bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple CO2 Generating System Incorporated with CDC Light Trap for Sampling Mosquito Vectors
Authors: Madang Sutasinee , Saingamsook Jassada , Saeung Atiporn , Somboon Pradya
Published: July 2022

Traps for capturing mosquitoes and other blood-feeding arthropods are often baited with carbon dioxide (CO2) as an attractant. Dry ice is popularly used as a CO2 source due to its high efficiency and ease of use. However, dry ice can be difficult to obtain in many rural and remote areas. The objective of this study was to develop a simple and inexpensive method that could continuously generate CO2 overnight (about 10 h) while being used with CDC light traps for sampling adult mosquitoes. In principle, CO2 was produced from the reaction between hydrochloric acid (HCl) (12% w/w) and limestone powder (mainly composed of calcium carbonate, CaCO3). In laboratory experiments, an average of 256 mL of CO2 was produced from 1 g of limestone. For continuous production of CO2, an intravenous drip infusion set, as commonly used in hospitals, was modified for dripping the acid solution (1 L in a normal saline bag) onto limestone powder (800 g in a 1.5 L bottle) at a flow rate of 30 drops/min (about 1.6 mL/min). With this procedure, an average of 55 mL of CO2 per min was obtained (approximately equivalent to the CO2 exhaled by two chickens). The performance of this CO2 generating system incorporated with CDC light traps for sampling mosquitoes was evaluated in three rural villages of Sanpatong District, Chiang Mai Province, Thailand. Three trap sets were used, i.e., Set I, light trap alone; Set II, light trap with dry ice (1 kg); and Set III, light trap with limestone and acid. In each village, mosquitoes were collected at three fixed sites, each with one of the three trap sets. They were rotated daily for three rounds (9 nights per village and 27 nights in total). A total of 1620 mosquitoes (97.7% being females) consisting of Aedes, Anopheles, Armigeres, Coquilletidia, Culex and Mansonia were captured across three different sampling sets from all villages. The predominant species collected were Culex vishnui (n = 760, 46.91%), Cx. bitaeniorhynchus (n = 504, 31.11%) and Cx. tritaeniorhynchus (n = 157, 9.69%). Light traps alone (Set I) collected very low numbers of mosquitoes (n = 12) and species (6 spp.), whereas light traps with dry ice (Set II) collected the highest numbers of mosquitoes (n = 1341) and species (14 spp.). Although the light trap with limestone and acid (Set III) collected fewer mosquitoes (n = 267) and species (9 spp.) than the trap set with dry ice (Set II), it collected all common vector species in the study areas as collected by Set II. The presence of an acid solution had no bias in the collection of mosquitoes with different physiological ages as determined by the parous rate. The present study demonstrated that this CO2 generating system is reliable, simple and inexpensive, and could be an alternative to dry ice. The system can be modified to increase the amount of CO2 generated for higher efficacy of mosquito collection. This CO2 production method can be applied to collect other blood-sucking arthropods as well.
The Influence of Non-Optimal Rearing Conditions and Substrates on the Performance of the Black Soldier Fly (Hermetia illucens)
Authors: Ribeiro Nuno , Costa Rui , Ameixa Olga M. C. C.
Published: July 2022

Among the insect species reared as alternative protein sources, Hermetia illucens (black soldier Fly, BSF) has shown a huge potential mostly due to its high protein content, its bioconversion rates, and versatility in using different feeding substrates. Insect rearing may use continuous or batch feeding regimes and, among the used substrates, supermarket feedstock waste has gained recent interest under a circular economy perspective, but several uncertainties remain regarding the heterogeneity and the potential effects of the quantity and quality of these substrates on BSF larvae (BSFL) development. In this experimental work, five replicates of a hundred BSFL were fed in a continuous feeding regime, using seven different isolated vegetables as substrates (wheat bran, pumpkin, apple, grape pomace, red onion, red cabbage, and spinach), at three different temperatures (20, 25, and 30 °C) and two substrate moisture conditions (natural and 70% substrate moisture), until 50% of the larvae achieved the prepupal stage. BSFL performance and bioconversion parameters were evaluated. Our results show that some substrates should be avoided when rearing Hermetia illucens on feedstocks. Among these, apple feed led to poorer and slower development performances with more than 100 days of larval stage, while grape pomace and spinach showed higher mortality rates, which may be due to some anti-nutritional compounds. Larvae fed on pumpkin, red cabbage, and red onion presented good bioconversion results with higher values of efficiency of conversion of digested feed between 14.4 and 25. This work delivers relevant results for black soldier fly reared on a continuous feeding system using vegetable feedstock substrates and their potential trade-offs.
Mitogenomics of Chinch Bugs from China and Implications for Its Coevolutionary Relationship with Grasses
Authors: Wang Shujing , Zhu Runqi , Xue Huaijun , Li Yanfei , Bu Wenjun
Published: July 2022

