bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness and clinical outcomes of intermittent/continuous proton pump inhibitors infusion in high bleeding risk of ulcers
Authors: Hsieh Hui-Hsia , Wu Tien-Yuan , Chen Chi-Hua , Hour Mann-Jen
Published: December 2021

The purpose of this study was to evaluate the clinical outcomes, including patient prognosis and medication expense, of proton pump inhibitors administered by high-dose continuous infusion (HDC, 80 mg loading dose, then 8 mg/h for 72 hours) or non-high-dose intermittent infusion (NHDI, 40 mg qd or 40 mg q12 h, for 3 days) regimens in high-risk patients with bleeding peptic ulcers.

In this retrospective cohort study, patients with peptic ulcers and endoscopic hemostasis between January, 2013 and December, 2015 were included. The primary endpoints were rebleeding and mortality rates within 7 days. The secondary endpoints were length of stay (LOS), transfusion units of packed red blood cells (PRBCs), and the number needed to treat.

A total of 335 patients met the inclusion criteria during the 3-year follow-up period. The cumulative incidence of rebleeding within 7 days was 20.4% and 11.2% in the HDC and NHDI groups, respectively, with a significant difference (P = .021). The mortality rate was 12.1% and 7.3% in the HDC and NHDI groups, respectively, with no significant difference (P = .136). Univariate Cox proportional hazards model analysis showed that the risk of rebleeding within 7 days in the HDC group was higher than that in the NHDI group. The hazard ratio for HDC vs. NHDI was 1.93 (P = .021). There were significant differences in LOS (P = .034) and PRBC units (P = .005) for risk of rebleeding within 7 days, as well as in transfusion units of PRBCs for mortality rate analysis (p < 0.001), between the HDC and NHDI groups. The results showed that the NHDI regimen could reduce the risk of rebleeding within 7 days in 1 of 11 patients (number needed to treat = 11) and could reduce medication cost by US$ 400 to 800.

The NHDI regimen showed a lower risk of rebleeding within 7 days, shorter LOS, and fewer PRBC units than that of the HDC regimen. Receiving NHDI has better cost-effective outcomes than that of HDC for patients with high-risk bleeding peptic ulcers.
Human herpesvirus 8-associated multicentric Castleman disease in a patient with advanced HIV infection
Authors: Guayboon Theerajet , Chinthammitr Yingyong , Sukpanichnant Sanya , Horthongkham Navin , Angkasekwinai Nasikarn
Published: December 2021

Rational:

Multicentric Castleman disease (MCD) is a nonclonal lymphoproliferative disorder that is rarely reported from Southeast Asian countries. Here, we report a case of human herpesvirus 8 (HHV-8)-associated MCD in a patient with advanced human immunodeficiency virus (HIV) infection who presented with prolonged intermittent fever, urticarial rash, hepatosplenomegaly, and generalized lymphadenopathy.

Patient concerns:

A 34-year-old man with advanced HIV infection who was in good compliance with his antiretroviral treatment regimen presented with intermittent fever, weight loss, marked hepatosplenomegaly, and generalized lymphadenopathy. Recurrent symptoms of high-grade fever, abdominal discomfort, pancytopenia, and high C-reactive protein level occurred for 16 months.

Diagnoses:

Histopathological findings of left inguinal lymph node revealed diffuse effacement of lymph node architecture with coexpression of HHV-8 latency-associated nuclear antigen 1 from immunohistochemical staining. The HHV-8 viral load was 335,391 copies/mL.

Interventions:

The patient was treated initially with one dose of intravenous rituximab (375 mg/m2) followed by subcutaneous rituximab (1400 mg) weekly for 5 weeks.

Outcomes:

The patient's recurrent systemic symptoms subsided dramatically, and he has now been in remission for almost two years.

Lessons:

HHV8-associated MCD remains a diagnostic challenge in advanced HIV disease and should be suspected in those with recurrent flares of systemic inflammatory symptoms. Lymph node histopathology is essential for diagnosis and for excluding clonal malignancy. HHV-8 viral load is also useful for diagnosis and for monitoring disease activity.
Behavioral interventions to reduce particulate matter exposure in patients with COPD
Authors: Kang Jieun , Jung Ji Ye , Huh Jin-Young , Ji Hyun Woo , Kim Hwan-Cheol , Lee Sei Won
Published: December 2021

Introduction:

Chronic obstructive pulmonary disease (COPD) is commonly affected by particulate matter (PM) exposure. In this study, we aimed to evaluate whether behavioral interventions to reduce PM exposure improve clinical outcomes in patients with COPD.

Methods:

A multicenter randomized controlled trial will be conducted involving 120 participants recruited from 3 hospitals in the capital region of the Republic of Korea. Patients aged 40 to 80 years with a diagnosis of COPD and a forced expiratory volume at 1 s <80% of the predicted value are eligible for inclusion. The participants will be randomized to either the intervention group or the usual care group (2:1). The behavioral interventions will comprise the following activities: checking air quality forecast; operating indoor air cleaners and regular check-ups of filters; ventilating the home regularly by opening windows; adhering to inhaler treatment; and refraining from going out on high air pollution days. “Internet-of-things”-based, gravimetric, and light-scattering methods will be used to measure indoor and outdoor PM concentrations. To estimate the degree of individual PM exposure, a time-activity diary and land use regression modeling will be used. The efficacy of the behavioral interventions on the following outcomes will be analyzed: amount of PM exposure, changes in forced expiratory volume at 1 s from the baseline, changes in respiratory symptoms and quality of life, risks of exacerbation, hospitalization, and death.

