bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Metformin Use During Hospitalization and Mortality in Critically Ill Adults With Type 2 Diabetes Mellitus and Sepsis*
Authors: Gómez Hernando , Del Rio-Pertuz Gaspar , Priyanka Priyanka , Manrique-Caballero Carlos L. , Chang Chung-Chou H. , Wang Shu , Liu Qing , Zuckerbraun Brian S. , Murugan Raghavan , Angus Derek C. , Kellum John A.
Published: February 2022

OBJECTIVES:

Whether metformin exposure is associated with improved outcomes in patients with type 2 diabetes mellitus and sepsis.

DESIGN:

Retrospective cohort study.

SETTING:

Patients admitted to ICUs in 16 hospitals in Pennsylvania from October 2008 to December 2014.

PATIENTS:

Adult critical ill patients with type 2 diabetes mellitus and sepsis.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We conducted a retrospective cohort study to compare 90-day mortality in diabetic patients with sepsis with and without exposure to metformin during hospitalization. Data were obtained from the electronic health record of a large healthcare system in Pennsylvania from October 2008 to December 2014, on patients admitted to the ICU at any of the 16 hospitals within the system. The primary outcome was mortality at 90 days. The absolute and adjusted odds ratio (OR) with 95% CI were calculated in a propensity score-matched cohort. Among 14,847 patients with type 2 diabetes mellitus and sepsis, 682 patients (4.6%) were exposed to metformin during hospitalization and 14,165 (95.4%) were not. Within a total of 2,691 patients subjected to propensity score-matching at a 1:4 ratio, exposure to metformin (n = 599) was associated with decreased 90-day mortality (71/599, 11.9% vs 475/2,092, 22.7%; OR, 0.46; 95% CI, 0.35–0.60), reduced severe acute kidney injury (50% vs 57%; OR, 0.75; 95% CI, 0.62–0.90), less Major Adverse Kidney Events at 1 year (OR, 0.27; 95% CI, 0.22–0.68), and increased renal recovery (95% vs 86%; OR, 6.43; 95% CI, 3.42–12.1).

CONCLUSIONS:

Metformin exposure during hospitalization is associated with a decrease in 90-day mortality in patients with type 2 diabetes mellitus and sepsis.
Combined Poroma and Verruca Plantaris
Authors: Kneiber Diana , Cassarino David S.
Published: February 2022

A 76-year-old female patient presented with a peculiar new exophytic-appearing, flesh-colored skin lesion on her left hallux. Owing to its atypical appearance, the neoplasm was biopsied. Histologic sections demonstrated numerous thickened, anastomosing cord-like structures composed of bland appearing adnexal keratinocytes attached to the epidermis and extending into the superficial dermis. Nearby areas exhibited papillomatosis, epidermal acanthosis, dense hyperparakeratosis, hypergranulosis, and superficial koilocytes, findings consistent with a verruca plantaris. A p16 stain was positive in many of the superficial epidermal keratinocytes. Human papillomavirus typing by in situ hybridization for the most common low-risk and high-risk types was also performed and was negative for these. We herein present an unusual case of a skin lesion which combines features of a poroma with a verruca plantaris. We further review what is known of the relationship between human papillomavirus and poroid neoplasms.
Descemet Membrane Endothelial Keratoplasty and Goniosynechialysis in Iridocorneal Endothelial Syndrome: Surgical Perspective and Long-Term Outcomes
Authors: Joshi Vineet Pramod , Vaddavalli Pravin Krishna
Published: February 2022

Purpose:

The purpose of this study was to report the long-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) with goniosynechialysis in eyes with iridocorneal endothelial syndrome with an emphasis on the surgical technique.

Methods:

This was a retrospective series of 5 eyes of 5 patients undergoing a DMEK procedure at a tertiary eye care institute by a single surgeon. Modifications in the standard surgical technique, including the release of peripheral anterior synechiae, peripheral descemetorhexis, the release of adherent membranes, maneuvers in the anterior chamber with or without cataract extraction were logged. Long-term outcomes of the surgery in these patients are reported.

Results:

Five DMEK procedures were performed in 5 eyes of 5 patients. The average age of the patients was 48.2 ± 10.8 years, and the donor was 55.2 ± 3.2 years with a mean endothelial cell density (ECD) of 2784.6 ± 231 cells/mm2. After a mean follow-up period of 29.6 months (24–41 mo), all the 5 grafts remained clear; the mean BCVA at the last follow-up was 0.18 ± 0.17 logarithm of the minimum angle of resolution with a mean ECD of 1086.2 ± 338 cells/mm2 with a 61.1% reduction in ECD. intra ocular pressure was normal in all the cases. None of the patients had graft detachments that required rebubbling, and all eyes had a clear graft at the last follow-up.

Conclusions:

DMEK can be performed successfully in a case with iridocorneal endothelial syndrome with good visual outcomes with modifications to the surgical technique, including peripheral anterior synechiae release and minimizing surgical manipulation.
Prevalence and Impact of Cornea Guttata in the Graft After Penetrating Keratoplasty in Germany
Authors: Schönit Silvana , Maamri Amine , Zemova Elena , Munteanu Cristian , Safi Tarek , Daas Loay , Seitz Berthold
Published: February 2022

Purpose:

The aim of this study was to analyze the prevalence and severity of corneal guttata (CG) in grafts after penetrating keratoplasty (PKP) and to determine its clinical significance.

