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Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, molecular typing using Randomly Amplified Polymorphic DNA (RAPD-PCR) was conducted on 16 original isolates of Metarhizium acridum obtained from locusts ( Schistocerca piceifrons ssp. piceifrons .) in Mexico (MX). The analysis included reference strains of the genus Metarhizium sourced from various geographical regions. The isolates were identified by phenotypic (macro and micromorphology) and genotypic methods (RAPD-PCR and Amplified Fragment Length Polymorphisms (AFLP), through a multidimensional analysis of principal coordinates (PCoA) and a minimum spanning network (MST). Subsequently, Sequences-Characterized Amplified Region (SCAR) markers were developed for the molecular detection of M. acridum , these markers were chosen from polymorphic patterns obtained with 14 primers via RAPD-PCR. Phenotypic and genotypic characterization identified the MX isolates as M. acridum . Of all the polymorphic patterns obtained, only OPA04 and OPA05 were chosen, which presented species-specific bands for M. acridum , and further utilized to create SCAR markers through cloning and sequencing of the specific bands. The specificity of these two markers was confirmed via Southern hybridization. The SCAR markers (Ma-160 OPA-05 and Ma-151 OPA-04 ) exhibit remarkable sensitivity, detecting down to less than 0.1 ng, as well as high specificity, as evidenced by their inability to cross-amplify or generate amplification with DNAs from other strains of Metarhizium (as Metarhizium anisopliae ) or different genera of entomopathogenic fungi ( Cordyceps fumosorosea and Akanthomyces lecanii ). These SCAR markers yield readily detectable results, showcasing high reproducibility. They serve as a valuable tool, especially in field applications.

