bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotype and genotype analysis of patients with severe factor XI deficiency in Shaanxi Province, China
Authors: Yuan Li , Chen Wei , Wang Xiaoqin , Zhang Heng
Published: July 2021

Congenital coagulation factor XI (FXI) deficiency is a rare bleeding disorder with a heterogeneous haemorrhagic phenotype and various hotspot gene mutations associated with race and geography. Studies on FXI deficiency in Shaanxi Province, China, are scarce. In this study, seven patients with severe FXI deficiency and several family members were analysed. The International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was applied to assess bleeding symptoms. FXI activity was determined using a one-stage method, and the FXI antigen was measured by enzyme-linked immunosorbent assay. Targeted capture next-generation sequencing and Sanger sequencing were applied to detect FXI gene mutations. The bleeding phenotype varied, although none of the participants had a history of spontaneous bleeding. One maternal received replacement therapy during the perinatal period, one female patient presented with menorrhagia, one male patient experienced severe postoperative bleeding and others were asymptomatic. Family members with heterozygous mutations were all asymptomatic. The FXI activity of all the patients ranged from less than 1 to 3.1 IU/dl, and a synchronous decrease in the FXI antigen was observed. Two missense mutations (p. Gly350Glu and p. Cys482Trp), one nonsense mutation (p. Gln384∗) and one novel frameshift mutation (p. Ser225Phefs∗16) were detected. The bleeding manifestations and severity of severe FXI deficiency varied and were not related to its activity. Three reported mutations and one novel frameshift mutation were identified, thus extending the mutation spectrum of FXI deficiency.
P-selectin expression assay in a repeatedly serotonin-release assay-negative patient with heparin-induced thrombocytopenia
Authors: Arora Kanika , Rodgers Shannon , Alkhatib Yaser , Onwubiko Ifeoma N. , Padmanabhan Anand , Otrock Zaher K.
Published: July 2021

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate platelets to propagate a hypercoagulable state culminating in life-threatening thrombosis. The serotonin-release assay (SRA) is considered the gold-standard test to diagnose HIT. However, the sensitivity of the SRA was questioned with reported cases of clinical diagnosis of HIT and negative SRA. Herein, we present the utility of platelet factor 4-dependent P-selectin expression assay (PEA) in diagnosing HIT in a patient with thrombocytopenia and recurrent thrombosis who repeatedly tested negative with SRA.
Update on sarcoidosis guidelines
Authors: Millward Kate , Fiddler Christine A. , Thillai Muhunthan
Published: July 2021

Purpose of review

The current review summarizes recent guidance in the diagnosis and management of sarcoidosis. Until recently, the main guidelines were the 1999 International Statement on Sarcoidosis. However, in 2020 two new guidelines were published by the American and British Thoracic Societies. They have a number of key updates and this review aims to summarize these.

Recent findings

The key findings from 2020 revolve around several themes. First, the need for a histological diagnosis should be supported by a multidisciplinary team approach. When a histological biopsy is needed of the lungs, thought is given to the approach taken for this and to whether an endobronchial ultrasound, endoscopic ultrasound or transbronchial biopsy is needed. Second, information regarding supporting tests including blood biomarkers, lung function and imaging. Third, a section specific to cardiac sarcoidosis. Finally, a summary of guidance for treating sarcoidosis including the need to treat fatigue.

The recent guidance suggests that a histological biopsy is only needed in cases of diagnostic uncertainty or in patients with typical long standing features on imaging. The guidelines also provide a clear pathway on the type of lung biopsy needed depending on the extent of mediastinal or parenchymal involvement. Support is given to steroid regimens and indication for second-line immunosuppression.
Detection of early phenotype cardiac sarcoidosis by cardiovascular magnetic resonance
Authors: Levin Benjamin , Baughman Robert P. , Sweiss Nadera J.
Published: July 2021

Purpose of review

Cardiac sarcoidosis has high prevalence in sarcoidosis patients and contributes to significant morbidity and mortality. Early detection of cardiac sarcoidosis is essential to improving patients’ symptoms and cardiovascular outcomes.

Recent findings

Cardiovascular magnetic resonance imaging (CMR) is an excellent diagnostic modality for cardiac sarcoidosis. However, early phenotypes of cardiac sarcoidosis have more mild imaging phenotypes. These mild and sometimes subtle imaging phenotypes of cardiac sarcoidosis have lower diagnostic sensitivity and specificity for cardiac sarcoidosis by CMR when compared with more severe imaging phenotypes of cardiac sarcoidosis. In addition, many sarcoidosis patient cohorts frequently have heterogenous potential alternative etiologies for mild myocardial disease detected by mild late gadolinium enhancement (LGE) findings. In early phenotype cardiac sarcoidosis, analysis of the LGE pattern and location can improve the diagnostic specificity of these mild LGE findings.

