bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Letters on the Foundations of Mathematics by Frank Plumpton Ramsey†
Authors: Mancosu Paolo
Published: November 2020

This article presents three hitherto unpublished letters by Frank Plumpton Ramsey on the foundations of mathematics with commentary. One of the letters was sent to Abraham Fraenkel and the other two letters to Heinrich Behmann. The transcription of the letters is preceded by an account that details the extent of Ramsey's known contacts with mathematical logicians on the Continent.
Interior of the horizon of the Bañados-Teitelboim-Zanelli black hole
Authors: Nakayama Ryuichi , Shiohara Kenji
Published: November 2020

A quantum scalar field inside the horizon of the non-rotating BTZ black hole is studied. Not only the near-horizon modes but also the normal modes deep inside the horizon are obtained. It is shown that the matching condition for the normal modes of a scalar field at the horizon does not uniquely determine the normal-mode expansion of a scalar field inside the horizon. By choosing a certain appropriate prescription for removing this ambiguity, an integral form of a new scalar propagator for points on both sides of the horizon are obtained. A similar problem may arise in higher-dimensional black holes.
Quantitative MRI adds to neuropsychiatric lupus diagnostics
Authors: Ramirez Giuseppe A , Rocca Maria A , Preziosa Paolo , Bozzolo Enrica P , Pagani Elisabetta , Canti Valentina , Moiola Lucia , Rovere-Querini Patrizia , Manfredi Angelo A , Filippi Massimo
Published: November 2020

Objective

Attributing neuropsychiatric manifestations to SLE is often challenging. Brain white matter lesions are frequent in SLE at MRI, but their diagnostic role is unclear. Here, we assessed whether white matter lesions count, volume and distribution measurement can help in the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE).

Methods

Brain dual-echo and 3D T1-weighted sequences were acquired from 32 patients with SLE and 32 healthy controls with a 3 T-scanner and employed to derive T2-hyperintense lesion volume (T2LV), number (T2LN) and probability maps (LPM) using a semi-automatic local thresholding segmentation technique. NPSLE was classified as per the ACR nomenclature, the Italian Society for Rheumatology algorithm and by clinical impression. Clinical descriptors including the SLE International Collaborating Clinics/ACR damage index (SDI) were also recorded.

Results

Higher T2LV were observed in SLE vs healthy controls (P < 0.001) and in NPSLE vs other SLE (P =0.006). Patients with NPSLE also had higher T2LN (P =0.003) compared with other SLE. In SLE, T2LPM revealed a high prevalence of lesions in the splenium of the corpus callosum, right superior longitudinal fasciculus and right corona radiata. T2LV and T2LN correlated with SLE duration (rho = 0.606; P <0.001 and rho = 0.483; P =0.005, respectively) and age (rho = 0.478; P =0.006 and rho = 0.362; P = 0.042, respectively). T2LV also correlated with SDI (rho = 0.352; P =0.048). SLE patients with fatigue had lower T2LN (P =0.038) compared with patients without fatigue. Thresholds of T2LV ≥ 0.423 cm3 or of T2LN ≥ 12 were associated with definite NPSLE and improved the classification of patients with possible NPSLE per clinical impression.

Conclusion

Brain white matter lesions (WML) quantitation adds to NPSLE diagnostics.
Towards a comprehensive research and development plan to support the control, elimination and eradication of neglected tropical diseases
Authors: Mabey David , Agler Ellen , Amuasi John H , Hernandez Leda , Hollingsworth T Déirdre , Hotez Peter J , Lammie Patrick J , Malecela Mwelecele N , Matendechero Sultani H , Ottesen Eric , Phillips Richard O , Reeder John C , Szwarcwald Célia Landmann , Shott Joseph P , Solomon Anthony W , Steer Andrew , Swaminathan Soumya
Published: November 2020

To maximise the likelihood of success, global health programmes need repeated, honest appraisal of their own weaknesses, with research undertaken to address any identified gaps. There is still much to be learned to optimise work against neglected tropical diseases. To facilitate that learning, a comprehensive research and development plan is required. Here, we discuss how such a plan might be developed.
Characterization of mutations in the reverse transcriptase region of hepatitis B virus in treated and untreated chronic hepatitis B patients
Authors: Zou Weihua , Qian Fuchu , Jin Fang , Li Dongli , Chen Jing
Published: November 2020

Background

The reverse transcriptase (RT) region of the hepatitis B virus (HBV) is the target of antiviral treatment. However, the discrepancy in RT mutations between nucleos(t)ide analogue (NA)-treated and -untreated chronic hepatitis B (CHB) patients is un clear.

Methods

Serum samples were collected from 119 NA-treated and 135 NA-untreated patients. The sampling time was decided by the clinician. Full-length HBV RT regions were amplified using nest polymerase chain reaction. The mutations within the RT region were analysed by direct sequencing.

Results

The incidence of RT mutations in treated patients was higher than that in untreated patients (p<0.05). The classic drug-resistant mutations were detected in 44.5% (53/119) of treated patients, which was significantly higher than in untreated patients (6.7% [9/135]) (p<0.05). The non-classical mutations showed their complexity and diversity in both patient groups. Multiple mutations (three or more) were more frequent in treated patients than in untreated patients (p<0.05). Several novel mutations might be related to NA resistance.

