bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Operative Treatment of Pediatric and Adolescent Forearm Fractures Among American Board of Orthopaedic Surgery Part II Candidates
Authors: Testa Edward J. , Medina Pérez Giancarlo , Tran Megan M. , Gao Burke , Cruz Aristides I.
Published: June 2021

Background:

Pediatric and adolescent forearm fractures are among the most common injuries treated by orthopaedic surgeons. Recent literature shows that there has been an increased interest in operative management for these injuries. The purpose of the current study was to examine the trends in case volume, patient age, surgeon fellowship training, and postoperative complications of surgically treated pediatric forearm fractures over >15-year period of American Board of Orthopaedic Surgery (ABOS) Part II Oral Examination candidates.

Methods:

ABOS Part II candidates’ Oral Examination Case List data from 2003 to 2019 was queried for all pediatric and adolescent (19 y of age and below) forearm fractures treated operatively. Patient demographics, fracture type, complications, and candidate fellowship type were identified for each case. Linear regression was used to delineate annual trends in patient age, complication rates, and case volume by fellowship type. Analysis of variance was performed to evaluate complication rates by fellowship type. Statistical significance for all comparative analyses was set at P-value <0.05.

Results:

A total of 4178 pediatric and adolescent forearm fractures (mean age: 12.6 y; SD: 3.7 y) were treated surgically among ABOS Part II Oral Examination candidates during their 6-month collection periods from 2003 to 2019. The mean patient age decreased significantly (P<0.001) over the study timeframe, while complication rates increased (P<0.001). Pediatric fellowship-trained orthopaedic surgeons performed significantly more cases than general orthopaedic surgeons over recent years (P<0.001). No significant trends were identified between fellowship type and complication rates. The overall surgical complication rate was 17%. The complication rate of open fractures was 24%, which was significantly >15% complication rate of closed fractures (P<0.001).

Conclusions:

Fellowship-trained pediatric orthopaedic surgeons are performing an increasing number of pediatric and adolescent forearm fracture fixation when compared with other orthopaedic surgeons. The mean age of surgically managed pediatric forearm fracture patients has decreased from 2003 to 2019. There has been an increase in the rate of overall reported complications following pediatric forearm fracture surgery over recent years, without any significant association to any particular subspecialty. Future studies should evaluate the comparative effectiveness of surgical treatment of pediatric forearm fractures compared with closed management.
Trends in Endotracheal Intubation During In-Hospital Cardiac Arrests: 2001–2018
Authors: Schwab Kristin , Buhr Russell G. , Grossetreuer Anne V. , Balaji Lakshman , Lee Edward S. , Moskowitz Ari L. ,   for the American Heart Association’s Get With the Guidelines-Resuscitation Investigators
Published: June 2021

OBJECTIVES:

Airway management during in-hospital cardiac arrest represents a fundamental component of resuscitative efforts, yet little is known about temporal trends in intubation during in-hospital cardiac arrest. Our objective was to investigate changes in in-hospital cardiac arrest airway management over time and in response to national guideline updates.

DESIGN:

Observational cohort study of a prospectively collected database.

SETTING:

Multicenter study of hospitals participating in the “Get With The Guidelines—Resuscitation” registry from January 1, 2001, to December 31, 2018.

SUBJECTS:

Adult patients who experienced an in-hospital cardiac arrest and did not have an invasive airway in place prior to the arrest.

INTERVENTIONS:

The primary outcome was the rate of intra-arrest intubation from 2001 to 2018. We constructed multivariable regression models with generalized estimating equations to determine the annual adjusted odds of intubation. We also assessed the timing of intubation relative to the onset of pulselessness and other arrest measures. We used an interrupted time-series analysis to assess the association between the 2010 Advanced Cardiac Life Support guideline update and intubation rates.

MEASUREMENTS AND MAIN RESULTS:

One thousand sixty-six eight hundred patients from 797 hospitals were included. From 2001 to 2018, the percentage of patients intubated during an arrest decreased from 69% to 55% for all rhythms, 73% to 60% for nonshockable rhythms, and 58% to 36% for shockable rhythms (p < 0.001 for trend for all 3 groups). The median time from onset of pulselessness to intubation increased from 5 minutes in 2001 (interquartile range, 2–8 min) to 6 minutes in 2018 (interquartile range, 4–10 min) (p < 0.001 for trend). Following the 2010 guideline update, there was a downward step change and a steeper decrease over time in the rate of intubation as compared to the preintervention period (p < 0.001).