Background: The decision to pursue lobectomy versus total thyroidectomy is highly individualized. The rate of thyroid hormone replacement therapy after lobectomy varies considerably (15%-48%) and studies are limited by short-term follow-up. We sought to assess long-term thyroid hormone replacement therapy-requirement for lobectomy., Methods: Patients undergoing lobectomy from January 2005 to July 2010 at an academic institution were reviewed. Demographic, laboratory, pathology, and thyroid hormone replacement therapy use were compared., Results: In total, 235 patients were included. The rate of thyroid hormone replacement therapy after lobectomy was 46.8% (110/235). The majority were female (84.7%), with a mean age of 52 ± 1 years, 97% with benign pathology, and the median duration of follow-up was 7.2 years. Among the 110 thyroid hormone replacement therapy, the mean postoperative thyroid stimulating hormone level 9.08 ± 0.96m IU/L and the time to thyroid hormone replacement therapy-initiation was 621 days; 24% started therapy ≥2 years after surgery. There was no difference in age, sex, or malignancy. Hashimoto thyroiditis was diagnosed in 21.8% patients who underwent thyroid hormone replacement therapy versus 8.0% of those without thyroid hormone replacement therapy (odds ratio 3.2; 95% confidence interval, 1.43-6.79; P < .001). On multivariate analysis, only Hashimoto thyroiditis was independently associated with thyroid hormone replacement therapy use (odds ratio 2.88; 95% confidence interval, 1.3-6.6; P = .012)., Conclusion: With long-term follow-up, nearly 50% of patients who underwent lobectomy for benign disease required thyroid hormone replacement therapy and nearly one-quarter of these patients not starting until ≥2 years after surgery. Therefore, patients who undergo thyroid lobectomy should be counseled appropriately and thyroid function followed for a minimum of 2 years., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Infectious keratitis and sclerokeratitis caused by filamentous fungi prevail in agricultural regions with tropical and subtropical climates and are related mostly to mild abrasive corneal trauma especially after vegetable matter related injury. Biotechnological advances have introduced biological control agents in agriculture such as fungal-based biocontrol agents that use Beauveria and Metarhizium species as bioinsecticides. Keratitis and sclerokeratitis are the most frequent pathologies associated to Beauveria and Metarhizium infection that are the main entomopathogenic fungi used in biological control, although other clinical cases such as sinus, skin lesions, and disseminated infections have been reported. Search of publications was carried out using the databases: Scopus, Pubmed, ScienceDirect, MedLine Scielo. A total of 30 articles were retrieved from 1984 - 2021. From these, 17 keratitis and one sclerokeratitis clinical cases were related to Beauveria infection, while Metarhizium was linked to 13 keratitis cases and two sclerokeratitis clinical cases. Female sex predominated in both Metarhizium and Beauveria clinical cases, there was no significant difference in sclerokeratitis / keratitis by sex. Contact lenses use was a factor reported in 66.6% cases of infection with Metarhizium and 22.2% with Beauveria. The review of clinical cases of keratitis and sclerokeratitis related to Beauveria and Metarhizium suggests the need to consider entomopathogenic fungi in ocular pathologies and the risk that imply the misuse of contact lenses and agricultural/gardening activities., Competing Interests: Declaration of competing interest No potential conflict of interest has been reported by the authors. All authors have reviewed and approved the manuscript, and it has not been previously published nor being considered for publication elsewhere., (Copyright © 2022 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe., Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries., Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease., Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale., Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis., Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017., Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis., Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68])., Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Aims: Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion., Methods: We retrospectively reviewed the medical records of 101 patients who underwent TTC fusion at the same institution between 2011 and 2019. Risk ratios (RRs) associated with age, sex, diabetes, cardiovascular disease, smoking, preoperative ankle deformity, and the use of bone graft during surgery were related to the postoperative complications. We determined from these data which pre- and perioperative factors significantly affected the outcome., Results: Out of the 101 patients included in the study, 29 (28.7%) had nonunion, five (4.9%) required below-knee amputation (BKA), 40 (39.6%) returned to the operating theatre, 16 (15.8%) had hardware failure, and 22 (21.8%) had a postoperative infection. Patients with a preoperative diagnosis of Charcot arthropathy and non-traumatic OA had significantly higher nonunion rates of 44.4% (12 patients) and 39.1% (18 patients) (p = 0.016) and infection rates of 29.6% (eight patients) and 37% (17 patients) compared to patients with traumatic arthritis, respectively (p = 0.002). There was a significantly increased rate of nonunion in diabetic patients (RR 2.22; p = 0.010). Patients with chronic kidney disease were 2.37-times more likely to have a nonunion (p = 0.006). Patients aged over 60 years had more than a three-fold increase in the rate of postoperative infection (RR 3.60; p = 0.006). The use of bone graft appeared to be significantly protective against postoperative infection (p = 0.019)., Conclusion: We were able to confirm, in the largest series of TTC ankle fusions currently in the literature, that there remains a high rate of complications following this procedure. We found that patients with a Charcot or non-traumatic arthropathy had an increased risk of nonunion and postoperative infection compared to individuals with traumatic arthritis. Those with diabetes, chronic kidney disease, or aged over 60 years had an increased risk of nonunion. These findings help to confirm those of previous studies. Additionally, our study adds to the literature by showing that autologous bone graft may help in decreasing infection rates. These data can be useful to surgeons and patients when considering, discussing and planning TTC fusion. It helps surgeons further understand which patients are at a higher risk for postoperative complications when undergoing TTC fusion. Cite this article: Bone Joint J . 2020;102-B(3):345-351.

Introduction: Tibiocalcaneal (TC) arthrodesis is commonly performed in patients with severe hindfoot disease. These include severe Charcot deformities, ankle malformations, chronic osteomyelitis (COM), and avascular necrosis (AVN). The talar vascular becomes disrupted to the point that the bone can no longer be salvaged. The procedure involves performing a talectomy and fusing the tibia to the calcaneus. This helps in preserving the remaining hindfoot anatomy, while allowing the patient to regain function and mobility. Our study highlights certain risk factors that influence the rate of postoperative complication after tibiocalcaneal surgery., Materials and Methods: We retrospectively reviewed the charts of 18 patients from a single institution who underwent tibiocalcaneal between the years of 2011 and 2019. Preoperative diagnoses, comorbidities, and post-operative outcomes were noted among all patients. Then, the rates of non-union, below-knee amputations, revision surgeries, postoperative infections, and hardware failure were recorded. These data were then analyzed to determine which preoperative and perioperative factors affected postoperative outcomes for patients after tibiocalcaneal arthrodesis surgery., Results: Nonunion was the most commonly reported complication in this series. Eight of the eighteen patients were documented to have nonunion including three patients with stable pseudarthrosis. Diabetic patients had a slightly higher incidence of nonunion (4 of 7 patients) compared to those without diabetes (4 of 11 patients). Of the nine patients diagnosed with Charcot arthropathy, five had nonunion. Three of the five individuals with a BMI ranging from 25 to 30, and four of the six individuals with a BMI of greater than 30 had a nonunion. Infection was a post-operative complication for four of the eighteen patients. Two of the four patients had multiple comorbidities in addition to chronic infections in the joint which were recurrent after surgery., Conclusion: In conclusion, TC arthrodesis provides a viable option for high-risk patients with complicated ankle pathology who have not had successful outcomes from previous treatment. It is not without complications considering the comorbidities the patients present with before requiring this procedure. Further studies are necessary to validate the trends of outcomes and comorbidities of patients with TC arthrodesis., Competing Interests: Conflict of interestNo benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (© Indian Orthopaedics Association 2020.)

