Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for C. difficile Infections Across Academic and Private Clinical Settings.

PURPOSE: Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. METHODS: Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. RESULTS: CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3 mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. CONCLUSIONS: In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.

Artificial Intelligence Tool for Assessment of Indeterminate Pulmonary Nodules Detected with CT.

Background Limited data are available regarding whether computer-aided diagnosis (CAD) improves assessment of malignancy risk in indeterminate pulmonary nodules (IPNs). Purpose To evaluate the effect of an artificial intelligence-based CAD tool on clinician IPN diagnostic performance and agreement for both malignancy risk categories and management recommendations. Materials and Methods This was a retrospective multireader multicase study performed in June and July 2020 on chest CT studies of IPNs. Readers used only CT imaging data and provided an estimate of malignancy risk and a management recommendation for each case without and with CAD. The effect of CAD on average reader diagnostic performance was assessed using the Obuchowski-Rockette and Dorfman-Berbaum-Metz method to calculate estimates of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Multirater Fleiss κ statistics were used to measure interobserver agreement for malignancy risk and management recommendations. Results A total of 300 chest CT scans of IPNs with maximal diameters of 5-30 mm (50.0% malignant) were reviewed by 12 readers (six radiologists, six pulmonologists) (patient median age, 65 years; IQR, 59-71 years; 164 [55%] men). Readers' average AUC improved from 0.82 to 0.89 with CAD (P < .001). At malignancy risk thresholds of 5% and 65%, use of CAD improved average sensitivity from 94.1% to 97.9% (P = .01) and from 52.6% to 63.1% (P < .001), respectively. Average reader specificity improved from 37.4% to 42.3% (P = .03) and from 87.3% to 89.9% (P = .05), respectively. Reader interobserver agreement improved with CAD for both the less than 5% (Fleiss κ, 0.50 vs 0.71; P < .001) and more than 65% (Fleiss κ, 0.54 vs 0.71; P < .001) malignancy risk categories. Overall reader interobserver agreement for management recommendation categories (no action, CT surveillance, diagnostic procedure) also improved with CAD (Fleiss κ, 0.44 vs 0.52; P = .001). Conclusion Use of computer-aided diagnosis improved estimation of indeterminate pulmonary nodule malignancy risk on chest CT scans and improved interobserver agreement for both risk stratification and management recommendations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Yanagawa in this issue.

The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis.

Mindfulness-based programs (MBPs) are increasingly utilized to improve mental health. Interest in the putative effects of MBPs on cognitive function is also growing. This is the first meta-analysis of objective cognitive outcomes across multiple domains from randomized MBP studies of adults. Seven databases were systematically searched to January 2020. Fifty-six unique studies (n = 2,931) were included, of which 45 (n = 2,238) were synthesized using robust variance estimation meta-analysis. Meta-regression and subgroup analyses evaluated moderators. Pooling data across cognitive domains, the summary effect size for all studies favored MBPs over comparators and was small in magnitude (g = 0.15; [0.05, 0.24]). Across subgroup analyses of individual cognitive domains/subdomains, MBPs outperformed comparators for executive function (g = 0.15; [0.02, 0.27]) and working memory outcomes (g = 0.23; [0.11, 0.36]) only. Subgroup analyses identified significant effects for studies of non-clinical samples, as well as for adults aged over 60. Across all studies, MBPs outperformed inactive, but not active comparators. Limitations include the primarily unclear within-study risk of bias (only a minority of studies were considered low risk), and that statistical constraints rendered some p-values unreliable. Together, results partially corroborate the hypothesized link between mindfulness practices and cognitive performance. This review was registered with PROSPERO [CRD42018100904].

JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 63 million people worldwide. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients due to their proven efficacy against diseases with excessive cytokine release and their direct antiviral ability against viruses including coronaviruses, respectively. METHODS: A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30th 2020 and included any study type that compared treatment outcomes of humans treated with Janus kinase-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan. RESULTS: Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03-0.39, p< 0.001) and ICU admission (OR, 0.05; 95% CI, 0.01-0.26, p< 0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68-48.54, p< 0.00001) when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04-0.85, p< 0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00-3.59, p=0.05). CONCLUSIONS: Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.