Methods:

This retrospective study included 1758 PKP performed in 1522 patients. In total, 6662 postoperative endothelial images revealed the prevalence and severity of CG (divided into categories G0 without CG and G1-G3 with increasing severity). Origin of the graft, postoperative corneal thickness, visual acuity, pleomorphism, polymegethism, and endothelial cell density (ECD) were analyzed.

Results:

CG was detected in 14.9% of the grafts within 9 months after PKP, most of them were low-grade G1 (13.6%). Grafts from Homburg/Saar showed significantly less CG cases compared with other eye banks (P = 0.034). The mean corrected distance visual acuity (logMAR) did not differ between G1 (0.45 ± 0.31) and G0 (0.46 ± 0.31). The mean ECD was lower in G1 compared with G0 (P < 0.001). The mean corneal thickness was higher in G3 (597 ± 101 μm) compared with G0 (541 ± 65 μm) (P < 0.001). Pleomorphism and polymegethism were correlated with CG (P < 0.001). A progression of CG severity was detected in 13.5% of the cases during a follow-up time of 25.0 ± 19.9 months.

Conclusions:

Our study suggested that CG are transplanted in 14.9% of PKP, most of which are low-grade CG not affecting the visual acuity but already leading to an increase in corneal thickness, loss of ECD, and alteration of endothelial cell morphology. In 13.5% of the cases, a progression was demonstrated in the postoperative course.
Low-Level Light Therapy Versus Intense Pulsed Light for the Treatment of Meibomian Gland Dysfunction: Preliminary Results From a Prospective Randomized Comparative Study
Authors: Giannaccare Giuseppe , Pellegrini Marco , Carnovale Scalzo Giovanna , Borselli Massimiliano , Ceravolo Domenico , Scorcia Vincenzo
Published: February 2022

Purpose:

The purpose of this study was to evaluate and compare the safety and efficacy of low-level light therapy (LLLT) and intense pulsed light (IPL) for the treatment of meibomian gland dysfunction (MGD).

Methods:

Forty eyes of 40 patients with MGD were randomized to receive either LLLT or IPL. Four weekly sessions of LLLT (MY MASK-E, Espansione Marketing S.p.A., Bologna, Italy) and IPL (Eye-light device, Espansione Marketing S.p.A., Bologna, Italy) were performed. The following parameters were evaluated before and 2 weeks after the last session for each treatment: Standard Patient Evaluation of Eye Dryness questionnaire, noninvasive break-up time, tear meniscus height, redness score, meiboscore, and meibomian gland loss.

Results:

All patients completed regularly all the scheduled sessions, and no adverse events were reported in any of the groups. The Standard Patient Evaluation of Eye Dryness score significantly decreased after both LLLT and IPL (P < 0.001) although the improvement was significantly greater in the LLLT compared with the IPL group (−9.9 ± 3.2 vs. −6.75 ± 4.5; P = 0.014). Patients in the LLLT group showed a significantly higher increase in tear meniscus height compared with those in the IPL group (0.06 ± 0.10 mm vs. −0.01 ± 0.014; P = 0.040). In both groups, the noninvasive break-up time, redness score, meiboscore, and meibomian gland loss did not vary significantly after treatment (all P > 0.05).

Conclusions:

Both LLLT and IPL were safe and effective in improving ocular discomfort symptoms in patients with MGD; however, the former determined a greater improvement in symptoms and an improvement of tear volume.
KeraKlear Artificial Cornea Implantation Assisted by Femtosecond Laser in Eyes With Aniridia
Authors: de Farias Charles Costa , Bezerra Fernanda Machado , Lamazales Luiz Luciano , Nosé Walton , Pereira Gomes José Álvaro
Published: February 2022

Purpose:

The purpose of this study was to evaluate the feasibility of treating aniridia-associated keratopathy with a nonpenetrating artificial cornea in 2 patients with corneal blindness secondary to aniridia.

Methods:

This was a prospective, nonrandomized, interventional study of 2 consecutive patients with corneal blindness caused by aniridia. Ophthalmological examination was performed before the nonpenetrating keratoprosthesis surgery and then repeated 1, 7, 15, 30, 90, and 180 days and subsequently every 90 days thereafter. Optical coherence tomography was performed 90 days postsurgery to assess the position of the implant.

Results:

Visual acuity improved significantly after the KeraKlear surgery. Postoperative findings included periprosthetic corneal thinning, neovascularization, and retroprosthetic opacity.

Conclusions:

KeraKlear nonpenetrating artificial corneas represent a promising alternative to keratolimbal allografts and Boston keratoprosthesis for the treatment of aniridia-associated keratopathy.
Neurotrophic Keratopathy After Herpes Zoster Ophthalmicus
Authors: Meyer Jay J. , Liu Kevin , McGhee Charles N. J. , Danesh-Meyer Helen V. , Niederer Rachael L.
Published: February 2022

Purpose:

The aim of this study was to describe risk factors for neurotrophic keratopathy (NK) after herpes zoster ophthalmicus (HZO).

Methods:

This study was a retrospective review of all patients seen at the Auckland District Health Board with HZO from 2006 through 2016. Cox proportional hazards analysis was performed to examine time to development of neurotrophic keratitis.

