bluuebunny/crossref_metadata_2025 huggingface dataset:
A Patient-specific Approach to Alignment and Proximal Junctional Kyphosis Risk Assessment in Adult Spinal Deformity Surgery
Authors: Hills Jeffrey M. , Weisenthal Benjamin M. , Wanner John P. , Gupta Rishabh , Steinle Anthony , Pennings Jacquelyn S. , Stephens Byron F.
Published: January 2022

Study Design:

This was a single-institution, retrospective cohort study.

Objective:

We aimed to develop a predictive model for proximal junctional kyphosis (PJK) severity that considers multiple preoperative variables and modifiable surgical alignment.

Summary of Background Data:

PJK is a common complication following adult deformity surgery. Current alignment targets account for age and pelvic incidence but not other risk factors.

Materials and Methods:

This is a single-institution, retrospective cohort study of adult deformity patients with a minimum 2-year follow-up undergoing instrumented fusion between 2009 and 2018. A proportional odds regression model was fit to estimate PJK probability and Hart-International Spine Study Group (ISSG) PJK severity score. Predictors included preoperative Charlson Comorbidity Index, vertebral Hounsfield Units near the upper instrumented vertebrae, pelvic incidence, T1-pelvic angle, and postoperative L1–L4 and L4–S1 lordosis. Predictor effects were assessed using adjusted odds ratios and a nomogram constructed for estimating PJK probability. Bootstrap resampling was used for internal validation.

Results:

Of 145 patients, 47 (32%) developed PJK. The median PJK severity score was 6 (interquartile range, 4–7.5). After adjusting for predictors, Charlson Comorbidity Index, Hounsfield Units, preoperative T1-pelvic angle, and postoperative L1–L4 and L4–S1 lordosis were significantly associated with PJK severity (P<0.05). After adjusting for potential overfitting, the model showed acceptable discrimination [C-statistic (area under the curve)=0.75] and accuracy (Brier score=0.10).

Conclusions:

We developed a model to predict PJK probability, adjusted for preoperative alignment, comorbidity burden, vertebral bone density, and modifiable postoperative L1–L4 and L4–S1 lordosis. This approach may help surgeons assess the patient-specific risk of developing PJK and provide a framework for future predictive models assessing PJK risk after adult deformity surgery.

Level of Evidence:

Level III.
Association of Baseline and Pharmacodynamic Biomarkers With Outcomes in Patients Treated With the PD-1 Inhibitor Budigalimab
Authors: Lambert Stacie L. , Zhang Chun , Guo Claire , Turan Tolga , Masica David L. , Englert Stefan , Fang Yuni , Sheridan James , McLaughlin Robert Tyler , Tribouley Catherine , Vosganian Greg , Afar Daniel
Published: January 2022

Budigalimab, a novel anti–PD-1 monoclonal antibody, demonstrated efficacy and biomarker pharmacodynamics in patients with head and neck squamous cell carcinoma (HNSCC) or non–small cell lung cancer (NSCLC) consistent with those reported by other PD-1 inhibitors. Herein are presented additional outcomes of biomarker analyses from the phase 1 study of budigalimab monotherapy in patients with HNSCC and NSCLC (NCT03000257). PD-1 inhibitor naive patients with advanced HNSCC (n=41) or NSCLC (n=40) received budigalimab intravenously at 250 mg every 2 weeks (Q2W) or 500 mg Q4W until progression. Archival tumor specimens were evaluated by immunohistochemistry for CD8 and tumor PD-1 ligand 1 (PD-L1) expression, RNA, and whole-exome sequencing. Serum and whole blood samples were acquired at baseline and at select on-treatment time points. As of October 2019, best overall response of 15% in HNSCC and 18% in NSCLC was observed in all treated patients; both cohorts reported responses in PD-L1+ and PD-L1– tumors. Treatment with budigalimab was associated with increases in multiple soluble biomarkers including interferon gamma-induced chemokines. Expanded overall T-cell counts, total CD8 T-cell counts, and percentages of CD8+CD45RA–CD62L– effector memory T cells were observed at cycle 1, day 15 in responders. Univariate analysis demonstrated an association between prolonged progression-free survival and higher tumor mutational burden/neoantigen load, smaller tumor size, lower platelet-lymphocyte ratios, lower CCL23, lower colony-stimulating factor 1, and lower interleukin-6 levels at baseline. The biomarker analysis presented herein identified additional early pharmacodynamic biomarkers associated with anti–PD-1 activity and improved clinical responses to budigalimab in patients with advanced HNSCC and NSCLC.
Beyond criminalization: reconsidering HIV criminalization in an era of reform
Authors: Hoppe Trevor , McClelland Alexander , Pass Kenneth
Published: January 2022