Isaria fumosorosea (formerly Paecilomyces fumosoroseus) is an entomopathogenic fungus that has been proposed as a low risk environmental alternative to the use of chemical insecticides to control agricultural pests and disease vectors. Although there are some mycoinsecticides already being marketed in many countries, not all their biosafety protocols have been published. The acute dermal toxicity test in an animal model is one in a series of biosafety protocols that must be developed, in order to provide information on health hazards, while taking into consideration the periods that the workers are in direct contact with the microbial agent when applied for the control of pests. For this test, we used I. fumosorosea monospore culture EH-506/3, isolated in Mexico from the Bemisia tabaci whitefly, applying a dose of 2 g/kg of animal body weight, on the shaved skin of 16 New Zealand rabbits, with an exposure time of 24 h. Clinical observations were conducted to evaluate the presence of erythema, edema and other alterations in the skin, as well as the behavior and health of the animals, for a period of 14 days. None of the rabbits showed clinical signs of any disease and their body weight corresponded to the expected weight for a healthy rabbit. The test showed no inflammatory reactions in the skin, supporting the safety of a single dose of this fungus in dermal exposure. Therefore, these data support the safety of I. fumosorosea EH-506/3 when applied to the skin.

Background: Lactate is one of the most useful biomarkers to screen patients with shock; therefore, the aim of this study was to establish the levels of lactate regarding the pulse pressure in that sort of patients., Methods: Observational, retrospective, cross-sectional and descriptive study of patients over 18 years diagnosed with shock from an emergency room of a tertiary care hospital. Lactate levels and pulse pressure were used as biomarkers. We used descriptive statistics, Student's t test and Pearson correlation coefficient., Results: We obtained 46 patients. The average age was 39.52 (SD 15.22), media initial lactate level was 5.88 mmol/L (SD 3.89) and media final lactate level 3.31 mmol/L (SD = 3.12); initial pulse pressure was 19.78 mmHg (SD 7.45) and final pulse pressure 31.52 mmHg (SD 31.52). The relation of secondary diagnosis did show predominance in chest trauma with 13 patients. There was a statistical significance in initial lactate and final lactate of r = 0.83 (p = 0.00), and initial pulse pressure and final pulse pressure: r = 0.57 (p = 0.001). There was not a significant correlation between final lactate and final pulse pressure (r: -0.184, p = 0.222)., Conclusion: Even when several studies emphasize the clinical significance of biomarkers in the diagnosis and management of patients with hypovolemic shock, it is necessary to do more studies in order to find the efficacy of the non-invasive screening in this type of pathology.

Seven cyclotetradepsipeptides, namely beauverolides C (1), F (2), I (3), Ja (4), L (5), M (6), and N (7), were isolated from the entomopathogenic fungus Isaria fumosorosea. The beauverolides were evaluated as potential calmodulin (CaM) inhibitors using the newly designed CaM biosensor hCaM M124C-AF350; these peptides displayed high affinity to the protein with dissociation constants (Kd) ranging from 0.078 μM to 3.44 μM. Beauverolide Ja, the only one containing a tryptophan residue in its structure, showed the highest affinity. The docking study predicted that beauverolides could bind to CaM in the same site of interaction as chlorpromazine, a well-known calmodulin ligand.

High sensitivity and specificity of molecular biology techniques have proven usefulness for the detection, identification and typing of different pathogens. The ITS (Internal Transcribed Spacer) regions of the ribosomal DNA are highly conserved non-coding regions, and have been widely used in different studies including the determination of the genetic diversity of human fungal pathogens. This article wants to contribute to the understanding of the intra- and interspecific genetic diversity of isolates of the Histoplasma capsulatum and Sporothrix schenckii species complexes by an analysis of the available sequences of the ITS regions from different sequence databases. ITS1-5.8S-ITS2 sequences of each fungus, either deposited in GenBank, or from our research groups (registered in the Fungi Barcode of Life Database), were analyzed using the maximum likelihood (ML) method. ML analysis of the ITS sequences discriminated isolates from distant geographic origins and particular wild hosts, depending on the fungal species analyzed. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012)., (Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