Results:

Eight hundred sixty-nine patients were included in the study with a median follow-up of 6.3 years (5504.4 patient-years). The median age was 65.5 years (interquartile range 52.9–75.4), and 456 subjects (52.5%) were male. NK developed in 58 patients (6.7%), with the highest hazard 1 to 2 years after onset of HZO. On univariate analysis, age, White ethnicity, best-corrected visual acuity (BCVA) at presentation, intraocular pressure, corneal involvement, uveitis, and number of recurrences were associated with increased risk of NK. On multivariate analysis, the following factors were significant: age (hazard ratio [HR] = 1.03; P = 0.021), White ethnicity (HR = 3.18; P = 0.015), BCVA (HR = 1.81; P = 0.026), uveitis (HR = 3.77; P = 0.001), and recurrence (HR = 1.34; P < 0.001). Vision loss (BCVA ≤6/15) was more frequent in subjects with NK (65.5% vs. 16.3%, P < 0.001).

Conclusions:

NK is a relatively common and serious complication of HZO and occurs more frequently in older White individuals, those with poor visual acuity at presentation, and those with uveitis. Vision loss occurs in approximately two-thirds of patients.
Transmastoid Repair of Otogenic Encephaloceles in Patients With Canal Wall Down Mastoidectomy
Authors: Patel Tirth R. , Roy Alexa S. , Piracha Ali Z. , Michaelides Elias , Wiet R. Mark
Published: February 2022

Objective:

Description of a series of cases in which otogenic encephaloceles in patients requiring canal wall down (CWD) mastoidectomies were repaired via a transmastoid approach.

Study Design:

Case series.

Setting:

Tertiary-care hospital.

Patients:

Eleven cases of otogenic encephaloceles in patients requiring CWD mastoidectomy for chronic ear disease.

Interventions:

Surgical repair of an otogenic encephalocele using a transmastoid approach.

Main Outcome Measures:

Success of repair, number and size of defects, materials used for repair, complications encountered in surgery, pure tone average air-bone gap (PTA-ABG).

Results:

Eleven cases were identified. Two of these patients had a prior CWD cavity while the remainder received CWD mastoidectomy simultaneously with encephalocele repair. None of the patients required revision of encephalocele repair. Mean preoperative PTA-ABG was 30 dB and mean postoperative PTA-ABG was 28 dB (p = 0.66).

Conclusions:

A single-stage strictly transmastoid approach to otogenic encephalocele repair may be effective in patients with prior CWD mastoid cavities or requiring concurrent CWD mastoidectomy for chronic ear disease and/or cholesteatoma.
Comparative Analysis of Recidivism After Endoscopic and Microscopic-Based Cholesteatoma Resection
Authors: Manzoor Nauman F. , Totten Douglas J. , McLeod Megan E. , Sherry Alexander D. , Perkins Elizabeth L. , Haynes David S. , Rivas Alejandro
Published: February 2022

Objectives:

1) To analyze outcomes of cholesteatoma resection utilizing postauricular microscopic and endoscopic ear surgery (EES) approaches.

2) To analyze predictors of residual and recurrent cholesteatoma.

Study Design:

Retrospective cohort study.

Setting:

Tertiary referral center.

Patients:

Three hundred seventy-five adult and pediatric patients with cholesteatoma (2012–2017).

Interventions:

Patients underwent surgical resection of cholesteatoma with EES (n = 122) and microscopic (n = 253) approach.

Main Outcome Measures:

Residual cholesteatoma, recurrent cholesteatoma, second-look procedures.

Results:

The endoscopic cohort included significantly more pediatric cases (p = 0.0008). There was no difference in laterality, gender distribution, congenital or acquired cholesteatoma, and revision cases between the cohorts. Out of 122 EES cases, 16 (13%) developed residual disease and 9 (7%) developed recurrent disease. Of 253 microscopic cases 16 (6%) developed residual disease while 11 (4%) developed recurrent disease. Second look procedures were more commonly used in EES cohort (50 vs 18%). Single predictor analysis revealed 12 predictors for residual disease and 5 for recurrent disease. Multivariable model identified pediatric case distribution and higher disease stage to be significant predictors for both residual (p = 0.04, 0.007) and recurrent disease (p = 0.02, 0.01). EES approach was associated with a weak significance for residual disease (p = 0.049) but not recurrent disease (p = 0.34).

Conclusions:

EES approach for cholesteatoma resection seems to perform similarly to microscopic approach with no difference in rates of recurrent disease. However, it is associated with a higher rate of residual disease; this may be a reflection of a greater rate of second look procedures done in this group.
Selection Criteria Optimal for Recovery of Inner Ear Tissues From Deceased Organ Donors
Authors: Aaron Ksenia A. , Hosseini Davood K. , Vaisbuch Yona , Scheibinger Mirko , Grillet Nicolas , Heller Stefan , Wang Tian , Cheng Alan G.
Published: February 2022

Objective:

To identify optimal conditions for recovering viable inner ear tissues from deceased organ donors.

Setting:

Tertiary recovery hospitals and Donor Network West Organ Recovery Center.

Interventions:

Recovering bilateral inner ear tissues and immunohistological analysis.

Main Outcome Measures:

Immunohistochemical analysis of utricles from human organ donors after brain death (DBD) or donors after cardiac death (DCD).

Results:

Vestibular tissues from 21 organ donors (39 ears) were recovered. Of these, 18 donors (33 utricles) were examined by immunofluorescence. The sensory epithelium was present in seven utricles (two from DBD and five from DCD). Relative to DBD utricles, DCD organs more commonly displayed dense populations of hair cells and supporting cells. Relative to DBD, DCD had significantly shorter postmortem interval time to tissue recovery (<48 h). Compared to donors with no sensory epithelium, donors with intact and viable sensory epithelium (both DCD and DBD) had significantly shorter lag time to resuscitation prior to hospital admission (6.4 ± 9.2 vs 35.6 ± 23.7 min, respectively) as well as a shorter time between pronouncements of death to organ recovery (22.6 ± 30.4 vs 64.8 ± 22.8 h, respectively).

