-Neelsen-negative samples. Since 2019, the laboratory has also analyzed 570 samples received from outside the CDTLUB of Pobè, 26.3% of which were positive for BU. Most of these samples were sent by the CDTLUBs of Lalo, Allada, and Zagnanado in Benin. The establishment of the laboratory in the CDTLUB of Pobè has been a huge success, with major benefits for both the medical staff and patients. Our findings illustrate that the usefulness and feasibility of having a diagnostic center in rural Africa, where the disease is endemic, is a key part of optimal patient care, and that FNA should be promoted to increase detection rates.

Learning Curve in Left Ventricular Assist Device Implantation: Low Volumes Do Not Equate Bad Outcomes.

INTRODUCTION: Most implantations of left ventricular assist devices (LVAD) are performed in low-volume centers. This study aimed to evaluate the procedural learning curve of HeartMate II (HM2) implantations by comparing outcomes between two time periods in a low-volume center. METHODS: All 51 consecutive patients undergoing HM2 implantation between January 2009 and December 2017 were reviewed and allocated into 2 groups: early-era group (from 2009 to 2014; n=25) and late-era group (from 2015 to 2017; n=26). The primary outcome was the 90-day mortality rate, and the secondary outcome was a composite of mortality, neurological event, reoperation for bleeding, need for temporary right ventricular assist device, and pump thrombosis at 90 days. Median follow-up time was 51 months (0-136). A cumulative sum (CUSUM) control analysis was used to establish a threshold of implantations that optimizes outcomes. RESULTS: Patients in the early era had a higher rate of diabetes, previous stroke, and inotrope support before HM2 implantation. The 90-day mortality rate was not significantly higher in the early era (24% vs. 15%, P=0.43), but the composite endpoint was significantly higher (76% vs. 42%, P=0.01). The CUSUM analysis found a threshold of 23 operations after which the composite endpoint was optimized. CONCLUSION: Patients undergoing HM2 implantation in a low-volume center have improving outcomes with number of cases and optimized results after a threshold of 23 cases. Significant changes in patient selection, surgical techniques, and patient management might lead to improved outcomes after LVAD implantation.

Learning Curve in Left Ventricular Assist Device Implantation: Low Volumes Do Not Equate Bad Outcomes

ABSTRACT Introduction: Most implantations of left ventricular assist devices (LVAD) are performed in low-volume centers. This study aimed to evaluate the procedural learning curve of HeartMate II (HM2) implantations by comparing outcomes between two time periods in a low-volume center. Methods: All 51 consecutive patients undergoing HM2 implantation between January 2009 and December 2017 were reviewed and allocated into 2 groups: early-era group (from 2009 to 2014; n=25) and late-era group (from 2015 to 2017; n=26). The primary outcome was the 90-day mortality rate, and the secondary outcome was a composite of mortality, neurological event, reoperation for bleeding, need for temporary right ventricular assist device, and pump thrombosis at 90 days. Median follow-up time was 51 months (0-136). A cumulative sum (CUSUM) control analysis was used to establish a threshold of implantations that optimizes outcomes. Results: Patients in the early era had a higher rate of diabetes, previous stroke, and inotrope support before HM2 implantation. The 90-day mortality rate was not significantly higher in the early era (24% vs. 15%, P=0.43), but the composite endpoint was significantly higher (76% vs. 42%, P=0.01). The CUSUM analysis found a threshold of 23 operations after which the composite endpoint was optimized. Conclusion: Patients undergoing HM2 implantation in a low-volume center have improving outcomes with number of cases and optimized results after a threshold of 23 cases. Significant changes in patient selection, surgical techniques, and patient management might lead to improved outcomes after LVAD implantation.

Never seen right gastrothorax: A case report.