Discussion:

Given the harmful effect of air pollutants, individual-level interventions to reduce exposure may be significant. However, there is a lack of evidence on how effective such interventions are to date. This study will be able to provide physicians and patients with evidence-based strategies to reduce PM exposure in daily life.

Trial registration number:

NCT04878367
Attitudes towards, knowledge about, and confidence to prescribe antiretroviral pre-exposure prophylaxis among healthcare providers in Thailand
Authors: Wisutep Pruettichai , Sirijatuphat Rujipas , Navanukroh Oranich , Phatharodom Phatharajit , Werarak Peerawong , Rattanasuwan Winai
Published: December 2021

HIV pre-exposure prophylaxis (HIV-PrEP) is an effective method for preventing HIV transmission, and it is recommended in several international guidelines. Perceptions and knowledge about HIV-PrEP prescription among healthcare providers have not been investigated in Thailand where HIV-PrEP is a novel healthcare topic. The objective of study was to determine healthcare providers’ attitudes towards, knowledge about, and confidence to prescribe HIV-PrEP in Thailand.

A questionnaire was administered to Thai healthcare providers during May 1, 2017 to September 5, 2018.

Of the 500 questionnaires that were distributed, 460 were returned (92%). Respondents included 336 physicians (48 infectious disease [ID] physicians, 288 non-ID physicians) and 124 non-physicians (70 nurses, 35 pharmacists, and 19 others). Eighty one percent of respondents had a positive attitude towards HIV-PrEP. Multivariate analysis revealed being a non-ID physician, having prior knowledge about HIV-PrEP, believing that HIV-PrEP can reduce the number of new patients, and believing that HIV-PrEP is not associated with a higher incidence of other sexually transmitted infections were all factors significantly associated with having a positive attitude towards HIV-PrEP. The issue of most concern to respondents who had a negative attitude toward HIV-PrEP was poor patient adherence to antiviral medications. Only 57% of respondents had confidence to prescribe HIV-PrEP. Factors associated with confidence to prescribe HIV-PrEP included being an ID physician, believing that HIV-PrEP can reduce the number of new patients, believing in the safety of antiviral medications, and believing that HIV-PrEP is not associated with increased development of HIV drug resistance. The results of HIV-PrEP knowledge testing (8 questions) were categorized into good score (≥7/8) and fair score (≤6/8). Fifty five percent of participants had a good score result. Using multivariate analysis, the factors associated with a good score result were ID physician, having HIV-PrEP prescription experience, and believing that HIV-PrEP can reduce the number of new patients.

Most Thai healthcare providers (81%) reported having a positive attitude towards HIV-PrEP. Successful HIV-PrEP implementation in Thailand will require steps to mitigate the described barriers, and training for healthcare providers, which will strengthen knowledge and improve both experience with and confidence to prescribe HIV-PrEP.
Successful treatment with denosumab for pelvic fibrous dysplasia
Authors: Ikuta Kunihiro , Sakai Tomohisa , Koike Hiroshi , Ito Kan , Imagama Shiro , Nishida Yoshihiro
Published: December 2021

Rationale:

Fibrous dysplasia is a rare disorder that results in fractures, pain, and disability and can affect any bone in the body. The treatment of symptomatic fibrous dysplasia is determined based on the affected bones. Although some lesions are often too extensive for surgical procedures, there are currently no effective or recommended medical treatments available for them.

Patient concerns:

A 27-year-old woman developed right buttock pain and was diagnosed with a bone tumor in the right ilium. Clinical images revealed an expansive osteolytic lesion with thinning of the cortex and cystic change from the acetabulum to the sacroiliac joint.

Diagnosis:

An incisional biopsy was performed, and the lesion was diagnosed as cystic fibrous dysplasia. Occasional osteoclast-like giant cells and woven bone were observed. The patient had no evidence of polyostotic lesions or findings of McCune-Albright syndrome. Biochemical blood test results showed no obvious abnormal values, except for an increase in serum tartrate-resistant acid phosphatase 5b to 459 mU/dL.

Interventions:

Since surgical treatment appeared to be challenging, she was treated with denosumab with decreased dose-intensity schedules.

Outcomes:

The administration of denosumab caused osteosclerosis within the lesion, resulting in the elimination of bone pain. The patient received denosumab treatment for 18 months. Pain relief and lesion radiodensity were maintained for 9 months after denosumab discontinuation. The serum level of tartrate-resistant acid phosphatase 5b was measured to monitor the response to denosumab, which was suppressed during denosumab treatment.