Quantification of bronchoalveolar neutrophil extracellular traps and phagocytosis in murine pneumonia.

The past two decades have witnessed a resurgence in neutrophil research, inspired in part by the discovery of neutrophil extracellular traps (NETs) and their myriad roles in health and disease. Within the lung, dysregulation of neutrophils and NETosis have been linked to an array of diseases including pneumonia, cystic fibrosis, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and severe asthma. However, our understanding of pathologic neutrophil responses in the lung remains incomplete. Two methodologic issues have contributed to this gap: first, an emphasis on studying neutrophils from blood rather than the lung and second, the technical difficulties of interrogating neutrophil responses in mice, which has largely restricted basic murine research to specialized laboratories. To address these limitations, we have developed a suite of techniques for studying neutrophil effector functions specifically in the mouse lung. These include ex vivo assays for phagocytosis and NETosis using bronchoalveolar neutrophils and in situ evaluation of NETosis in a murine model of pneumonia. Throughout, we have prioritized technical ease and robust, quantitative readouts. We hope these assays will help to standardize research on lung neutrophils and improve accessibility to this burgeoning field.

Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia.

INTRODUCTION: Procalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis. METHODS: We conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection. RESULTS: Patients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p<0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dropped substantially, from 72% to 61%. In fact, receiver operating characteristic curve analysis showed that procalcitonin was a better indicator of multiple indices of severity (eg, organ failures and mortality) than of coinfection. Accordingly, patients with severe viral infection had elevated procalcitonin. In murine and cellular models of influenza infection, procalcitonin was also elevated despite bacteriologic sterility and correlated with markers of severity. Interferon signalling did not abrogate procalcitonin synthesis. DISCUSSION: These studies reveal that procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.

Algorithm for Temple Reconstruction With Consideration of Anatomic and Defect Characteristics.

The temple is an intriguing region of the face with unique anatomic features, such as the temporal hairline, concave contour, and close proximity to vital structures like the frontal branch of the facial nerve. However, cancerous skin lesions can plague this sun-exposed region and, when excised, it can result in large and significant defects. Reconstruction in this area is a formidable challenge for surgeons, as it requires comprehensive knowledge of temple morphology and the use of creative techniques in order to minimize disruption of surrounding functional and aesthetic structures. In this study, we describe our experience with temple reconstruction in patients of varying defect size and depth. Based on these defect characteristics, anatomic and aesthetic principles of the temple, we propose a surgical algorithm for temple reconstruction to aid surgeons in achieving optimal results.

Convolutional Neural Networks for Radiologic Images: A Radiologist's Guide.

Deep learning has rapidly advanced in various fields within the past few years and has recently gained particular attention in the radiology community. This article provides an introduction to deep learning technology and presents the stages that are entailed in the design process of deep learning radiology research. In addition, the article details the results of a survey of the application of deep learning-specifically, the application of convolutional neural networks-to radiologic imaging that was focused on the following five major system organs: chest, breast, brain, musculoskeletal system, and abdomen and pelvis. The survey of the studies is followed by a discussion about current challenges and future trends and their potential implications for radiology. This article may be used as a guide for radiologists planning research in the field of radiologic image analysis using convolutional neural networks.

Impact of a lung ultrasound course for rheumatology specialists (IMPACT-2).

OBJECTIVES: Lung ultrasound (LUS) plays an increasing role in diagnosis and monitoring of interstitial lung disease (ILD). Connective tissue disorders (CTD) frequently cause ILD, and often presents symptomatically after irreversible fibrosis has ensued. As point-of-care musculoskeletal ultrasound (US) is commonly utilised by rheumatologists, translating this US expertise towards LUS places the rheumatologist in a position to screen for ILD. However, a standardised curriculum for the rheumatology community is lacking. The aim of this study is to determine the effectiveness of a formalised lung US training course for rheumatologists. METHODS: Four rheumatology fellows and four board-certified rheumatologists participated in a 4-hour training session. Pre-course, post-course and 6-month follow-up surveys evaluated perceptions towards previous US experience, training, clinical utility and attitudes toward lung US. Didactics explained the protocols utilised in ILD evaluation. Evaluation of knowledge in US physiology, lung anatomy, artifact and pathology recognition were done through written exams before, after training, and at 6 months and through a practical exam using live models and simulation. RESULTS: Temporally there was overall improvement in written test scores. Improvement was noted in overall practical skill score following training course (17.4% vs. 92.9%, p<0.001), in written test scores 49.3% vs. 72.5% p<0.001), and pathology identification (26.5% vs. 79.6%, p<0.001). Six-month follow assessments were similar to post-test results revealing similar written scores (70.6%) and practical scores (89.7%). CONCLUSIONS: This formalised lung ultrasound training course was effective in improving skills and knowledge of rheumatology specialists.