Blissidae (the Chinch bug) is a group with high species richness in Lygaeoidea, but there are only a few descriptions of mitochondrial genomes available. We obtained mitogenomes from 10 species of eight genera from Blissidae through second-generation sequencing technology. The length of the mitochondrial genome (excluding the control region) is between 14643 and 14385 bp; the content of AT is between 74.1% and 77.9%. The sequence of the evolution rate of protein coding genes was as follows: ND5 > ATP8 > ND6 > ND2 > ND4 > ND4L > ND1 > ATP6 > ND3 > COIII > COII > CYTB > COI. The mitogenomic structure of Blissidae is highly conservative. Gene rearrangement is only found in Pirkimeru japonicus (PiGXBS1), which is formed as the duplication of tRNA-H. The intergenic spacer between ND4 and tRNA-H, which form an obvious stem-and-loop structure, was found in all samples in this study. The phylogenetic trees generated by BI and ML indicated that Blissidae can be divided into three major clades: Clade A (only included Macropes); Clade B ((Pirkimerus + Bochrus) + Iphicrates); and Clade C ((Ischnodemus + Capodemus) + (Cavelerius + Dimorphopterus)). The divergence within the Blissidae began at about 56 Ma. At the genus level, the divergence was concentrated at 30–51 Ma, slightly later than the diversification of Poaceae. The consistency of divergence time between Blissidae and Poaceae might hint at the coevolutionary relationship between them, but further molecular and biological evidence is still needed to prove it.
Assessing the Diversity and Systematics of Brachyopini Hoverflies (Diptera: Syrphidae) in the Iberian Peninsula, Including the Descriptions of Two New Species
Authors: Ricarte Antonio , Nedeljković Zorica , Aguado-Aranda Pablo , Marcos-García Mª Ángeles
Published: July 2022

Five genera of Brachyopini, Chrysogaster Meigen, 1800, Melanogaster Rondani, 1857, Lejogaster Rondani, 1857, Orthonevra Macquart, 1829 and Riponnensia Maibach et al. 1994a are here revised from the Iberian region. Two new species, Melanogaster baetica Ricarte and Nedeljković, sp. n. and Orthonevra arcana Ricarte and Nedeljković sp. n., are described from Spain, and a third species, Chrysogaster coerulea Strobl in Czerny and Strobl, 1909 stat. n., is reinstated as valid and redescribed. A lectotype is designated for Orthonevra plumbago (Loew, 1840). The holotype of Orthonevra incisa (Loew, 1843) and the lectotype of O. plumbago are described in detail and illustrated. Melanogaster baetica sp. n. is similar to Melanogaster parumplicata (Loew, 1840) in male genitalia morphology, while O. arcana sp. n. is similar to O. incisa in the entirely-pollinose sternum I and the conspicuous incision on the posterior margin of tergum V in female. The first Iberian record of Chrysogaster rondanii Maibach and Goeldlin de Tiefenau, 1995 is provided, whilst Melanogaster aerosa is removed from the Iberian checklist of Syrphidae. Identification keys are presented to the five Brachyopini genera and 18 species now reported from the Iberian Peninsula (Chrysogaster, 6 spp.; Lejogaster, 2 spp.; Melanogaster, 3 spp.; Orthonevra, 5 spp.; Riponnensia, 2 spp.). COI (Cytochrome c oxidase subunit I) barcodes of the two new species plus C. coerulea, Chrysogaster solstitialis (Fallén, 1817), Orthonevra nobilis (Fallén, 1817) and Orthonevra frontalis (Loew, 1843) were successfully obtained from Spanish specimens. A COI-based tree was produced to locate these taxa in a wider systematic framework within the tribe.
Characteristics and Treatment Outcomes in Advanced-Stage Non-Small Cell Lung Cancer Patients with a KRAS G12C Mutation: A Real-World Study
Authors: Illini Oliver , Fabikan Hannah , Hochmair Maximilian Johannes , Weinlinger Christoph , Krenbek Dagmar , Brcic Luka , Setinek Ulrike , Terbuch Angelika , Absenger Gudrun , Konjić Selma , Valipour Arschang
Published: July 2022

About 15% of patients with non-small cell lung cancer (NSCLC) harbor the Kirsten rat sarcoma homolog G12C mutation (KRASG12C). Selective KRASG12C inhibitors offer new treatment opportunities, but little is known about the prevalence, characteristics, and outcomes of standard-of-care treatment (SOC) in this population. We retrospectively assessed the clinicopathological features of patients with KRASG12C-mutated advanced NSCLC and responses to SOC at two high-volume centers in Austria. Out of 2495 NSCLC patients tested, we identified 174 patients with advanced-stage disease carrying a KRASG12C mutation. Most patients were ≥65 years old (55%), heavy smokers (55%), and presented with comorbidities. The most frequent co-alteration was TP53 (18%). PD-L1 expression was high (TPS ≥ 50%) in 31%, very high (TPS ≥ 90%) in 11%, and negative in 31% of patients. A total of 138 patients (79%) received oncologic systemic treatment. The most common first-line therapy (1 L) was anti-PD-1/PD-L1 plus platinum-based chemotherapy. Median overall survival measured from 1 L treatment was 15.3 months (95% CI, 8.6–21.9), 9.4 (95% CI, 5.3–13.5) from 2 L treatment, and 8.4 (95% CI, 1.7–15.1) from 3 L treatment. The time-to-next-treatment was 8.4 (95% CI, 5.2–11.6) from 1 L and 6.1 (95% CI, 2.7–9.7) months from 2 L to 3 L. These poor outcomes underscore the need for the implementation of new treatment options and for specific molecular testing.
Rituximab in Mucous Membrane Pemphigoid: A Monocentric Retrospective Study in 10 Patients with Severe/Refractory Disease
Authors: Baffa Maria Efenesia , Corrà Alberto , Maglie Roberto , Mariotti Elena Biancamaria , Montefusco Francesca , Pipitò Carlo , Senatore Stefano , Quintarelli Lavinia , Caproni Marzia , Antiga Emiliano
Published: July 2022

Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen indicated in an increasing number of immune-mediated diseases. While its efficacy in pemphigus vulgaris has been widely investigated, only a few data about its possible role in pemphigoid diseases have been reported in the literature. Accordingly, herein we evaluated a case series of patients with mucous membrane pemphigoid (MMP) treated with RTX. We included patients with a history of severe/refractory MMP who received at least one cycle of intravenous RTX between May 2018 and December 2021 and had 6 months of follow-up time. Disease control (DC) was our early endpoint, while complete remission (CR) and partial remission (PR) were late endpoints. CR off-therapy, relapses, and adverse events were evaluated as well. Our population included 10 MMP patients. Eight out of ten patients (80%) achieved DC in a mean of 8 weeks, while two patients with ocular MMP were non-responders. Among the eight patients who achieved DC, two reached CR off therapy, two CR on minimal therapy, and two achieved PR on minimal therapy. In our case series, the addition of RTX to conventional therapies was demonstrated to be safe and effective in reaching rapid disease control in the majority of refractory MMP patients.
Advanced Glycation End Product (AGE) and Soluble Receptor of AGE (sRAGE) Levels in Relation to Periodontitis Severity and as Putative 3-Year Outcome Predictors in Patients Undergoing Coronary Artery Bypass Grafting (CABG)
Authors: Reichert Stefan , Hofmann Britt , Kohnert Michael , Santos Alexander Navarrete , Friebe Lisa , Grollmitz Julia , Schaller Hans-Günter , Schulz Susanne
Published: July 2022

Tissue concentrations of advanced glycation end product (AGE) and peripheral soluble receptor of AGE (sRAGE) levels may be associated with periodontitis severity. Both parameters and periodontitis might serve as outcome predictors for patients undergoing coronary artery bypass grafting (CABG). This study aimed to investigate possible associations between periodontitis and AGE/sRAGE. Ultimately, we wanted to examine whether AGE, sRAGE, and severe periodontitis are associated with the incidence of new cardiovascular events within 3 years of follow-up after CABG. Ninety-five patients with coronary vascular disease (CVD) (age 69 years, 88.3% males) needing CABG surgery were included. Periodontal diagnosis was made according to the guidelines of the “Centers for Disease Control and Prevention (CDC)” (2007) and staged according to the new classification of periodontal diseases (2018). AGE tissue concentrations were assessed as skin autofluorescence (sAF). sRAGE levels were determined by using a commercially available enzyme-linked immunoabsorbance assay (ELISA) kit. Univariate and multivariate baseline and survival analyses were carried out with Mann–Whitney U test, Chi² test, Kaplan–Meier curves with Log-Rank test, and logistic and Cox regression. sAF was identified as an independent risk indicator for severe periodontitis with respect to the cofactors age, gender, plaque index, and diabetes (adjusted odds ratio [OR] = 2.9, p = 0.028). The degree of subgingival inflammation assessed as a percentage of sites with bleeding on probing (BOP) was inversely correlated with sRAGE concentration (r = −0.189, p = 0.034). Both sAF (Hazard Ratio [HR] = 2.4, p = 0.004) and sRAGE (HR = 1.9, p = 0.031) increased the crude risk for new adverse events after CABG. The occurrence of severe periodontitis trends towards a higher risk for new cardiovascular events (HR = 1.8, p = 0.115). Applying multivariate Cox regression, only peripheral arterial disease (adjusted HR = 2.7, p = 0.006) and history of myocardial infarction (adjusted HR = 2.8, p = 0.010) proved to be independent risk factors for cardiovascular outcome. We conclude that sAF may represent a new, independent risk indicator for severe periodontitis. In contrast, sAF, sRAGE, and severe periodontitis were not independent prognostic factors for postoperative outcome in patients undergoing CABG.
Forearm Fracture Nonunion with and without Bone Loss: An Overview of Adult and Child Populations
Authors: Dimartino Sara , Pavone Vito , Carnazza Michela , Cuffaro Enrica Rosalia , Sergi Francesco , Testa Gianluca
Published: July 2022

Nonunion occurs in 2–10% of all forearm fractures due to different mechanical and biological factors, patient characteristics, and surgeon-dependent causes. It is a condition that causes functional and psychosocial disability for the patient because it is a unique anatomical segment in which all the bones and structures involved embody a complex functional unit; therefore, it is a challenge for the orthopedic surgeon. The ultimate goal of the care of these patients is the restoration of function and limitations related to impairment and disability. The aim of this review is to provide an extended description of nonunion forearm fractures, related risk factors, diagnosis, classification systems, and the available evidence for different types of treatment as a tool to better manage this pathology.
Personalized Medicine and Machine Learning: A Roadmap for the Future
Authors: Sebastiani Marco , Vacchi Caterina , Manfredi Andreina , Cassone Giulia
Published: July 2022

In the last ten years, many advances have been made in the treatment and diagnosis of immune-mediated diseases [...]
Platelet Count in Patients with SARS-CoV-2 Infection: A Prognostic Factor in COVID-19
Authors: Boccatonda Andrea , D’Ardes Damiano , Rossi Ilaria , Grignaschi Alice , Lanotte Antonella , Cipollone Francesco , Guagnano Maria Teresa , Giostra Fabrizio
Published: July 2022