Lessons:

We described successful denosumab treatment in a patient with cystic fibrous dysplasia (FD) who maintained efficacy for 9 months after treatment. Although the use of denosumab in fibrous dysplasia is currently off-label, our experience with this patient supports the potential of denosumab therapy for patients for whom surgical treatment is challenging.
Estimation of sex based on metrics of the sternum in a contemporary Jordanian population
Authors: Kalbouneh Heba , Mubarak Nidaa , Daradkeh Salah , Ashour Omar , Alkhatib Ahmad Muneer , Suboh Lojayn , Nofal Amani , Mahafzah Waleed , Alsalem Mohammad
Published: December 2021

There is a paucity of osteometric standards for sex estimation from unknown skeletal remains in Jordan and the sexual dimorphism of the sternum has not yet been investigated. The aim of this study was to evaluate the sexual dimorphism in sternal measurements using 3D multidetector computed tomography (MDCT), and to assess their reliability for sex estimation in a Jordanian population. A total of 600 MDCT scans (300 males and 300 females) were used and a total of 8 sternal measurements were studied (manubrium length, sternal body length, combined length of manubrium and body, corpus sterni width at 1st and 3rd sternebrae, sternal index and area). Sexual dimorphism was evaluated by means of discriminant function analyses. Significant sexual dimorphism was found mainly in middle-aged and older adults. Including all subjects, multivariate, and stepwise functions gave an overall accuracy of 83.0% and 84.0%, respectively. Additionally, multivariate and stepwise analyses were conducted separately for each age group. The accuracy of sex estimation in multivariate analysis (all variables) varied from 63.2% in the young, and 83.7% in the middle adults to 84.9% for older adults. In stepwise analysis, the highest accuracy rates were provided by only sternal area in young adults (81.6%), and sternal area combined with sternal body length in middle-aged and older adults (84.2% and 85.3%, respectively). The best sex discriminator using univariate analysis (single variable) was sternal area followed by sternal body length (84.0% and 80.8% respectively). Notably, univariate analyses for most variables gave relatively higher classification accuracies in females but were poor at predicting males in the sample (sex bias ranged between −6.4% and −20%). Our data suggest that dimorphism in the human sternum increases with advancing age and separate discriminant functions are needed for each age group in Jordanians. In addition, multivariate and stepwise analyses using sternum gave higher classification accuracies with comparatively lower sex biases compared to univariate analyses.
Efficacy of Lycium barbarum L. on plasma lipid concentration in adults
Authors: Zeng Xueyuan , Zhao Weimin , Xu Yunlong , Zhang Chengwei , Wu Junliang , Xia Libo , Tian Ziyue , Ren Jixiang
Published: December 2021

Background:

Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease. Lycium barbarum L. are widely used as medicinal and functional food and may be particularly beneficial for patients with dyslipidemia. This systematic review protocol is designed to be used to evaluate the effects of Lycium barbarum L. on plasma lipid concentration through systematic reviews and meta-analysis.

Methods:

The Following electronic databases will be searched from inception to October 2021: the China National Knowledge Infrastructure, PubMed, Cochrane Library, Web of Science, and Wan-fang database. All randomized controlled trial designs evaluated the effects of Lycium barbarum L. on plasma concentrations of lipids will be included. Two researchers will operate literature retrieval, screening, information extraction, quality assessment, and data analysis independently. The analysis will be conducted using Rstudio software (Version 1.4.1717).

Results:

The findings will be submitted to a peer-reviewed publication.

Conclusion:

This study will provide practical and targeted evidence in investigating the impact of Lycium barbarum L. on plasma lipid concentration in adults.

Registration number:

INPLASY2021110043
Efficacy of moxibustion in diabetes peripheral neuropathy
Authors: Tay Jing Sheng , Kim Yun Jin
Published: December 2021

Background:

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. The main clinical manifestations of DPN include pain, numbness, paraesthesia, and weakness of the lower limbs which often leads to diabetic foot ulceration, eventually resulting in amputation. Based on Traditional Chinese Medicine theory, moxibustion has a great effect on treating and preventing DPN. However, randomized clinical trials done to evaluate the efficacy of this treatment are still lacking. Hence, this study is carried out to evaluate the effectiveness and safety of moxibustion therapy on diabetic peripheral neuropathy.

Methods:

This study will be a pilot, interventional, randomized, 2-armed, parallel, singled-masked, controlled trial. A total of 40 diabetes mellitus patients with peripheral neuropathy will be recruited and assigned randomly into 2 groups (moxibustion group and waiting group) at a 1:1 ratio. This trial consists of an 8-week intervention period and a 4-week follow-up period. During the intervention period, the moxibustion group will take 3 moxibustion sessions per week, whereas no intervention will be done on the waiting group to act as the control group. The outcome will be assessed by an outcome assessor who is unaware of the group assignment. The primary outcome will be pain assessment measured with algometry, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, visual analogue scale, and neuropathy pain scale. The secondary outcome will be an evaluation of functional performance capacity with 6 minutes walking test, evaluation of the Foot and Ankle Ability Measure, and serum HbA1c and albumin levels.

Discussion:

We hope that this trial will provide valuable insights on the efficacy of moxibustion in the management of diabetic peripheral neuropathy.

Trial registration:

ClinicalTrials.gov Registry No.: NCT04894461 (URL: https://clinicaltrials.gov/ct2/show/NCT04894461?term=NCT04894461&draw=2&rank=1) Registered on May 20, 2021.
Development of bullous pemphigoid following radiation therapy combined with nivolumab for renal cell carcinoma
Authors: Huynh Linda My , Bonebrake Benjamin T. , DiMaio Dominick J. , Baine Michael J. , Teply Benjamin A.
Published: December 2021

Rationale:

Concern for immune-related adverse events from immunotherapy and radiation therapy are well-documented; however, side effects are mostly mild to moderate. However, high-grade, potentially life-threatening adverse events are increasing. While case reports regarding immunotherapy-related bullous pemphigoid (BP) have been rising, only 1 has described BP following concomitant use of both nivolumab and radiation therapy (RT). For that patient, nivolumab was used for 10 weeks prior to RT and development of PB followed 7 weeks later. This case presents a patient who tolerated nivolumab well for 38 months prior to developing BP less than 2 weeks after completing RT.