Conclusions:

Organ donors are a novel resource for bilateral inner ear organs. Selecting tissue donors within defined parameters can optimize the quality of recovered inner ear tissues, thereby facilitating future research investigating sensory and nonsensory cells.
Interrupted sleep by ambulatory blood pressure monitoring does not affect blood pressure
Authors: Geng Xue , Li Feng , Mao Zhuofeng , Hu Haijuan , Cui Wei
Published: February 2022

Background

For the past 20 years, many hypertension guidelines have strongly recommended the practical use of ambulatory blood pressure monitoring (ABPM) to the diagnosis and management of hypertension. However, whether different sleep conditions during ABPM will affect blood pressure (BP) fluctuations and lead to inaccurate measurement results is a concern of clinicians.

Method

This was a prospective cohort study in the real-world setting. The participants were recruited between June 2018 and June 2019 in Hebei Province, China. There are three types of sleep during ABPM: undisturbed sleep, disturbed sleep and severely disturbed sleep. The people were divided into three groups according to their sleep types during ABPM. The primary outcome is 24-h mean BP, circadian rhythm of BP and variation coefficient of 24-h BP. Comparisons between groups are tested by Kruskal–Wallis H test.

Results

In total 1154 people completed the study. There was no significant difference in 24-h mean BP and circadian rhythm of BP among the three groups. There are statistically significant differences among the three groups in the variation coefficient of 24-h BP for the general population and noninsomnia population. There was no significant difference in mean BP, circadian rhythm of BP and variation coefficient of BP among the three groups for the insomnia people.

Conclusion

Regardless of the insomniac or noninsomniac population, sleep conditions during ABPM do not affect BP value and BP rhythm. For noninsomniac people, the sleep situation during ABPM may affect the BP variation coefficient.
Usefulness of the additional contrast agents to identify offending nerve root in selective nerve root block
Authors: Ko Sangbong , Nam Junho , Lee Jaejun
Published: February 2022

It is hypothesized that if it is confirmed that the pain caused by the injection needle coincides with the lower leg radiating pain(LLRP) that the patient mainly complains of, then the contrast agents may be used less. This study aims to understand if the identification of lancinating identical pain in the procedure could replace the use of contrast agents that causes additional pain provocation using control arm of randomized clinical trial.

This retrospective study included 165 patients who met exclusion criteria from among patients who underwent Selective nerve root block for the treatment of LLRP. With the identical and lancinating pain confirmed in the same site of the patient, consistent with that of the original symptom, the subjects were divided into 2 groups: 1 without contrast injection (Non-Dye [ND] group; 57 patients) and the other with contrast injection (Dye [D] group; 108 patients). The degree of LLRP in the 2 groups was evaluated using visual analog scale (VAS) before injection, 2, 6, and 12 weeks after injection. Functional outcomes were measured using Owestry Disability Index and Rolland-Morris Disability Questionnair, whereas quality of life was measured using Physical component score and Mental component score of Short Form 36 (SF-36) before injection and 3 months after injection.

There was no statistically significant difference in the LLRP severity in both groups at all times and no statistical difference in the degree of VAS improvement relative to the before-injection VAS value between the 2 groups at 2 and 6 weeks after injection (all P > .05). At 12 weeks after injection, there was a statistically significant difference, but they were below Minimum Clinical Important Difference, bearing little clinical implications. There was no statistically significant difference between the 2 groups in Owestry Disability Index, Rolland-Morris Disability Questionnair, SF-36 Physical component score, and SF-36 Mental component score at every interval (all P > .05).

Instead of contrast agent injections that have been used for accurate nerve root identification during Selective Nerve Root Block, the method of merely checking if the needle-induced pain under fluoroscopic imaging is consistent with the LLRP that the patient predominantly experiences shows the same effect in the patient's pain control and functional outcome.
Comparative efficacy of Chinese herbal injections for septic shock
Authors: Huang Peiying , Chen Yan , Liu Qiang , Lei Sisi , Feng Yuchao , Wu Qihua , Zhang Haobo , Chen Bojun , Zeng Zhongyi
Published: February 2022

Background:

Septic shock is a life-threatening syndrome. Despite Western medicine guidelines being continually updated on septic shock, the disease still has a high mortality rate. Chinese herbal injections (CHIs) are injections made from effective components of traditional Chinese medicine, which have a potential therapeutic effect on septic shock and are recommended as the adjunctive treatment for septic shock in China. Although pairwise meta-analysis has been published for category-single CHIs about treatment effects of septic shock, there is no meta-analysis comparing more than 3 various types of CHIs used for septic shock.

Methods:

Chinese and English databases will be retrieved for randomized controlled trials from the establishment of the databases to September 30, 2021. Two reviewers will perform literature searches and data extractions while another 2 reviewers for risk assessments. RevMan V.5.4 software, Stata V.14.0 software, and R V. 4.1.1 software will be applied to perform pairwise meta-analysis and network meta-analysis. We will apply the Cochrane risk of bias tool to assess the risk of bias while the Grades of Recommendation, Assessment, Development, and Evaluation approach will be used to summarize the results of the study. The PRISMA-P guideline was followed for this protocol.

Results:

The current study will explore the therapeutic effect of CHIs in the treatment of septic shock through pairwise meta-analysis and network meta-analysis.