COVID-19 patients may manifest thrombocytopenia and some of these patients succumb to infection due to coagulopathy. The aim of our study was to examine platelet count values in patients infected with SARS-CoV-2, comparing them to a control group consisting of non-COVID-19 patients. Moreover, we evaluated the correlation between the platelet value and the respiratory alteration parameters and the outcome (hospitalization and mortality) in COVID-19 patients. The mean platelet values (×109/L) differed between patients with positive or negative SARS-CoV-2 swabs (242.1 ± 92.1 in SARS-CoV-2 negative vs. 215.2 ± 82.8 in COVID-19 patients, p < 0.001). In COVID-19 patients, the platelet count correlated with the A-aO2 gradient (p = 0.001, rho = −0.149), with its increase over the expected (p = 0.013; rho = −0.115), with the PaO2 values (p = 0.036; rho = 0.093), with the PCO2 values (p = 0.003; rho = 0.134) and with the pH values (p = 0.016; rho = −0.108). In COVID-19 negative patients, the platelet values correlated only with the A-aO2 gradient: (p = 0.028; rho = −0.101). Patients discharged from emergency department had a mean platelet value of 234.3 ± 68.7, those hospitalized in ordinary wards had a mean value of 204.3 ± 82.5 and in patients admitted to sub-intensive/intensive care, the mean value was 201.7 ± 75.1. In COVID-19 patients, the survivors had an average platelet value at entry to the emergency department of 220.1 ± 81.4, while that of those who died was 206.4 ± 87.7. Our data confirm that SARS-CoV-2 infection may induce thrombocytopenia, and that the reduction in platelet counts could be correlated with the main blood gas parameters and with clinical outcome; as a consequence, platelet count could be an important prognostic factor to evaluate and stratify COVID-19 patients.
Post-Laryngectomy Voice Prosthesis Changes by Speech-Language Pathologists: Preliminary Results
Authors: Hans Stéphane , Vialatte de Pemille Grégoire , Baudouin Robin , Julien-Laferriere Aude , Couineau Florent , Crevier-Buchman Lise , Circiu Marta P. , Lechien Jérôme R.
Published: July 2022

Background: In the present study, we assess the feasibility and success outcomes of voice prosthesis (VP) changes when performed by a speech-language pathologist (SLP). Methods: Patients treated with total laryngectomy (TL) from January 2020 to December 2020 were prospectively recruited from our medical center. Patients benefited from tracheoesophageal puncture. The VP changes were performed by the senior SLP and the following data were collected for each VP change: date of placement; change or removal; VP type and size; reason for change or removal; and use of a washer for periprosthetic leakage. A patient-reported outcome questionnaire including six items was proposed to patients at each VP change. Items were assessed with a 10-point Likert-scale. Results: Fifty-two VP changes were performed by the senior SLP during the study period. The mean duration of the SLP consultation, including patient history, examination and VP change procedure, was 20 min (range: 15–30). The median prosthesis lifetime was 88 days. The main reasons for VP changes were transprosthetic (n = 34; 79%) and periprosthetic (n = 7; 21%) leakages. SLP successfully performed all VP changes. He did not change one VP, but used a periprosthetic silastic to stop the periprosthetic leakages. In two cases, SLP needed the surgeon’s examination to discuss the following indication: implant mucosa inclusion and autologous fat injection. The patient satisfaction was high according to the speed and the quality of care by the SLP. Conclusions: The delegation of VP change from the otolaryngologist–head and neck surgeon to the speech-language pathologist (SLP) may be achieved without significant complications. The delegation of VP change procedure to SLP may be interesting in some rural regions with otolaryngologist shortages.
Clostridioides difficile Infection: A Never-Ending Challenge
Authors: Petrosillo Nicola
Published: July 2022

The most common worldwide cause of antibiotic-associated diarrhea/colitis is the toxin-producing bacterium Clostridioides difficile [...]
Cervical Paraspinal Chordoma: A Literature Review with a Novel Case Report
Authors: Jabbar Redwan , Jankowski Jakub , Pawełczyk Agnieszka , Szmyd Bartosz , Solek Julia , Pierzak Olaf , Wojdyn Maciej , Radek Maciej
Published: July 2022

Chordomas are rare malignant neoplasms, accounting for 1–4% of all primary bone tumors. Most spinal chordomas occur in the sacrococcygeal region and the base of the skull; however, 6% of chordomas are observed in the cervical spine. In these cases, the lesion is mainly located in the midline. These tumors slowly grow before becoming symptomatic and encase the surrounding vascular and nerve structures. Patients with advanced chordoma have a poor prognosis due to local recurrence with infiltration and destruction of adjacent bone and tissues. Systemic chemotherapy options have not been fully effective in these tumors, especially for recurrent chordomas. Thus, new combinations of currently available targeted molecular and biological therapies with radiotherapy have been proposed as potential treatment modalities. Here, the present paper describes the case of a 41-year-old male with a C2–C4 chordoma located paravertebrally, who underwent surgical resection with a debulking procedure for a cervical chordoma. Computed tomography angiography revealed a paraspinal mass with bone remodeling and the MRI showed a paravertebral mass penetrating to the spinal canal with a widening of the intervertebral C2–C3 foramen. Initially, the tumor was diagnosed as schwannoma based on its localization and imaging features; however, the histopathology specimen confirmed the diagnosis of chordoma. This case study highlights the effectivity of radical surgical resection as a mainstay treatment for chordomas, discusses neuroimaging, diagnosis, and the use of currently available targeted therapies and forthcoming treatment strategies, as alternative treatment options for chordoma.
Association between Wait Time for Transthoracic Echocardiography and 28-Day Mortality in Patients with Septic Shock: A Cohort Study
Authors: Zheng Jiezhao , Yang Qilin , Kong Tianyu , Chen Xiaohua , Wang Rundong , Huo Jiaxian , Huang Weichao , Wen Deliang , Xiong Xuming , Zhang Zhenhui
Published: July 2022