Purpose of review

This paper reviews recent studies examining the application of human immunodeficiency virus (HIV)-specific criminal laws in North America (particularly the United States and Canada). In the wake of the development of new biomedical prevention strategies, many states in the United States (US) have recently begun to reform or repeal their HIV-specific laws. These findings can help inform efforts to ‘modernize’ HIV laws (or, to revise in ways that reflect recent scientific advances in HIV treatment and prevention).

Recent findings

Recent studies suggest that HIV-specific laws disproportionately impact Black men, white women, and Black women. The media sensationally covers criminal trials under these laws, especially when they involve Black defendants who they often describe in racialized terms as predators. Activists contest these laws and raise concerns about new phylogenetic HIV surveillance techniques that have the potential to be harnessed for law enforcement purposes.

These findings collectively raise urgent concerns for the continued use of HIV-specific criminal laws. These policies disproportionately impact marginalized groups – particularly Black men. Media coverage of these cases often helps to spread misinformation and stigmatizing rhetoric about people living with HIV and promulgate racist stereotypes. Although well-intentioned, new phylogenetic HIV surveillance technologies have the potential to exacerbate these issues if law enforcement is able to gain access to these public health tools.
Activity restriction and preterm birth prevention
Authors: Nuss Emily E. , Sciscione Anthony C.
Published: January 2022

Purpose of review

Since the 1900s, activity restriction (AR) has been widely prescribed as a strategy for preventing preterm birth (PTB). Over the past decade, the practice has been called into question as numerous studies have demonstrated that AR does not improve obstetrical and perinatal outcomes but does confer significant physical and psychological risks. The purpose of this review is to offer clinicians a summary of the latest data on the risks, benefits, and efficacy of AR for the prevention of PTB.

Recent findings

Both retrospective and prospective studies have demonstrated that AR does not significantly prolong pregnancy including those with multiple gestations, short cervices, ruptured membranes, and increased body mass indexes. Several studies have also shown that physical activity during pregnancy is associated with a higher incidence of vaginal delivery, a lower incidence of gestational diabetes mellitus, and a lower incidence of hypertensive disorders without increasing the risk of adverse neonatal outcomes.

The culmination of these data led to the Society for Maternal-Fetal Medicines’ release of an updated committee recommendation in August of 2020; AR should not be routinely prescribed as a treatment to prevent PTB.
Low sexual function is associated with menopausal status in mid-aged women with human immunodeficiency virus infection
Authors: Mezones-Holguín Edward , Arriola-Montenegro José , Cutimanco-Pacheco Víctor , Al-kassab-Córdova Ali , Niño-García Roberto , Zeta Ludwing A. , Urrunaga-Pastor Diego , Blümel Juan E. , Chedraui Peter , Pérez-López Faustino R.
Published: January 2022

Objective:

To assess the association between menopausal status and female sexual function among mid-aged women with human immunodeficiency virus (HIV) infection.