Conclusion:

This study will seek out the best-performed CHIs under various indicators for septic shock, providing supporting evidence for clinical selection of CHIs for septic shock.
CDK9 is up-regulated and associated with prognosis in patients with papillary thyroid carcinoma
Authors: Guo Tao , Liu De-Feng , Peng Shi-Hao
Published: February 2022

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy but shows excellent prognosis. We investigated the clinical significance of cyclin-dependent kinase 9 (CDK9) in patients with PTC.

This prospective observational study included 192 patients with PTC, who visited our hospital between August 2018 and February 2020. We obtained 93 tissue samples from patients with benign thyroid disease during the same period as controls. Immunohistochemical evaluation and reverse transcription-quantitative polymerase chain reaction assay were performed to evaluate CDK9 expression. Patients’ demographic and clinical characteristics were analyzed.

Delphian lymph node (DLN) metastasis in patients with PTC was associated with clinicopathological characteristics. CDK9 expression was up-regulated in patients with PTC, and those with DLN metastasis showed higher CDK9 expression. We also observed that tumor size, capsule invasion, tumor-node-metastasis classification (TNM) stage, and multifocality were the risk factors for DLN metastasis in patients with PTC. Additionally, CDK9 expression was strongly associated with tumor size, capsule invasion, TNM stage, and multifocality and weakly associated with the number of metastatic DLN.

CDK9 is up-regulated in patients with PTC and associated with prognosis in these patients.
ERCP in critically ill patients is safe and does not increase mortality
Authors: Buechter Matthias , Katsounas Antonios , Saner Fuat , Gerken Guido , Canbay Ali , Dechêne Alexander
Published: February 2022

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for minimally-invasive treatment of biliary or pancreatic tract disease. When treating patients on intensive care units (ICU) with ERCP, interventionalists are faced with considerably higher morbidity compared to patients in ambulatory settings. However, data on complications and outcome of critical ill patients undergoing emergency ERCP are limited.

A retrospective analysis of 102 patients treated on ICUs undergoing 121 ERCP procedures at the University Hospital of Essen, Germany between 2002 and 2016 was performed. Indications, interventional success, outcome including survival and procedure-related complications were analyzed. Patients’ condition pre-ERCP was categorized by using the “Simplified Acute Physiology Score” (SAPS 3).

66/102 patients (64.7%) were referred to ERCP from surgical ICU, 36/102 (35.3%) from nonsurgical ICU. The majority of patients were male (63.7%), the mean age was 54.1 ± 14.9 [21–88] years. Indications for ERCP were biliary complications after liver transplantation (n = 34, 33.3%), biliary leakage after hepatobiliary surgery (n = 32, 31.4%), and cholangitis/biliary sepsis (n = 36; 35.3%), respectively. 117/121 (96.7%) ERCPs were successful, 1 patient (1.0%) died during ERCP. Post-ERCP pancreatitis occurred in 11.8% of interventions. The median simplified acute physiology score 3 was 65 points, predicting a risk-adjusted estimated mortality of 48.8%, corresponding to an observed mortality of 52.2% (P = n.s.).

ERCP is safe in critically ill patients on ICU, it does not increase overall mortality rate and has a relatively low rate of procedure-associated complications.
Acute respiratory distress syndrome associated with macrophage activation syndrome in systemic lupus erythematosus
Authors: Chang En-Shuo , Yu Han-Hua , Wu Chiao-En , Chan Tien-Ming
Published: February 2022

Rationale:

Previous treatment for macrophage activation syndrome (MAS) includes high-dose intravenous methylprednisolone along with intravenous immunoglobulin G. If MAS worsened, second-line therapy consisted of anakinra; if the disease remained refractory, third-line therapy with etoposide was considered. In addition, cyclosporine A plays a role in early MAS and in preventing recurrence. Some studies have reported the use of cytokine-targeting agents other than anakinra, such as canakinumab, tocilizumab, abatacept, and tofacitinib.

Patient concerns:

The patient with systemic lupus erythematosus (SLE) had an uncommon combination of intermittent fever, hyperferritinemia, hypertriglyceridemia, jaundice, and significantly abnormal liver function test results. The patient reported a history of daily fever of 38 to 39°C, painful oral ulcer, anorexia, abdominal bloating, diarrhea, and malar rash progression for 2 weeks, and jaundice, tea-colored urine, and clay-colored stool for 1 week preceding hospital admission.

Diagnosis:

SLE flareups in the patient were initially suspected. However, the final diagnosis was acute respiratory distress syndrome (ARDS) associated with MAS.

Interventions:

The treatment included disease-modifying antirheumatic drugs (DMARDs), such as azathioprine, and titrated steroid doses of methylprednisolone (40 mg q8 h) and dexamethasone (15 mg q8 h), after the patient had ARDS and was intubated.

Dose-adjusted monotherapy with dexamethasone was found to be effective; this may be attributed to some DMARDs being unsuitable for cytokine storms, that is, some DMARDs may cause complications in cytokine storms.

Outcomes:

After dexamethasone 15 mg q8 h treatment, the patient's fever subsided within 2 days, and liver function became normal within 3 weeks. The patient regularly attended scheduled outpatient follow-up visits after discharge. After 2 years, the patient reported no symptoms or signs of SLE with 2 mg/d oral dexamethasone.

