bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra- and inter-host evolution of H9N2 influenza A virus in Japanese quail
Authors: Ferreri Lucas M , Geiger Ginger , Seibert Brittany , Obadan Adebimpe , Rajao Daniela , Lowen Anice C , Perez Daniel R
Published: January 2022

Influenza A viruses (IAVs) are constantly evolving. Crucial steps in the infection cycle, such as sialic acid (SA) receptor binding on the host cell surface, can either promote or hamper the emergence of new variants. We previously assessed the relative fitness in Japanese quail of H9N2 variant viruses differing at a single amino acid position, residue 216 in the hemagglutinin (HA) viral surface protein. This site is known to modulate SA recognition. Our prior study generated a valuable set of longitudinal samples from quail transmission groups where the inoculum comprised different mixed populations of HA 216 variant viruses. Here, we leveraged these samples to examine the evolutionary dynamics of viral populations within and between inoculated and naïve contact quails. We found that positive selection dominated HA gene evolution, but fixation of the fittest variant depended on the competition mixture. Analysis of the whole genome revealed further evidence of positive selection acting both within and between hosts. Positive selection drove fixation of variants in non-HA segments within inoculated and contact quails. Importantly, transmission bottlenecks were modulated by the molecular signature at HA 216, revealing viral receptor usage as a determinant of transmitted diversity. Overall, we show that selection strongly shaped the evolutionary dynamics within and between quails. These findings support the notion that selective processes act effectively on IAV populations in poultry hosts, facilitating rapid viral evolution in this ecological niche.
Pre-Eclampsia
Authors: Chappell Lucy C. , Cluver Catherine A. , Kingdom John , Tong Stephen
Published: January 2022

(Abstracted from Lancet 2021;398:341–354)

Preeclampsia affects approximately 3% to 5% of all pregnancies and is a substantial contributor to maternal morbidity and mortality. The hallmark features are hypertension and proteinuria, and significant complications of multiorgan injury include eclamptic seizures, pulmonary edema, epigastric pain and liver failure, and placental abruption.
Widespread Implementation of a Low-Cost Telehealth Service in the Delivery of Antenatal Care During the COVID-19 Pandemic: An Interrupted Time-Series Analysis
Authors: Palmer Kirsten R. , Tanner Michael , Davies-Tuck Miranda , Rindt Andrea , Papacostas Kerrie , Giles Michelle L. , Brown Kate , Diamandis Helen , Fradkin Rebecca , Stewart Alice E. , Rolnik Daniel L. , Stripp Andrew , Wallace Euan M. , Mol Ben W. , Hodges Ryan J.
Published: January 2022

(Abstracted from Lancet 2021;398:41–52)

In response to the COVID-19 pandemic, health care systems around the world had to quickly adapt to protect patients and staff from exposure. In Australia, a government initiative was launched to temporarily change public health funding to support the use of telehealth.
Evidence for Early Cyclosporine Treatment for Hunner Lesion Interstitial Cystitis
Authors: Vollstedt Annah , Tennyson Lauren , Turner Katherine , Hasenau Deborah , Saon Md , McCartney Teresa , Beck Dana , Gilleran Jason , Peters Kenneth
Published: January 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2021; doi: 10.1097/SPV.0000000000001108)

Hunner lesion interstitial cystitis (HLIC) is a form of interstitial cystitis/bladder pain syndrome (IC/BPS), occurring in 5%–57% of patients. HLIC is diagnosed by the presence of Hunner lesions on cystoscopy.
Mouse Oocyte Vitrification With and Without Dimethyl Sulfoxide: Influence on Cryo-Survival, Development, and Maternal Imprinted Gene Expression
Authors: Cantatore Clementina , George Jenny S. , Depalo Raffaella , D'Amato Giuseppe , Moravek Molly , Smith Gary D.
Published: January 2022

(Abstracted from J Assist Reprod Genet 2021;38:2129–2138)

Oocyte preservation allows preservation of fertility in women for a multitude of reasons including those at genetic risk of diminished ovarian reserve, those undergoing cancer treatment, or those aiming to protect against future infertility due to reproductive aging. The 2 primary methods of human oocyte cryopreservation include slow rate freezing/thawing and vitrification/warming.
N-myristoyltransferase 2–based Blood Test for the Detection of Colorectal Adenomatous Polyps and Cancer
Authors: Rathinagopal Tharmini , Bhanot Shiv , Yegrov Sergey , Min Jordan , Hu Nan , Fang John , Greene Tom H. , Varma Shrivastav Shailly , Singh Harminder , Shrivastav Anuraag
Published: January 2022

Background:

Colorectal cancer is the second leading cause of cancer-related deaths. This study demonstrates the utility of a simple blood test with high sensitivity and specificity for colorectal adenomatous polyps and cancer. A simple blood test with high sensitivity and specificity for adenomas would help identify individuals for a follow-up colonoscopy during which any adenomatous polyps found could be removed, thus preventing colorectal cancer (CRC).

Methods:

We determined the H-score by using immunohistochemical analyses of N-myristoyltransferase 2 (NMT2) in peripheral blood mononuclear cells (PBMC) isolated from the blood. We determined the sensitivity and specificity of the NMT2-based blood test in identifying colorectal adenomatous polyps and cancer.

Design:

All experimental procedures were performed by research personnel blinded to the colonoscopy status of the participants.

Setting:

In this cohort study, participants were recruited from those coming for an outpatient colonoscopy at a referral center.