Conclusions

The selection pressures of NAs accelerated the development of RT mutations, especially within the functional domain. Mutations in the RT region occurred not only at classical sites, but also at other non-classical sites, which might be related to drug resistance and/or viral replication. The biological function and fitness of HBV isolates harbouring these novel mutations need further in vitro and in vivo verification experiments.
Standard versus sequential anti-tubercular treatment in patients with tuberculous meningitis: a randomized controlled trial
Authors: Misra Usha Kant , Kumar Mritunjai , Kalita Jayantee
Published: November 2020

Background

To compare the safety and efficacy of sequential anti-tubercular treatment (ATT) regimen with the standard regimen in tuberculous meningitis (TBM).

Methods

This single-centre, open-label, parallel group randomized controlled trial was conducted from May 2017 to June 2019 in India. Treatment-naïve patients with TBM fulfilling the inclusion criteria were randomized to four drug ATT regimens (rifampicin, isoniazid, ethambutol and pyrazinamide) administered either simultaneously (standard arm) or one after another (sequential arm) in a 1 : 1 ratio. The primary endpoint was drug-induced hepatitis (DIH) and the secondary endpoints were in-hospital death and disability at 3 and 6 months using a modified Rankin Scale.

Results

A total of 97 patients with TBM were recruited; 15 did not meet the inclusion criteria and 2 refused to participate. The median age of the patients was 26 y (range 15–75) and 37 (46.2%) were males. The patients in the sequential arm had fewer cases of DIH (20% vs 42.5%; p=0.03). The patients in the sequential arm had lower in-hospital mortality (2.5% vs 17.5%; p=0.025) and better 6-month outcomes (25.0% vs 50.0%; p=0.02) compared with the standard arm.

Conclusions

Sequential ATT was associated with a lower frequency of DIH, lower in-hospital mortality and better 6-month outcome.

Trial registration

Clinical Trials Registry of India (ctri.nic.in) identifier: REF/2016/09/012214/CTRI/2017/10/010072.
Provider Continuity in the Prescribing of Buprenorphine/Naloxone Within Medicare Part D
Authors: Strickland Justin C. , Huhn Andrew S. , Bergeria Cecilia L. , Strain Eric C. , Dunn Kelly E.
Published: November 2020

Objectives:

Efforts to improve buprenorphine access for opioid use disorder have focused on increasing the number of waivered providers. However, it is unknown how efforts to increase initial prescribing result in a sustained pool of prescribers. We examine the prevalence of year-to-year provider-level buprenorphine prescribing, and provider- and state-level factors associated with provider continuity.

Methods:

Providers prescribing buprenorphine/naloxone within the Medicare Part D claims database were evaluated from 2013 to 2017 with prescriber continuity measured as prescriptions made in consecutive years from the same provider (N = 14,222 unique providers; 6670 in 2013).

Results:

The number of providers prescribing buprenorphine/naloxone within Medicare Part D increased from 2013 to 2017. The majority of providers prescribed buprenorphine/naloxone to 10 or fewer beneficiaries. Approximately 84% of providers prescribing buprenorphine/naloxone in 1 year prescribed it in the following year. Continuous prescribing from 2013 to 2017 was 59.4%, which was 86% the rate of a comparator chronic health medication (ie, lisinopril). Survival analyses indicated that female providers (adjusted hazard ratios [AHR] = 1.30, P < 0.001) and clinical neuroscience specialties such as psychiatry (AHR = 1.21, P < 0.001) exhibited greater discontinuation rates, whereas those with higher buprenorphine/naloxone beneficiary loads (AHR = 0.50, P < 0.001) and in states with a greater increase in overdose mortality rates (AHR = 0.88, P < 0.05) showed lower discontinuation rates.

Conclusions:

These data support evidence that providers who begin prescribing buprenorphine continue prescribing, although short of maximum capacity. Efforts to help providers become waivered, understand the impact of overdose fatalities in their area, and prescribe to multiple patients are likely to generate an enduring positive contribution to the number of treated patients.
The Impacts of COVID-19 on Mental Health, Substance Use, and Overdose Concerns of People Who Use Drugs in Rural Communities
Authors: Stack Erin , Leichtling Gillian , Larsen Jessica E. , Gray Mary , Pope Justine , Leahy Judith M. , Gelberg Lillian , Seaman Andrew , Korthuis Philip Todd
Published: November 2020

Objectives:

The objective of this study was to investigate the impact of COVID-19 on the mental health, substance use, and overdose concerns among people who use drugs (PWUDs) in rural communities to explore reasons for changes and ways to mitigate COVID-19 impact in the future.

Methods:

We conducted semi-structured in-depth interviews with PWUDs in 5 rural Oregon counties with high overdose rates. Participants were identified through participant-driven sampling along with flyer and text advertising (n = 36). Research staff conducted audio-recorded in-depth interviews via telephone, assessing COVID-19 effects on substance use, mental health, and overdose risk. Transcribed interviewers were coded for themes using a semantic approach.