Lessons:

Early diagnosis of MAS and dexamethasone treatment for MAS with ARDS appear to be crucial for these patients.
COVID-19 information received by the Peruvian population, during the first phase of the pandemic, and its association with developing psychological distress
Authors: Gómez-Salgado Juan , Palomino-Baldeón Juan Carlos , Ortega-Moreno Mónica , Fagundo-Rivera Javier , Allande-Cussó Regina , Ruiz-Frutos Carlos
Published: February 2022

It is suspected that the information the population has about coronavirus disease 2019 (COVID-19) determines both its preventive measures and its effects on mental health. The internet and social media are the sources that have largely replaced the official and traditional channels of information. The objective of this study is to analyse the influence of the sources used by the population in Peru to obtain information on COVID-19 and its association with developing psychological distress (PD) and preventive measures against contagion.

1699 questionnaires were analysed. A previously validated instrument adapted to Peru was used. Participants were questioned about the information received regarding COVID-19, its sources, time of exposition, assessment, or beliefs about it. Mental health was measured with the Goldberg General Health Questionnaire. Descriptive and bivariate analysis were performed, developing a classification and regression tree for PD based on beliefs and information about the pandemic.

The most used source of information on COVID-19 in Peru was social media and this is associated with developing PD, both in the general population and among health professionals. The quality of the information about treatments for COVID-19 is associated with PD in the general population, whereas prognosis generates more distress among healthcare professionals. The biggest concern is transmitting the virus to family members, close persons, or patients, with more confidence in health professionals than in the health system.

The health authorities should use the social media to transmit quality information about COVID-19 and, at the same time, to gather in real time the opinions on the implemented preventive measures. For all, this it is necessary to have higher credibility in the population to increase the confidence in the health system, looking at basic aspects for compliance with prevention measures and improvement of mental health.
Evaluation of integrated neuromuscular training on the recovery of joint injury
Authors: Zeng Jing , Liu Qing , Lei Zhengfang , Sun Zhe , Wang Yang
Published: February 2022

Background:

Integrated neuromuscular training (INT) is a comprehensive and holistic training method. It combines general functional movement training with specialized strength, balance, speed, sensitivity, coordination, enhanced training or rapid telescopic compound training. From the existing research results, the mechanism of INT mainly lies in improving the proprioception of the human body and cognitive level to achieve the impact on the motor sensory system, so as to effectively prevent joint injury and promote the recovery after joint injury.

Method:

This article is assisted by the third and fourth authors to search the relevant literature. The search strategy is divided into 2 parts: English literature and Chinese literature. English literature search: the keywords “integrated neurological training”, “joint investigation”, and “restoration” are jointly searched with “meta analysis” and “system evaluation”, respectively. The search databases include PsycINFO, Science Direct, PubMed, Eric, and Willey. Chinese literature search: the keywords “integrated neuromuscular training”, “joint injury”, and “recovery” are jointly searched with “meta analysis” and “system evaluation”, respectively. The search databases include the general library of online publishing of academic journals of China Knowledge Network (CNKI) and the full-text database of excellent doctoral theses of China Knowledge Network (CNKI). At the same time, the supplementary search is carried out through literature backtracking, Google Scholar.

Results:

This study will provide new evidence for the effect of INT on the recovery of joint injury.

Conclusion:

To provide a method to help the prevention and restoration of joint injury by INT.

INPLASY registration number:

INPLASY2021120136.
Data-independent acquisition-based proteomics analysis correlating type 2 diabetes mellitus with osteoarthritis in total knee arthroplasty patients
Authors: Zhao Lulu , Wu Tong , Li Jiayi , Cai Chunyan , Yao Qingqiang , Zhu Yi-Shen
Published: February 2022

Background:

To explore the effects of type 2 diabetes mellitus (T2DM) on osteoarthritis (OA), 12 bone tissue samples were obtained surgically from the human total knee arthroplasty patients and analyzed by quantitative proteomics.

Methods:

Based on patient clinical histories, patient samples were assigned to diabetes mellitus osteoarthritis (DMOA) and OA groups. A data-independent acquisition method for data collection was used with proteomic data analysis to assess intergroup proteomic differences. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis were used to further find the correlation between T2DM and OA.

Results:

GO functional analysis found 153 differentially expressed proteins between DMOA and OA groups, of which 92 differentially expressed proteins were significantly up-regulated and 61 were significantly down-regulated. Kyoto Encyclopedia of Genes and Genome pathway analysis found 180 pathways, including 9 pathways significantly enriched. Further data analysis revealed that 6 signaling pathways were closely associated with T2DM and OA.

Conclusion:

OA and DMOA onset and progression were closely related to synthesis and metabolism of extracellular matrix components (e.g., fibronectin, decorin, etc.). The effects of T2DM on OA occur though 2 major ways of oxidative stress and low-grade chronic inflammation, involving in 2 inhibited signaling pathways and 4 activated signaling pathways.
Association between Unc-51-like autophagy activating kinase 2 gene polymorphisms and schizophrenia in the Korean population
Authors: Kang Won Sub , Lee Sang Min , Hwang Dongkee , Park Hae Jeong , Kim Jong Woo
Published: February 2022

Accumulating evidence indicates that the autophagy process is involved in the pathogenesis of schizophrenia. Autophagy plays a fundamental role in neuronal survival and function, and autophagy-related genes have been suggested to be associated with the pathogenesis of schizophrenia. The Unc-51-like autophagy activating kinase 2 (ULK2) gene has been implicated in autophagy regulation; therefore, we hypothesized that ULK2 polymorphisms may be associated with schizophrenia susceptibility.

This study explored the association between polymorphisms of ULK2 and schizophrenia.

Two single nucleotide polymorphisms (SNPs) (rs55730189 and rs150122) of ULK2 were genotyped in 279 patients with schizophrenia and 403 healthy individuals using Fluidigm SNPtype assays. We analyzed the genotype distribution of 2 SNPs and haplotypes between patients with schizophrenia and control subjects.