Participants:

PBMC were collected from 74 subjects at the Health Sciences Centre, Winnipeg, Canada. Samples were collected from colonoscopy patients prior to colonoscopy. All 74 subjects were included in CRC vs. non-CRC analysis, whereas only 70 subjects were analyzed for colorectal adenomatous polyps and cancer versus individuals with no evidence of disease and non-adenomatous polyps. NMT2 expression was tested in samples by immunohistochemistry.

Results:

The expression of NMT2 was significantly higher in PBMC of subjects with colorectal adenomatous polyps and cancer (n = 34) compared with individuals with non-adenomatous polyps or no evidence of disease (n = 36) (P < 0.0001). The test had an overall sensitivity of 91% (95% confidence intervals: 84.49–97.80) and specificity of 81% (95% confidence intervals: 71.28–89.83) in detecting colorectal adenomatous polyps and cancer (all stages).

Conclusions:

Our results suggest that the sensitivity of NMT2 in detecting adenomatous polyps is high (91%). A simple blood-based CRC screening test using NMT2 expression detects colorectal adenomatous polyps and cancer with high sensitivity and specificity has the potential of increasing the compliance for CRC screening as has been reported for other blood-based CRC screening tests.
Radiation Exposure Among Orthopaedic Trauma Surgeons: Deconstructing Commonly Held Myths and Misperceptions
Authors: Raffetto Michael L. , Blum Laura E. , Abbenhaus Eric J. , Hautala Gavin S. , Lemieux Bryan , Pease Tyler , Wright Raymond D. , Moghadamian Eric S. , Aneja Arun , Blair James A. , Matuszewski Paul E.
Published: January 2022

Objectives:

To review and evaluate the validity of common perceptions and practices regarding radiation safety in orthopaedic trauma.

Design:

Retrospective study.

Setting:

Level 1 trauma center.

Subjects:

N/A.

Intervention:

The intervention involved personal protective equipment.

Main Outcome Measurements:

The main outcome measurements included radiation dose estimates.

Results:

Surgeon radiation exposure estimates performed at the level of the thyroid, chest, and pelvis demonstrate an estimated total annual exposure of 1521 mR, 2452 mR, and 1129 mR, respectively. In all cases, wearing lead provides a significant reduction (90% or better) in the amount of radiation exposure (in both radiation risk and levels of radiation reaching the body) received by the surgeon. Surgeons are inadequately protected from radiation exposure with noncircumferential lead. The commonly accepted notion that there is negligible exposure when standing greater than 6 feet from the radiation source is misleading, particularly when cumulative exposure is considered. Finally, we demonstrated that trauma surgeons specializing in pelvis and acetabular fracture care are at an increased risk of exposure to potentially dangerous levels of radiation, given the amount of radiation required for their caseload.

Conclusion:

Common myths and misperceptions regarding radiation in orthopaedic trauma are unfounded. Proper use of circumferential personal protective equipment is critical in preventing excess radiation exposure.
Evaluation of a Novel Multidisciplinary Preoperative Workup Strategy for Geriatric Hip Fractures
Authors: Steffensmeier Andrew , Hoge Connor , Shah Nihar , Matar Robert , Rice Morgan , Grawe Erin , Held Justin , Budde Bradley , Laughlin Richard , Sagi H. Claude
Published: January 2022

Objective:

To determine the financial and clinical impact of a standardized, multidisciplinary team for surgical clearance and optimization in geriatric hip fracture patients.

Design:

Retrospective case series.

Setting:

Level-1 trauma center.

Patients:

One hundred twenty-four geriatric patients (age >65 years old) in the preprotocol group (cohort 1; January 2017–December 2018) and 98 geriatric patients in the postprotocol group (cohort 2; October 2019–January 2021) with operative hip fractures.

Intervention:

Implementation of a multidisciplinary team protocol consisting of Anesthesiology, Internal Medicine and Orthopedic Surgery departments for the assessment of medical readiness and optimization for surgical intervention in geriatric hip fractures.

Main Outcome Measures:

Rate of cardiology consultation, need for cardiac workup (echocardiography stress testing, heath catheterization), time to medical readiness (TTMR), time to surgery, case-cancellation rate, length of stay (LOS), and total hospitalization charges.

Results:

Following implementation of the new protocol, there were significant (P < 0.001) decreases in TTMR (19 vs. 11 hours), LOS (149 vs. 120 hours), case cancellation rate, and total hospital charges ($84,000 vs. $62,000). There were no significant differences with respect to in-hospital complications or readmission rates/mortality rates at 1 year.

Conclusions:

Following implementation of a protocolized, multidisciplinary approach to optimizing geriatric fracture patients, we were able to demonstrate a reduction in unnecessary preoperative testing, TTMR for surgery, case cancellation rate, LOS, and total hospitalization charge—without a concomitant increase in complications or mortality. This study highlights that standardization of the perioperative care for geriatric hip fracture patients can provide effective patient care while also lowering financial and logistical burden in care for these injuries.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Histopathological and Clinical Analysis of Skin Rashes in Children With Multisystem Inflammatory Syndrome Associated With COVID-19
Authors: Yuksel Selcuk , Demirkan Nese Calli , Comut Erdem , Yilmaz Munevver , Gurses Dolunay
Published: January 2022

Introduction:

A new entity, which occurs a few weeks after SARS-CoV-2 infection and resembling incomplete Kawasaki disease or toxic shock syndrome, has been defined and named multisystem inflammatory syndrome (MIS-C) associated with COVID-19 in children. The aim of our study was to describe histopathological characteristics of skin lesions of MIS-C patients to reveal whether there is a relationship between histopathological features and clinical manifestations.