CONCLUSIONS:

Endotracheal intubation rates during in-hospital cardiac arrest have decreased significantly over time, with a more substantial decline following the updated 2010 guideline that prioritized chest compressions over airway management.
Corneal Allograft Rejection Associated With Herpes Zoster Recombinant Adjuvanted Vaccine
Authors: Matoba Alice
Published: June 2021

Purpose:

The purpose of this article is to report 3 cases of corneal allograft rejection that occurred in temporal proximity to administration of the zoster subunit vaccine (RZV).

Methods:

Three cases of corneal transplant rejection that developed after RZV administration were identified. Clinical history, including existence of other risk factors, timing of rejection, corticosteroid therapy at the time of onset of rejection, and course were reviewed.

Results:

The onset of symptoms occurred 5 weeks after the first RZV dose in 1 patient and 1 and 6 weeks after the second dose in the other 2 patients. Coexisting risk factors included history of endothelial keratoplasty in the fellow eye in 1 patient and previous failure of a penetrating keratoplasty because of rejection in a second patient. The third patient had a history of 1 episode of rejection in a previous graft that resolved and then experienced graft failure over several years. In 2 patients, rejection developed despite relatively high levels of topical steroid therapy: prednisolone acetate 1%, 4 × per day in 1 patient and difluprednate 0.05%, 3 × per day in a second patient.

Conclusions:

RZV, which elicits a more robust immune reaction than the zoster live-attenuated vaccine, ZVL, may increase the risk of allograft rejection in immunocompetent patients with preexisting corneal endothelial or penetrating transplants. Based on the available data, it may be reasonable to increase the topical corticosteroid regimen before the first dose, until approximately 3 months after the second dose of ZVL.
A case report of malignant hyperthermia in a patient with myotonic dystrophy type I
Authors: Yoo Seon Woo , Baek Seon Ju , Kim Dong-Chan , Doo A Ram
Published: June 2021

Rationale:

Several hereditary myopathies that can predispose to malignant hyperthermia (MH) are reported. However, the risk of MH in myotonic dystrophy type I (DM1) has been suggested equal to general population, although the evidence is limited to only a few case reports.

Patient concerns:

We encountered a rare case of MH during anesthesia induction with sevoflurane in a male adolescent with previously undiagnosed DM1.

Diagnoses:

After the event, genetic testing revealed the presence of a previously unknown heterozygous missense mutation in ryanodine receptor 1 (RYR1) associated with MH (c.6898T > C; p.ser2300Pro). Concomitantly, the patient was diagnosed with DM1 with abnormal cytosine-thymine-guanine triplet expansion in the DMPK gene.

Interventions:

Dantrolene was administered to treat the hypermetabolic manifestations in 20 minutes after the identification of MH.

Outcomes:

The patient was successfully treated and discharged without any complications. Laboratory abnormalities were recovered to baseline at postoperative 4 days.

Lessons:

The authors suggest that possible MH susceptibility in DM1 patients may be refocused. Genetic testing can be a screening tool for MH susceptibility in these population, prior to receiving general anesthesia.
A case report of monoarthritis in a COVID-19 patient and literature review
Authors: Cincinelli Gilberto , Di Taranto Raffaele , Orsini Francesco , Rindone Andrea , Murgo Antonella , Caporali Roberto
Published: June 2021

Rationale:

COVID-19 presentation is multifaceted and up to 44% of patients affected by COVID-19 experience musculoskeletal complaints, mostly in the form of diffuse aspecific arthromyalgias. Nevertheless, only a few cases of arthritis following SARS-CoV2 infection are reported.

Patient concerns:

A 27-year-old man affected by nail psoriasis presented with monoarthritis 2 weeks after being diagnosed with COVID-19.

Diagnoses:

Diagnostic work-up and differential diagnosis were made difficult by patient isolation, absence of lab tests, and his visit via telemedicine, even though signs of first metacarpophalangeal joint involvement were clear.

Interventions:

Due to the inefficacy of acetaminophen and nonsteroidal anti-inflammatory drugs, the patient was prescribed oral steroids with a rapid benefit.

Outcomes:

The patient's response to oral steroid was prompt and maintained even after therapy tapering. Even so, a formal diagnosis was not possible due to a difficult diagnostic work-up and lack of a long-term follow-up.