The T allele frequency of rs55730189 showed a significant association between patients with schizophrenia and control subjects (P = .003). Genotype frequencies of rs55710189 were found to be significantly different between patients with schizophrenia and control subjects (odds ratio = 6.89, 95% confidence interval = 1.91–24.90, P < .001 in the dominant model [C/T + T/T vs C/C], OR = 6.50, 95% confidence interval = 1.83–23.01, P < .001 in the log-additive model (C/T vs T/T vs C/C)]. In haplotype analysis, the TT haplotype for these 2 SNPs was significantly associated with schizophrenia (P < .001, χ2 = 12.231).

Our findings suggest that specific ULK2 polymorphisms may be associated with susceptibility to schizophrenia in the Korean population.
Health-Related Behaviors and Perceived Addictions
Authors: Canas-Simião Hugo , Reis Cátia , Carreiras Diogo , Espada-Santos Pedro , Paiva Teresa
Published: February 2022

The COVID-19 pandemic led to a worldwide implementation of measures to contain the virus from spreading, and social isolation was one of those measures. Social isolation is associated with increased susceptibility to various neuropsychiatric disorders, including depression. Because this risk varies between populations and their respective habits, understanding which behaviors play a positive or harmful role is fundamental for people with depression under these conditions. This study aims to 1) compare health-related behaviors (HRBs) and perceived addictions between healthy individuals and individuals who reported having a depressive disorder at the time of the first outbreak of the COVID-19 pandemic in Portugal, and 2) test which HRB and perceived addictions are associated with depression. Participants were a matched for age and sex and comprised 968 adults divided into two groups: healthy (484, 50%) and depressed (484, 50%). They completed online self-report questionnaires, and the data were analyzed in SPSS. Logistic regressions showed that being a health professional, getting up in a later time during weekends, and a higher consumption of soft drinks increased the risk for depression. In contrast, higher education and higher intensity of physical activity decreased this risk. Perceived addictions to TV, social networking, and gaming increased the risk for depression. HRBs and the identified addictions associated with depression during the confinement should be targeted in clinical and community interventions.
An Antiracism Approach to Conducting, Reporting, and Evaluating Pediatric Critical Care Research
Authors: Zurca Adrian D. , Suttle Markita L , October Tessie W.
Published: February 2022

Reporting race and ethnicity without consideration for the complexity of these variables is unfortunately common in research. This practice exacerbates the systemic racism present in healthcare and research, of which pediatric critical care is not immune. Scientifically, this approach lacks rigor, as people are grouped into socially derived categories that are often not scientifically justified, and the field is denied the opportunity to examine closely the true associations between race/ethnicity and clinical outcomes. In this Special Article for Pediatric Critical Care Medicine, we introduce an antiracism approach to conducting, reporting, and evaluating pediatric critical care research. We propose four recommendations: 1) race and ethnicity are social constructs that should be evaluated as such, with researchers considering the context and relevance of related social determinants of health; 2) race and ethnicity data should be collected with sufficient detail to allow detection of meaningful results and minimize the risk of overgeneralizing findings; 3) as health equity research evolves, the pediatric critical care research field must adapt and proactively strive for inclusivity; and 4) the research community, including investigators, authors, research ethics committees, funding organizations, professional organizations, and journal editorial boards, are all accountable for rigorously conducting and reporting race/ethnicity in research. Taking an antiracism approach to research requires the field to ask the difficult question of why racial/ethnic differences exist to eliminate healthcare disparities and optimize healthcare outcomes for all children.
Post–COVID-19 Unusual Inflammatory Syndromes Detected on 18F-FDG PET/CT Scan
Authors: Pereira Melvika , Shivdasani Divya , Roy Debdip , Rungta Rachita , Dang Shreya , Singh Natasha
Published: February 2022

SARS-CoV-2 is primarily known to cause respiratory symptoms. However, in this global COVID-19 pandemic, we have come across many extrapulmonary manifestations during and in the immediate post-COVID phase such as gastrointestinal symptoms, kidney and liver injury, myocardial dysfunction and acute coronary syndromes, and neurological, thromboembolic, dermatological, and musculoskeletal disorders. We present 2 such unusual cases of post-COVID complications—diffuse panniculitis and inflammatory myositis, as well as their clinical and FDG PET/CT imaging features.
Foreign Body Reaction Following Use of a Novel Bone Graft Substitute in Pediatric Cranioplasty
Authors: Badiee Ryan K. , Rowland Jon M. , Sun Peter P.
Published: February 2022

Pediatric cranioplasty is indicated to repair skull defects with a wide variety of etiologies. The choice of graft material used to fill the defect is of paramount importance to the long-term success of this procedure. A variety of synthetic products have been commercially developed to avoid donor site morbidity. Here, the authors present the case of a 13-year-old boy with cranial Langerhans cell histiocytosis who underwent cranioplasty with a novel, calcium phosphate-based bone graft substitute (Montage). The patient presented 2 years postoperatively with a foreign body giant cell reaction that required explantation of the graft. The authors discuss potential considerations in choosing the most appropriate graft, potential contributors to this late adverse outcome, and the need for further research into the use of novel allograft materials in pediatric cranioplasty.
Does Maxillomandibular Fixation Affect Respiratory Function? A Systematic Review
Authors: de Carvalho Sampaio Thaisa Reis , Barbosa Lívia Mirelle , Lopes André Coelho , de Albuquerque Cavalcanti Almeida Renata , do Egito Vasconcelos Belmiro Cavalcanti , Gomes Ana Claudia Amorim , de Souza Andrade Emanuel Savio
Published: February 2022