Results:

Participants reported various mental health symptoms and experiences due to COVID-19, including increased feelings of boredom, loneliness, and depression; increased worry and stress; and increased suicidal ideation. Participants described varying impacts of COVID-19 on substance use. Overall, participants who used only methamphetamine reported decreased use and people who used only heroin or heroin with methamphetamine reported increased use. Most participants reported that they were not concerned about overdose and that COVID-19 did not impact their concerns about overdose, despite increases in risky use and suicidal ideations.

Conclusions:

As rural communities respond to the evolving impacts of COVID-19, there is increasing need to identify strategies to address PWUD's mental, physical, and social health needs during COVID-19.
Pulsed Electromagnetic Fields Accelerate Sensorimotor Recovery Following Experimental Disc Herniation
Authors: Chan Andrew K. , Ballatori Alexander , Nyayapati Priya , Mummaneni Nikhil V. , Coughlin Dezba , Liebenberg Ellen , Külling Fabrice A. , Zhang Nianli , Waldorff Erik I. , Ryaby James T. , Lotz Jeffrey C.
Published: November 2020

Study Design.

An experimental animal study.

Objective.

The aim of this study was to investigate the effect of pulsed electromagnetic fields (PEMF) on recovery of sensorimotor function in a rodent model of disc herniation (DH).

Summary of Background Data.

Radiculopathy associated with DH is mediated by proinflammatory cytokines. Although we have demonstrated the anti-inflammatory effects of PEMF on various tissues, we have not investigated the potential therapeutic effect of PEMF on radiculopathy resulting from DH.

Methods.

Nineteen rats were divided into three groups: positive control (PC; left L4 nerve ligation) (n = 6), DH alone (DH; exposure of left L4 dorsal root ganglion [DRG] to harvested nucleus pulposus and DRG displacement) (n = 6), and DH + PEMF (n = 7). Rodents from the DH + PEMF group were exposed to PEMF immediately postoperatively and for 3 hours/day until the end of the study. Sensory function was assessed via paw withdrawal thresholds to non-noxious stimuli preoperatively and 1 and 3 days postoperatively, and every 7 days thereafter until 7 weeks after surgery. Motor function was assessed via DigiGait treadmill analysis preoperatively and weekly starting 7 days following surgery until 7 weeks following surgery.

Results.

All groups demonstrated marked increases in the left hindlimb response threshold postoperatively. However, 1 week following surgery, there was a significant effect of condition on left hindlimb withdrawal thresholds (one-way analysis of variance: F = 3.82, df = 2, P = 0.044) where a more rapid recovery to baseline threshold was evident for DH + PEMF compared to PC and DH alone. All groups demonstrated gait disturbance postoperatively. However, DH + PEMF rodents were able to regain baseline gait speeds before DH and PC rodents. When comparing gait parameters, DH + PEMF showed consistently less impairment postoperatively suggesting that PEMF treatment was associated with less severe gait disturbance.

Conclusion.

These data demonstrate that PEMF accelerates sensorimotor recovery in a rodent model of DH, suggesting that PEMF may be reasonable to evaluate for the clinical management of patients with herniation-associated radiculopathy.

Level of Evidence: N/A
Semitendinosus Tendon Augmentation for Prevention of Proximal Junctional Failure
Authors: Alluri Ram , Kim Andrew , Ton Andy , Kang Hyunwoo , Acosta Frank , Hah Raymond
Published: November 2020

Study Design.

Retrospective cohort study.

Objective.

The aim of this study was to compare the incidence of proximal junctional kyphosis (PJK), proximal junctional failure (PJF), and clinical outcomes of patients who did and did not receive posterior ligament complex (PLC) augmentation using a semitendinosus allograft when undergoing long-segment posterior spinal fusion for adult spinal deformity.

Summary of Background Data.

Clinical research on the augmentation of the PLC to prevent PJK and PJF has been limited to small case series without a comparable control group.

Methods.

From 2014 to 2019, a consecutive series of patients with adult spinal deformity who underwent posterior long-segment spinal fusion with semitendinosus allograft to augment the PLC (allograft) or without PLC augmentation (control) were identified. Preoperative and postoperative spinopelvic parameters were measured. PJK, PJF, and Oswestry Disability Index (ODI) scores were recorded and compared between the two groups. Univariate and multivariate analysis was performed. P ≤ 0.05 was considered significant.

Results.

Forty-nine patients in the allograft group and 34 patients in the control group were identified. There were no significant differences in demographic variables or operative characteristics between the allograft and control group. Preoperative and postoperative spinopelvic parameters were also similar between the two groups. PJK was present in 33% of patients in the allograft group and 32% of patients in the control group (P = 0.31). PJF did not occur in the allograft group, whereas six patients (18%) in the control group developed PJF (P = 0.01). Postoperative absolute ODI was significantly better in the allograft group (P = 0.007).

Conclusion.

The utilization of semitendinosus allograft tendon to augment the PLC at the upper instrumented vertebrae in patients undergoing long-segment posterior spinal fusion for adult deformity resulted in a significant decrease in PJF incidence and improved functional outcomes when compared to a cohort with similar risk of developing PJK and PJF

Level of Evidence: 3
Concordance Between Patients’ and Surgeons’ Expectations of Lumbar Surgery
Authors: Mancuso Carol A. , Duculan Roland , Cammisa Frank P. , Sama Andrew A. , Hughes Alexander P. , Lebl Darren R. , Yang Jingyan , Ghomrawi Hassan M.K. , Girardi Federico P.
Published: November 2020

Study Design.