Lessons:

Like many other viral diseases, SARS-CoV2 can play as a causative agent or as a trigger for inflammatory arthritis development in predisposed individuals.
Liver stiffness measured by magnetic resonance elastography in early recurrence of hepatocellular carcinoma after treatment
Authors: Zhao Huiyan , Zhang Lijun , Chen Huadong
Published: June 2021

Background:

With high diagnostic accuracy, magnetic resonance elastography (MRE) is a noninvasive tool and can be adopted to measure liver stiffness (LS). In this study, meta-analysis was carried out to further evaluate whether LS measured by MRE can predict early recurrence in patients with hepatocellular carcinoma (HCC).

Methods:

PUBMED, EMBASE, Web of Science, China National Knowledge Infrastructure, and Cochrane Library database were searched for studies related to LS measured by MRE in the prediction of recurrence in patients with HCC. Survival outcome was estimated by hazard ratios and 95% confidence intervals. Meta-analysis was conducted with the Stata 16.0.

Results:

The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusion:

This study will provide evidence support for LS measured by MRE in predicting the recurrence of HCC.

Ethics and dissemination:

The private information from individuals will not be published. This systematic review also should not damage participants’ rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.

OSF Registration Number:

DOI 10.17605/ OSF.IO / SURH3.
Postoperative incision scars and cosmetic satisfaction of living liver donors
Authors: Hsu Ya-Lan , Hsieh Chia-En , Lin Ping-Yi , Lin Shin-Lung , Lin Kuo-Hua , Weng Li-Chueh , Chen Yao-Li
Published: June 2021

Cosmetic appearance is a major concern for living donors. However, little is known about the impact of a surgical scar on body image changes in living liver donors. The aim of this study was to identify potential factors that cause displeasing upper midline incision scar, and to evaluate the overall satisfaction regarding body image and scarring after living donor hepatectomy.

Donors who underwent right lobe hepatectomy were recruited. Exclusion criteria included reoperation, refusal to participate, and lost follow-up. All donors were invited to complete the Vancouver Scar Scale (VSS) and the body image questionnaire. According to the VSS results of upper midline incision scar, donors were divided into 2 groups: good scarring group (VSS ≤4) and bad scarring group (VSS >4). we compared the clinical outcomes, including the demographics, preoperation, intraoperation, and postoperation variables. The study also analyzed the results of the body image questionnaire.

The proportion of male donors was 48.9%. The bad scarring group consisted of 63% of the donors. On multivariate analysis, being a male donor was found to be an independent predictor of a cosmetically displeasing upper midline incision scar with statistical significance. The results of body image questionnaires, there were significant differences in cosmetic score and confidence score among the 2 groups.

The upper midline incision and male donors have higher rates of scarring in comparison with the transverse incision and female donors. Donors who reported having a higher satisfaction with their scar appearance usually had more self-confidence. However, the body image won’t be affected. Medical staff should encourage donors to take active participation in wound care and continuously observe the impact of surgical scars on psychological changes in living liver donors.
Tuina for diabetic peripheral neuropathy
Authors: Wang Fengyang , Wang Fengjuan , Pan Ting , Wu Zhenzhong , Wang Yufeng , Liu Peng , Yu Ziyang , Shang Rui , Song Bailin
Published: June 2021

Background:

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes mellitus, with an incidence ranging from 60% to 90%. With the change in modern dietary structure, the incidence of diabetes is increasing year by year, and DPN is also on the rise. Tuina therapy has been widely used in the treatment of DPN, but there is no systematic review on the treatment of DPN. Therefore, this study aimed to conduct a meta-analysis of Tuina in the treatment of DPN to clarify its efficacy.

Methods:

The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and May 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. Clinical randomized controlled trials related to Tuina for diabetic peripheral neuropathy were included in this study. Language is limited to both Chinese and English. Research selection, data extraction, and research quality assessments were independently completed by two researchers. We then assessed the quality and risk of the included studies and observed the outcome measures.

Results:

This study provides a high-quality synthesis to assess the effectiveness and safety of Tuina for treating diabetic peripheral neuropathy.

Conclusion:

This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for patients with diabetic peripheral neuropathy.

Ethics and dissemination:

The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences.