Patient concerns:

We present the case of DH, a 67-year-old gentleman on nivolumab for metastatic renal cell carcinoma to the lung since May of 2017. Following progressing lung nodules, the patient had his nivolumab paused and completed a course of short-beam radiation therapy. After restarting nivolumab post-radiation, the patient presented with itchy rash and blisters on his arm, legs, and trunk.

Diagnosis:

DH consulted dermatology following development of rash and was diagnosed with bullous dermatosis, likely bullous pemphigoid. Bullous pemphigoid following concomitant nivolumab (OPDIVO), despite prior tolerance and no history of autoimmune disease, was confirmed by biopsy a month later.

Interventions:

Initial treatment was betamethasone 0.05% cream mixed 1:1 with powder to form paste applied twice daily. Given progressive symptoms and confirmatory biopsy of BP, nivolumab was held and 100 mg doxycycline and 80 mg prednisone daily was prescribed for a week, reduced to 60 mg during the second week.

Outcomes:

A week following discontinuation of nivolumab and beginning of doxycycline and prednisone, the blistering and rash was almost entirely resolved. Four months later, nivolumab was restarted and the patient continued low-dose tapering of prednisone until December. Since completing prednisone, the patient has shown no recurrence of bullous pemphigoid and has not developed any other immune-related adverse events to nivolumab upon rechallenge. Follow-up through October 2021 demonstrates the patient's sites of disease, both in- and out-field, have remained responsive to treatment.

Lessons:

Treating physicians should be aware of off-target effects of radiotherapy for oligoprogressive disease, which may include abscopal toxicities and the development of new immune-related adverse effects.
Necrotizing sarcoid granulomatosis simulating pulmonary malignancy
Authors: Kim Jun Hyeok , Nam Bo Da , Hwang Jung Hwa , Kim Dong Won , Kim Ki-Up , Park Young Woo
Published: December 2021

Rationale:

Necrotizing sarcoid granulomatosis (NSG) has recently been termed “sarcoidosis with NSG pattern” for the disease entity representing nodular sarcoidosis with granulomatous pulmonary angiitis. It is characterized by sarcoid-like granulomas, vasculitis, and a variable degree of necrosis. Its rarity and nonspecific clinical symptoms can easily lead to misdiagnosis or delayed diagnosis.

Patient concerns:

We report a 67-year-old female with a biopsy-confirmed sarcoidosis with NSG pattern mimicking pulmonary malignancy on initial chest computed tomography scan.

Diagnoses:

Sarcoidosis with NSG pattern.

Interventions:

The patient underwent video-assisted thoracoscopic surgery with a lung biopsy. No further treatment was performed after the lung biopsy.

Outcomes:

Follow-up imaging studies revealed spontaneous regression of the disease after 2 months.

Lessons:

Awareness of this rare benign disease entity and overlapping radiologic manifestations with pulmonary malignancy or other granulomatous diseases can be helpful for making a precise diagnosis with a better differential diagnosis.
A successful approach for angiosarcoma of the scalp using helical tomotherapy and customized surface mold brachytherapy
Authors: Suzuki Gen , Masui Koji , Watanabe Sho , Yamazaki Hideya , Takenaka Tadashi , Asai Jun , Maruyama Ayano , Yamada Kei
Published: December 2021

Rationale:

Angiosarcoma of the scalp (ASS) is a rare solid tumor with a high risk of local recurrence. Effective treatment strategies are not currently available for angiosarcoma of the scalp (ASS). The aim of this study was to report the utility of high-dose-rate brachytherapy (HDRBT) as a boost treatment for ASS following total scalp irradiation using helical tomotherapy (HT). This is the first report of successful treatment of ASS using HT and HDRBT.

Patient concerns:

An 81-year-old woman presented with hemorrhagic nodular skin tumors of the scalp. The patient first noticed the scalp mass 3 months before consultation, which became significantly enlarged within a short period. The tumor was positioned mostly in the parietal area, although the skin color change was widely spread to the surrounding scalp.

Diagnosis:

The patient underwent biopsy of the skin lesion at the right parietal region, which revealed the presence of angiosarcoma on pathological examination. There was neither regional lymphadenopathy nor distant metastases on PET/CT.

Interventions:

Considering the patient's old age and poor performance status because of a history of cerebral infarction, we considered that she was eligible for definitive chemoradiotherapy of the scalp. We adopted an individual surface mold HDRBT boost of 18 Gy in three fractions following total scalp irradiation with 50 Gy in 25 fractions delivered using HT. Docetaxel (40 mg/m2) was administered every 4 weeks, concurrently with radiotherapy.

Outcomes:

Treatment tolerance was good, and severe toxicity has not been observed to date. At 18 months after radiotherapy, the patient does not have any evidence of recurrence.

Conclusion:

Customized surface mold HDRBT following total scalp irradiation using HT resulted in excellent disease control and minimal toxicity; thus, it may be a promising therapeutic option for ASS.
Links between ceramides and cardiac function
Authors: Park Lauren K. , Garr Barry Valene , Hong Juan , Heebink John , Sah Rajan , Peterson Linda R.
Published: December 2021

Purpose of review

Total ceramide levels in cardiac tissue relate to cardiac dysfunction in animal models. However, emerging evidence suggests that the fatty acyl chain length of ceramides also impacts their relationship to cardiac function. This review explores evidence regarding the relationship between ceramides and left ventricular dysfunction and heart failure. It further explores possible mechanisms underlying these relationships.