Augmented Reality-Assisted Percutaneous Dilatational Tracheostomy in Critically Ill Patients With Chronic Respiratory Disease.

Percutaneous dilatational tracheostomy is a minimally invasive procedure performed for those who require prolonged mechanical ventilation. It is a procedure that is performed routinely at the bedside in the intensive care unit. Complications nonetheless still occur, and as a result, several technique modifications have been employed. At Loma Linda University Medical Center, we have implemented a novel technique using augmented reality during percutaneous dilatational tracheostomy placement in an attempt to minimize such complications. Using Brother's AiRScouter WD-200B head mounted display, the tracheostomy operator is able to focus on the surgical field without having to significantly break line of sight to view the traditional bronchoscopy monitor. Six cases have been treated with this procedure to date with good success and excellent user feedback. We aim to assess augmented reality-assisted percutaneous dilatational tracheostomy and determine its overall efficacy when compared to traditional percutaneous dilatational tracheostomy.

One-Step Triple-Layer Reconstruction of an Exposed Calvarium in a Patient With Radiated Tinea Capitis.

Full-thickness large scalp defects with underlying exposed calvarium pose a significant reconstructive challenge. Traditional reconstructive techniques are usually not an option in patients with irradiated scalp with thin skin and reduced laxity.Dermal substitutes-based reconstruction techniques have been described in recent years. A common approach is the staged methodology, with the initial application of skin substitute followed by a split-thickness skin graft few weeks later; however, this method involves a prolonged period of local wound management prior to skin grafting and is often associated with complications that interfere with wound healing.This report describes a single-stage triple-layer technique for the reconstruction of a large scalp defect with exposed bone in a patient with a history of radiation treatment, using 3 turnover pericranial flaps in conjunction with a Matriderm dermal substitute and split-thickness skin graft. This immediate multilayered reconstruction provides a long-lasting structural and aesthetic outcome, with minimal donor site morbidity and reduced complications.

[DEMOGRAPHIC AND ANATOMIC CHARACTERISTICS AND SURGERY RESULTS IN CHILDREN WHO WERE TREATED IN SOROKA FOR CRANIOSYNOSTOSIS].

BACKGROUND: Craniosynostosis, the premature fusion of one or more of the cranial sutures, can occur as a part of a syndrome or as an isolated deformity. When not treated properly it may have major physical and social implications. STUDY HYPOTHESIS: We assumed that our center's results are similar to those reported in the literature, in terms of gender and anatomic characteristics, and different in terms of the number of syndromic cases. We also assume that only a few patients needed a second surgery and that this medical problem effects quality of life in term of cognitive impairment and aesthetic results. METHODS: A retrospective chart review was conducted of patients who were treated for craniosynostosis in Soroka University Medical Center between the years 1991-2005. RESULTS: A total of 63 patients were treated in Soroka during those years: 30 (47.6%) were females and 33 (50.8%) were males; 27 (42.9%) had coronal synostosis, 20 (31.8%) had sagital synostosis, 10 (15.8%) had metopic synostosis, 5 (7.9%) had lambdoid synostosis. A total of 5 (7.9%) cases were syndromic and the rest were isolated; 6 patients (9.5%) needed a second surgery for correction of the defect; 8 out of 30 patients (26.7%) 6 years or older at the present time suffer from attention deficit disorder. Parents' satisfaction from aesthetic results on a scale of 1-5 was 4.77 with SD of 0.504, while the doctors' score was 3.93 with SD 0.980 (p = 0.01). CONCLUSIONS: Craniosynostosis is a complex surgical problem, however with prompt treatment it may attain high levels of satisfaction among parents and patients. We found high rates 26.7% vs 10% (in the general population) of ADD in children affected by the disease.