Registration number:

INPLASY202150027.
Efficacy and safety of acupuncture combined with analgesics on lung cancer pain
Authors: Kuang Renqing , Xiong Guojiang , Lv Wei , Zhao Yun , Yu Min , Jiang Jiawang
Published: June 2021

Background:

Lung cancer (LC) is the malignant tumor with the highest incidence in the world, and treatment methods include surgery, radiotherapy, chemotherapy, and immunotherapy. Cancer pain is a common symptom in patients with LC, and the clinical treatment is to relieve it with analgesics. Acupuncture can relieve cancer pain. This study aims to systematically study the efficacy and safety of acupuncture combined with analgesics on cancer pain in patients with LC.

Methods:

From the beginning to April 2021, search Medline, Embase, Cochrane Central Controlled Trials Register (Central), China National Knowledge Infrastructure (CNKI), Wanfang Database, China Biomedical Literature Database (CBM), and Chinese Science Journal Database (VIP database). Search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing or unpublished trials. The main outcome indicator is the total effective rate of analgesia, and the secondary outcome indicator is pain intensity score and adverse reactions. The RevMan 5.4 software will be used for statistical analysis.

Results:

This study will provide the latest evidence for acupuncture combined with analgesics to relieve LC pain.

Conclusion:

The conclusion of this study is to evaluate the effectiveness and safety of acupuncture combined with analgesics in alleviating LC pain.

INPLASY registration number:

INPLASY202150051
Shaofu Zhuyu decoction for primary dysmenorrhea
Authors: Yuan Lei , Lin Dan , Kang XueLiang , Ye Yu
Published: June 2021

Background:

Primary dysmenorrhea (PD), one of the common gynecological diseases, is more common in adolescent women. According to epidemiological investigation, the incidence of PD accounts for about 60% of all patients with dysmenorrhea, and its symptoms seriously affect the normal working life of women, so it is important to find a more safe and effective treatment. In recent years, traditional Chinese medicine has made a lot of achievements in the treatment of female PD, among which a number of clinical studies have shown that Shaofu Zhuyu decoction (SFZY) can significantly improve the symptoms of dysmenorrhea and improve the therapeutic effect. Therefore, we intend to conduct a systematic review to further clarify the efficacy and safety of SFZY in the treatment of PD.

Methods:

We will search each database from the built-in until May 2021. The English literature mainly searches Cochrane Library, PubMed, excerpt medica database, and Web of Science, while the Chinese literature comes from China National Knowledge Infrastructure, Chinese biomedical literature database, VIP, and Wanfang database. Simultaneously we will retrieval clinical registration tests and grey literatures. This study only screen the clinical randomized controlled trials about XFZY for PD to assess its efficacy and safety. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk, and the continuous is expressed by mean difference (MD) or standard mean difference, eventually the data is synthesized using a fixed effect model or a random effect model depending on whether or not heterogeneity exists. The clinical efficacy and the score of dysmenorrhea symptoms were evaluated as the main outcomes. The artery pulsatility index (API), resistance index (RI), peak systolic/diastolic peak (S/D) were secondary outcomes. Finally, meta-analysis was conducted by RevMan software version 5.3.

Results:

This study will provide high-quality evidence for treatment of PD with SFZY in terms of effectiveness and safety.

Conclusion:

This systematic review aims to provide new options for SFZY treatment of PD in terms of its efficacy and safety.

Ethics and dissemination:

This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.

OSF registration number:

DOI: 10.17605/OSF.IO/DXZHR.
Comparative efficacy and safety of metronomic chemotherapy in breast cancer
Authors: Xie Ying , Chen Xinjie , Li Bingxue , Wang Xiaoming
Published: June 2021

Background:

Metronomic chemotherapy (MC) strategy has been used in breast cancer for more than a decade since it was first proposed. The purpose of this study is to systematically evaluate its efficacy and safety for breast cancer patients at various stages, as well as to clarify the most effective medication strategy when applying MC and discover its most sensitive subpopulation in breast cancer patients.

Method:

We will systematically retrieve random controlled trials evaluating the efficacy and safety of MC in breast cancer on PubMed, Cochrane Library, Embase, and web of science to perform this network meta-analysis. Markov chain Monte Carlo method based on Bayesian Theory will be used to conduct network meta-analysis and the efficacy and safety will be ranked by combining direct and indirect evidence in mixed treatment comparisons. We will assess the quality of literatures with the Cochrane Risk Bias Assessment Tool and assess the strength of the evidence using the GRADE methodology. Data analysis will be completed with the WinBUGS, R, Stata and RevMan softwares.