Methods:

We carried out a cross-sectional study of 221 sexually active HIV-infected women ages 40 to 59 years, based on a secondary analysis of a three-hospital survey in Lima, Perú. We classified menopausal status according to Stages of Reproductive Aging Workshop criteria (STRAW+10); this exposure variable was categorized as binary (non-postmenopausal and postmenopausal) and—for exploratory analysis—as multinomial (pre-, peri-, and postmenopausal). We defined low sexual function (LSF) using the 6-item Female Sexual Function Index (total score ≤19). Socio-demographic and clinical variables were assessed, including age, used highly active antiretroviral therapy scheme, disease duration, depressive symptoms, and co-morbidities. We performed Poisson generalized linear models with a robust variance to estimate 95% confidence interval (CI), crude prevalence ratios (cPRs), and adjusted prevalence ratios (aPRs) by epidemiological and statistical approaches using nonparametric method of bias-corrected and accelerated bootstrap resampling with 1,000 repetitions.

Results:

Studied women had a median age of 47.0 years (interquartile range: 7.5); 25.3% were premenopausal, 25.8% were perimenopausal, and 48.9% were postmenopausal. Also, 64.3% had LSF. The frequency of LSF was 53.6% in non-postmenopausal and 75.0% in postmenopausal women. Postmenopausal status was associated with LSF in both the crude (cPR = 1.39; 95% CI: 1.13-1.71) and the adjusted regression models (aPR = 1.38; 95% CI: 1.12-1.71).

Conclusions:

HIV-infected postmenopausal women have a higher prevalence of LSF than those non-postmenopausal ones, even when adjusting for multiple potential confounders.
NT-pro B-type natriuretic peptide, early menopause, and incident heart failure in postmenopausal women of the ARIC study
Authors: Ebong Imo A. , Wilson Machelle D. , Chang Patricia , Appiah Duke , Polonsky Tamar , Ballantyne Christie , Bertoni Alain G.
Published: January 2022

Objective:

N-Terminal pro B-type Natriuretic Peptide (NT-proBNP), a biomarker of heart failure (HF) has been associated with early menopause. We evaluated the modifying role of early menopause on the association of NT-proBNP with incident HF, and separately for HF subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).

Methods:

We included 4,352 postmenopausal women including 1,174 with early menopause, ages 63.5 ± 5.5 years, without prevalent HF at the Atherosclerosis Risk in Communities study Visit 4. Binary log-transformation was performed for NT-proBNP. Cox proportional hazards models were used to examine the association of NT-proBNP with incident HF, and separately for incident HFpEF and incident HFrEF, testing for effect modification by early menopause and adjusting for HF risk factors.

Results:

We observed 881 HF events over a mean follow-up of 16.5 years. The interaction terms of NT-proBNP and early menopause were not significant for incident HF (P
interaction
0.95) and incident HFpEF (P
interaction
0.17) but were significant for incident HFrEF (P
interaction
0.03). The adjusted hazard ratios resulting from each doubling of NT-proBNP levels amongst women with and without early menopause were 1.33 (1.20-1.47) and 1.34 (1.24-1.44), respectively, for incident HF; 1.57 (1.34-1.86) and 1.38 (1.24-1.54), respectively, for incident HFpEF; and 1.68 (1.42-1.99) and 1.36 (1.22-1.52), respectively, for incident HFrEF.

Conclusions:

The association of NT-proBNP with incident HFpEF is similar irrespective of early menopause status. However, the association of NT-proBNP with incident HFrEF is greater among women with early menopause when compared to those without early menopause.

Video Summary:

http://links.lww.com/MENO/A893.
Resilience and psychosocial factors linked to symptom experience during the menopause transition for women living with HIV*
Authors: King Elizabeth M. , Kaida Angela , Prior Jerilynn , Albert Arianne , Frank Peggy , Abdul-Noor Rahma , Kwaramba Gladys , Gormley Rebecca , de Pokomandy Alexandra , Loutfy Mona , Murray Melanie C. M.
Published: January 2022

Objective:

Women living with HIV (WLWH) are commonly symptomatic during perimenopause and menopause (≥1 y without menstruation), however, little is known of risks for symptoms and their timing. We analyzed these unwanted experiences to inform care.