Traumatic gastrothorax, or stomach herniation into the chest post-trauma, is a rare but dangerous condition that can lead to respiratory distress and obstructive shock. Its diagnosis is challenging and requires a high index of suspicion. Immediate stomach decompression is an important, often life-saving step of the treatment, prior to definitive surgical repair. We report herein the case of a 59 year-old female patient, who was involved in a severe motor vehicle accident resulting in multiple injuries. Her right-sided gastrothorax, manifesting as solely nausea at first, was only diagnosed 16 days after trauma, intraoperatively. Worse, her herniated stomach had ruptured within the right pleural cavity causing pneumothorax, spillage of contents and pleuritis. It was an erroneous radiological diagnosis of right lung necrosis which halted surgical management. Right gastrothorax has never been reported previously. This article also reviews the condition's pathophysiology, along with diagnostic and therapeutic modalities, and sheds light on the importance of its early recognition and treatment.

Aerobic training suppresses exercise-induced lipid peroxidation and inflammation in overweight/obese adolescent girls.

This study aimed to determine whether aerobic training could reduce lipid peroxidation and inflammation at rest and after maximal exhaustive exercise in overweight/obese adolescent girls. Thirty-nine adolescent girls (14-19 years old) were classified as nonobese or overweight/obese and then randomly assigned to either the nontrained or trained group (12-week multivariate aerobic training program). Measurements at the beginning of the experiment and at 3 months consisted of body composition, aerobic fitness (VO2peak) and the following blood assays: pre- and postexercise lipid peroxidation (15F2a-isoprostanes [F2-Isop], lipid hydroperoxide [ROOH], oxidized LDL [ox-LDL]) and inflammation (myeloperoxidase [MPO]) markers. In the overweight/ obese group, the training program significantly increased their fat-free mass (FFM) and decreased their percentage of fat mass (%FM) and hip circumference but did not modify their VO2peak. Conversely, in the nontrained overweight/obese group, weight and %FM increased, and VO2peak decreased, during the same period. Training also prevented exercise-induced lipid peroxidation and/or inflammation in overweight/obese girls (F2-Isop, ROOH, ox-LDL, MPO). In addition, in the trained overweight/obese group, exercise-induced changes in ROOH, ox-LDL and F2-Isop were correlated with improvements in anthropometric parameters (waist-to-hip ratio, %FM and FFM). In conclusion aerobic training increased tolerance to exercise-induced oxidative stress in overweight/obese adolescent girls partly as a result of improved body composition.

[Sleep quality is a determinant of hip bone mineral density in a group of young Lebanese men]. / La qualité du sommeil est un déterminant de la densité minérale osseuse de la hanche chez un groupe de jeunes hommes libanais.

INTRODUCTION: The aim of this study was to explore the relationship between sleep quality and bone mineral density (BMD) of the hip in a group of young Lebanese men. METHODS AND RESULTS: Fourteen Lebanese young men from 18 to 30 years (mean age 22.6 years) participated in this study. Weight and height were measured and body mass index (BMI) was calculated. BMD of the total hip (TH) and the femoral neck (FN) was measured by DXA. Daily protein intake (DPI), daily calcium intake (DCI) and sleep quality were evaluated by validated questionnaires. The Pittsburgh sleep quality index (PSQI) was used to assess sleep habits and quality; higher scores represent worse sleep quality. Weight, height, BMI, DCI, DPI and sleep duration were not correlated to BMD values. The Pittsburgh sleep quality index was negatively correlated to femoral neck BMD (r = -0.82; p < 0.001) and to TH BMD (r = -0.54; p < 0.05). CONCLUSION: This study suggests that poor sleep quality affects negatively BMD of the hip in young adult men. Our findings may lead to the development of better preventive approaches to osteoporosis.