Results and conclusion:

Through the analysis, we can obtain the ranking of efficacy and safety in different MC strategy, and reveal the specific breast cancer groups that are more sensitive to MC. We access the effectiveness by disease free survival, progress free survival, time to progress, objective response rate, and overall survival, and measure the toxicity by dose-limiting toxicity. The result of our study could provide evidence for clinicians to make a better choice when they consider MC.

Inplasy registration number:

INPLASY202140142.
The comparison of Nice knots and traditional methods as an auxiliary reduction-fixation technique in pre-contoured locking plate fixation for comminuted Robinson type 2B clavicle fracture
Authors: Hong Shengkun , Wang Wei , Guo Jinku , He Feixiong , Wang Cong
Published: June 2021

Open reduction and pre-contoured locking plate fixation is a popular treatment option for displaced midshaft clavicle fracture. Lag screw and cerclage are 2 main intraoperative techniques to reduce and fix fragments. However, both lag screw and metallic cerclage have disadvantages. The doubled-suture Nice knot has been reported in many areas of orthopedic surgery for its effectiveness. This study aims to compare the outcomes of comminuted mid-shaft clavicle fractures reduced by Nice knots vs traditional techniques (lag screw or/and metallic cerclage) when bridged with pre-contoured locking plates.

We retrospectively reviewed 101 patients (65 females and 36 males) diagnosed with midshaft clavicle fractures with at least one wedge fragment reduced by either Nice knots or traditional methods and bridged with pre-contoured locking plates between December 2016 and April 2019. Operation time, functional outcomes, pain, patient satisfaction, fracture healing, and complications were assessed at a follow-up of 12 to 40 months.

The mean age of all the patients was 50.8 years. There were 52 and 49 patients in the Nice knot group and traditional group respectively, and no differences between 2 groups were found in general patient characteristics, fracture type, follow up and injury-to-surgery duration. The Nice knot group had significant less operation time (P < .01) than the traditional group (mean and standard deviation [SD], 78.6 ± 19.0 compared with 94.4 ± 29.9 minutes, respectively). For healing time, functional score, pain, satisfaction and complications, there were no significant differences between groups, despite the Nice knot group had slightly better results.

Both Nice knots and traditional methods treated for comminuted Robinson type 2B clavicle fractures were effective and safe. And the Nice knots seemed to be superior with significant less operation time.
Therapeutic efficacy of arthroscopy-assisted transosseous fixation with the Versalok suture anchor for tibial eminence fractures in adults
Authors: She Yuanshi , Guo Dongsheng , Chen Guangxiang , Xu Youjia
Published: June 2021

To investigate the clinical outcomes of arthroscopy-assisted transosseous fixation of tibial eminence fractures with the Versalok suture anchor in adults.

A total of 23 adult cases of tibial eminence fractures treated between June 2016 and March 2019 were retrospectively analyzed. The results of the preoperative drawer test and Lachman test were positive. Radiography and computed tomography were performed before and after the procedure. Magnetic resonance imaging was performed in every patient after admission. Arthroscopy-assisted fracture reduction and Orthocord high-strength suture fixation with two Versalok anchors were performed in all the patients. The International Knee Documentation Committee scale and the Lysholm Knee Scoring Scale were used to evaluate outcomes during the follow-up period. Additionally, the KT-2000 knee stability test was performed.

At the final follow-up, all the fractures had proceeded to bony union and no wound infection was observed. The average Lysholm Knee Score of the affected knees was 93.1 (range, 90–98), which was not significantly different from that of the healthy knees (t = 0.732, P = .132). Based on the International Knee Documentation Committee scale results, 21 patients were graded as normal and the other 2 patients were graded as nearly normal. The KT-2000 test showed that the anterior displacement of the affected side and the healthy side was less than 3.6 mm in all cases.

The outcomes indicated firm fixation and good fracture healing with minimal trauma. Thus, arthroscopy-assisted transosseous fixation with Versalok suture anchors for adult tibial eminence fractures seems to have satisfactory clinical outcomes.
The therapeutic effects of glucagon-like peptide-1 receptor agonists and metformin on polycystic ovary syndrome
Authors: Ma Ruilin , Ding Xuesong , Wang Yanfang , Deng Yan , Sun Aijun
Published: June 2021

Background:

Obesity and insulin resistance (IR) are common in polycystic ovary syndrome (PCOS), which contribute to reproductive and metabolic abnormalities. Metformin increases insulin sensitivity, but it is associated with unsatisfied benefits of weight loss. Recent studies have reported that glucagon-like peptide 1 (GLP-1) receptor agonists improve IR and reduce weight in women with PCOS. We conducted a systematic review and meta-analysis to compare the effects between GLP-1 receptor agonists and metformin, and between GLP-1 receptor agonist-metformin combination and GLP-1 receptor agonists in overweight/obese women with PCOS on anthropometric, metabolic, reproductive outcomes.