Materials and Methods:

Seventeen who had skin involvement of 57 patients who were diagnosed with MIS-C between December 2020 and February 2021 were included in this prospective study. Demographic information, laboratory findings, and patients' managements were recorded. Skin biopsies were taken simultaneously of each patient. Formalin-fixed, paraffin-embedded skin samples were examined microscopically.

Results:

The rate of skin rash was 30% in patients with MIS-C and was predominantly the maculopapular type. The anatomical distribution of the rash was evaluated as localized in 10 and generalized in 7 patients. In patients with myocarditis, C-reactive protein and fibrinogen were found to be significantly higher, and lymphocyte and albumin values were found to be low. Herpes-like inclusions were found in the microscopic examination of 2 patients with a history of zona zoster in themselves or in their mother. There was a significant difference between keratinocyte necrosis and some clinical parameters.

Discussion:

Localized skin lesions appear to be associated with a more severe inflammatory.
Adsorption of Plutonium onto Several Natural Sediments
Authors: Yu Jing , Zhang Qingyu
Published: January 2022

The adsorption of plutonium (Pu) onto several natural sediments was studied using batch experiments to determine the different factors influencing Pu adsorption. These factors include the possible effect of different methods for adding Pu solution, the initial oxidation state of Pu, the particle size of the sediments, the pH, and the ionic strength of solution. The method used for adding Pu solution greatly influenced the species of Pu in sediment-groundwater systems and the adsorption behavior of Pu onto the sediments. Initial oxidation state of Pu, clay mineral content, particle size of sediment, pH, and ionic strength all appear to impact adsorption. The sediments preferred to adsorb Pu(IV) rather than Pu(V). The adsorption of Pu depended on the particle size and clay mineral content of the sediments; the higher the clay mineral content and the smaller the particle size, the more adsorption for Pu. The insoluble species of Pu formed in sediment-groundwater systems at pH 9.3 resulted in the decrease of adsorption capacity. The adsorption capacity increased with pH increasing at pH < 9. Ion exchange was the dominant mechanism for Pu adsorption onto the sediments at pH < 7.5. It appeared that the ionic strength had a stronger influence on adsorption capacity than pH.
Testing the NASA BioSentinel Pixel Dosimeter Using Gamma-ray and Neutron Sources at the LLNL Calibration Lab
Authors: Homan J. , Lusby T. C. , Ricco A. J. , Mintz J. L. , Braby L. A. , Straume T.
Published: January 2022

The objective of this paper is to evaluate the accuracy of the NASA BioSentinel Pixel Dosimeter (BPD) using gamma-ray and neutron sources in a standard calibration lab. The dosimeter tested here is the ground-based version of the BPD that will be onboard the BioSentinel mission. The BPD was exposed to radiation from 60Co, 137Cs, and 252Cf at selected distances (dose rates) at the Lawrence Livermore National Laboratory (LLNL) Radiation Calibration Laboratory (RCL), and the results were compared with NIST traceable benchmark values. It is recognized that these sources are not analogs for the space environment but do provide direct comparisons between BPD response and well characterized calibration lab values. For gamma rays, the BPD measured absorbed dose agrees to ≤ 3.8% compared with RCL benchmark values. For neutrons, the results show that the BPD is insensitive, i.e., the BPD detected only the gamma-ray dose component from 252Cf. The LET spectra obtained for gamma rays from 60Co and 252Cf are consistent with expectations for these gamma-ray energies, but the LET spectrum from the 137Cs gamma rays differs substantially. The potential causes for this difference are the high dose rate from 137Cs and the lower secondary electron energy produced by 137Cs gamma rays. However, neither of these results in errors in the absorbed dose. Based on comparisons with NIST-traceable standards, it is evident that the BPD can measure absorbed dose accurately from low LET charged particles. The sensor’s insensitivity to neutrons is unlikely to be a limitation for the BioSentinel mission due to the expected low secondary neutron fluence.
Neuroinflammation, Early-Life Adversity, and Brain Development
Authors: Andersen Susan L.
Published: January 2022

The overarching objective is to review how early exposure to adversity interacts with inflammation to alter brain maturation. Both adversity and inflammation are significant risk factors for psychopathology. Literature relevant to the effects of adversity in children and adolescents on brain development is reviewed. These studies are supported by research in animals exposed to species-relevant stressors during development. While it is known that exposure to adversity at any age increases inflammation, the effects of inflammation are exacerbated at developmental stages when the immature brain is uniquely sensitive to experiences. Microglia play a vital role in this process, as they scavenge cellular debris and prune synapses to optimize performance. In essence, microglia modify the synapse to match environmental demands, which is necessary for someone with a history of adversity. Overall, by piecing together clinical and preclinical research areas, what emerges is a picture of how adversity uniquely sculpts the brain. Microglia interactions with the inhibitory neurotransmitter GABA (specifically, the subtype expressing parvalbumin) are discussed within contexts of development and adversity. A review of inflammation markers in individuals with a history of abuse is combined with preclinical studies to describe their effects on maturation. Inconsistencies within the literature are discussed, with a call for standardizing methodologies relating to the age of assessing adversity effects, measures to quantify stress and inflammation, and more brain-based measures of biochemistry. Preclinical studies pave the way for interventions using anti-inflammation-based agents (COX-2 inhibitors, CB2 agonists, meditation/yoga) by identifying where, when, and how the developmental trajectory goes awry.
Prolonged Viral Shedding in Three Young Adult Cases of COVID-19
Authors: Dong Wen-Yi , Zhou Ming-Ju , Huang Lei , Zhang Chao , Wang Fu-Sheng , Xie Zhou-Hua
Published: January 2022

Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.
A Resident-driven Quality Improvement Project to Increase Primary Care Follow-up after Congestive Heart Failure Exacerbation: Use of a Quality and Safety Award
Authors: Monday Lea M. , Sebastian Joseph , Nguyen Paul , Yazdanpanah Omid , Solokowski Caleb , Chi Jane , Bazzy Kareem
Published: January 2022

Objectives:

Congestive heart failure (CHF) is the most common cause of 30-day inpatient readmission. Studies have found that early follow-up with primary care physicians (PCP) within 7 days of discharge may improve 30-day readmission rates; however, many have used a multidisciplinary discharge coordination team, which is not a resource at all centers. Here, the authors present a resident-driven quality improvement initiative using a monthly quality and safety award to increase early PCP follow-up for veterans discharged following admissions due to a CHF exacerbation. Primary outcomes were percentage of PCP follow-up within 7 days and median time to PCP follow-up. Secondary outcomes included percentage of patients attending a PCP visit within 7 days, 30-day readmission, and 30-day mortality.

Methods:

This prepost quasi-experimental cohort study evaluated 3 concurrent quality improvement interventions to increase PCP follow-up after CHF exacerbation. Process maps and Ishikawa diagrams examined the discharge process. Interventions included a standardized discharge scheduling order, monthly education on the process, and monthly aggregated performance feedback for each medical resident. A patient safety and quality award was given to the team with the highest rate of PCP appointments scheduled within 7 days. Patient characteristics and outcomes were gathered for a 6-month historic period and 6-month intervention period. Test of proportions and Wilcoxon Rank-Sum test were used to compare groups.

Results:

A total of 294 patients were discharged (161 in historic group and 133 in intervention group). Appointments scheduled within 7 days of discharge increased from 43% to 79% (P < 0.001). Median time to PCP follow-up decreased from 8 to 6 days (P < 0.001). Patients who completed (showed up to) a PCP appointment within 7 days increased from 16% to 41% (P < 0.001). There was no impact on 30-day readmission or mortality; however, the number of study subjects was too small to rule out an effect.

Conclusions:

A standardized discharge scheduling order, more robust resident education, and a monthly patient safety and quality award resulted in a significant increase in the rate of primary care follow-up within 7 days of CHF exacerbation.
Sports-Related Concussions in Adults Presenting to Canadian Emergency Departments
Authors: Rowe Brian H. , Yang Esther H. , Gaudet Lindsay A. , Lowes Justin , Eliyahu Leeor , Villa-Roel Cristina , Beach Jeremy , Mrazik Martin , Cummings Garnet , Voaklander Donald
Published: January 2022

Objective:

To document the occurrence and recovery outcomes of sports-related concussions (SRCs) presenting to the Emergency Department (ED) in a community-based sample.

Design:

A prospective observational cohort study was conducted in 3 Canadian hospitals.

Setting:

Emergency Department.

Patients:

Adults (≥17 years) presenting with a concussion to participating EDs with a Glasgow Coma Scale score ≥13 were recruited.

Interventions:

Patient demographics (eg, age and sex), clinical characteristics (eg, history of depression or anxiety), injury characteristics (eg, injury mechanisms and loss of consciousness and duration), and ED management and outcomes (eg, imaging, consultations, and ED length of stay) were collected.

Main outcome measures:

Patients' self-reported persistent concussion symptoms, return to physical activity status, and health-related quality of life at 30 and 90 days after ED discharge.

Results:

Overall, 248 patients were enrolled, and 25% had a SRC. Patients with SRCs were younger and reported more physical activity before the event. Although most of the patients with SRCs returned to their normal physical activities at 30 days, postconcussive symptoms persisted in 40% at 90 days of follow-up. After adjustment, there was no significant association between SRCs and persistent symptoms; however, patients with concussion from motor vehicle collisions were more likely to have persistent symptoms.

Conclusion:

Although physically active individuals may recover faster after a concussion, patients returning to their physical activities before full resolution of symptoms are at higher risk of persistent symptoms and further injury. Patient–clinician communications and tailored recommendations should be encouraged to guide appropriate acute management of concussions.
Mesenchymal cystic hamartoma of the lung
Authors: Yuan Ligong , Wang Shuaibo , Wei Jiacong , Yang Kun , Mao Yousheng
Published: January 2022

Rationale:

Mesenchymal cystic pulmonary hamartoma is a rare type of hamartoma that has been reported in all cases in the literature. Most patients were reported to have spontaneous pneumothorax and were treated by surgery, and finally confirmed to be caused by rupture of the cystic hamartoma. Here, we report a case of mesenchymal cystic pulmonary hamartoma detected using computed tomography (CT) during a health check-up without obvious symptoms.

Patient concerns:

A 60-year-old woman was detected using CT during her health check-up. She was a non-smoker and had no symptoms or history of specific diseases.

Diagnosis:

The final pathological examination confirmed that the lesion was a mesenchymal cystic hamartoma of the lung.

Interventions:

A uniportal video-assisted thoracic surgery wedge resection was performed for biopsy.

Outcomes:

The patient recovered smoothly and was discharged on postoperative day 3.