Autism in children and correlates in Lebanon: a pilot case-control study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurological disorder typically appearing before the age of three. The exact cause of autism remains uncertain, and several factors may be involved in its onset: genetic factors and possible environmental factors. The aim of this study was to assess the correlates of autism in the Lebanese population. METHODS: We investigated the association of autism with several factors in 86 autism cases from specialized schools for children with developmental disabilities and 172 control children from regular public schools in the same regions. Several risk factors for autism were investigated after comparison with a cohort control on parental age, sex, maternal unhappy feeling during pregnancy, consanguineous marriage, and province of residence. The Chi-square test was used to compare nominal variables, and Fisher exact test was used in case expected values within cells were inferior to five. For quantitative variables, we used t-test to compare means between two groups, after checking their distribution normality. For multivariate analysis, we used a forward stepwise likelihood ratio logistic regression. RESULTS: We observed male predominance (79.1%) among autistic infants. There was a significant association between autism and older parents age (OR=1.27), male sex (OR=3.38), unhappy maternal feeling during pregnancy (OR=5.77), living close to industry (OR=6.58), previous childhood infection (OR=8.85), but none concerning maternal age, paternal age and consanguinity. CONCLUSIONS: In this pilot epidemiological study of autism in Lebanon, we found several prenatal and perinatal risk factors for autism that could be modified.

Geometric indices of hip bone strength in obese, overweight, and normal-weight adolescent girls.

The aim of this study was to compare hip bone strength indices in obese, overweight, and normal-weight adolescent girls using hip structure analysis (HSA). This study included 64 postmenarcheal adolescent girls (14 obese, 21 overweight, and 29 normal weight). The 3 groups (obese, overweight, and normal weight) were matched for maturity (years since menarche). Body composition and bone mineral density (BMD) of whole body, lumbar spine, and proximal femur were assessed by dual-energy X-ray absorptiometry (DXA). To evaluate hip bone strength, DXA scans were analyzed at the femoral neck (FN) at its narrow neck (NN) region, the intertrochanteric (IT), and the femoral shaft (FS) by the HSA program. Cross-sectional area and section modulus were measured from hip BMD profiles. Total hip BMD and FN BMD were significantly higher in obese and overweight girls in comparison with normal-weight girls (p < 0.05). However, after adjusting for weight, using a one-way analysis of covariance, there were no significant differences among the 3 groups regarding HSA variables. This study suggests that in obese and overweight adolescent girls, axial strength and bending strength indices of the NN, IT, and FS are adapted to the increased body weight.

Bone mineral content and density in obese, overweight and normal weight adolescent boys.

AIM OF THE STUDY: The aim of this study was to compare bone mineral content (BMC), bone mineral density (BMD) and bone mineral apparent density (BMAD) in obese, overweight and normal weight adolescent boys. METHODS & RESULTS: This study included 23 obese, 19 overweight and 25 normal weight adolescents (aged 14-20 years) boys. The three groups (obese, overweight and normal weight) were matched for age and maturation index. Body composition, BMC and BMD were assessed by dual-energy X-ray absorptiometry (DXA). The expressions whole body (WB) BMC/height and WB BMD/height were used to adjust for WB bone size. BMAD was calculated for the WB. WB BMC, WB BMC/height, total hip (TH) BMD, femoral neck (FN) BMD and ultra distal (UD) radius BMD) were higher in obese and overweight boys in comparison to normal weight boys (p < 0.05). WB BMAD was lower in obese boys in comparison to overweight and normal weight boys (p < 0.05). After adjustment for either weight or lean mass, obese boys displayed lower WB BMC, WB BMC/height and WB BMD values in comparison to overweight and normal weight boys (p < 0.05). CONCLUSION: This study suggests that WB BMC, WB BMC/height and WB BMD do not adapt to the increased body weight in obese adolescent boys.

Influence of the weight status on hip bone strength indices in a group of sedentary adolescent girls.