Recent findings

In large, community-based cohorts, a higher ratio of specific plasma ceramides, C16 : 0/C24 : 0, related to worse left ventricular dysfunction. Increased left ventricular mass correlated with plasma C16 : 0/C24 : 0, but this relationship became nonsignificant after adjustment for multiple comparisons. Decreased left atrial function and increased left atrial size also related to C16 : 0/C24 : 0. Furthermore, increased incident heart failure, overall cardiovascular disease (CVD) mortality and all-cause mortality were associated with higher C16 : 0/C24 : 0 (or lower C24 : 0/C16 : 0). Finally, a number of possible biological mechanisms are outlined supporting the link between C16 : 0/C24 : 0 ceramides, ceramide signalling and CVD.

High cardiac levels of total ceramides are noted in heart failure. In the plasma, C16 : 0/C24 : 0 ceramides may be a valuable biomarker of preclinical left ventricular dysfunction, remodelling, heart failure and mortality. Continued exploration of the mechanisms underlying these profound relationships may help develop specific lipid modulators to combat cardiac dysfunction and heart failure.
Quality of life in sinonasal tumors: an up-to-date review
Authors: Chow Vanessa Jane , Tsetsos Nikolaos , Poutoglidis Alexandros , Georgalas Christos
Published: December 2021

Purpose of review

To assess the impact of benign and malignant sinonasal tumors and their management on patients’ Quality of Life (QOL) as measured by Patient Reported Outcome Measures (PROMS).

Recent findings

Although there is a growing consensus that endoscopic surgical management in carefully selected patients with sinonasal tumors is at least as (and probably more) effective than open resection, it is not clear to what extent this translates to better QOL outcomes. Earlier studies reported better outcomes in the emotional and physical function domains after endoscopic resection, and it seems that postsurgical morbidity is less in endoscopic compared to open approaches. QoL after endoscopic surgery for sinonasal and anterior skull base tumors seems to improve within several months of surgery in both benign and malignant tumor groups. However, patients with benign sinonasal tumors have a higher QOL pre and post operatively compared to those with malignancy mainly due to absence of (neo) - adjuvant radiotherapy and/or chemotherapy. Factors that seem to be associated with worse QoL include > 60 years, less than 6 months from surgery, prior and adjuvant chemo and radiotherapy, smoking history, advanced staging and malignancy.

There is not a universally accepted PROM for use in patients with sinonasal benign and malignant tumors: A variety of different PROMs have been used with different degrees of effectiveness. Most likely a combination of disease-specific (such as SNOT 22 and anterior skull base questionnaire) and generic (such as Short Form health survey questionnaire (SF-36) and Karnofsky Performance Status) health outcome measures provide the most insight into QOL of patients with sinonasal tumors. QOL of these patients appears to undergo a bimodal impact with patients experiencing an initial dip in QOL after surgical treatment followed by a slow improvement over time. However, while patients with benign tumors’ return to their status quo ante QOL, this is not the case for patients with malignant tumors who stabilize at a lower than initially QOL. To a large extent this seems to be the effect of (neo) adjuvant chemo radiotherapy.
Management of the middle turbinate during and after sinus surgery
Authors: Tang Dennis M. , Roxbury Christopher R.
Published: December 2021

Purpose of review

Treatment of the middle turbinate (MT) during and after endoscopic sinus surgery (ESS) has been controversial. Historically, there has been concern that resection of the MT may result in smell loss and frontal sinus stenosis. However, these concerns must be balanced by knowledge that a residual diseased MT may result in surgical failure. This review discusses the current evidence on treatment of the MT during and after ESS.

Recent findings

Several review articles have shown the safety of performing MT resection. Studies have not shown increase rates of frontal sinus stenosis, olfactory loss, or empty nose syndrome. However, the benefit of MT resection is highly debated. There have also been many recent advances and technological developments to assist in management of the postoperative MT.

The literature supports the safety of performing MT resection, however, the benefit of resection over preservation is controversial. New technologies and techniques exist that may aid in preventing postoperative MT lateralization.
Vision, Driving Exposure, and Collisions in Bioptic Drivers
Authors: Zhou Alicia M. , Flom Roanne E. , Raasch Thomas W. , Segerstrom Ellen E. , Dougherty Bradley E.
Published: December 2021

SIGNIFICANCE

Lack of knowledge regarding the mileage driven by drivers with low vision who use bioptic telescopes could obscure the relationship between vision and road safety. This study provides data suggesting that worse vision is correlated with less mileage driven but more collisions per mile in bioptic drivers.

PURPOSE

The purpose of this study was to determine whether vision or demographic factors predict mileage driven in bioptic drivers and per-mile motor vehicle collision rate and also to compare the collision rate of bioptic drivers with previous estimates for the general population.

METHODS

Driver data were collected retrospectively from clinic records. Collision data were collected from the Ohio Bureau of Motor Vehicles database. Subjects were also asked to estimate their yearly mileage. Regression models were used to investigate relationships between vision and collision rates.