The current review focuses on the current strengths and challenges in CMR detection of early phenotypes of cardiac sarcoidosis by the LGE technique.
Sarcoidosis and autoimmunity
Authors: Song Minhyuk , Manansala Michael , Parmar Prashant J. , Ascoli Christian , Rubinstein Israel , Sweiss Nadera J.
Published: July 2021

Purpose of review

Sarcoidosis is a poorly understood multisystem granulomatous disease that frequently involves the lungs but can affect any organ system. In this review, we summarize recent developments in the understanding of the immune dysregulation seen in sarcoidosis and propose a new expanded definition of human autoimmunity in sarcoidosis, and the implications it would have on treating sarcoidosis with targeted immunotherapy regimens in the future.

Recent findings

Sarcoidosis has been linked to infectious organisms like Mycobacterium and Cutibacterium, and certain manifestations of sarcoidosis have been linked to specific HLA alleles, but the overall pathogenesis remains uncertain. Sarcoidosis patients have similar patterns of cellular immune dysregulation seen in other autoimmune diseases like rheumatoid arthritis, and recent large-scale population studies show that sarcoidosis frequently presents with other autoimmune diseases.

Advancements in the understanding of sarcoidosis support its consideration as an autoimmune disease. Sarcoidosis patients carry a higher risk of comorbid autoimmune conditions which offers an excellent opportunity to further understand autoimmunity and explore biologic therapies in sarcoidosis treatment, and furthermore will better targeted immunotherapy regimens for sarcoidosis patients in the future.
Optimization of Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea With Ultrasound Assessment of Tongue Movement
Authors: Korotun Maksim , Quintero Luis , Shikowitz Mark , Mayo Paul , Greenberg Harly
Published: July 2021

Background:

Hypoglossal nerve stimulation (HGNS) is an Food and Drug Administration-approved therapy for obstructive sleep apnea. Initial programming of HGNS is based on the observation of anterior tongue movement, which may not reflect opening at the retroglossal airway. We developed an ultrasonographic technique to assess the base of tongue movement with HGNS to be used to optimize the initial voltage settings.

Study Question:

This study aimed to investigate the use of ultrasound to assess tongue movement with HGNS and related this measure to the apnea hypopnea index (AHI) on subsequent home sleep apnea testing or in-laboratory polysomnography with therapy.

Study Design:

Seventeen subjects (n = 17) implanted with HGNS were enrolled at least 1 month postimplantation. Ultrasonographic measures were then used to optimize HGNS voltage to produce observable base of tongue protrusion without producing discomfort. Responders were defined as a reduction in AHI > 50% and an AHI of <20 events/h.

Results:

There were 17 subjects, 11 men and 6 women, with age = 64.6 ± 9.8 years, body mass index = 27.9 ± 2.7 kg/m2, and pretreatment AHI = 36.5 ± 14.4/h, T-90% = 10.7 ± 14.8%. The mean hyoid bone excursion (HBE) in responders = 1.0 ± 0.13 cm versus 0.82 ± 0.12 cm in nonresponders (P = 0.017). HBE was correlated with AHI during HGNS treatment (coef. −0.54, P = 0.03). Best subsets regression analysis using treatment-based AHI as the dependent variable and age, body mass index, baseline AHI, HBE, and HGNS voltage as independent variables showed that HBE (coef. −44.6, P = 0.044) was the only independent predictor of response. Receiver operator curve analysis showed that HBE > 0.85 cm had a sensitivity of 83.3% and specificity of 80.0% with a positive likelihood ratio of 4.17 to predict responder status.

Conclusion:

We demonstrated that ultrasound assessment of HBE during HGNS programming is a useful tool to optimize therapy.
Managing abnormal liver tests in children with inflammatory bowel disease
Authors: van Rheenen Patrick F.
Published: July 2021

Purpose of review

Liver test abnormalities in children with inflammatory bowel disease (IBD) are usually insidious in onset. By the time that symptoms referable to liver disease have appeared, the liver injury may be well advanced. It is, therefore, important that children with an incidental finding of abnormal liver tests are investigated in an appropriate and timely manner.

Recent findings

The most prevalent cause of liver test elevations in paediatric IBD is immune-related liver disease, including primary sclerosing cholangitis, autoimmune sclerosing cholangitis, and autoimmune hepatitis. Although less common, drugs used in the treatment of IBD can also cause liver injury. The diagnosis of drug-induced liver injury relies largely on excluding other causes of liver injury, such as viral hepatitis, nonalcoholic fatty liver disease, and biliary and vascular complications.