Methods:

WLWH (≥40 y) in the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study rated midlife experiences for seven symptoms and a symptom composite (from 0 to 21). Timing was categorized into four phases: i) perimenopause (flow in the last year), ii) 1-2 years from final menstrual period (FMP), iii) 2-5 years post-FMP; and iv) >5 years post-FMP. Resilience (standardized out of 100) was assessed based on Wagnild’s Resilience Scale. Univariable/multivariable mixed effects linear regression assessed correlates of symptom intensity by composite score.

Results:

Among 457 peri-/menopausal women mean age 54.7 (±6.6) over two time points (703 observations), 88% experienced ≥1 mild symptom; 75% were of moderate and 55% severe intensity. The most frequently reported symptoms were joint/muscle stiffness (67%), depressed mood (67%), and hot flashes (57%). After adjusting for reproductive phase, we found that women with greater resilience had fewer/lower intensity symptoms (symptom score 1.37 [2.30 to 0.44] lower; P = 0.004); those with depressive symptoms and recreational drug use (respectively) had more/higher intensity symptoms (scores 1.71 [0.61 to 2.82] [P = 0.002]; 2.89 [2.09 to 3.77] [P<0.001] higher). Symptoms were most intense in perimenopause and declined with increasing menopausal years (P = 0.03).

Conclusions:

WLWH experiences a high burden of midlife symptoms, decreased by resilience and most intense during perimenopause. Unwanted experiences were linked to psychosocial and behavioral factors. These data encourage HIV providers to adopt a bio-psychosocial approach to midlife management.
Resilience and sexual health among menopausal women: a cross-sectional study
Authors: Oliva Agustin , Serrano-García Irene , Asenjo Juan E. , Cedeira Elisa , Gil-Prados Inés , Herraiz Miguel A. , Coronado Pluvio J.
Published: January 2022

Objectives:

Resilience can be defined as the capacity to overcome stressful situations, such as menopausal transition. Female sexual dysfunction is a problem that prevents women from experiencing satisfaction from sexual activity. In this study, we assessed resilience, sexual function, and quality of life among a sample of mid-aged Spanish menopausal women.

Methods:

This cross-sectional study was performed in 101 symptomatic menopausal women. Participants filled out the 14-item Wagnild and Young Resilience Scale, the 19-item Female Sexual Function Index (FSFI), the 16-item Cervantes-SF form, and a sociodemographic questionnaire.

Results:

Resilience scores were significantly higher among women with high sexual function scores (FSFI > 26), with a 14-item Wagnild and Young Resilience Scale total valuation of 86 [80-94] versus 74 [66-79.50] (P<0.001). Sexual function was significantly worse in the low resilience subgroup of participants, with an FSFI total score of 18.90 [14.10-24] versus 29.40 [24.60-33] in the mid-high resilience one (P<0.001). Menopauserelated quality of life was significantly worse among low resilient women, with a Cervantes-SF total score of 42.50 [34.17-56.70] versus 30.80 [20.80-44.90] in the mid-high resilience one (P = 0.004).

Conclusions:

In our sample, resilience was related to sexual health. Higher resilience scores seem to be linked to a better quality of life during the menopausal transition.
Effects of menopause on the retinal nerve fiber layer and ganglion cell complex and on intraocular pressure
Authors: Alpogan Oksan , Tekcan Hatice
Published: January 2022

Objective:

To compare the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness and intraocular pressure in reproductive age and postmenopausal women.

Methods:

The study included 94 eyes of 47 reproductive age women (Group 1) and 94 eyes of 47 postmenopausal women (Group 2). In all women, RNFL and GCC thicknesses were measured by optical coherence tomography. Intraocular pressure levels were measured by Goldmann applanation tonometry. Generalized linear mixed models were conducted to test the differences between groups. Age- and body mass index (BMI)-adjusted partial correlation analysis was used to examine the associations between parameters.

Results:

There was a statistically significant difference in age and BMI between the two groups (P<0.001, P<0.001, respectively). There was no difference in all RNFL and GCC values between the reproductive age and postmenopausal women. The duration of postmenopause versus average, superior hemisphere, and superior values of RNFL and superior and inferior values of GCC were positively correlated with statistical significance in age- and BMI-adjusted partial correlation coefficient tests (r = 0.254, P = 0.017; r = 0.303, P = 0.004; r = 0.317, P = 0.003; r = 0.301, P = 0.004; r = 0.313, P = 0.003; r = 0.271, P = 0.011, with 95% confidence, respectively).