OBJECTIVE: The aim of this study was to compare femoral shaft and intertrochanteric geometry in overweight and normal weight adolescent girls. METHODS AND RESULTS: This study included 22 overweight (Body mass index (BMI) > 25 kg/m2) adolescent girls (15.4 +/- 2.4 years old) and 20 maturation-matched (15.2 +/- 1.9 years old) controls (BMI < 25 kg/m2). Body composition and BMD were assessed by dual-energy X-ray absorptiometry (DXA). To evaluate bone geometry, DXA scans were analyzed at the femoral shaft and the intertrochanteric region by the Hip Structure Analysis (HSA) program. Cross-sectional area (CSA), an index of axial compression strength, section modulus (Z), an index of bending strength, cross-sectional moment of inertia (CSMI), cortical thickness (CT) and buckling ratio (BR) were measured from bone mass profiles. Lean mass, body weight, fat mass and BMI were higher in overweight girls compared to controls (p < 0.001). CSA, Z, CSMI and CT were higher in overweight girls compared to controls (p < 0.05) at the two regions (femoral shaft and intertrochanteric). After adjustment for maturation index (years since menarche), CSA, Z, CSMI and CT of the intertrochanteric region and CSA of the femoral shaft were higher in overweight girls compared to controls (p < 0.05). After adjustment for either body weight, lean mass or BMI, using a one-way analysis of covariance (ANCOVA), there were no differences between the two groups (overweight and controls) regarding the HSA variables (CSA, CSMI, Z, CT and BR) at the femoral shaft and the intertrochanteric. CONCLUSION: This study suggests that overweight adolescent girls have greater indices of bone axial and bending strength in comparison to controls at the intertrochanteric after adjustment for maturation index.

[Influence of being overweight on bone mineral apparent density in a group of Lebanese adolescent girls]. / Influence de la surcharge pondérale sur la densité minérale osseuse apparente chez des adolescentes Libanaises.

AIM OF THE STUDY: To explore the effects of being overweight on lumbar spine (L2-L4) and femoral neck (FN) bone mineral apparent density (BMAD) in a group of Lebanese adolescent girls. METHODS AND RESULTS: Forty-two Lebanese postmenarchal adolescent girls participated in this study (22 overweight [BMI > 25 kg/m2] adolescent girls [15.4 +/- 2.4 years old] and 20 maturation-matched [15.2 +/- 1.9 years old] controls [BMI < 25 kg/m2]). Body composition and bone mineral density (BMD) were measured with dual-energy X-ray absorptiometry (DXA). Calculation of the BMAD was completed for the FN and for the L2-L4. FN and L2-L4 BMAD values were higher (p < 0.01) in overweight girls compared to normal-weighted girls. In the whole population, fat mass was a positive determinant of L2-L4 and FN BMAD (p < 0.001 and p < 0.05 respectively). CONCLUSION: In this study group, being overweight is associated with higher L2-L4 and femoral neck BMAD values.

Hip bone strength indices in overweight and control adolescent boys.

The influence of being overweight on bone strength in adolescents remains controversial. The aim of this study was to compare hip bone strength indices in overweight and control adolescent boys using hip structure analysis (HSA). This study included 25 overweight adolescent boys [body mass index (BMI) >25 kg/m(2)] and 31 maturation-matched controls (BMI <25 kg/m(2)). Body composition and bone mineral density were assessed by dual-energy X-ray absorptiometry (DXA). To evaluate hip bone strength, DXA scans were analyzed at femoral neck, intertrochanteric, and femoral shaft by the HSA program. Cross-sectional area (CSA), an index of axial compression strength, section modulus (Z), an index of bending strength, cross-sectional moment of inertia (CSMI), cortical thickness (CT), and buckling ratio (BR) were measured from bone mass profiles. Body weight, lean mass, fat mass, and BMI were higher in overweight boys compared to controls (P < 0.001). CSA, CSMI, and Z of the three sites (femoral neck, intertrochanteric, and femoral shaft) were higher in overweight boys compared to controls (P < 0.01). BR was not significantly different between the two groups at the three sites. After adjustment for either body weight, BMI, or fat mass, using a one-way analysis of covariance, there were no differences between the two groups regarding the HSA variables (CSA, Z, CSMI, CT, and BR). After adjusting for lean mass, overweight boys displayed higher values of femoral shaft CSA, CSMI, and Z in comparison to controls (P < 0.05). In conclusion, this study suggests that overweight adolescent boys have greater indices of bone axial and bending strength in comparison to controls at the femoral neck, the intertrochanteric, and the femoral shaft.