This review highlights an avenue to a step-wise approach for investigating children with IBD and silent liver test elevations. Central to the timing of diagnostic actions is grading the severity of liver test elevations.
Preliminary Evidence for Heterogeneity of Beliefs About Auditory Verbal Hallucinations Intent
Authors: Zanello Adriano , Dugré Jules R.
Published: July 2021

Perceptions of patient's auditory verbal hallucinations (AVHs), commonly termed voices, have important impacts on their everyday lives. Despite research emphasizing the consequences of malevolent voices, preliminary results suggest that beliefs about voices may not be mutually exclusive. As such, we aimed to characterize the heterogeneity of beliefs about AVHs and describe their clinical correlates. We recruited 78 patients referred to a Voices group therapy for refractory and distressing voices. Based on the Revised Beliefs About Voices Questionnaire, clustering analysis yielded four subgroups of patients with distinct pattern of beliefs about AVHs. These subgroups differed significantly in terms of affective disturbances, engagement, and resistance to their voices. Furthermore, no significant changes in beliefs about voices were observed after 6 weeks. Results of the current study suggest that the heterogeneity regarding the beliefs about AVHs should be targeted in treatment to reduce their associated negative outcomes.
Feasibility and Acceptability of a Reiki Intervention With Very Young Children Receiving Palliative Care
Authors: Thrane Susan E. , Grossoehme Daniel H. , Tan Alai , Shaner Valerie , Friebert Sarah
Published: July 2021

Background

Very little research has been reported examining nonpharmacological symptom management strategies for very young, hospitalized children receiving palliative care, and none has involved Reiki—a light touch therapy.

Objectives

The aim of this study was to determine if completing a Reiki intervention with hospitalized 1- to 5-year-old children with chronic, life-limiting conditions receiving palliative care was feasible and acceptable.

Methods

Children ages 1–5 years receiving palliative care who were expected to be hospitalized for at least 3 weeks were recruited for a single-arm, mixed-methods, quasi-experimental pre- and poststudy. Six protocolized Reiki sessions were conducted over 3 weeks. We calculated feasibility by the percentage of families enrolled in the study and acceptability by the percentage of families who completed all measures and five out of six Reiki sessions. Measures were collected at baseline, at the end of the intervention period, and 3 weeks later. At the final follow-up visit, parents were verbally asked questions relating to the acceptability of the intervention in a short structured interview.

Results

We screened 90 families, approached 31 families, and recruited 16 families, whereas 15 families declined. Reasons for not participating included that the child had “a lot going on,” would be discharged soon, and families were overwhelmed. Of those enrolled, most completed all measures at three time points and five out of six Reiki sessions. We completed nearly all scheduled Reiki sessions for families that finished the study. All parents reported that they would continue the Reiki if they could, and almost all said they would participate in the study again; only one parent was unsure.

Discussion

Young children and their parents found Reiki acceptable; these results are comparable to an earlier study of children 7–16 years of age receiving palliative care at home and a study of massage for symptom management for hospitalized children with cancer. These findings add to the literature and support further investigation of Reiki’s efficacy as a nonpharmacological symptom management intervention.
Acceptability of a Gonococcal Vaccine Among Sexually Active Men Who Have Sex With Men
Authors: Abara Winston E. , Kirkcaldy Robert D. , Bernstein Kyle T. , Zlotorzynska Maria , Sanchez Travis
Published: July 2021

Background

Prospects for a gonococcal vaccine have advanced. Vaccine acceptability is crucial to maximizing population-level protection among key groups, such as men who have sex with men (MSM). We assessed the prevalence of gonococcal vaccine acceptability among sexually active MSM in the United States.

Methods

We used data from the American Men's Internet Study conducted from August 2019 to December 2019. We calculated frequencies of sociodemographic characteristics, vaccine acceptability, and preferred location for vaccine receipt. Using log-binomial regression analyses, we calculated unadjusted prevalence rates (PRs) and 95% confidence intervals (CIs) to evaluate factors associated with vaccine acceptability.

Results

Of 4951 MSM, 83.5% were willing to accept a vaccine and 16.5% were unwilling. Preferred vaccination locations were primary care provider's clinics (83.5%) and sexually transmitted disease (STD) clinics (64.6%). Vaccine acceptability was greater among young MSM (15–24 years [PR, 1.09; 95% CI, 1.05–1.12], 25–29 years [PR, 1.13; 95% CI, 1.09–1.17], and 30–39 years [PR, 1.10; 95% CI, 1.05–1.14] compared with MSM ≥40 years), MSM living with HIV (PR, 1.05; 95% CI, 1.02–1.09), and MSM who reported (in the past 12 months) condomless anal sex (PR, 1.09; 95% CI, 1.06–1.12), a bacterial STD test (PR, 1.18; 95% CI, 1.15–1.21), HIV preexposure prophylaxis use (PR, 1.17; 95% CI, 1.14–1.19), a bacterial STD diagnosis (PR, 1.04; 95% CI, 1.02–1.07), or a health care provider visit (PR, 1.11; 95% CI, 1.06–1.16). Men who have sex with men who reported ≤high school education (PR, 0.93; 95% CI, 0.91–0.97) were less willing to accept a vaccine compared with those with >high school education.

Conclusions

Most respondents were willing to accept a gonococcal vaccine. These findings can inform the planning and implementation of a future gonococcal vaccination program that focuses on MSM.
Pediatric Chronic Critical Illness: Validation, Prevalence, and Impact in a Children’s Hospital
Authors: Shappley Rebekah K. H. , Noles Danielle L , Spentzas Thomas
Published: July 2021

OBJECTIVES:

Large populations of chronically critically ill patients test the critical care system’s resource utilization ability. Defining and tracking this group is necessary for census predictions.

DESIGN:

Retrospective cohort analysis.