Background: the optimal timing of Transthoracic echocardiography (TTE) performance for patients with septic shock remains unexplored. Methods: a retrospective cohort study included patients with septic shock in the MIMIC-Ⅲ database. Risk-adjusted restricted cubic splines modeled the 28-day mortality according to time elapsed from ICU admission to receive TTE. The cut point when a smooth curve inflected was selected to define early and delayed group. We applied propensity score matching (PSM) to ensure our findings were reliable. Causal mediation analysis was used to assess the intermediate effect of fluid balance within 72 h after ICU admission. Results: 3264 participants were enrolled and the risk of 28-day mortality increased until the wait time was around 10 h (Early group) and then was relatively flat afterwards (Delayed group). A beneficial effect of early TTE in terms of the 28-day mortality was observed (HRs 0.73–0.78, all p < 0.05) in the PSM. The indirect effect brought by the fluid balance on day 2 and 3 was significant (both p = 0.006). Conclusion: early TTE performance might be associated with lower risk-adjusted 28-day mortality in patients with septic shock. Better fluid balance may have mediated this effect. A wait time within 10 h after ICU may represent a threshold defining progressively increasing risk.
Mitochondrial Respiration in Peripheral Blood Mononuclear Cells Negatively Correlates with Disease Severity in Pulmonary Arterial Hypertension
Authors: Sommer Natascha , Theine Finn Fabian , Pak Oleg , Tello Khodr , Richter Manuel , Gall Henning , Wilhelm Jochen , Savai Rajkumar , Weissmann Norbert , Seeger Werner , Ghofrani Hossein A. , Hecker Matthias
Published: July 2022

Mitochondrial and immune cell dysfunction contributes to the development of pulmonary arterial hypertension (PAH). We thus aimed to investigate mitochondrial respiration and mitochondrial gene expression patterns in the peripheral blood mononuclear cells (PBMC) of patients with idiopathic and hereditary PAH and their correlation to disease parameters. Mitochondrial respiration determined using high-resolution respirometry was not significantly different in PBMC when comparing an outpatient cohort of PAH patients with healthy controls. However, when directly comparing mitochondrial respiration to the hemodynamic parameters of an inpatient PAH cohort, mitochondrial respiration negatively correlated with pulmonary vascular resistance (PVR) and positively correlated with the cardiac index (CI). Furthermore, microarray analysis shows upregulation of mitochondrial erythroid-specific 5-aminolevulinate synthase 2 (ALAS2), as well as the regulation of genes involved in iron and heme metabolism, in the PBMC of patients with PAH, with ALAS2 upregulation in PAH patients being confirmed on the protein level. Multiple regression analysis with age and gender as confounders showed that both PVR and hemoglobin content negatively correlated with maximal respiration. Therefore, we conclude that mitochondrial function in the PBMC of PAH patients is affected by disease severity. However, further studies to investigate cell-type-specific alterations and functional consequences are necessary.
Comparison of Hyperspectral Imaging and Microvascular Doppler for Perfusion Monitoring of Free Flaps in an In Vivo Rodent Model
Authors: Becker Philipp , Blatt Sebastian , Pabst Andreas , Heimes Diana , Al-Nawas Bilal , Kämmerer Peer W. , Thiem Daniel G. E.
Published: July 2022

To reduce microvascular free flap failure (MFF), monitoring is crucial for the early detection of malperfusion and allows timely salvage. Therefore, the aim of this study was to evaluate hyperspectral imaging (HSI) in comparison to micro-Doppler sonography (MDS) to monitor MFF perfusion in an in vivo rodent model. Bilateral groin flaps were raised on 20 Sprague–Dawley rats. The femoral artery was transected on the trial side and re-anastomosed. Flaps and anastomoses were assessed before, during, and after the period of ischemia every ten minutes for overall 60 min using HSI and MDS. The contralateral sides’ flaps served as controls. Tissue-oxygenation saturation (StO2), near-infrared perfusion index (NPI), hemoglobin (THI), and water distribution (TWI) were assessed by HSI, while blood flow was assessed by MDS. HSI correlates with the MDS signal in the case of sufficient and completely interrupted perfusion. HSI was able to validly and reproducibly detect tissue perfusion status using StO2 and NPI. After 40 min, flap perfusion decreased due to the general aggravation of hemodynamic circulatory situation, which resulted in a significant drop of StO2 (p < 0.005) and NPI (p < 0.005), whereas the Doppler signal remained unchanged. In accordance, HSI might be suitable to detect MFF general complications in an early stage and further decrease MFF failure rates, whereas MDS may only be used for direct complications at the anastomose site.
Assessment of Antibiotic Pharmacokinetics, Molecular Biomarkers and Clinical Status in Critically Ill Adults Diagnosed with Community-Acquired Pneumonia and Receiving Intravenous Piperacillin/Tazobactam and Hydrocortisone over the First Five Days of Intensive Care: An Observational Study (STROBE Compliant)
Authors: Vincze István , Czermann Rita , Nagy Zsuzsanna , Kovács Mária , Neely Michael , Farkas Róbert , Kocsis Ibolya , Karvaly Gellért Balázs , Kopitkó Csaba
Published: July 2022

Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties of these drugs may lead to therapeutic failure. The impact of systemic inflammation, as well as of hydrocortisone on the altered pharmacokinetics of piperacillin is largely unknown. The protocol of a clinical study aimed at the characterization of the pharmacokinetics of piperacillin and tazobactam and its association with the concentrations of inflammatory markers and adrenal steroids during CAP therapy will be investigated in up to 40 critically ill patients. The serum concentrations of piperacillin and tazobactam, cortisol, cortisone, corticosterone and 11-deoxycortisol and interleukin-6 levels, as well as routine clinical chemistry and hematology parameters will be monitored from the beginning of treatment for up to five days. Nonparametric population pharmacokinetic modeling and Monte-Carlo simulations will be performed to make estimates of the pharmacokinetics of piperacillin and tazobactam and the probability of pharmacokinetic-pharmacodynamic target attainment. The observed individual characteristics and changes will be correlated with clinical and laboratory findings. The protocol of the observational study will be designed following the STROBE guideline.
Chronic Lung Allograft Dysfunction Is Associated with Increased Levels of Cell-Free Mitochondrial DNA in Bronchoalveolar Lavage Fluid of Lung Transplant Recipients
Authors: Schneck Emmanuel , Askevold Ingolf , Rath Ramona , Hecker Andreas , Reichert Martin , Guth Stefan , Koch Christian , Sander Michael , Seeger Werner , Mayer Konstantin , Padberg Winfried , Sommer Natascha , Kuhnert Stefan , Hecker Matthias
Published: July 2022

Chronic Lung Allograft Dysfunction (CLAD) is a life-threatening complication that limits the long-term survival of lung transplantation patients. Early diagnosis remains the basis of efficient management of CLAD, making the need for distinctive biomarkers critical. This explorative study aimed to investigate the predictive power of mitochondrial DNA (mtDNA) derived from bronchoalveolar lavages (BAL) to detect CLAD. The study included 106 lung transplant recipients and analyzed 286 BAL samples for cell count, cell differentiation, and inflammatory and mitochondrial biomarkers, including mtDNA. A receiver operating curve analysis of mtDNA levels was used to assess its ability to detect CLAD. The results revealed a discriminatory pro-inflammatory cytokine profile in the BAL fluid of CLAD patients. The concentration of mtDNA increased in step with each CLAD stage, reaching its highest concentration in stage 4, and correlated significantly with decreasing FEV1. The receiver operating curve analysis of mtDNA in BAL revealed a moderate prediction of CLAD when all stages were grouped together (AUROC 0.75, p-value < 0.0001). This study has found the concentration mtDNA in BAL to be a potential predictor for the early detection of CLAD and the differentiation of different CLAD stages, independent of the underlying pathology.
Effect of the Crohn’s Disease Exclusion Diet (CDED) on the Fecal Calprotectin Level in Children with Active Crohn’s Disease
Authors: Matuszczyk Małgorzata , Meglicka Monika , Wiernicka Anna , Jarzębicka Dorota , Osiecki Marcin , Kotkowicz-Szczur Marta , Kierkuś Jarosław
Published: July 2022

(1) Background: The CDED + PEN (partial enteral nutrition) is a promising method of nutritional treatment in active Crohn’s disease (CD). An increase in fecal calprotectin (FCP) level—a marker of mucosal inflammation—happens to be the first evidence of Crohn’s disease exacerbation that appears ahead of clinical symptoms and usually co-exists with them. In this study, we present our own experience with using the CDED + PEN in the treatment of children with CD and an increased FCP level. (2) Methods: In total, 48 children (male/female: 27/21) aged 4–17 years (median value = 13.43; IQR = 4.00) were treated with CDED + PEN between June 2019 and July 2021. The main inclusion criteria for the study was active CD defined as an FCP level ≥ 250.00 µg/g. Patients with severe clinical manifestation of CD (PCDAI >40.00), as well as ones who started any new concomitant CD treatment later than at least 4 weeks before the start of dietary intervention, were excluded from the analysis. The PCDAI and fecal calprotectin level were assessed at weeks 0 and 12. The primary endpoint was ITT normalization of FCP level, i.e., a result < 250.00 µg/g at week 12. The Wilcoxon Matched Pairs Test was used for statistical analysis. (3) Results: The normalization of the FCP level was obtained in 17 children (35.42%) and an FCP level decrease of at least 50% occurred in 26 patients (54.17%). The reduction in fecal calprotectin level between week 0 and week 12 was statistically significant with a median value of 1045.00 µg/g; IQR = 1188.00, and 363.00 µg/g; IQR = 665.00, respectively (p < 0.05). Among 29 patients who were not in clinical remission at baseline, 16 (55.17%) achieved clinical remission (PCDAI < 10.00) at week 12 and 20 (68.97%) obtained a clinical response defined as at least a 12.50 point drop in PCDAI or remission. In this group, the reduction in PCDAI between baseline and week 12 was statistically significant (median value = 20.00 points; IQR = 7.50 and 5.00 points; IQR = 5.00, respectively (p < 0.05)). All patients with a normal FCP level at week 12 were in clinical remission and 16 (94.13%) of them had a normal CRP (C-reactive protein) value. In 10 children (20.83%) the full course of 12 weeks with CDED + PEN was not completed or the concomitant therapy had been started before week 12 due to the lack of efficacy/intolerance of nutritional treatment. (4) Conclusions: The 12-week course of treatment with the CDED + PEN has a beneficial effect on the fecal calprotectin level in children with active CD. The dietary intervention led to a significant decrease in the FCP level in the studied group and to the normalization of this parameter in every third patient.
Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
Authors: Piona Claudia , Mozzillo Enza , Tosco Antonella , Volpi Sonia , Rosanio Francesco Maria , Cimbalo Chiara , Franzese Adriana , Raia Valeria , Zusi Chiara , Emiliani Federica , Boselli Maria Linda , Trombetta Maddalena , Bonadonna Riccardo Crocina , Cipolli Marco , Maffeis Claudio
Published: July 2022