Cohort study of patients with advanced cancer: outcomes associated with duration of antibiotic therapy for non-ventilator hospital-acquired pneumonia.

In this single-center observational study of 118 older adults with advanced cancer who developed non-ventilator hospital-acquired pneumonia, prolonged antibiotic durations (8-14 and ≥15 vs ≤7 d) were not associated with reduced adjusted odds of 90-day all-cause readmission or death. These data may inform antimicrobial stewardship efforts in palliative care settings.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Dual function of the O-antigen WaaL ligase of Aggregatibacter actinomycetemcomitans.

Protein glycosylation is critical to the quaternary structure and collagen-binding activity of the extracellular matrix protein adhesin A (EmaA) associated with Aggregatibacter actinomycetemcomitans. The glycosylation of this large, trimeric autotransporter adhesin is postulated to be mediated by WaaL, an enzyme with the canonical function to ligate the O-polysaccharide (O-PS) antigen with a terminal sugar of the lipid A-core oligosaccharide of lipopolysaccharide (LPS). In this study, we have determined that the Escherichia coli waaL ortholog (rflA) does not restore collagen binding of a waaL mutant strain of A. actinomycetemcomitans but does restore O-PS ligase activity following transformation of a plasmid expressing waaL. Therefore, a heterologous E. coli expression system was developed constituted of two independently replicating plasmids expressing either waaL or emaA of A. actinomycetemcomitans to directly demonstrate the necessity of ligase activity for EmaA collagen binding. Proper expression of the protein encoded by each plasmid was characterized, and the individually transformed strains did not promote collagen binding. However, coexpression of the two plasmids resulted in a strain with a significant increase in collagen binding activity and a change in the biochemical properties of the protein. These results provide additional data supporting the novel hypothesis that the WaaL ligase of A. actinomycetemcomitans shares a dual role as a ligase in LPS biosynthesis and is required for collagen binding activity of EmaA.

Nonutility of procalcitonin for diagnosing bacterial pneumonia in patients with severe COVID-19.

Background: Patients hospitalized with COVID-19 are at significant risk for superimposed bacterial pneumonia. However, diagnosing superinfection is challenging due to its clinical resemblance to severe COVID-19. We therefore evaluated whether the immune biomarker, procalcitonin, could facilitate the diagnosis of bacterial superinfection. Methods: We retrospectively identified 185 patients hospitalized with severe COVID-19 who underwent lower respiratory culture; 85 had evidence of bacterial superinfection. Receiver operating characteristic curve and area under the curve (AUC) analyses were performed to assess the utility of procalcitonin for diagnosing superinfection. Results: This approach demonstrated that procalcitonin measured at the time of culture was incapable of distinguishing patients with bacterial infection (AUC, 0.52). The AUC not affected by exposure to antibiotics, treatment with immunomodulatory agents, or timing of procalcitonin measurement. Conclusion: Static measurement of procalcitonin does not aid in the diagnosis of superinfection in severe COVID-19.

The Liver Tumor Segmentation Benchmark (LiTS).

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.

Medical Students' Knowledge of Plastic Surgery as a Reflection of the Public Perception.

Plastic surgery is a broad field that requires a mixed skillset. Therefore, it is important that students be exposed to all its various subspecialties to make informed career decisions and to properly refer patients in different clinical situations. A nationwide survey was conducted of Israeli medical students to investigate their knowledge and perceptions regarding the field of plastic surgery and its subspecialties, and the impact of a clinical rotation in plastic surgery on these factors. A total of 300 subjects responded. Approximately, 61% of the cohort was female and 70% were enrolled in a 6-year program. About one-third stated that their field of interest was surgical rather than medical. Significant variability was noted in the accuracy of responses to questions about different procedures encompassed in the scope of plastic surgery. Although 90% of the students were aware of some common plastic surgery procedures that are also often thought to be well known to the public, only 50% were able to correctly identify lesser-known surgeries performed by plastic surgeons. Knowledge about plastic surgery was unrelated to an interest in the field. We recommend adjusting preclinical instruction and clinical rotations in plastic surgery to better prepare students to select a specialty best suited to their future goals, as well as to improve their ability to refer patients to other specialists as necessary.