Lessons:

For cystic pulmonary hamartoma, it is usually difficult to make a correct diagnosis using CT imaging. A chest magnetic resonance imaging examination may be helpful for differentiation diagnosis before video-assisted thoracic surgery biopsy.
Treatment of intertrochanteric femur fracture with closed external fixation in high-risk geriatric patients: can it be the most reliable method that reduces mortality to minimum compared to proximal femoral nail and hemiarthroplasty?
Authors: Bedrettin Akar , Sahin Fatih , Yucel Mucahid Osman
Published: January 2022

The optimal surgical treatment of intertrochanteric femur fractures (ITF) to minimize the increased mortality in geriatric patients with high anesthetic risk was investigated by comparing closed external fixation (EF), a minimal invasive and biological osteosynthesis technique, proximal femoral nail (PFN) and hemiarthroplasty (HA) methods.

Three different surgical methods were performed to 167 patients who were admitted to our clinic for ITF between 2014 and 2020 and considered at high risk (American Society of Anesthesiologists III – American Society of Anesthesiologists IV) by the Anesthesiology and Reanimation Department. Patients with multi-trauma, osteoarthritis, those with malignancies and developmental hip dysplasia were excluded from the study. Group I included patients who underwent closed reduction - external fixation (n = 46), Group II included patients who underwent partial arthroplasty (n = 77), and Group III included those who received PFN (n = 44). All fractures were classified according to the Modified Evans (Kyle) method and divided into 2 categories as type 1-2 (stable) and type 3-4 (unstable).

The mean operation duration was 23 minutes and follow-up time was 14 months in Group 1, in which there was no in-hospital mortality. Five patients died due to non-operative reasons within 1 year. The mean operation duration and follow-up time in Group 2 were 40 minutes and 12 months, respectively. Six patients (7.8%) died during the operation or hospitalization, while 17 patients died due to comorbidities within 1 year. In Group 3, the mean operation duration and follow-up time were 40 minutes and 13 months, respectively. One patient died during the operation and 1 patient (n = 2, 4.5%), within 24 hours in the postoperative intensive care unit. Seven patients died due to comorbidities within 1 year. Statistical analysis revealed that the mean duration of operation, postoperative hospital stay, overall mortality and blood product transfusion amount were significantly lower in the EF group compared to other treatment methods.

Closed EF is the most reliable surgical method that can minimize mortality in geriatric patients compared to other surgical options, due to the short duration of the operation, no evacuation of the fracture hematoma, early mobilization, lack of blood transfusion requirement, and early union.
Modified internal limiting membrane flap technique for large chronic macular hole
Authors: Li Keran , Zhou Yunfan , Yang Weihua , Jiang Qin , Xu Xiangzhong
Published: January 2022

Rationale:

Internal limiting membrane (ILM) peeling and gas tamponade are the standardized treatments for macular holes (MHs). However, the close rate is low, and postoperative vision is unsatisfactory in large, chronic MHs. Currently, various modifications of the ILM flap techniques are being gradually applied for large MHs in the hope of obtaining better postoperative effects. This study described 2 successful cases achieved by “Sandwich-type” modified ILM flap covering technique in patients with large, chronic MHs.

Patient concerns:

A 62-year-old woman presented with decreased vision and visual distortion of the left eye for 18 months. Optical coherence tomography (OCT) showed the absence of full-thickness neuroepithelial tissue in the central fovea, with a minimum MH diameter of 742 μm and a base diameter of 1630 μm. A 57-year-old man experienced decreased visual acuity for 8 months. OCT showed the absence of full-thickness neuroepithelial tissue in the central fovea, with a minimum MH diameter of 713 μm and a basal diameter of 939 μm.

Diagnoses:

Two patients were diagnosed with large, chronic MH based on the OCT results and duration of the hole.

Interventions:

The 2 patients were treated with the “sandwich-type” modified ILM flap covering technique.

Outcomes:

Large, chronic MH closure was observed using SD-OCT, and the BCVA improved. The patients were very satisfied with the postoperative results.

Lessons:

“Sandwich-type” modified ILM flap covering technique may be a safe, effective way for large, chronic MH.
Management of severe hypertension due to lenvatinib in patients with advanced thymic carcinoma
Authors: Matsumoto Kinnosuke , Shiroyama Takayuki , Miyake Kotaro , Yamamoto Yuji , Kuge Tomoki , Yoneda Midori , Yamamoto Makoto , Naito Yujiro , Suga Yasuhiko , Fukushima Kiyoharu , Koyama Shohei , Iwahori Kota , Hirata Haruhiko , Nagatomo Izumi , Takeda Yoshito , Kumanogoh Atsushi
Published: January 2022

Rationale:

Thymic carcinoma (TC) is a malignant mediastinal tumor, and there are no established treatments for pre-treated patients with advanced TC. Recently, lenvatinib was approved for such patients in Japan, ahead of other countries. Higher dose lenvatinib may be more efficacious than conventional treatments, although many patients experience grade 3 hypertension. Therefore, lenvatinib dose reduction remains controversial in terms of efficacy and tolerability.

Patient concerns:

Case 1 involves a 72-year-old woman who underwent complete resection of TC and was taking cilnidipine and azilsartan for hypertension. Six years later, multiple lung metastases were observed, and lenvatinib was started. Case 2 involves a 60-year-old man with TC, and was taking amlodipine for hypertension. A chest computed tomography showed progression in primary and metastatic lesions, and the patient started lenvatinib.