Metarhizium anisopliae var. acridum, monospore culture EH-502/8 (CNRCB MaPL40), isolated in Mexico from Schistocerca piceifrons ssp. piceifrons (Orthoptera: Acrididae) was tested for acute oral intragastric pathogenicity and toxicity in CD-1 mice. Animals were inoculated with one dose (10(8) conidia/animal) of viable (72 mice), non-viable (24 mice) conidia and compared to 18 control mice. Clinical observations were done daily; mycological and histological tests were performed during necropsies after the inoculation. No mice showed clinical symptoms of illness or died during the study. The fungus was able to persist in some organs until day 3, but did not cause any damage to the host. The gross pathology observed was splenomegaly in mice inoculated with viable and non-viable conidia. Non-germinated conidia, observed in several organs, suggest hematogenous spread, but without any histopathological tissue reaction. Results support the non-pathogenic and non-toxic status of this fungal strain when administered in a single intragastric dose to mice.

Paecilomyces fumosoroseus, monospore culture EH-506/3, isolated in Mexico from Bemisia tabaci whitefly was tested for acute oral intragastric pathogenicity and toxicity in CD-1 mice. Animals were inoculated by gavage with only one dose (10(8) conidia/animal) of viable (72 mice), heat-killed (24 mice) fungus and compared to 18 control mice. Clinical observations were done daily; mycological and histological tests were performed during necropsies at days 3, 10, 17, and 21 after the inoculation. No mice were clinically ill or died. At the end of the study, their mean weight corresponded to healthy adults. Positive fungal cultures of feces were obtained only 24 h after inoculation. Positive cultures were found in 15 out of 360 organs (liver, spleen, kidney, brain, lung) in 12 of 72 mice inoculated with viable conidia. Gross pathology exhibited splenomegaly and liver paleness in mice inoculated with viable and heat-killed fungus. Non-germinated conidia were observed in studied organs, without any pathological tissue reaction, suggesting no mycological or histopathological evidence of fungal multiplication. The fungus was able to persist, but did not cause permanent damage to the host. This study supports the non-pathogenic/toxic status of P. fumosoroseus EH-506/3 when administered intragastrically in mice.

Sporothrix schenckii isolates of fixed and lymphocutaneous clinical forms from Mexico (MX), Guatemala (GT), and Colombia (CO) as well as environmental isolates from MX were studied by analyzing their phenotypic characteristics (conidial length, thermotolerance by percent growth inhibition [GI] at 35 and 37 degrees C, median lethal dose [LD(50)]) and genotypic characteristics (by random amplified polymorphic DNA [RAPD] analysis-PCR). A significant difference (P < 0.01) in the mean conidial length of S. schenckii clinical isolates from CO ( = 4.03 +/- 1.04 microm) compared with those of clinical isolates from MX ( = 2.06 +/- 0.53 microm) and GT ( = 2.68 +/- 0.83 microm) was observed. The lowest thermotolerance, as determined by measurement of percent GI, was exhibited by isolates from CO at 35 degrees C ( = 50.1% +/- 15.9%) and 37 degrees C ( = 72.7% +/- 10.9%). In general, the highest virulence, as determined by measurement of the LD(50) for mice, was observed for the MX environmental isolates. RAPD analysis-PCR with 10-mer primers OPBG-01, OPBG-14, and OPBG-19 generated 52 reproducible bands. The 44 Sporothrix isolates fell into four major groups by hierarchical cluster analysis. The first group (group I), formed by 25 (of 27) isolates from MX, had two subgroups: subgroup Ia with 10 environmental isolates and subgroup Ib with 14 clinical isolates. The second group (group II) had two subgroups: subgroup IIa, formed by isolates from CO, and subgroup IIb, formed by isolates from GT. Groups III and IV each had only one clinical isolate from MX. A principal-component analysis of the same data yielded three distinct groups, depending on the geographical origins of the isolates, including the isolates in groups III and IV from MX, which were grouped with the isolates from MX by principal-component analysis. This study revealed that isolates from CO had low thermotolerances at 35 and 37 degrees C and could be associated with superficial skin lesions in patients with fixed clinical forms of sporotrichosis, the most frequent form of the disease in CO. Distinct patterns dependent on geographical origins were also revealed by RAPD analysis-PCR, but these had no relation to the clinical form of the disease.