Settings:

Tertiary academic center in United States.

PATIENTS:

Patients admitted to PICU or neonatal ICU.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Demographics and resource utilization variables were sampled in PICU, intermediate care unit, cardiovascular ICU, and neonatal ICU on 3 random days in 3 consecutive months. The attendings’ perception of pediatric chronic critical illness was contrasted to Shapiro’s definition of chronic critical care criteria. Each unit’s active and maximal capacity census was computed: the occurrence rate of pediatric chronic critical illness was 34%, the prevalence was 44.5%, and the tolerance, or percentage pediatric chronic critical illness patients to all available beds, was 36.8%. The median length of stay for the nonpatients with pediatric critical care illness to patients with pediatric critical care illness was 9 versus 46 days (1/5.1). The attending’s decision was 58 times more concordant with the criteria. Pediatric chronic critical illness bed occupancy was 40.6% in PICU, 97.2% in intermediate care unit, 47.8% in cardiovascular ICU, and 33.9% in neonatal ICU.

CONCLUSIONS:

Pediatric chronic critical illness patients occupied more than one third of the ICU beds and have five times longer stay. This mounting load needs to be uniformly defined, addressed at regional and national levels, and considered in the current pandemic planning.
Transport Medical Control Education for Pediatric Critical Care Fellows: A National Needs Assessment Study
Authors: Good Ryan J. , Zurca Adrian D. , Turner David A. , Bjorklund Ashley R. , Boyer Donald L. , Krennerich Emily C. , Petrillo Toni , Rozenfeld Ranna A. , Sasser William C. , Schuette Jennifer , Tcharmtchi M. Hossein , Watson Christopher M. , Czaja Angela S. ,   Education in Pediatric Intensive Care (EPIC) Investigators
Published: July 2021

OBJECTIVES:

Characterize transport medical control education in Pediatric Critical Care Medicine fellowship.

DESIGN:

Cross-sectional survey study.

SETTING:

Pediatric Critical Care Medicine fellowship programs in the United States.

Subjects:

Pediatric Critical Care Medicine fellowship program directors.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We achieved a 74% (53/72) response rate. A majority of programs (85%) require fellows to serve as transport medical control, usually while carrying out other clinical responsibilities and sometimes without supervision. Fellows at most programs (80%) also accompany the transport team on patient retrievals. Most respondents (72%) reported formalized transport medical control teaching, primarily in a didactic format (76%). Few programs (25%) use a standardized assessment tool. Transport medical control was identified as requiring all six Accreditation Council for Graduate Medical Education competencies, with emphasis on professionalism and interpersonal and communication skills.

CONCLUSIONS:

Transport medical control responsibilities are common for Pediatric Critical Care Medicine fellows, but training is inconsistent, assessment is not standardized, and supervision may be lacking. Fellow performance in transport medical control may help inform assessment in multiple domains of competencies. Further study is needed to identify effective methods for transport medical control education.
Botulinum Toxin Type A Injection in the Treatment of Postparetic Facial Synkinesis
Authors: Tavares Helena , Oliveira Mafalda , Costa Rui , Amorim Hugo
Published: July 2021

This study aimed to review the recent literature about botulinum toxin type A treatment patterns, including muscle targets, doses, duration of effect, adverse effects, and clinical outcomes in patients with postparetic synkinesis. A bibliographic research of studies published in the last 10 yrs was carried out on PubMed database, using the medical subject heading terms: botulinum toxin and synkinesis. English-language cohort studies or randomized controlled trials about botulinum toxin type A treatment on patients with postparetic synkinesis were eligible for inclusion. Ten studies met the inclusion criteria, seven prospective studies, two retrospective studies, and one randomized controlled trial, involving 23–99 patients. The target facial muscles included frontalis, corrugator supercilli, orbicularis oculi, levator labii superioris, zygomaticus major, orbicularis oris, risorius, buccinator, depressor anguli oris, depressor labii inferioris, mentalis, and platysma. The dose of onabotulinumtoxinA administered per injection site ranged between 0.5 and 10 U. Adverse effects were rare and temporary. The mean duration of onabotulinumtoxinA effect ranges from 66 days to 4 mos. There was a statistically significant improvement in posttreatment evaluation, both in objective and subjective assessments. There is scientific evidence of the benefit of botulinum toxin type A treatment for postparetic synkinesis, but there is lack of standardized treatment protocols.
Role of Lower Limb Muscle Strength in Knee Osteoarthritis Progression for Patients With Mild and Moderate Knee Osteoarthritis
Authors: Xu Chunyan , Nie Yong , Tan Chaowei , Zeng Yi , Si HaiBo , Zhou ZongKe , Shen Bin , Song Weiwei , Li Kang
Published: July 2021

Objective

We aimed to elucidate the association of lower limb muscle strength with the volume loss of cartilages/menisci for patients with mild and moderate knee osteoarthritis.

Design

One hundred seventy individuals with mild and moderate knee osteoarthritis were included from the Osteoarthritis Initiative database. Five muscle strength variables were measured from isometric strength test. The measurement of volume on medial and lateral menisci and seven subregional cartilages from knee magnetic resonance scans were used for assessing 2-yr osteoarthritis progression.