Diagnoses:

In both patients, grade 3 hypertension was observed after the administration of lenvatinib.

Interventions:

In Case 1, lenvatinib dose was reduced 3 times because lenvatinib was not interrupted despite grade 3 hypertension. In contrast, in Case 2, lenvatinib was interrupted when grade 3 hypertension occurred and was resumed after a decrease in blood pressure to baseline.

Outcomes:

In Case 2, higher tumor regression may have been achieved because of the maintenance of a high dose of lenvatinib compared with that in Case 1.

Lessons:

Lenvatinib is a promising agent for advanced TC; however, hypertension should be addressed cautiously, especially at the outset of administration. Lenvatinib may have to be appropriately interrupted and resumed as soon as the blood pressure is controlled to maximize efficacy and minimize toxicity.
VV-ECMO combined with prone position ventilation in the treatment of Pneumocystis jirovecii pneumonia
Authors: Jia Lijing , Zhang Zhiyang , Bai Yinxiang , Du Quansheng
Published: January 2022

Introduction:

Pneumocystis jirovecii pneumonia (PJP) occurs in immunocompromised hosts. It is classified as PJP with human immunodeficiency virus (HIV) infection (HIV-PJP) and PJP without HIV infection (non-HIV PJP). Compared with HIV-PJP, non-HIV PJP is more likely to develop rapidly into respiratory failure, with difficult diagnosis and high mortality.

Patient concerns:

A 46-year-old male with membranous nephropathy was treated with oral corticosteroids and tacrolimus. He was admitted to our hospital for fever and dyspnea which developed 4 days ago. Laboratory data revealed that leukocytes were 10.99 × 109/L, neutrophils 87.7%, lymphocytes 9.6%, C-reactive protein 252.92 mg/L, New coronavirus nucleic acid detection negative. CT scan of chest revealed ground-glass opacity in both lungs. He was admitted to the respiratory department of our hospital, and then transferred to ICU because of his critical condition.

Diagnosis:

High throughput gene detection of pathogenic microorganisms in alveolar lavage fluid showed that the detection sequence of Pneumocystis yersiniae increased significantly. The serum HIV-antibody was negative. Therefore, the patient was diagnosed as non-HIV PJP.

Interventions:

After admission, the patient was assisted by noninvasive ventilator and treated with compound trimethoprim-sulfamethoxazole (SMX-TMP) and caspofungin. The patient's condition continued to deteriorate, and then underwent endotracheal intubation and veno-venous extracorporeal membrane oxygenation (VV-ECMO) combined with prone position ventilation until the lung lesion improved.

Outcomes:

VV-ECMO was stopped on day 12, tracheal intubation was removed after 2 days. The patient was transferred to the respiratory department on day 15, discharged after 12 days without complications. Two months later, the follow-up showed that the patient was in good condition.

Conclusion:

VV-ECMO combined with prone position ventilation could be a useful choice for respiratory assistance in non-HIV PJP patients.
Hypothyroidism risk associated with rheumatoid arthritis
Authors: Huang Chung-Ming , Sung Fung-Chang , Chen Hsuan-Ju , Lin Che-Chen , Lin Cheng-Li , Huang Po-Hao
Published: January 2022

Studies on the thyroid disease risk in patients with rheumatoid arthritis (RA) associated with comorbidities are limited. This population-based retrospective cohort study investigated the hypothyroidism risk in patients with RA and the role of comorbidities.

We used Taiwan National Health Insurance Research Database to identify 16,714 RA patients newly diagnosed in 2000 to 2008 and 66,856 control persons without RA, frequency matched by sex, age, and index year. Incidence and the RA group to controls hazard ratio of hypothyroidism were estimated.

The hypothyroidism incidence was 1.74-fold higher in the RA group than in controls (16.6 vs 9.52 per 10,000 person–years), with the Cox method estimated adjusted hazard ratio of 1.67 (95% confidence interval = 1.39–2.00) after controlling for covariates. Near 75% of the study population were women, with the incidence 3.6-time higher than men in both groups. The hypothyroidism incidence increased with age, from 12.1 per 1000 person–years in 20 to 39 years to 20.0 per 1000 person–years in 60+ years in RA patients, higher than that in controls (7.17 vs 10.0 per 1000 person–years, respectively by age). Each comorbidity was related to an increased incidence and higher in the RA group than in controls. Among all comorbidities, stroke exerted the greatest impact in the RA group with an adjusted hazard ratio of 3.85 (95% confidence interval = 1.24–12.0).

RA patients have an increased risk of developing hypothyroidism; this risk was pronounced in women and the elderly. RA patients should be closely monitored to prevent the development of hypothyroidism.
Prognosis-related autophagy genes in female lung adenocarcinoma
Authors: Liu Zhongxiang , Zhang Koudong , Zhao Zhangyan , Qin Zhu , Tang Haicheng
Published: January 2022

To screen the prognosis-related autophagy genes of female lung adenocarcinoma by the transcriptome data and clinical data from The Cancer Genome Atlas (TCGA) database.

In this study, screen meaningful female lung adenocarcinoma differential genes in TCGA, use univariate Cox proportional regression model to select genes related to prognosis, and establish the best risk model. In this study, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were applied for carrying out bioinformatics analysis of gene function.