Background: To date, no consistent data are available on the possible impact of CFTR modulators on glucose metabolism. The aim of this study was to test the hypothesis that treatment with CFTR modulators is associated with an improvement in the key direct determinants of glucose regulation in children and young adults affected by Cystic Fibrosis (CF). Methods: In this study, 21 CF patients aged 10–25 underwent oral glucose tolerance test (OGTT) before and after 12–18 months of treatment with Lumacaftor/Ivacaftor or Elexacaftor-Ivacaftor-Tezacaftor. β-cell function (i.e., first and second phase of insulin secretion measured as derivative and proportional control, respectively) and insulin clearance were estimated by OGTT mathematical modelling. Insulin sensitivity was estimated by the Oral Glucose Sensitivity Index (OGIS). The dynamic interplay between β-cell function, insulin clearance and insulin sensitivity was analysed by vector plots of glucose-stimulated insulin bioavailability vs. insulin sensitivity. Results: No changes in glucose tolerance occurred after either treatment, whereas a significant improvement in pulmonary function and chronic bacterial infection was observed. Beta cell function and insulin clearance did not change in both treatment groups. Insulin sensitivity worsened in the Lumacaftor/Ivacaftor group. The analysis of vector plots confirmed that glucose regulation was stable in both groups. Conclusions: Treatment of CF patients with CFTR modulators does not significantly ameliorate glucose homeostasis and/or any of its direct determinants.
Far and Near Contrast Sensitivity and Quality of Vision with Six Presbyopia Correcting Intraocular Lenses
Authors: Gil Miguel Á. , Varón Consuelo , Cardona Genis , Buil José A.
Published: July 2022

The objective of this prospective, randomized, double-masked study was to compare the contrast sensitivity and quality of vision of patients bilaterally implanted with the following six different presbyopia correcting intraocular lenses (IOLs): SV25T0 (n = 19), ATLISA 809M (n = 18), ATLISA TRI 839MP (n = 19), ZKB00 (n = 20), ZLB00 (n = 20) and Symfony ZXR00 (n = 20). For comparison purposes, 36 patients were implanted with a monofocal lens (ZA9003). Contrast sensitivity was assessed binocularly at distance under photopic, mesopic and mesopic plus glare conditions, and at near under photopic conditions. Quality of vision was explored in terms of photic phenomena and spectacle independence. Overall, the monofocal lens offered better contrast sensitivity, under all illumination conditions, and less occurrence and intensity of photic phenomena. Amongst the multifocal IOL (MIOL) designs, the extended depth of focus Symfony ZXR00 provided better contrast sensitivity than the other MIOLs, particularly at intermediate and high spatial frequencies. Up to 40% and 50% of patients implanted with MIOLs reported glare and halos, respectively. The SV25T0 resulted in less occurrence and intensity of halos. The evaluation of photic phenomena and contrast sensitivity under different illumination conditions may reflect real-life, visually challenging situations, and thus provide insightful information to assist ophthalmic surgeons when selecting the best intraocular lens for their patients.
Greater Muscular Strength Is Associated with a Lower Risk of Pulmonary Dysfunction in Individuals with Non-Alcoholic Fatty Liver Disease
Authors: Cho Jinkyung , Johnson Bruce D. , Watt Kymberly D. , Kim Chul-Ho
Published: July 2022