Results

Along with the decreased lower limb muscle strength, the volume of patellar cartilage, medial meniscus, and lateral meniscus decreased more than cartilage on tibia and weight-bearing femoral condyle. However, the cartilage volume on the entire medial and lateral femoral condyle increased significantly. The maximum quadricep strength was the most sensitive muscle strength variable, and we found that it was more positively correlated with lateral meniscus volume than with other subregions at baseline and 24-mo follow-up.

Conclusions

This study shows the relationship between lower limb muscle strength and volumes of cartilage and meniscus for patients with mild and moderate knee osteoarthritis. In addition, our study indicates a biomechanical mechanism of quadricep strength and meniscus-related knee dynamic stability in progression of mild-to-moderate knee osteoarthritis.
Impact of HIV status on systemic inflammation during pregnancy
Authors: Vyas Pooja , Mathad Jyoti S. , Leu Cheng-Shiun , Naik Shilpa , Alexander Mallika , Araújo-Pereira Mariana , Kulkarni Vandana , Deshpande Prasad , Yadana Su , Andrade Bruno B. , Bhosale Ramesh , Kumar Pavan , Babu Subash , Gupta Amita , Shivakoti Rupak
Published: July 2021

Objective:

There are limited studies on the association of HIV infection with systemic inflammation during pregnancy.

Design:

A cohort study (N = 220) of pregnant women with HIV (N = 70) (all on antiretroviral therapy) and without HIV (N = 150) were enrolled from an antenatal clinic in Pune, India.

Methods:

The following systemic inflammatory markers were measured in plasma samples using immunoassays: soluble CD163 (sCD163), soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP), interferon-β (IFNβ), interferon-γ (IFNγ), interleukin (IL)-1β, IL-6, IL-13, IL-17A, and tumor necrosis factor α (TNFα). Generalized estimating equation (GEE) and linear regression models were used to assess the association of HIV status with each inflammatory marker during pregnancy and by trimester, respectively.

Results:

Pregnant women with HIV had higher levels of markers for gut barrier dysfunction (I-FABP), monocyte activation (sCD14) and markers of systemic inflammation (IL-6 and TNFα), but surprisingly lower levels of AGP, an acute phase protein, compared with pregnant women without HIV, with some trimester-specific differences.

Conclusion:

Our data show that women with HIV had higher levels of markers of gut barrier dysfunction, monocyte activation and systemic inflammation. These markers, some of which are associated with preterm birth, might help explain the increase in adverse birth outcomes in women with HIV and could suggest targets for potential interventions.
CD4+ cell count and outcomes among HIV-infected compared with uninfected medical ICU survivors in a national cohort
Authors: Akgün Kathleen M. , Krishnan Supriya , Butt Adeel A. , Gibert Cynthia L. , Graber Christopher J. , Huang Laurence , Pisani Margaret A. , Rodriguez-Barradas Maria C. , Hoo Guy W. Soo , Justice Amy C. , Crothers Kristina , Tate Janet P.
Published: July 2021

Background:

People with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count.

Setting:

We studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015.

Methods:

Primary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200–349; 50–199; <50), comorbidity and prior healthcare utilization using proportional hazards models. We also adjusted for severity of illness using discharge VACS Index (VI) 2.0 among VA-based survivors.

Results:

In adjusted models, CD4+ categories <350 cells/μl were associated with increased risk for both outcomes up to 6 months, and risk increased with lower CD4+ categories (e.g. 6-month mortality CD4+ 200–349 hazard ratio [HR] = 1.35 [1.12–1.63]; CD4+ <50 HR = 2.14 [1.72–2.66]); unsuppressed status was not associated with outcomes. After adjusting for VI in models stratified by HIV, VI quintiles were strongly associated with both outcomes at both time points.

Conclusion:

PWH who survive MICU admissions are at increased risk for worse outcomes compared with uninfected, especially those without CD4+ cell recovery. Severity of illness at discharge is the strongest predictor for outcomes regardless of HIV status. Strategies including intensive case management for HIV-specific and general organ dysfunction may improve outcomes for MICU survivors.
Antimicrobial-resistant bacteria in international travelers
Authors: Sridhar Sushmita , Turbett Sarah E. , Harris Jason B. , LaRocque Regina C.
Published: July 2021

Purpose of review

Antimicrobial resistance (AMR) in bacteria poses a major risk to global public health, with many factors contributing to the observed increase in AMR. International travel is one recognized contributor. The purpose of this review is to summarize current knowledge regarding the acquisition, carriage and spread of AMR bacteria by international travelers.

Recent findings

Recent studies have highlighted that travel is an important risk factor for the acquisition of AMR bacteria, with approximately 30% of studied travelers returning with an acquired AMR bacterium. Epidemiological studies have shown there are three major risk factors for acquisition: travel destination, antimicrobial usage and travelers’ diarrhea (TD). Analyses have begun to illustrate the AMR genes that are acquired and spread by travelers, risk factors for acquisition and carriage of AMR bacteria, and local transmission of imported AMR organisms.