Longitudinal cohort.

Objective.

The aims of this study were to measure concordance between patients’ and surgeons’ preoperative expectations of lumbar surgery, and determine which member of the dyad more closely predicted fulfillment of expectations, defined as patient-reported status postoperatively.

Summary of Background Data.

Concordant patient–surgeon expectations reflect effective communication and should foster better outcomes.

Methods.

Preoperatively patients and surgeons completed identical surveys measuring expectations for improvement in symptoms and physical/psychosocial function. Responses ranged from “complete improvement” to “do not have this expectation”; scores for each survey ranged from 0 to 100 (greatest expectations). Concordance between pairs of patient–surgeon scores was measured with the intraclass correlation coefficient (ICC). Postoperatively, fulfillment of expectations was measured from patient-reported amount of improvement received and was calculated as the proportion of patient-reported postoperative score relative to patient-reported preoperative score, and surgeon-reported preoperative score (range 0 [no expectations fulfilled] to >1.2 [expectations surpassed]). Clinical measures included patient-reported spine-related disability.

Results.

For 402 patient–surgeon pairs, mean survey scores were 73 ± 19 (patients) and 57 ± 16 (surgeons); 84% of patients had higher scores than surgeons, mainly due to expecting complete improvement, whereas surgeons expected a lot/moderate/little improvement. The ICC for the entire sample was .31 (fair agreement); for subgroups, the greatest difference in ICC was for patients with more spine-related disability (ICC = .10, 95% confidence interval [CI]:0.00–0.23) versus less disability (ICC = .46, 95% CI: 0.34–0.56). 96% of patients were contacted ≥2.0 years postoperatively. Proportions of expectations fulfilled were 0.79 (0–3.00) (patients) and 1.01 (0–2.29) (surgeons). Thus patients were less likely to anticipate subsequent postoperative status (odds ratio [OR] 0.34, 95% CI 0.25–0.45) versus surgeons who were more likely to anticipate patient-reported postoperative status (OR 2.98, 95% CI: 2.22–4.00).

Conclusion.

Concordance between patients’ and surgeons’ expectations was fair; due mostly to patients expecting complete improvement whereas surgeons expected a lot/moderate/little improvement. Compared to patients’ expectations, surgeons’ expectations more closely coincided with patient-reported fulfillment of expectations 2 years postoperatively.

Level of Evidence: 1
Primary Extraosseous Spinal Ewing Sarcomas
Authors: Amelot Aymeric , Peyre Matthieu , Mokhtari Karima , Carpentier Alexandre , Nouet Aurélien , Bielle Franck , Clemenceau Stephane , Kalamarides Michel , Mathon Bertrand
Published: November 2020

Study Design.

Single-center retrospective study

Objective.

We discuss the widespread misdiagnosis of primary extraosseous spinal Ewing Sarcomas (PESES) to begnin tumors leading to poor treatment

Summary of Background Data.

PESES is a particular entity of spinal Ewing sarcoma (SES) appearing in a similar shape and features to benign tumors such as schwannomas. This imaging mimicry and subsequent possible misdiagnosis lead to primary surgery, without neoadjuvant chemotherapy, which remains deleterious for survival and progression.

Methods.

We identified a total of 13 patients: seven women (53.8%) and six men operated between 2001 and 2018 for PESES and initially misdiagnosed as schwannomas or ependymomas

Results.

The mean age of our series was 35.8 years (range, 18.1–47.2 years). The first clinical symptom was neuralgia (61.5%) followed or associated with nerves deficits (38.5%). Median progression-free survival (PFS) was 31.7 months (SD 5.8). Tumor recurrence rates at 1 and 3 years were respectively 21.2% (SD 3.1) and 60.1% (SD 15.8). Median overall survival (OS) was 61.5 months (SD 16.27). The 1-year, 2-year, and 5-year survival estimates were 100.0%, 88.9% (SD 10.5), and 44.4% (SD 16.6). Six patients (46.13%) died following their SES. In univariate analyses, patients with metastastic PESES had a significantly lower OS than others (41.2 months, P = 0.03).

Conclusion.

PESES must be ruled out at diagnosis of a spinal tumor when facing a fast-growing lesion with neurological deficits in a young adult. Thoracoabdominopelvic extension should be carried out. Presurgical biopsy must be performed. In case of PESES, neoadjuvant chemotherapy must be established before considering surgical intervention.

Level of Evidence: 4
Sagittal Alignment in Patients with Thoracic Myelopathy Caused by the Ossification of the Ligamentum Flavum
Authors: Chang Sam Yeol , Kim Yeonho , Kim Junho , Kim Hyoungmin , Kim Ho-Joong , Yeom Jin S. , Lee Choon-Ki , Chang Bong-Soon
Published: November 2020

Study design.

Retrospective case–control study

Objective.

The aim of this study was to describe and compare the sagittal spinal alignment between patients with and without the ossification of the ligamentum flavum in the thoracic spine (TOLF).

Summary of Background Data.

Although mechanical factors play an important role in the development of TOLF, limited evidence exists on the association of sagittal spinal alignment and TOLF in the literature.