This study investigated the combined effect of handgrip strength (HGS) and non-alcoholic fatty liver disease (NAFLD) on pulmonary function using the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 to 2018. For the present study, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), the FEV1/FVC ratio, handgrip strength (HGS) and the hepatic steatosis index (HSI) to estimate NAFLD were obtained from nationwide cross-sectional surveys. For HGS, subjects were divided into higher HGS (upper 50%) and lower HGS (lower 50%). For NAFLD, subjects were divided into the NAFLD cohort (HSI > 36) and the normal cohort (HSI ≤ 36). Of 1651 subjects (men, n = 601), 25.5% of subjects (n = 421) met the HSI > 36. Based on the normal cohort with high HGS, the normal cohort with low HGS showed an increased risk of reduced FVC (OR = 3.062, 95% CI = 2.46–4.83, p < 0.001) and the NAFLD cohort with low HGS showed a further increased risk of reduced FVC (OR = 4.489, 95% CI = 3.43–7.09, p < 0.001). However, the risk of reduced FVC was not significantly increased in NAFLD with high HGS (OR = 1.297, 95% CI = 0.67–2.50, p = 0.436). After adjusted for covariates such as age, sex, smoking, FBG, HDL-C, TG, SBP, DBP, CRP and alcohol consumption, the results remained similar. More importantly, these results were consistent in the obesity-stratified analysis. The current findings of the study suggest that higher muscle strength is associated with a lower risk of reduced pulmonary function in individuals with NAFLD.
Clinical Significance of Antineutrophil Cytoplasmic Antibody Positivity in Patients Infected with SARS-CoV-2
Authors: Lee Lucy Eunju , Jeong Wooyong , Park Yong-Beom , Jeong Su Jin , Lee Sang-Won
Published: July 2022

Objectives: To investigate the rate of antineutrophil cytoplasmic antibody (ANCA) positivity and its clinical significance in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This study included 178 patients infected with SARS-CoV-2 who were enrolled in a cohort at a single centre. Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA levels in stored blood sera were measured using immunoassay kits. Mortality, mechanical ventilator care, and severe infection were assessed as three poor outcomes. The 2022 American College of Rheumatology and the European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for the three subtypes of AAV were applied only to patients who had MPO-ANCA or PR3-ANCA among study subjects. Results: The detection rate of ANCA positivity was 18.5%. MPO-ANCA and PR3-ANCA were found in 22 (12.4%) and 14 (7.9%) patients, respectively. However, neither MPO-ANCA nor PR3-ANCA affected the three poor outcomes. According to the new criteria, 12 (6.7%) and 21 (11.8%) patients were classified as having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), respectively. Conclusions: SARS-CoV-2 infection may increase the rate of ANCA positivity. Although it might not affect poor outcomes, it might contribute to the classification of GPA and MPA despite uncertain clinical significance.
Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Buchrits Shira , Itzhaki Oranit , Avni Tomer , Raanani Pia , Gafter-Gvili Anat
Published: July 2022

Background: The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. Materials and methods: All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I2 > 40%), in which we used a random effects model. Results: A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55–0.95) with a number needed to treat of 20 (95% CI 11–100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01–1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88–1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76–1.57; 8 trials). Conclusions: IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.
Visual Outcomes of Small-Incision Lenticule Extraction (SMILE) in Thin Corneas
Authors: Eskina Erika , Klokova Olga , Damashauskas Roman , Davtyan Karine , Pajic Bojan , Movsesian Marina
Published: July 2022

We aimed to find out whether thin (≤500 μm) or normal (>500 μm, control) corneal thickness would impact efficacy and safety outcomes of small-incision lenticule extraction (SMILE). We retrospectively analyzed medical records of adult patients who had undergone SMILE. A total of 57 eyes were included in the “thin corneas” group and 180 eyes in the “control” group. At one month after surgery, rates of patients with uncorrected distance visual activity (UDVA) ≥ 0.8 were significantly higher in patients from the control group compared to the “thin corneas” group (87 vs. 71%, respectively p < 0.01), though rates were comparable at 3 months (87 vs. 76%, respectively, p > 0.05). SMILE had comparable safety in patients with thin and normal corneas. Procedure result predictability was comparable between groups. Regression analysis demonstrated that cap thickness impacted posterior corneal biomechanics, and the volume of removed tissue had a higher influence in patients with thin corneas. Moreover, an increase in cap thickness was associated with better final BCVA. Further study is needed for the evaluation of the impact of thin corneas on SMILE outcomes and planning. Our study also indicates that patients with thin corneas might require a different approach to nomogram calculation.
Main Barriers to the Introduction of a Home Haemodialysis Programme in Poland: A Review of the Challenges for Implementation and Criteria for a Successful Programme
Authors: Kendzia Dana , Lima Federica , Zawierucha Jacek , Busink Ellen , Apel Christian , Malyszko Jacek Stanislaw , Zebrowski Pawel , Malyszko Jolanta
Published: July 2022

Introduction: Home dialysis in Poland is restricted to the peritoneal dialysis (PD) modality, with the majority of dialysis patients treated using in-centre haemodialysis (ICHD). Home haemodialysis (HHD) is an additional home therapy to PD and provides an attractive alternative to ICHD that combines dialysis with social distancing; eliminates transportation needs; and offers clinical, economic, and quality of life benefits. However, HHD is not currently provided in Poland. This review was performed to provide an overview of the main barriers to the introduction of a HHD programme in Poland. Main findings: The main high-level barrier to introducing HHD in Poland is the absence of specific health legislation required for clinician prescribing of HHD. Other barriers to overcome include clear definition of reimbursement, patient training and education (including infrastructure and experienced personnel), organisation of logistics, and management of complications. Partnering with a large care network for HHD represents an alternative option to payers for the provision of a new HHD service. This may reduce some of the barriers which need to be overcome when compared with the creation of a new HHD service and its supporting network due to the pre-existing infrastructure, processes, and staff of a large care network. Conclusions: Provision of HHD is not solely about the provision of home treatment, but also the organisation and definition of a range of support services that are required to deliver the service. HHD should be viewed as an additional, complementary option to existing dialysis modalities which enables choice of modality best suited to a patient’s needs.