International travel is a contributor to the acquisition and dissemination of AMR organisms globally. Efforts to reduce the burden of AMR organisms should include a focus on international travelers. Routine genomic surveillance would further elucidate the role of international travel in the global spread of AMR bacteria.
Continuous versus intermittent infusion of antibiotics in Gram-negative multidrug-resistant infections
Authors: Gatti Milo , Pea Federico
Published: July 2021

Purpose of review

The aim of this review was to perform a critical reappraisal of the real-world evidence supporting administration by prolonged infusion of novel beta-lactams for the management of multidrug-resistant Gram-negative infections.

Recent findings

Real-world evidence support the use of novel beta-lactams by prolonged infusion over intermittent infusion in terms of achieving aggressive pharmacokinetic/pharmacodynamic (PK/PD) target for either maximizing efficacy and clinical outcome or suppressing the emergence of resistance development. Continuous infusion of ceftolozane-tazobactam showed a marked superiority toward both intermittent and extended infusion (EI) in achieving a PK/PD target of 100%fT> 4 X MIC in infections caused by less-susceptible Pseudomonas aeruginosa isolates. No resistance development was found in critically ill or immunocompromised patients treated with EI ceftolozane-tazobactam compared to intermittent infusion. Prolonged infusion of ceftazidime-avibactam was negatively associated with mortality in patients affected by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infections. Different challenging scenarios (patients showing augmented renal clearance of affected by deep-seated infections) could benefit from prolonged infusion to optimize the efficacy of novel agents.

Although available data are still limited, real-world evidence regarding mainly ceftolozane-tazobactam and ceftazidime-avibactam could support the administration of novel beta-lactams by prolonged infusion in some specific scenarios in which achievement of aggressive PK/PD target is quite challenging.
Emerging treatment options for cryptosporidiosis
Authors: Love Melissa S. , Choy Robert K.M.
Published: July 2021

Purpose of review

Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is associated with diarrhea, malnutrition, growth stunting, cognitive deficits, and oral vaccine failure in children living in low-resource settings.

Recent findings

Various drug discovery approaches have generated promising lead candidates. The repurposed antimycobacterial drug clofazimine was tested in Malawian HIV patients with cryptosporidiosis but was ineffective. Target-based screens identified inhibitors of lysyl-tRNA synthetase, phenylalanyl-tRNA synthetase, methionyl-tRNA synthetase, and calcium-dependent protein kinase 1. Phenotypic screens led to discovery of a phosphatidylinositol 4-kinase inhibitor, the piperazine MMV665917, and the benzoxaborole AN7973. The relationship between pharmacokinetic properties and in-vivo efficacy is gradually emerging. A pathway to clinical trials, regulatory approval, and introduction has been proposed but additional work is needed to strengthen the route.

Several lead compounds with potent activity in animal models and a favorable safety profile have been identified. A sustained effort will be required to advance at least one to clinical proof-of-concept studies. The demonstrated risk of resistance indicates multiple candidates should be advanced as potential components of a combination therapy.
Coronavirus disease 2019 in children
Authors: Levy Emily R. , Blumenthal Jennifer , Chiotos Kathleen
Published: July 2021

Purpose of review

Over the course of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that the clinical features, epidemiology, and outcomes of COVID-19 are distinct in children relative to adults. In this review, we will present recent pediatric studies informing our current understanding of COVID-19 in children, and review pediatric considerations surrounding disease transmission, currently available therapies, and vaccination.

Recent findings

Recent studies have shed light on the clinical epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, identifying a high prevalence of asymptomatic and mild infections, with severe COVID-19 infrequently reported. Several adult clinical trials have informed the use of remdesivir, anti-SARS-CoV-2 monoclonal antibodies, dexamethasone, and tocilizumab in the management of COVID-19. Associations between underlying comorbid medical conditions and severe outcomes, as well as transmission dynamics of SARS-CoV-2 in children, are complex and warrant further study. Finally, highly efficacious vaccines are available for adults and adolescents, with pediatric trials ongoing.

Children generally fare well with acute COVID-19 infection, though critical illness is possible. Future research should focus on clarifying the role of children in SARS-CoV-2 transmission and optimal prevention strategies, particularly in the school setting, as well as evaluating pediatric vaccine candidates.
Prevalence of Metabolic Syndrome in Psoriatic Arthritis
Authors: Urruticoechea-Arana Ana , Castañeda Santos , Otón Teresa , Benavent Diego , Loza Estíbaliz , Martín-Martínez María A. , González-Gay Miguel Ángel
Published: July 2021

Objective

To analyze the prevalence of metabolic syndrome (MetS) in patients with psoriatic arthritis (PsA) in a systematic literature review (SLR) and in the Spanish CArdiovascular in RheuMAtology (CARMA) cohort.