RESULTS

Seventy-three licensed Ohio bioptic drivers (36 male) were included. Mean ± standard deviation age was 51 ± 16 years. Mean logMAR visual acuity was 0.67 (approximately 20/100). Mean log contrast sensitivity was 1.57. Mean reported annual mileage was 9746. Age, sex, and previous (nonbioptic) driving experience were not associated with mileage. LogMAR visual acuity was inversely related to mileage (P = .02), and contrast sensitivity (P = .01) and horizontal visual field (P = .02) were directly associated with mileage. Visual acuity (P = .02) and visual field (P = .005), but not contrast sensitivity (P = .19), were associated with number of collisions.

CONCLUSIONS

Visual acuity, visual field, and contrast sensitivity were associated with driving exposure in bioptic drivers (with drivers with poorer vision reporting lower annual mileage), and poorer visual acuity and visual field were associated with more collisions. The per-mile collision rate for bioptic drivers was within the range of that previously reported for fully sighted drivers, although higher than would be expected for fully sighted drivers of similar age distribution.
Measurement and Analysis of Whole-surface Power Distribution in Single Tilted Spectacle Lenses
Authors: Huang Ching-Yao
Published: December 2021

SIGNIFICANCE

Face-form tilt spectacles are sometimes tilted such that the optical properties of the embedded prescription lenses and the lens power change. If the lens power is not plano, the vision quality of the wearer may be affected.

PURPOSE

This study aimed to measure the whole-surface power distributions of tilted spectacle lenses for different lens powers and tilt angles.

METHODS

Spherical spectacle lenses with a refractive index of 1.56 and powers of −4.00 D, −2.00 D, plano, +2.00 D, and +4.00 D were measured. Their whole-surface power distributions were measured at different tilt angles, up to 20°, using a commercially available Hartmann wavefront aberrometer. The measured data were limited within a 40-mm diameter and analyzed to obtain contour plots of the spherical equivalent (M) and astigmatism (J).

RESULTS

The measured whole-surface power profiles of the nontilted lenses showed both M and J as being symmetrical and increasing outward up to −0.52 and +0.24 D, respectively, for the −4.00 D lens and +0.22 and +0.05 D, respectively, for the +4.00 D lens, corresponding to the spherical design. The profiles of the tilted lenses showed both M and J as unevenly increasing from the center to the peripheral area along the downward tilt direction; however, the plano lens exhibited no effect of tilt on both M and J. The powers at the optical center of the lens increased with tilt angle and lens power. The maximum differences for M and J at a 15° tilt angle in the −4.00 D lens were −2.46 and +1.43 D, respectively. Conversely, at a 17° tilt angle, the maximum differences in the +4.00 D lens were +0.96 D in M and +0.46 D in J.

CONCLUSIONS

Tilt angle and lens power strongly affect the power profiles of tilted spectacle lenses.
Lower Neurocognitive Functioning in HIV-Exposed Uninfected Children Compared With That in HIV-Unexposed Children
Authors: Benki-Nugent Sarah F. , Yunusa Rabi , Mueni Alice , Laboso Tony , Tamasha Nancy , Njuguna Irene , Gómez Laurén , Wamalwa Dalton C. , Tapia Kenneth , Maleche-Obimbo Elizabeth , Bangirana Paul , Boivin Michael J. , John-Stewart Grace C.
Published: December 2021

Background:

Perinatal HIV and antiretroviral therapy exposure may influence neurocognitive outcomes, although evidence is mixed and most studies are limited to outcomes in the first 24 months. We compared neurocognitive outcomes in school-aged children who were HIV exposed uninfected (CHEU) with those in children who were HIV unexposed uninfected (CHUU).

Setting:

Children were recruited from a health center in Nairobi, Kenya.

Methods:

Key inclusion criteria were children aged 5–12 years and confirmed child and maternal HIV status; for CHEU, mothers reported knowing HIV-positive status before or at delivery of the index child. Children underwent a detailed battery of neuropsychological tests and behavioral assessment, and comparisons of scores between CHEU and CHUU were conducted using linear regression.

Results:

Among 56 CHEU and 65 CHUU, the median age and sex distributions were 6.8 and 7.0 years (P = 0.8) and 48% and 60% girls (P = 0.2), respectively. In analyses adjusted for child's age and sex and caregiver's age, education, and household rent, CHEU had significantly lower mean z scores for global cognitive ability than CHUU [−0.35, 95% confidence interval (CI): −0.64 to −0.05; P = 0.02], short-term memory (−0.44, 95% CI: −0.76 to −0.12; P = 0.008), delayed memory (−0.43, 95% CI: −0.79 to −0.08; P = 0.02), attention (−0.41, 95% CI: −0.78 to −0.05; P = 0.03), and processing speed (−0.76, 95% CI: −1.37 to −0.16; P = 0.01). Models adjusted for child nutritional status, household food security, and orphanhood yielded similar results.

Conclusions:

Children exposed to HIV had poorer long-term neurocognitive outcomes than CHUU. These data suggest that long-term studies of neurocognitive and educational attainment in CHEU are warranted.
Neopterin Relates to Lifetime Depression in Older Adults With HIV on Suppressive Antiretroviral Therapy
Authors: Saloner Rowan , Savini Natalie , Letendre Scott L. , Moore David J. , Montoya Jessica L.
Published: December 2021

Background:

Chronic inflammation contributes to the pathogenesis of depression in persons with HIV (PWH). Neopterin, a biomarker of HIV-related immune activation that partially normalizes with antiretroviral therapy (ART), correlates with major depressive disorder (MDD) and subclinical depressive symptoms in persons without HIV and acutely infected, young PWH. The sensitivity of neopterin, however, to both lifetime and current depression is poorly understood in older PWH on suppressive ART.