The gene expression and clinical data of 264 female lung adenocarcinoma patient samples were downloaded from TCGA. Twelve down-regulated genes: NRG3, DLC1, NLRC4, DAPK2, HSPB8, PPP1R15A, FOS, NRG1, PRKCQ, GRID1, MAP1LC3C, GABARAPL1. Up-regulated 15 genes: PARP1, BNIP3, P4HB, ATIC, IKBKE, ITGB4, VMP1, PTK6, EIF4EBP1, GAPDH, ATG9B, ERO1A, TMEM74, CDKN2A, BIRC5. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that these genes were significantly associated with autophagy and mitochondria (animals). Multifactor Cox analysis of autophagy-related genes showed that ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as independent prognostic indicators. According to the multivariate Cox proportional hazard regression model, there was a significant difference in the survival rate observed between the high-risk group (n = 124) and the low-risk group (n = 126) during the 10-year follow-up (P < .05). Univariate Cox analysis showed that tumor stage, T, M, and N stages, and risk score were all related to the survival rate of female lung adenocarcinoma patients. Multivariate Cox analysis found that autophagy-related risk scores were independent predictors, with an area under curve (AUC) value of 0.842. At last, there is autophagy genes differentially expressed among various clinicopathological parameters: ATG4A, BAK1, CCR2, DLC1, ERO1A, FKBP1A, ITGA6.

The risk score can be used as an independent prognostic indicator for female patients with lung adenocarcinoma. The autophagy genes ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as prognostic genes in female lung adenocarcinoma, which may be the targets of treatment in the future.
The association of statin use and biochemical recurrence after curative treatment for prostate cancer
Authors: Yin Peng , Han Sheng , Hu Qingfeng , Tong Shijun
Published: January 2022

Objectives

: To investigate the association between statin use and biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP) or radiotherapy (RT) as a curative treatment, a systematic review and meta-analysis was performed.

Methods

: We conducted a literature search of online databases for studies assessing BCR associated with statin use in patients with prostate cancer undergoing RP or RT. We performed a pooled analysis of BCR-free survival with subgroup analysis of treatment, cancer risk, and medication.

Results

: We identified 27 studies and found that statin use was associated with a potential tendency to improve BCR-free survival in patients undergoing curative treatment (P = .05). In addition, we revealed that statin use after curative treatment did not improve BCR-free survival (P = .33), whereas statin use could improve BCR-free survival in high-risk patients (P < .01).

Conclusions

: Statin use is associated with a potential tendency to improve BCR-free survival in prostate cancer and could reduce BCR in high-risk patients.
Immune-related lncRNA pairs as novel signature to predict prognosis and immune landscape in melanoma patients
Authors: Li Zhehong , Wei Junqiang , Zheng Honghong , Gan Xintian , Song Mingze , Zhang Yafang , Jin Yu
Published: January 2022

To investigate immune-related long non-coding RNA (irlncRNA) signatures for predicting survival and the immune landscape in melanoma patients.

We retrieved gene expression files from The Cancer Genome Atlas and the Genotype-Tissue Expression database and extracted all the long non-coding RNAs from the original data. Then, we selected immune-related long non-coding RNAs (irlncRNAs) using co-expression networks and screened differentially expressed irlncRNAs (DEirlncRNAs) to form pairs. We also performed univariate analysis and Least absolute shrinkage and selection operator (LASSO) penalized regression analysis to identify prognostic DEirlncRNA pairs, constructed receiver operating characteristic curves, compared the areas under the curves, and calculated the optimal cut-off point to divide patients into high-risk and low-risk groups. Finally, we performed multivariate Cox regression analysis, Kaplan–Meier (K–M) survival analysis, clinical correlation analysis, and investigated correlations with tumor-infiltrating immune cells, chemotherapeutic effectiveness, and immunogene biomarkers.

A total of 297 DEirlncRNAs were identified, of which 16 DEirlncRNA pairs were associated with prognosis in melanoma. After grouping patients by the optimal cut-off value, we could better distinguish melanoma patients with different survival outcomes, clinical characteristics, tumor immune status changes, chemotherapeutic drug sensitivity, and specific immunogene biomarkers.

The DEirlncRNA pairs showed potential as novel biomarkers to predict the prognosis of melanoma patients. Furthermore, these DEirlncRNA pairs could be used to evaluate treatment efficacy in the future.
The new horizon of biomarker in melanoma patients
Authors: Li Zhehong , Wei Junqiang , Zheng Honghong , Zhang Yafang , Song Mingze , Cao Haiying , Jin Yu
Published: January 2022

Autophagy-related long non-coding RNAs (arlncRNAs) play a crucial role in the pathogenesis and development of the tumor. However, there is a lack of systematic analysis of arlncRNAs in melanoma patients.

Melanoma data for analysis were obtained from The Cancer Genome Atlas (TCGA) database. By establishing a co-expression network of autophagy-related mRNAs-lncRNAs, we identified arlncRNAs in melanoma patients. We evaluated the prognostic value of arlncRNAs by univariate and multivariate Cox analysis and constructed an arlncRNAs risk model. Patients were divided into high- and low-risk groups based on the arlncRNAs risk score. This model was evaluated by Kaplan–Meier (K–M) analysis, univariate-multivariate Cox regression analysis, and receiver operating characteristic (ROC) curve analysis. Characteristics of autophagy genes and co-expressive tendency were analyzed by principal component analysis and Gene Set Enrichment Analysis (GSEA) functional annotation.