Methods.

The present study assessed the preoperative sagittal alignment parameters in consecutive patients who underwent posterior decompression for TOLF in a single institution between January 2014 and December 2019. The sagittal parameters of the patients with TOLF were compared to those of the age- and sex-matched control group with lumbar spondylosis.

Results.

The TOLF group (n = 43 [23 men, 20 women]), with a mean age of 69.5 (range: 41–86) years, and the control group (n = 86) were compared. The TOLF group had a significantly smaller sacral slope (27.60 ± 7.49 vs. 30.61 ± 8.15, P = 0.045) and lumbar lordosis (36.84 ± 13.63 vs. 45.08 ± 9.90, P < 0.001) and a larger pelvic incidence minus lumbar lordosis (PI-LL, 8.06 ± 15.05 vs.1.00 ± 11.34, P = 0.004) than the control group. Moreover, the thoracic kyphosis was smaller in the TOLF group, although the difference was not statistically significant (25.73 ± 11.29 vs. 28.22 ± 9.34, P = 0.187). The TOLF group had a significantly smaller slope angle at the inflection point (11.97 ± 5.85 vs. 15.78 ± 5.62, P < 0.001) and a higher tendency to have a Roussouly type 2 morphology (46.5% vs. 36.0%, P = 0.252) than the control group.

Conclusion.

This is the first study to describe the sagittal alignment in patients with TOLF. The TOLF group showed a hypolordotic spine with a larger PI-LL mismatch compared to the age- and sex-matched control group with lumbar spondylosis.

Level of Evidence: 4
Disparity of human immunodeficiency virus incidence and drug resistance in college student, non-student youth and older men who have sex with men: a cross-sectional study from seven major cities of China
Authors: Zhang Jing , Xu Jun-Jie , Chu Zhen-Xing , Hu Qing-Hai , Han Xiao-Xu , Zhao Bin , Jiang Yong-Jun , Geng Wen-Qing , Shang Hong
Published: November 2020

Background:

Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM.

Methods:

We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance.

Results:

Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0–5.8).

Conclusions:

College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.
Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China
Authors: Sun Jian-Jun , Liu Li , Wang Jiang-Rong , Shen Yin-Zhong , Qi Tang-Kai , Wang Zhen-Yan , Tang Yang , Song Wei , Chen Jun , Zhang Ren-Fang
Published: November 2020

Background:

Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).

Methods:

A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.

Results:

A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8–29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.

Conclusions:

Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.
Hypopigmented Mycosis Fungoides Mimicking Vitiligo
Authors: Kim Jin Cheol , Kim You Chan
Published: November 2020

Hypopigmented mycosis fungoides (HMF) is a clinical variant of MF with a presentation similar to other hypopigmented diseases, especially vitiligo. In this article, we report an adult case of HMF mimicking vitiligo. A 53-year-old man presented with an asymptomatic well-defined focal and hypopigmented patch with erythematous to brownish macules on the flank which had been developing over several months without other cutaneous findings. He had no past medical or trauma history. Skin biopsy from the hypopigmented patch indicated a slightly band-like, superficial dermal infiltrate of lymphocytes with mild cytologic atypia and epidermotropism. Fontana-Masson and Mart-1 stains showed a decrease in the epidermal pigment and the number of basal melanocytes. In addition, CD4 and CD8 stains were positive, predominantly the CD8 stain, and loss of CD7 stain was noted in the epidermal atypical lymphocytes. A T-cell receptor gene rearrangement study from the hyperpigmented area showed monoclonality. Finally, we diagnosed the patient with HMF. After about 17 months of treatment with narrow-band ultraviolet B, the hypopigmented lesion had notably improved in both the clinical and histological aspects. The clinical appearance of our case was similar to vitiligo while clinical improvement was also exceptionally similar to the skin findings from follicular repigmentation after narrow-band ultraviolet B treatment in vitiligo. Therefore, dermatologists should consider the clinical differential diagnosis of HMF in patients with an asymptomatic hypopigmentation, especially in dark-skinned Asian patients.
Recurrent Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Induced by Levamisole-Adulterated Cocaine
Authors: Macias Alonso Begoña , Bashyam Arjun M. , Eginli Ariana N. , Ahn Christine S. , McMichael Amy J.
Published: November 2020

Levamisole, an anthelmintic and immunomodulatory drug, was withdrawn from the US market in 1999 due to adverse effects, including agranulocytosis and vasculitis. In recent years, levamisole has been used as a common cocaine adulterant, and its use has led to an autoimmune syndrome characterized by an antineutrophil cytoplasmic antibody–associated vasculitis presenting with necrotic retiform purpura on the face and extremities. We present a case of recurrent levamisole-induced vasculitis initially misdiagnosed as systemic lupus erythematosus to highlight this easily misdiagnosed entity and to demonstrate re-exposure leading to recurrent vasculitis with more extensive clinical manifestations.
Integrated Genomic, Functional, and Prognostic Characterization of Atypical Chronic Myeloid Leukemia
Authors: Fontana Diletta , Ramazzotti Daniele , Aroldi Andrea , Redaelli Sara , Magistroni Vera , Pirola Alessandra , Niro Antonio , Massimino Luca , Mastini Cristina , Brambilla Virginia , Bombelli Silvia , Bungaro Silvia , Morotti Alessandro , Rea Delphine , Stagno Fabio , Martino Bruno , Campiotti Leonardo , Caocci Giovanni , Usala Emilio , Merli Michele , Onida Francesco , Bregni Marco , Elli Elena Maria , Fumagalli Monica , Ciceri Fabio , Perego Roberto A. , Pagni Fabio , Mologni Luca , Piazza Rocco , Gambacorti‐Passerini Carlo
Published: November 2020