Methods

A SLR and a subanalysis of the CARMA cohort were performed. In the SLR, PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov up to March 2019 were searched. Systematic literature reviews, clinical trials, and observational studies that analyzed the prevalence or frequency of MetS in PsA were analyzed. Two reviewers selected the articles, assessed the quality of the studies, and collected data, independently. In addition, data on sociodemographic characteristics and MetS in patients with PsA from the CARMA cohort were collected and analyzed. Comparative descriptive analysis was performed.

Results

The SLR included 18 articles, of moderate to high quality, with PsA patients of both sexes, with mean ages between 42 and 59 years. The rate of MetS varied from 23.5% to 62.9%. The most commonly used classification method was that of the National Cholesterol Education Program. Additionally, 724 PsA patients from the CARMA cohort were analyzed; 327 (45.4%) were women, 157 (21.8%) smokers, with a mean age of 51 years and a mean PsA disease duration of 9 years. Hypertension was the most common abnormal finding (66.8%), followed by hyperglycemia (42.6%) and hypertriglyceridemia (30.6%). Notably, 222 patients (30.6%) had MetS.

Conclusions

The prevalence of MetS in PsA varies, depending on the definition. Whereas 23.5% to 62.9% of PsA patients have MetS, in the CARMA cohort almost a third of patients with PsA have MetS.
Determination of Extra Craniofacial Abnormalities in Patients With Craniofacial Microsomia
Authors: Raposo Barbara Kawano , Ferreira Guilherme Bail , Silva Alfredo Benjamin Duarte e , Ono Maria Cecília Closs , de Souza Josiane , da Silva Freitas Renato
Published: July 2021

Introduction:

Craniofacial microsomia (CFM) is caused by abnormalities in the development of the first and second pharyngeal arches. One-third to half of the patients with CFM also present with extra craniofacial (ECF) malformations. The knowledge of the visceral alteration related to CFM is vital for optimized care and a better prognosis.

Aim:

To describe the incidence of ECF malformations in patients with CFM and to infer if there was a correlation between CFM and ECF malformations.

Materials and Methods:

The authors analyzed medical records of patients diagnosed with CFM from 1996 to 2006. The data collected included age, gender, category of craniofacial alteration, and the type of ECF malformation when present. The sample was inspected to find possible correlations between craniofacial abnormalities and ECF malformations.

Results:

The sample included 102 patients, with a mean age of 7 years and a predominance of males (61.8%). Ear malformations (93.1%) followed by mandible (59.8%) and facial nerve (10.8%) abnormalities were the most common CFM. Among patients with CFM, 37.2% had ECF involvement, mainly in vertebrae (20%), heart (11%), and limbs (9.8%). Multivariate analysis revealed that the presence of ear malformations was related to a higher incidence of nonspecific visceral malformations (P = 0.034) and that mandible malformation was related to an increased incidence of vertebral malformations (P = 0.008).

Conclusion:

A significant percentage of patients with CFM presented associated ECF impairment. Ear and mandible involvement may be predictors of nonspecific visceral malformation and vertebral malformations, respectively.
Changes in Quality of Life After Secondary Closure of Palatal Defects: Prosthetic Obturation Versus Surgical Reconstruction
Authors: Matsumoto Hiroshi , Ota Tomoyuki , Takeda Seiko , Mizukawa Nobuyoshi , Kimata Yoshihiro
Published: July 2021

Background:

The closure of palatal defects after tumor resection or irradiation is performed with either a prosthesis or autogenous tissue; however, there are no clear criteria regarding selection of the method. Thus, this study aimed to investigate the real-world situation and problems of palatal closure using prostheses, and examined patient opinion on how palatal closure using autogenous tissue improved their postoperative quality of life (QOL).

Methods:

In 5 patients whose palatal defects resulted from treatment for head and neck cancer and were closed with a prosthesis, the palate was closed secondarily with autogenous tissue; a questionnaire on daily life was administered pre- and post-operatively.

Results:

Functional improvements in terms of speech and eating were achieved in all and in 4 of 5 cases, respectively. In all cases, the QOL was better for palatal closure with autogenous tissue than with the prosthesis.

Conclusions:

As postoperative QOL was considered to be better when reconstructing the palate with autogenous tissue than with the prosthesis, we recommend to actively select autogenous tissue for palate reconstruction.
Endoscopic Modified Medial Maxillectomy for Inverted Papilloma of the Maxillary Sinus
Authors: Liu Qinghua , Weng Cuilian , Zheng Hao , Wu Lihua , Huang Shaopeng
Published: July 2021

Background:

Sinonasal inverted papilloma (SNIP) is a benign tumor that can be surgically managed by an endoscopic approach. However, SNIP has a high recurrence rate, mainly due to incomplete resection.

Aim:

This study aimed to analyze the outcomes of endoscopic modified medial maxillectomy in treating SINP originating from the maxillary sinus.

Methods:

The authors retrospectively analyzed 24 patients treated for SNIP via endoscopic modified medial maxillectomy at our institution between August 2014 and June 2019. During surgery, the mucosa involved in the tumor was stripped, and the bone underlying the tumor base was completely excised. Demographic data, surgical technique, location of SNIP attachment, complications, follow-up duration, and recurrence were recorded.