Nine arlncRNAs (USP30-AS1, LINC00665, PCED1B-AS1, LINC00324, LINC01871, ZEB1-AS1, LINC01527, AC018553.1, and HLA-DQB1-AS1) were identified to be related to the prognosis of melanoma patients. Otherwise, the 9 arlncRNAs constituted an arlncRNAs prognostic risk model. K–M analysis and ROC curve analysis showed that the arlncRNAs risk model has good discrimination. Univariate and multivariate Cox regression analysis showed that arlncRNAs risk model was an independent prognostic factor in melanoma patients. Principal component analysis and GSEA functional annotation showed different autophagy and carcinogenic status in the high- and low-risk groups.

This novel arlncRNAs risk model plays an essential role in predicting of the prognosis of melanoma patients. The model reveals new prognosis-related biomarkers for autophagy, promotes precision medicine, and provides a lurking target for melanoma's autophagy-related treatment.
Hyperparathyroidism in Pregnancy: A Review of the Literature
Authors: Strebeck Ryan J. , Schneider Allison M. , Whitcombe Dayna D. , Sward Lindsey B. , Dajani Nafisa K. , Whittington Julie R. , Magann Everett F.
Published: January 2022

Importance

Maternal hyperparathyroidism can be associated with significant maternal and fetal morbidity and fetal mortality. Because the maternal symptoms are typically nonspecific, the disorder may not be recognized leading to adverse pregnancy outcomes.

Objective

The aim of this study was to review the literature on the etiology/prevalence, pathophysiology, diagnosis, management (medical and surgical), and the maternal/neonatal complications associated with pregnancies complicated by hyperparathyroidism.

Evidence Acquisition

A literature search was undertaken by our university librarian using the search engines PubMed and Web of Science. Search terms used included “hyperparathyroidism” AND “pregnancy” OR “pregnancy complications” OR “maternal.” The number of years searched was not limited, but the abstracts had to be in English.

Results

There were 309 abstracts identified, 164 of which are the basis of this review. This includes 137 articles of the 269 individual case reports in the literature since the first case report in 1947. The articles and case reports reviewed the etiology, risk factors, diagnosis, management, complications, and maternal/fetal outcomes of pregnancies complicated by hyperparathyroidism.

Conclusions and Relevance

Undiagnosed maternal hyperparathyroidism can result in critical maternal and fetal outcomes during pregnancy. This review highlights what is currently known about hyperparathyroidism during pregnancy to increase the awareness of this serious pregnancy disorder.

Target Audience

Obstetricians and gynecologists, and family physicians

Learning Objectives

After completing this activity, the learner should be better able to identify the causes of hyperparathyroidism in pregnancy; explain its pathophysiology; detect the nonspecific symptoms/conditions; evaluate the medical and surgical management; and describe the maternal and fetal complications.
Talc, Body Powder, and Ovarian Cancer: A Summary of the Epidemiologic Evidence
Authors: Wentzensen Nicolas , O'Brien Katie M.
Published: January 2022

(Abstracted from Gynecol Oncol 2021;163:199–208)

Talc is a soft and inert mineral with a high capacity to bind water, making it a popular component of baby powder and feminine hygiene products as a drying agent. Talc has similar chemical features and often cooccurs with asbestos, a known carcinogen.
Recurrent Cesarean Scar Pregnancy: Case Series and Literature Review
Authors: Timor-Tritsch I. E. , Horwitz G. , D'Antonio F. , Monteagudo A. , Bornstein E. , Chervenak J. , Messina L. , Morlando M. , Cali G.
Published: January 2022

(Abstracted from Ultrasound Obstet Gynecol 2021;58:121–126)

There has been an increase in the number of cesarean deliveries (CDs) over the years and, with it, the publication of more cesarean scar pregnancy (CSP) data. Several authors have reported that, even with successful CSP treatment, there is a risk of recurrence.
Vaginal Electrical Stimulation for Postpartum Neuromuscular Recovery: A Randomized Clinical Trial
Authors: Brown Oluwateniola , Heliker Bhumy Davé , Geynisman-Tan Julia , Tavathia Meera , Mueller Margaret G. , Collins Sarah , Kenton Kimberly , Lewicky-Gaupp Christina
Published: January 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27:659–666)

Obstetric anal sphincter injuries (OASIS) have been established as risk factors for anal incontinence (AI). Several studies have shown that women with OASIS were more likely to have AI than those without anal sphincter lacerations or tears.
Association Between Iatrogenic Delivery for Suspected Fetal Growth Restriction and Childhood School Outcomes
Authors: Selvaratnam Roshan John , Wallace Euan Morrison , Wolfe Rory , Anderson Peter John , Davey Mary-Ann
Published: January 2022

(Abstracted from JAMA 2021;326:145–153)

One of the larger contributors to stillbirth in late pregnancy is fetal growth restriction (FGR). When undetected, the rate of stillbirth between 2000 and 2017 was 16.4 per 1000 births.
The Ultra-Long Study: A Randomized Controlled Trial Evaluating Long-Term GnRH Downregulation Prior to ART in Women With Endometriosis
Authors: Tomassetti C. , Beukeleirs T. , Conforti A. , Debrock S. , Peeraer K. , Meuleman C. , D'Hooghe T.
Published: January 2022

(Abstracted from Hum Reprod 2021;36:2676–2686)

Although the adverse effect of endometriosis on pregnancy rate is well established, the impact of endometriosis on pregnancy rate after treatment with assisted reproductive technology (ART) remains unclear. There is evidence that the use of prolonged pituitary downregulation before ART in women with any degree of endometriosis increases the odds of clinical pregnancy significantly (up to 4-fold); however, this evidence is limited by potential methodology and publication bias.