Supplemental Digital Content is available for this article.
Comparison of Corneal Biomechanical Properties and Corneal Tomography Between Customized and Accelerated Corneal Crosslinking in Eyes with Keratoconus
Authors: Nishida Tomoya , Kojima Takashi , Kataoka Takahiro , Isogai Naoki , Yoshida Yoko , Nakamura Tomoaki
Published: November 2020

Purpose:

To compare the changes in corneal biomechanical properties and corneal tomography between transepithelial customized corneal crosslinking (C-CXL) and epithelium-off accelerated corneal crosslinking (A-CXL) in eyes with keratoconus.

Methods:

Twenty eyes in 20 consecutive patients who underwent C-CXL (C-CXL group) and 20 eyes in 20 patients who underwent A-CXL (A-CXL group) were included in this retrospective comparative study. The corneal biomechanical properties were analyzed using a Scheimpflug-based tonometer, and all corneas were examined by anterior segment optical coherence tomography (AS-OCT) before and 3 months after surgery. The corneal biomechanical parameters analyzed were the maximum inverse radius, deformation amplitude (DA) ratio max (2 mm), stiffness parameter at applanation 1, and integrated radius. The AS-OCT parameters analyzed included average keratometry, corneal astigmatism, maximum keratometry reading (Kmax), higher-order irregularity, and asymmetry.

Results:

In the C-CXL group, there were significant improvements in biomechanical parameters, including the maximum inverse radius, the DA ratio max (2 mm), and the integrated radius after surgery (P = 0.037, P = 0.002, and P = 0.003, respectively). In the C-CXL group, there was a significant decrease in the Kmax, higher-order irregularity, and asymmetry components (P = 0.014, P = 0.008, and P = 0.016, respectively). The biomechanical properties and AS-OCT parameters did not change significantly in the A-CXL group after surgery. According to multiple regression analyses, C-CXL had a greater effect than A-CXL in improving the maximum inverse radius, DA ratio max (2 mm), integrated radius, Kmax, asymmetry component, and higher-order irregularity component.

Conclusions:

C-CXL might improve the biomechanical properties and irregular shape of the cornea from the early postoperative period to a greater extent than A-CXL.
Inhibition of Fibrotic Contraction by Sirolimus (Rapamycin) in an Ex Vivo Model of Thyroid Eye Disease
Authors: Roos Jonathan C. P. , Eglitis Viesturs , Murthy Rachna
Published: November 2020

Background:

Thyroid eye disease (TED) is characterized by orbital inflammation and complicated by extraocular muscle fibrosis. Treatment with rapamycin/sirolimus has been reported to improve ocular motility and disease manifestations in TED. Whether this resulted from a primary antifibrotic effect on fibroblasts or was secondary to immune-suppression is unclear.

Methods:

In vitro contractility studies of primary orbital fibroblasts. Cells from patients with TED and controls were treated with rapamycin [mechanistic target of rapamycin an (mTOR) inhibitor] and MHY1485 (an mTOR stimulator) as well as inhibitors upstream in the same signaling cascade (saracatinib and befatinib).

Results:

At concentrations consistent with the therapeutic dosing range in humans, rapamycin/sirolimus significantly reduces fibrosis in orbital fibroblasts from TED patients and controls in vitro. This effect is separate from, and in addition to, its immune suppressive effect. mTOR-driven fibrotic activity is greater in TED-derived fibroblasts and can be blocked also upstream of mTOR by inhibition of src. There was no adverse effect on cell survival.

Conclusion:

The authors present evidence for a direct antifibrotic effect of rapamycin/sirolimus in primary orbital fibroblasts. Targeting mTOR signaling presents a further and adjunctive treatment of TED alongside other immune-suppressive agents. By acting downstream of IGF1-R, sirolimus may offer a cost-effective alternative to teprotumumab therapy. Clinical case reports, now supplemented by this in vitro evidence, support the initiation of a clinical trial to treat the fibrotic sequelae of TED with this already-approved agent. Such an “off-the-shelf” therapy is a welcome prospect for TED treatment, particularly one available at a low price.
Volumetric Versus Empirical Determination of Enucleation Implant Size
Authors: Custer Philip L. , Maamari Robi N. , Huecker Julia B. , Gordon Mae O.
Published: November 2020

Purpose:

To compare the use of sizing implants versus intraoperative volume measurements for individualization of enucleation implant size, and to identify preoperative factors affecting the choice of implant.

Methods:

In this retrospective observational cohort study, 2 implant sizing methods were compared using clinical records and photographs in 139 patients who underwent enucleation between 2007 and 2016.