Methods:

Databases including PubMed, EMBASE, Web of Science, and Cochrane Library were selected to search for randomized controlled trials (RCTs) published in English up to March 2020. Eligible studies were identified according to the inclusion criteria. The primary outcomes included menstrual frequency, body mass index (BMI), total testosterone, and the homeostatic model assessment of insulin resistance. GRADE criteria were implemented to assess the quality of evidence for primary outcomes.

Results:

Seven RCTs were selected for analysis, comprising 464 overweight/obese women with PCOS. In the low-quality evidence, a meta-analysis demonstrated that GLP-1 receptor agonists showed better effects relative to metformin on the reduction of body mass index (mean difference − 1.72; 95% confidence interval −2.46 to −0.99, P < .001) and homeostatic model assessment of insulin resistance (standard mean difference −0.37; 95% confidence interval − 0.60,− 0.15, P = .001). Moreover, the combination therapy exhibited similar effects on primary outcomes relative to GLP-1 receptor agonist alone. GLP-1 receptor agonists were also found to be associated with lower abdominal girth compared to metformin. A meta-analysis of gastrointestinal discomfort showed no significant difference between GLP-1 receptor agonist and metformin therapies, and between the combination therapy and GLP-1 receptor agonist alone.

Conclusions:

GLP-1 receptor agonists appear to be more beneficial for weight loss and IR improvement compared to metformin for overweight/obese women with PCOS. However, the combination treatment displays comparable effects with GLP-1 receptor agonist alone. The incidence of gastrointestinal discomforts was similar in different groups. However, the quality of the body of evidence is “low.” Further prospective RCTs and cost-effectiveness analyses are also warranted to guide GLP-1 receptor agonists to treat women with PCOS.
Delayed pneumocephalus induced by repeated percutaneous aspiration after spinal surgery
Authors: Zhao Yu , Cao Liming , Sheng Qi , Liu Ruifang , Dong Gaolei , Tong Xibao
Published: June 2021

Rationale:

Severe tension pneumocephalus can lead to drowsiness, coma, and even brain hernia and death. The occurrence of delayed pneumocephalus after spinal surgery is rarely reported and often ignored. Herein, we report a case of delayed pneumocephalus after repeated percutaneous aspiration following spinal surgery.

Patient concerns:

A 55-year-old man was admitted in October 2020 because of aggravation in bilateral lower limb weakness and dysuria for seven days. He was diagnosed with liver cancer a year ago, and he underwent several operations because of tumor recurrence. The patient underwent thoracic vertebrae tumor excision on this admission, and no cerebrospinal fluid leakage was discovered during surgery. After the third drainage by percutaneous aspiration, the patient complained of severe headache and vomiting on postoperative day 16.

Diagnosis:

Emergency brain computed tomography revealed massive pneumocephalus.

Interventions:

Thereafter, suction drainage was discontinued, and he was placed on bed rest and administered intravenous mannitol.

Outcomes:

Repeated computed tomography showed complete resolution of the pneumocephalus after five days.

Lessons:

Wound exudates and cystic fluid after spinal surgery should be differentiated from cerebrospinal fluid leakage. Reckless percutaneous aspirations can form pneumocephalus in patients with an occult dural injury, and pneumocephalus can occur up to 16 days after surgery. Early diagnosis of pneumocephalus is crucial to avoid severe consequences.
GABAA receptor encephalitis associated with human parvovirus B19 virus infection
Authors: Valle Daniel Almeida do , Santos Mara Lúcia S. Ferreira , Spinosa Mônica J. , Telles Bruno A. , Prando Carolina , Cordeiro Mara L.
Published: June 2021

Rationale:

Human parvovirus B19 (B19) infection can produce a spectrum of clinical syndromes, including neurological manifestations, most notably encephalitis. Although symptoms suggestive of autoimmune disease in patients with B19 infection have been previously described, a clear association of autoimmune encephalitis with B19 infection has yet to be established.