This systematic review was carried out to determine if maxillomandibular fixation, used in the treatment of maxillary fractures, interferes with respiratory function, and appraised studies that evaluated pulmonary function using spirometry on patients with and without maxillomandibular fixation. Searches were conducted on the following databases: Medline/Pubmed, Embase, Cochrane, Web of Science, Scopus, and Scielo, in addition to a search of the grey literature and a manual search. Five studies were included in the qualitative analysis, but it was not possible to conduct a quantitative study due to the lack of data. Forced vital capacity, forced expiratory volume in the first second, the ratio of these values, and peak expiratory flow were the parameters studied. In all the studies included in this review, it was possible to observe the lowest respiratory parameter values during maxillomandibular fixation and, after removal, normal respiratory function was restored. Accordingly, it was possible to conclude that maxillo-mandibular fixation temporarily affects respiratory function, during use, but it is restored on removal, therefore, not precluding its use on healthy patients who have good nasal breathing prior to the procedure. However, in patients suffering from some form of respiratory limitation or pulmonary disease, and also mouth breathers, maxillomandibular fixation should not be used so as to avoid more severe respiratory complications, underlining the importance of preoperative pulmonary evaluation.
Human germline biallelic complete NFAT1 deficiency causes the triad of progressive joint contractures, osteochondromas, and susceptibility to B cell malignancy
Authors: Sharma Mehul , Fu Maggie P. , Lu Henry Y. , Sharma Ashish A. , Modi Bhavi P. , Michalski Christina , Lin Susan , Dalmann Joshua , Salman Areesha , Del Bel Kate L. , Waqas Meriam , Terry Jefferson , Setiadi Audi , Lavoie Pascal M. , Wasserman Wyeth W. , Mwenifumbo Jill , Kobor Michael S. , Lee Anna F. , Lehman Anna , Cheng Sylvia , Cooper Anthony , Patel Millan S. , Turvey Stuart E.
Published: February 2022

Discovery of humans with monogenic disorders has a rich history of generating new insights into biology. Here we report the first human identified with complete deficiency of nuclear factor of activated T cells 1 (NFAT1). NFAT1, encoded by NFATC2, mediates calcium-calcineurin signals that drive cell activation, proliferation, and survival. The patient is homozygous for a damaging germline NFATC2 variant (c.2023_2026delTACC; p.Tyr675Thrfs*18) and presented with joint contractures, osteochondromas, and B cell lymphoma. Absence of NFAT1 protein in chondrocytes caused enrichment in pro-survival and inflammatory genes. Systematic single-cell-omic analyses revealed an environment that promotes lymphomagenesis with accumulation of naïve B cells (with oncogenic signatures - MYC, JAK1), exhausted CD4+ T cells, impaired T follicular helper cells, and aberrant CD8+ T cells. This work highlights the pleiotropic role of human NFAT1, will empower the diagnosis of additional patients with NFAT1 deficiency, and further define detrimental effects a long-term use of calcineurin inhibitors.
Peptide-based drug predictions for cancer therapy using deep learning
Authors: Sun Yih-Yun , Lin Tzu-Tang , Cheng Wei-Chih , Lu I-Hsuan , Chen Shu-Hwa , Lin Chung-Yen
Published: February 2022

Background

Therapeutic drugs used in cancer treatment have ineffectiveness and resistance to drug action problems. Anticancer peptides (ACPs) are selective and toxic to cancer cells and quickly produced. Thus, ACPs can be a satisfactory substitute for therapeutic drugs. We developed AI4ACP, a user-friendly web-server ACP predictor that can predict the anticancer property of query peptides, thus promoting the discovery of peptides with anticancer activity.

Result

Our results revealed that the performance of our ACP predictor trained using the new ACP collection was superior to that of the available high-performance ACP predictors.

Conclusions

AI4ACP is a user-friendly web-server ACP predictor that can be used to determine whether a query sequence is an ACP. This tool can be beneficial for drug development for cancer treatment. AI4ACP is freely accessible at https://axp.iis.sinica.edu.tw/AI4ACP/
Crumpled polymer with loops recapitulates key features of chromosome organization
Authors: Polovnikov Kirill E. , Slavov Bogdan , Belan Sergey , Imakaev Maxim , Brandão Hugo B. , Mirny Leonid A.
Published: February 2022

Chromosomes are exceedingly long topologically-constrained polymers compacted in a cell nucleus. We recently suggested that chromosomes are organized into loops by an active process of loop extrusion. Yet loops remain elusive to direct observations in living cells; detection and characterization of myriads of such loops is a major challenge. The lack of a tractable physical model of a polymer folded into loops limits our ability to interpret experimental data and detect loops. Here, we introduce a new physical model – a polymer folded into a sequence of loops, and solve it analytically. Our model and a simple geometrical argument show how loops affect statistics of contacts in a polymer across different scales, explaining universally observed shapes of the contact probability. Moreover, we reveal that folding into loops reduces the density of topological entanglements, a novel phenomenon we refer as “the dilution of entanglements”. Supported by simulations this finding suggests that up to ∼ 1 − 2Mb chromosomes with loops are not topologically constrained, yet become crumpled at larger scales. Our theoretical framework allows inference of loop characteristics, draws a new picture of chromosome organization, and shows how folding into loops affects topological properties of crumpled polymers.