Results:

There was no difference in mean implant (p = 0.6562) or prosthetic (p = 0.1990) enophthalmos between the 2 methods, or when comparing patients with and without conjunctival-Tenons fibrosis. The incidence and severity of superior sulcus deformity was similar between the methods (p = 0.6394). Preoperative phthisis (p < 0.0001) and intraoperative conjunctival-Tenons fibrosis (p = 0.0010) were more common in the sizing implant group. Among all study patients, mean implant size was larger in males (21.3 mm, n = 80) than females (20.7 mm, n = 59) (p = 0.0027). Implants >20 mm were more frequently inserted in patients with a wider Hertel exophthalmometry base (80% of males >95 mm; 77% of females >97 mm). Approximately 21.0% of patients demonstrated ≥8 mm of implant enophthalmos, suggesting an undersized implant. The authors estimate that 11% of patients could have received a sphere larger than 22 mm.

Conclusions:

Individualization of enucleation implant size can reduce the incidence of anophthalmic socket syndrome. The empirical use of sizing implants provided similar results as intraoperative volumetric measurements, when evaluated by postoperative superior sulcus depth and prosthetic or implant enophthalmos. Preoperative exophthalmometry may facilitate selection of implant size. Preexisting conjunctival-Tenon fascial fibrosis often did not limit implant size and was not associated with a higher prevalence of wound breakdown or implant exposure.
Toe Absence Related to Verrucous Carcinoma
Authors: Zheng Xiao-Li , Yi Fei , Jiang Yi-Qun , Wang Qian-Qiu , Liang Guan-Zhao , Yin Yue-Ping , Zhang Guo-Yi
Published: November 2020

Introduction:

Verrucous carcinoma is a rare variant of squamous cell carcinoma. It generally grows exogenously and bone erosion is rare.

Here we present a case of verrucous carcinoma on the foot with toe absence.

Case presentation:

A 64-year-old man presented with a 6-year history of a slowly growing exogenous hyperkeratotic verrucous lesion on the right fifth toe, which had been absent for 1 year. Before the lesion appeared, he had undergone nail extraction on this toe. The culture of fungi and mycobacteria were negative. Three-dimensional computed tomography showed that the fifth toe of the right foot was absent. Histopathological examination showed that the lesion was exogenous and verrucous and exhibited moderate keratinocyte hyperplasia. Combined with clinical manifestation and histopathological examination, verrucous carcinoma is suggested. The lesion was surgically excised, and the patient was followed up for more than 6 months without recurrence.

Discussion:

Verrucous carcinoma is an exophytic tumor with verrucous growth at the beginning, which can invade deep tissues and even cause limb mutilation. When encountering a patient with a wart-like plaque on the foot that responds poorly to conventional treatments, clinicians should maintain a high degree of clinical vigilance and a low threshold for biopsy.

Conclusion:

We observed a rare outcome of toe absence associated with verrucous carcinoma. Therefore, early diagnosis of verrucous carcinoma is very important. Surgical excision is an effective treatment at present. Extensive resection is usually required to avoid recurrence.
Role of Tight Junctions and Their Protein Expression in Atopic Dermatitis
Authors: Namrata Kunwar , Bai Bing-Xue
Published: November 2020

Atopic dermatitis (AD) is a chronic inflammatory skin disease with xerosis, itchiness, as well as interconnection with immunoglobulin E (Ig E), mediated foods including airborne allergies. AD is not only related to the diminished stratum corneum barrier but also presents with an unusual expression of tight junctions (TJs) proteins. TJ barrier dysfunction leads to impairment in the stratum corneum (SC) barrier. The significant role of TJs in the epidermal barrier as indicated by Claudin-1 (Cldn-1) deficient mice that undergo high transepidermal water loss (TEWL) and skin dehydration. In atopic dermatitis, downregulation of Cldn-1 was observed due to inflammation. Still, a lack of distinct understanding exists in considering tight junction barrier impairment as a cause or outcome in atopic dermatitis. This review summarizes TJs main role in skin barrier function and TJ proteins (TJPs) expression observed in AD patients.
A Study of Normal Epidermal Melanocyte Distribution
Authors: Sun Kai-Lv , Liu Wan , Gao Xiao-Man , Yang Min , Chang Jian-Min
Published: November 2020

Objective:

To elucidate the epidermal melanocyte distribution according to sex, age, and body part with the goal of providing benchmark data for the diagnosis and therapeutic effect evaluation of pigmentary skin diseases.

Methods:

Epidermal melanocytes and keratinocytes were assessed using direct immunofluorescence staining, and the melanocyte density and epidermal thickness were calculated. The obtained data were statistically analyzed using SPSS Version 20.0 software. An independent-samples t test was used to compare the data between two groups, while data among three or more groups were compared by one-way analysis of variance. Data correlations were evaluated using Pearson correlation analysis.

Results:

Melanocytes were uniformly distributed among the keratinocytes in the basal layer, and the average ratio of melanocytes to keratinocytes was 1:7. Among them, the ratio in males was 1:6.5 and that in females was 1:7.4, with no significant difference (P = 0.127). The melanocyte density gradually declined as age increased; the ratio was 1:5.8 before 50 years of age without an obvious downtrend. The average melanocyte density was 1:7.9 within 51 to 65 years of age and 1:8.5 at >65 years of age, and the difference was statistically significant (P < 0.01). Obvious differences were found in the melanocyte density among different body parts; in descending order, these densities were as follows: face (1:4.0) >neck (1:5.1) >hip (1:5.7) >upper limb (1:7.4) >lower limb (1:8.3) >lower back (1:9.2) >thorax and abdomen (1:9.9). The melanocyte density was not related to the epidermal thickness.