Results:

Twenty four patients with SNIP were identified (16 males). All patients had Krouse stage-III disease. Eleven patients presented with single attachment and 13 with multiple attachments. None of the patients had any complications during surgery. Four patients had postsurgical facial numbness around the cheek and upper lip. After a mean follow-up of 35.12 ± 14.98 months, no recurrence of SNIP was observed.

Conclusions and Significance:

Endoscopic modified medial maxillectomy is a safe and effective technique for treating SNIP. Recurrence can be reduced by complete excision of the attachment sites.
Age Related Changes of Superior Orbicularis Oris Muscle in Terms of Tone and Viscoelastic Properties
Authors: Ramazanoglu Engin , Turhan Begümhan , Usgu Serkan
Published: July 2021

Objective:

To examine the age-related changes in the viscoelastic properties and tone of the superior orbicularis oris muscle by a portablehand-held myotonometer.

Methods:

A total of 128 individuals (65 female, 63 male) who met the inclusion criteria were evaluated. Individuals were divided into 2 groups as under 40 years old (Group 1), and above (Group 2). The viscoelastic properties and muscle tone of orbicularis oris muscle were evaluated bilaterally in supine position with the Myoton PRO (Myoton AS, Estonia) device from the skin overlying the orbicularis oris. The reference point is accepted as the right and left paramedial philtrum dimple. The statistical analysis was performed.

Results:

There was no statistically significant difference in the elasticity values of the right and left orbicularis oris muscles of the Group 1 and Group 2 individuals. There was a difference between the groups when the tone and stiffness values of both groups were compared. It was determined that individuals over the age of 40 had higher muscle tone and stiffness. All mechanical properties of the superior orbicularis oris muscle between the male and female individuals in Group 1 were different. The values are higher in the female gender. The elasticity values in both genders in Group 2 were similar. Tone and stiffness parameters were different between genders.

Conclusions:

Myoton PRO can be recommended as an alternative device in the quantitative evaluations of post-operative follow-ups, and pre/post rehabilitation in terms of viscoelastic parameters of the muscle.
Elevated Plasma Levels of Matrix Metalloproteinase-3 and Tissue-Inhibitor of Matrix Metalloproteinases-1 Associate With Organ Dysfunction and Mortality in Sepsis
Authors: Jones Tiffanie K. , Reilly John P. , Anderson Brian J. , Miano Todd A. , Dunn Thomas G. , Weisman Ariel R. , Agyekum Roseline , Feng Rui , Ittner Caroline A.G. , Shashaty Michael G.S. , Meyer Nuala J.
Published: July 2021

Background:

Matrix Metalloproteinases (MMP) respond to tissue damage during sepsis. Higher plasma concentrations of MMPs and the tissue-inhibitor of matrix metalloproteinases (TIMP) have been reported in sepsis compared with healthy controls. The objective of this study was to examine if plasma levels of MMP-3, MMP-9, and TIMP-1 associate with mortality and organ dysfunction during sepsis.

Methods:

We conducted a prospective cohort study of critically ill patients with sepsis adjudicated per Sepsis-3 criteria at a tertiary academic medical center. We measured plasma concentrations of MMP-3, MMP-9, and TIMP-1 on intensive care unit admission. We phenotyped the subjects for shock, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality at 30 days. We used logistic regression to test the associations between the MMPs and TIMP-1 with shock, ARDS, AKI, and mortality.

Results:

Higher plasma TIMP-1 levels were associated with shock (odds ratio [OR] 1.51 per log increase [95% CI 1.25, 1.83]), ARDS (OR 1.24 [95% CI 1.05, 1.46]), AKI (OR 1.18 [95% CI 1.01, 1.38]), and mortality (OR 1.20 [95% CI 1.05, 1.46]. Higher plasma MMP-3 concentrations were associated with shock (OR 1.40 [95% CI 1.12, 1.75]) and mortality (OR 1.24 [95% CI 1.03, 1.48]) whereas MMP-9 levels were not associated with outcomes. Higher plasma TIMP-1 to MMP-3 ratios were associated with shock (OR 1.41 [95% CI 1.15, 1.72], P = 0.02).

Conclusion:

Elevated plasma concentrations of TIMP-1 associate with organ dysfunction and mortality in sepsis. Higher plasma levels of MMP-3 associate with shock and mortality. Plasma MMP and TIMP-1 may warrant further investigation as emerging sepsis theragnostic biomarkers.
Participation in a Chronic Limb Threatening Ischemia Randomized Trial Is Inversely Correlated With Regional Amputation Rate in Limb Threatening Ischemia Patients
Authors: Siracuse Jeffrey J. , Goodney Philip P. , Menard Matthew T. , Rosenfield Kenneth , Van Over Maxwell , Hamza Taye H. , Eid Mark , Villarreal Maria F. , Strong Michael B. , Farber Alik
Published: July 2021

Objective:

The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI.

Methods:

We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007–2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson's correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients.

Results:

Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n = 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R= −0.61, P = 0.39).

Conclusions:

Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management.