Relative importance of lean mass and fat mass on bone mineral density in a group of Lebanese postmenopausal women.

The aim of this study was to determine the relative importance of lean mass and fat mass on bone mineral density (BMD) in a group of Lebanese postmenopausal women. One hundred ten Lebanese postmenopausal women (aged 65-84 yr) participated in this study. Age and years since menopause were recorded. Body weight and height were measured and body mass index (BMI) was calculated. Body composition (lean mass, fat mass, and fat mass percentage) was assessed by dual-energy X-ray absorptiometry (DXA). Bone mineral content (BMC) of the whole body (WB) and BMD of the WB, the lumbar spine (L1-L4), the total hip (TH), the femoral neck (FN), the ultra distal (UD) Radius, and the 1/3 Radius were measured by DXA. The expressions WB BMC/height and WB BMD/height were also used. Weight, BMI, fat mass, and lean mass were positively correlated to WB BMC, WB BMC/height, WB BMD/height, and to WB, L1-L4, TH, FN, UD Radius, and 1/3 Radius BMD. However, using multiple linear regression analyses, fat mass was more strongly correlated to BMC and to BMD values than lean mass after controlling for years since menopause. This study suggests that fat mass is a stronger determinant of BMC and BMD than lean mass in Lebanese postmenopausal women.

Bone mineral content and density in overweight and control adolescent boys.

The aim of this study was to compare bone mineral content (BMC) and areal bone mineral density (aBMD) in overweight and control adolescent boys. This study included 27 overweight (body mass index [BMI] > 25 kg/m²) adolescent (17.1 ± 2.1 yr old) boys and 29 maturation-matched (16.7 ± 2.0 yr old) controls (BMI< 25 kg/m²). Bone mineral area (BMA), BMC, and aBMD were assessed by dual-energy X-ray absorptiometry (DXA) at the whole body (WB), lumbar spine (L2-L4), total hip (TH), femoral neck (FN), and left forearm (ultra distal [UD], mid Radius, 1/3 Radius, and total Radius). Body composition (lean mass, fat mass, and fat mass percentage) was assessed also by DXA. The expressions WB BMC/height, WB aBMD/height, and WB BMAD were used to adjust for WB bone size. WB BMC, WB BMC/height, WB BMA, L2-L4 aBMD, TH aBMD, FN aBMD, and UD aBMD were higher in overweight boys compared with controls (p < 0.05). However, WB BMAD was lower in overweight boys compared with controls (p < 0.05). After adjustment for weight, lean mass, or BMI, using a one-way analysis of covariance, there were no differences between the 2 groups (overweight and controls) regarding bone characteristics (BMC, BMA, aBMD, BMC/height, aBMD/height, and BMAD of the WB and aBMD of the lumbar spine; the TH; the FN; and the forearm). In conclusion, this study shows that after adjusting for weight, lean mass, or BMI, there are no differences between overweight and control adolescent boys regarding aBMD values.

Birth weight a negative determinant of whole body bone mineral apparent density in a group of adolescent boys.

The aim of this study was to explore the relation between birth weight and bone mass in a group of adolescent boys. This study included 44 adolescent (aged 14-20yr) boys. Anthropometric characteristics (height and weight) were measured and birth weights were obtained from the obstetric records. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Bone mineral content (BMC) and bone mineral density (BMD) of the whole body (WB) and the lumbar spine (L2-L4) were also assessed by DXA. Calculations of the bone mineral apparent density (BMAD) were completed for the WB and at the lumbar spine (L2-L4). The expressions WB BMC/height and WB BMD/height were calculated to adjust for WB bone size. Birth weight was positively correlated to body weight (r=0.37; p<0.05), body mass index (r=0.38; p<0.01), body fat percentage (r=0.44; p<0.01), and negatively associated with WB BMAD (r=-0.46; p<0.01). In conclusion, this study suggests that birth weight is a positive determinant of body weight, body mass index, and body fat percent but a negative determinant of WB BMAD in adolescent boys.