Conclusion:

The melanocyte density showed a declining trend with age and significantly changed after 50 years of age. The melanocyte density was associated with body part; specifically, the density in the face, neck, and hip was higher than that in the limbs and torso. However, the melanocyte density was not associated with sex or epidermal thickness.
Kidney Stones Are Prevalent in Individuals with Pseudoxanthoma Elasticum, a Genetic Ectopic Mineralization Disorder
Authors: Ralph Douglas , Allawh Rina , Terry Ian F. , Terry Sharon F. , Uitto Jouni , Li Qiao-Li
Published: November 2020

Objective:

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder caused by loss-of-function mutations in the ABCC6 gene. While PXE is characterized by ectopic mineralization of connective tissues clinically affecting the skin, eyes, and cardiovascular system, kidney stones were reported in some individuals with PXE. The aim of this study is to determine whether kidney stones are an incidental finding or a frequent manifestation of PXE.

Methods:

We first investigated the genetic basis of two siblings diagnosed with PXE. The younger patient presented with recurrent kidney stones since 8 years old. Secondly, to address whether kidney stones are associated with PXE, the prevalence of kidney stones in a survey cohort of 563 respondents with PXE was compared to that of a general U.S. population survey, National Health and Nutrition Examination Survey, with 28,629 participants.

Results:

Genetic analysis in both patients identified compound heterozygous mutations in ABCC6, c.2787+1G>T, and c.3774_3775insC. The analysis of participants 20 years old and older revealed that 23.4% of PXE patients had previously had a kidney stone, a significant increase compared to 9.2% in the general population (P < 0.01). In addition, 17.8% of PXE patients reported their first kidney stone episode before age of 18 years old.

Conclusions:

PXE correlates with an increased risk of developing kidney stones with considerable morbidity and health-care cost.
Circulating MicroRNAs as Potential Biomarkers in the Diagnosis of Neurosyphilis: A Case Control Study
Authors: Wu Kai-Qi , Zhang Su-Fang , Bao Chao-Hui , Zou Xin , Gu Xin , Wang Cui-Ni , Gong Wei-Ming , Shi Mei , Lou Yong-Liang , Huang Jian , Zhou Ping-Yu
Published: November 2020

Objective:

Laboratory diagnosis of neurosyphilis (NS) remains a great challenge. This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS, non-neurosyphilis, and healthy controls (HCs).

Methods:

We analyzed miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from six patients with NS, eight patients with secondary syphilis (SS), and five HCs using microarray technology. The differentially expressed miRNAs were validated in 33 NS samples, 31 SS samples, and 30 HC samples using TaqMan miRNA real-time qPCR (qRT-PCR).

Results:

Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs. Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR. All miRNAs were upregulated in SS and NS samples compared with HC. qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort (76 samples) showed that the average expression levels of nine miRNAs were higher in SS than in NS (SS: 0.185, NS: 0.136, P=3.8E-10), while the expressions of the other four miRNAs were lower in SS than in NS (SS: 0.000757, NS: 0.000873, P=0.022). ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs, 1.00 for distinguishing NS patients from HCs, 1.00 for distinguishing SS and NS patients from HCs, and 0.968 for distinguishing NS from SS patients.

Conclusion:

The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS. Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.
A Case Report of Pemphigoid Nodularis as Masquerader of Neurotic Excoriations
Authors: Tan Chee Hian , Tey Hong Liang
Published: November 2020

Introduction:

Pemphigoid nodularis is a rare clinical variant of bullous pemphigoid characterized by both prurigo nodularis-like lesions and pemphigoid-like blisters.

Herein, we report a case of pemphigoid nodularis in a cognitively-impaired patient who has been managed as extensive prurigo nodularis with neurotic exocriations for many years.

Case presentation:

A 72-year-old Chinese man has been on follow-up at an outpatient Dermatology unit for extensive prurigo nodularis for past 4 to 5 years until an inpatient stay when he was admitted for labile mood and erratic behavior due to the intense pruritus and skin lesions. During the admission, the inpatient team noticed tense hemorrhagic blisters on his right thigh for which histological examination confirmed the diagnosis of bullous pemphigoid. He was treated with oral prednisolone, doxycycline, and nicotinamide, which led to clinical improvement.

Discussion:

Pemphigoid nodularis can be easily misdiagnosed as prurigo nodularis. We discuss clinical clues that can raise the suspicion of an underlying immunobullous disorder, including erythematous nodules with a much larger surface area affected by central erosions and ulceration. Pruritus associated with larger areas of erosions and ulceration is clues that lesions can be more than mere excoriations.

Conclusion:

It is important for clinicians to be aware of the presentation of prurigo nodularis in association with bullous pemphigoid such that effective treatment can be promptly instituted. This is especially illustrated in this case, as the treatment of bullous pemphigoid not only improved his skin condition but it also improved his psychological health and behavior with the resolution of itch.