Methods:

Participants were 70 PWH and 35 persons without HIV (HIV−) who were at least 50 years old and completed standardized neurobehavioral and neuromedical assessments. Depressive symptoms in the past 2 weeks, measured with the Beck Depression Inventory-II (BDI-II), and lifetime MDD diagnoses, defined as meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a depressive episode at any point in one's lifetime, were separately modeled as a function of plasma neopterin levels in the full sample and by HIV serostatus.

Results:

Compared with HIV− adults, PWH had higher neopterin levels (P < 0.001) and BDI-II scores (P < 0.01) and were more likely to have lifetime MDD (P < 0.01). Higher neopterin related to lifetime MDD, but only in PWH, even after controlling for clinically relevant comorbidities and treatment factors in logistic regression (odds ratio = 3.11, P = 0.002). Higher neopterin correlated with higher BDI-II scores in the full sample (rs = 0.25; P = 0.010), but not within either group (PWH: rs = 0.03, P = 0.819; HIV−: rs = 0.09, P = 0.588).

Conclusion:

Neopterin was associated with lifetime MDD, but not current depressive symptoms in older PWH on suppressive ART. This may reflect a legacy of inflammation-related disruptions to amino acid metabolism and neurotransmitter synthesis, similar to prior observations. Identification of biopsychosocial and resilience factors underlying the null association between neopterin and current depression in older PWH is warranted.
Vestibular function testing in the 21st century: video head impulse test, vestibular evoked myogenic potential, video nystagmography; which tests will provide answers?
Authors: Rosengren Sally M. , Young Allison S. , Taylor Rachael L. , Welgampola Miriam S.
Published: December 2021

Purpose of review

To most neurologists, assessing the patient with vertigo is an unpleasant and worrisome task. A structured history and focused examination can be complemented by carefully selected laboratory tests, to reach an early and accurate diagnosis. We provide evidence-based recommendations for vestibular test selection.

Recent findings

The video head impulse test (vHIT), cervical and ocular vestibular evoked myogenic potential (VEMP) and home-video nystagmography are four modern, noninvasive methods of assessing vestibular function, which are equally applicable in the hospital and office-practice. Collectively, they enable assessment of all five vestibular end-organs. The prevalence and patterns of test abnormalities are distinct for each vestibular disorder. We summarize typical abnormalities encountered in four common vestibular syndromes.

In the context of acute vestibular syndrome, an abnormal vHIT with low gain and large amplitude refixation saccades and an asymmetric oVEMP separates innocuous vestibular neuritis from stroke. In episodic spontaneous vertigo, high-velocity ictal nystagmus and asymmetric cVEMP help separate Ménière's disease from vestibular migraine. In chronic imbalance, all three tests help detect unilateral or bilateral vestibular loss as the root cause. Recurrent positional vertigo requires no laboratory test and can be diagnosed and treated at the bedside, guided by video nystagmography.
Reactivation of Q fever: case report of osteoarticular infection developing at the site of a soft tissue injury
Authors: McKew Genevieve L. , Gottlieb Thomas
Published: December 2021

Coxiella burnetii

, the causative agent of Q fever, is known to cause acute and persistent infection, but reactivation of infection is rarely reported. This case demonstrates reactivation of a distant, untreated Q fever infection after a relatively innocuous soft tissue injury in an adjacent joint without pre-existing pathology. A 52-year-old male abbatoir worker sustained an adductor muscle tear in a workplace injury. He was unable to walk thereafter, and developed a chronic, progressive, destructive septic arthritis of the adjacent hip with surrounding osteomyelitis of the femur and acetabulum. He had evidence of prior Q fever infection, with a positive skin test and serology 15 years beforehand. He was diagnosed with chronic osteoarticular Q fever on the basis of markedly elevated phase I antibodies, and symptomatic and serological response to prolonged antibiotic treatment with doxycycline and hydroxychloroquine. He required a two-stage hip arthroplasty. This case illustrates reactivation of latent

C. burnetii

infection at the site of a soft tissue injury. Clinicians need to be aware of this possibility in patients with previous Q fever infection, and in the setting of undiagnosed osteoarticular pathology following soft tissue injury.
JMM Profile: Carbapenems: a broad-spectrum antibiotic
Authors: Armstrong Tom , Fenn Samuel Jacob , Hardie Kim R.
Published: December 2021

Carbapenems are potent members of the β-lactam family that inhibit bacterial cell-wall biosynthesis inhibitors . They are highly effective against Gram-negative and Gram-positive drug-resistant infections . As such, carbapenems are typically reserved as an antibiotic of last resort. The WHO lists meropenem as an essential medicine. Nausea and vomiting are reported in ≤20% of carbapenem recipients, with 1.5% suffering seizures. Enzymatic hydrolysis of the β-lactam ring is the main driver of clinical resistance. These enzymes can be classified as Class A, B and D. Classes A and D are serine β-lactamases, whereas Class B rely on metal-mediated hydrolysis, typically through zinc.
Experimental evolution under varying sex ratio and nutrient availability modulates male mating success in Drosophila melanogaster
Authors: Sepil Irem , Perry Jennifer C. , Dore Alice , Chapman Tracey , Wigby Stuart
Published: December 2021