Patient concerns:

We describe the case of a 6-year-old boy who was hospitalized due to status epilepticus, which evolved to super-refractory status epilepticus that was only mildly responsive to anticonvulsant drugs.

Diagnosis:

A cerebrospinal fluid study identified slight pleocytosis and B19 positivity. A subsequent autoimmunity cerebrospinal fluid study revealed the presence of anti-γ-aminobutyric acid type A (GABAA) receptor antibodies.

Interventions:

After pulse therapy with methylprednisolone and continuous therapy with prednisolone with cyclosporine, the patient experiencing seizure persistence with disordered motor function manifestations and only minor improvement in consciousness, and so, plasmapheresis was performed. With continued immunosuppressive treatments with cyclosporine and prednisolone, the patient's clinical picture showed progressive improvement, with good control of seizures. Although the patient tolerated withdrawal of the anticonvulsant drugs well, he developed seizures when corticosteroid therapy withdrawal was attempted, so was started on azathioprine.

Outcomes:

After immunosuppressive therapy, the patient evolved with complete remission of symptoms, normal neurological examination and age-appropriate neuropsychomotor development.

Lessons:

The present case characteristics, together with previous findings, support the hypothesis that autoimmunity may be triggered by extensive antigen release due to degeneration of infected neurons. This case highlights the importance of early clinical suspicion and treatment.
The impact of atherosclerotic cardiovascular disease, dyslipidaemia and lipid lowering therapy on Coronavirus disease 2019 outcomes: an examination of the available evidence
Authors: Adam Safwaan , Ho Jan Hoong , Bashir Bilal , Iqbal Zohaib , Ferdousi Maryam , Syed Akheel A. , Soran Handrean
Published: June 2021

Purpose of review

Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit.

Recent findings

There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these.

In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.
A Comparison of 18F-PSMA-1007 and 64Cu-PSMA in 2 Patients With Metastatic Prostate Cancer
Authors: Cardoza-Ochoa David R. , Rivera-Bravo Belén
Published: June 2021

18F–prostate-specific membrane antigen (PSMA) 1007 is one of the most promising radiotracers for PET imaging in prostate cancer, minimal urinary clearance, and higher spatial resolution, which are the most outstanding features. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. We present images of metastatic prostate cancer in two patients, where 64Cu-PSMA PET/CT was performed one day after 18F-PSMA-1007 PET/CT. In the two patients, both radiotracers provided high image quality and a similar range of detection for metastatic lesions.
Repurposing of Clinically Approved Poly-(ADP-Ribose) Polymerase Inhibitors for the Therapy of Sepsis
Authors: Santos Sidnéia Sousa , Brunialti Milena Karina Colo , Soriano Francisco Garcia , Szabo Csaba , Salomão Reinaldo
Published: June 2021

Sepsis’ pathogenesis involves multiple mechanisms that lead to a dysregulation of the host's response. Significant efforts have been made in search of interventions that can reverse this situation and increase patient survival. Poly (ADP-polymerase) (PARP) is a constitutive nuclear and mitochondrial enzyme, which functions as a co-activator and co-repressor of gene transcription, thus regulating the production of inflammatory mediators. Several studies have already demonstrated an overactivation of PARP1 in various human pathophysiological conditions and that its inhibition has benefits in regulating intracellular processes. The PARP inhibitor olaparib, originally developed for cancer therapy, paved the way for the expansion of its clinical use for nononcological indications. In this review we discuss sepsis as one of the possible indications for the use of olaparib and other clinically approved PARP inhibitors as modulators of the inflammatory response and cellular dysfunction. The benefit of olaparib and other clinically approved PARP inhibitors has already been demonstrated in several experimental models of human diseases, such as neurodegeneration and neuroinflammation, acute hepatitis, skeletal muscle disorders, aging and acute ischemic stroke, protecting, for example, from the deterioration of the blood–brain barrier, restoring the cellular levels of NAD+, improving mitochondrial function and biogenesis and, among other effects, reducing oxidative stress and pro-inflammatory mediators, such as TNF-α, IL1-β, IL-6, and VCAM1. These data demonstrated that repositioning of clinically approved PARP inhibitors may be effective in protecting against hemodynamic dysfunction, metabolic dysfunction, and multiple organ failure in patients with sepsis. Age and gender affect the response to PARP inhibitors, the mechanisms underlying the lack of many protective effects in females and aged animals should be further investigated and be cautiously considered in designing clinical trials.
Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile
Authors: Sharifi Fatemeh , Sharififar Fariba , Pournamdari Mostafa , Ansari Mehdi , Tavakoli Oliaee Razieh , Bamorovat Mehdi , Khosravi Ahmad , Keyhani Ali Reza , Salarkia Ehsan , Mortazaeizdeh Abbas , Dabiri Shahriar , Khamesipour Ali , Sharifi Iraj
Published: June 2021

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.

Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.

Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.

Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.

Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.

Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.
Evaluating the utility of high-resolution proximity metrics in predicting the spread of COVID-19
Authors: Mehrab Zakaria , Adiga Aniruddha , Marathe Madhav V. , Venkatramanan Srinivasan , Swarup Samarth
Published: June 2021

Abstract

High resolution mobility datasets have become increasingly available in the past few years and have enabled detailed models for infectious disease spread including those for COVID-19. However, there are open questions on how such a mobility data can be used effectively within epidemic models and for which tasks they are best suited. In this paper, we extract a number of graph-based proximity metrics from high resolution cellphone trace data from X-Mode and use it to study COVID-19 epidemic spread in 50 land grant university counties in the US. We present an approach to estimate the effect of mobility on cases by fitting an ODE based model and performing multivariate linear regression to explain the estimated time varying transmissibility. We find that, while mobility plays a significant role, the contribution is heterogeneous across the counties, as exemplified by a subsequent correlation analysis. We subsequently evaluate the metrics’ utility for case surge prediction defined as a supervised classification problem, and show that the learnt model can predict surges with 95% accuracy and 87% F1-score.
Acetylated microtubules are required for maintenance of the barrier between two adjacent tissues
Authors: Antel Matthew , Simao Taylor , Bener Muhammed Burak , Inaba Mayu
Published: June 2021

Microtubule acetylation is found in populations of stable, long-lived microtubules, occurring on the conserved lysine 40 (K40) residue of α-tubulin, catalyzed by α-tubulin acetyltransferases (αTATs). K40 acetylation has been shown to stabilize microtubules via enhancing microtubule resilience against mechanical stress. Here we show that Drosophila CG17003/leaky (Lky), an αTAT, is required for proper oogenesis. We found that loss of lky disrupted the cell junction between germline cyst and follicle epithelial cells, adjacent cells that form an egg chamber. This resulted in leakage of germline contents into somatic follicle cells. The follicle cells that received germline-derived nanos gene product failed to maintain their cell fate, leading to an egg chamber fusion. The same phenotype was observed upon replacement of major α-tubulin84BK40 with α-tubulin84BK40A (non-acetylable tubulin), suggesting α-tubulinK40 acetylation is required for the boundary integrity of these two adjacent tissues. Taken together, this study provides the first in vivo function of tubulin acetylation in maintaining the integrity of a tissue barrier.
Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments
Authors: Stahl Aaron , Noyes Nathaniel C. , Boto Tamara , Jing Miao , Zeng Jianzhi , King Lanikea B. , Li Yulong , Davis Ronald L. , Tomchik Seth M.
Published: June 2021

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which was required to maintain responsivity to odors in untrained conditions. Downstream from the mushroom body, a set of MBONs that receive their input from the γ3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which discriminative effects influence appetitive memory and decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.
Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation induced tissue damage
Authors: Rognoni Emanuel , Goss Georgina , Hiratsuka Toru , Kober Katharina I , Lui Prudence PokWai , Tsang Victoria SK , Hawkshaw Nathan J , Pilkington Suzanne M , Sipilä Kalle H , Cho Inchul , Ali Niwa , Rhodes Lesley E , Watt Fiona M
Published: June 2021

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt-signalling in skin, stimulation of fibroblast proliferation by epidermal β-catenin stabilisation did not support papillary dermis repair. Acute UVR triggered an infiltrate of neutrophils and T cell subpopulations and increased pro-inflammatory prostaglandin signalling in skin. Depletion of CD4 and CD8 positive cells resulted in increased papillary fibroblast depletion, which correlated with an increase in DNA damage and reduction in fibroblast proliferation. Conversely, topical COX-2 inhibition prevented fibroblast depletion and neutrophil infiltration after UVR. We conclude that loss of papillary fibroblasts is primarily induced by a deregulated inflammatory response, with infiltrating T cells supporting fibroblast survival upon UVR-induced environmental stress.

Graphical abstract