Biased population sex ratios can alter optimal male mating strategies, and allocation to reproductive traits depends on nutrient availability. However, there is little information on how nutrition interacts with sex ratio to influence the evolution of pre-copulatory and post-copulatory traits separately. To address this omission, here we test how male mating success and reproductive investment evolve under varying sex ratios and adult diet in Drosophila melanogaster using an experimental evolution approach. We found that sex ratio and nutrient availability interacted to determine male pre-copulatory performance. Males from female-biased populations were slow to mate when they evolved on a protein-restricted diet. On the other hand, we found direct and non-interacting effects of sex ratio and nutrient availability on post-copulatory success, without interactions between them. Males that evolved on a protein-restricted diet were poor at suppressing female remating. Males that evolved under equal sex ratios fathered more offspring and were better at supressing female remating, relative to males from male-biased or female-biased populations. These results support the idea that sex ratios and nutrition interact to determine the evolution of pre-copulatory mating traits, but independently influence the evolution of post-copulatory traits.
A novel bacterial protease inhibitor adjuvant in RBD-based COVID-19 vaccine formulations increases neutralizing antibodies, specific germinal center B cells and confers protection against SARS-CoV-2 infection
Authors: Coria Lorena M. , Saposnik Lucas M. , Castro Celeste Pueblas , Castro Eliana F. , Bruno Laura A. , Stone William B. , Pérez Paula S. , Darriba M. Laura , Chemes Lucia B. , Alcain Julieta , Mazzitelli Ignacio , Varese Augusto , Salvatori Melina , Auguste Albert J. , Álvarez Diego E , Pasquevich Karina A. , Cassataro Juliana
Published: December 2021

In this work we evaluated recombinant receptor binding domain (RBD) based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus Alum, AddaS03, AddaVax or the combination of Alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and Alum as adjuvants have a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus Alum, AddaVax or AddaS03. Antibodies induced with the formulation containing U-Omp19 not only increased their neutralization capacity against the wild-type virus but also cross neutralized alpha, lambda and gamma variants with similar potency. Also, addition of U-Omp19 to vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+Alum formulation induced RBD-specific Th1 and CD8+ T cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal SARS-CoV-2 challenge of K18-hACE2 mice.
Interfacing Spinal Motor Units in Non-Human Primates Identifies a Principal Neural Component for Force Control Constrained by the Size Principle
Authors: Del Vecchio Alessandro , Jones Rachael H. A. , Schofield Ian S. , Kinfe Thomas M , Ibáñez Jaime , Farina Dario , Baker Stuart N.
Published: December 2021

Motor units convert the last neural code of movement into muscle forces. The classic view of motor unit control is that the central nervous system sends common synaptic inputs to motoneuron pools and that motoneurons respond in an orderly fashion dictated by the size principle. This view however is in contrast with the large number of dimensions observed in motor cortex which may allow individual and flexible control of motor units. Evidence for flexible control of motor units may be obtained by tracking motor units longitudinally during the performance of tasks with some level of behavioural variability. Here we identified and tracked populations of motor units in the brachioradialis muscle of two macaque monkeys during ten sessions spanning over one month during high force isometric contractions with a broad range of rate of force development (1.8 – 38.6 N·m·s-1). During the same sessions we recorded intramuscular EMG signals from 16 arm muscles of both limbs and elicited the full recruitment through neural stimulation of the median and deep radial nerves. We found a very stable recruitment order and discharge characteristics of the motor units over sessions and contraction trials. The small deviations from orderly recruitment were observed between motor units with close recruitment thresholds, and only during high rate of force development. Moreover, we also found that one component explained more than ~50% of the motor unit discharge rate variance, and that the remaining components could be described as a time-shifted version of the first, as it could be predicted from the interplay between the size principle of recruitment and one common input. In conclusion, our results show that motoneurons recruitment is determined by the interplay of the size principle and common input and that this recruitment scheme is not violated over time nor by the speed of the contractions.
Deep Mutational Engineering of broadly-neutralizing and picomolar affinity nanobodies to accommodate SARS-CoV-1 & 2 antigenic polymorphism
Authors: Laroche Adrien , Orsini Delgado Maria Lucia , Cuniasse Philippe , Dubois Steven , Sierocki Raphaël , Gallais Fabrice , Debroas Stéphanie , Bellanger Laurent , Simon Stéphanie , Maillère Bernard , Nozach Hervé
Published: December 2021

We report in this study the molecular engineering of nanobodies that bind with picomolar affinity to both SARS-CoV-1 and SARS-CoV-2 Receptor Binding Domains (RBD) and are highly neutralizing. We applied Deep Mutational Engineering to VHH72, a nanobody initially specific for SARS-CoV-1 RBD with little cross-reactivity to SARS-CoV-2 antigen. We first identified all the individual VHH substitutions that increase binding to SARS-CoV-2 RBD and then screened highly focused combinatorial libraries to isolate engineered nanobodies with improved properties. The corresponding VHH-Fc molecules show high affinities for SARS-CoV-2 antigens from various emerging variants and SARS-CoV-1, block the interaction between ACE2 and RBD and neutralize the virus with high efficiency. Its rare specificity across sarbecovirus relies on its peculiar epitope outside the immunodominant regions. The engineered nanobodies share a common motif of three amino acids, which contribute to the broad specificity of recognition. These nanobodies appears as promising therapeutic candidates to fight SARS-CoV-2 infection.