Conclusions:

In this study, there was no significant difference in all RNFL and GCC values between the reproductive age and postmenopausal women after adjusting for age and BMI. However, we observed that a long postmenopausal period was associated with higher RNFL and GCC values.
Transdermal estrogen therapy in menopausal women at increased risk for thrombotic events: a scoping review
Authors: Sobel Talia H. , Shen Wen
Published: January 2022

Importance and Objective:

It is estimated that over 45% of women in the United States are menopausal. Many of these women suffer from vasomotor symptoms of menopause, for which the gold standard treatment is menopause hormone therapy (MHT). However, MHT use has been controversial since the Women's Health Initiative (WHI) study in 2001. Transdermal MHT has been shown to be effective for treatment of vasomotor symptoms and does not increase the risk of venous thromboembolism (VTE) when used in healthy postmenopausal women. However, there is little data on its safety in women at increased risk for VTE such as women with prior VTE, increased body mass index, thrombophilia, tobacco use, autoimmune disease, chronic inflammatory disorders, recent surgery, trauma, or immobilization. This scoping review of the literature provides clinicians with an overview of the evidence on the risk profile of transdermal MHT use in these postmenopausal women at increased risk of VTE.

Methods:

We searched all published studies from 2000 to 2020 and included 13 primary articles on transdermal MHT use in postmenopausal women at increased risk of VTE.

Discussion and Conclusion:

In women with prior VTE, two studies found a decrease in coagulability and no increased risk of recurrent VTE with transdermal MHT use. In women with increased body mass index, three studies found no increased VTE risk in transdermal MHT users. In women with prothrombotic genetic polymorphisms, three studies found minimal to no increased VTE risk in transdermal MHT users. In women with various proinflammatory comorbidities, five studies found an improved thrombotic profile and no increased VTE risk with transdermal MHT use. This scoping review provides data regarding the safety of transdermal MHT use in postmenopausal women with risk factors for VTE, and clinicians should have risk versus benefit discussions with each patient regarding its use.
Translabial ultrasound indices of failed pessary fittings in women with symptomatic pelvic organ prolapse
Authors: Xu Hainan , Wu Wenjing , Wang Xinlu , Xia Zhijun
Published: January 2022

Objective:

To investigate translabial ultrasound (TLUS) parameters that may predict failed pessary fittings in women with symptomatic pelvic organ prolapse (POP).

Methods:

All participants in this retrospective study presented to the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 seeking treatment for symptomatic POP. Each had chosen vaginal pessary as first-line treatment, undergoing TLUS in advance of placement. Participants were grouped by outcomes of pessary fittings as successful or failed. Group-wise demographic and clinical characteristics, including TLUS parameters, were then subjected to uni- and multi-variate logistic regression.

Results:

A total of 373 women qualified for analysis, 255 (68.4%) achieved success, and were fitted with acceptable pessaries. Predictors of failed fittings included younger age (61.54 ± 10.25 y vs 64.72 ± 10.30 y; P = 0.006), premenopausal status (14.4% vs 5.9%; P = 0.006), sizeable hiatal circumference (20.36 ± 2.33 cm vs 19.70 ± 2.50 cm; P = 0.02) and hiatal area (HA) (29.67 ± 7.14 cm2 vs 27.27 ± 6.99 cm2; P = 0.003), levator ani muscle (LAM) avulsion (odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.62-6.46; P = 0.001), enterocele (OR = 2.51, 95% CI = 1.11-5.68; P = 0.03), and the inferiormost aspect of cervix situated below symphysis pubis (OR = 0.52, 95% CI = 0.29-0.95; P = 0.03). In multivariate logistic regression, younger age (OR = 0.98, 95% CI = 0.95-1.00; P = 0.04), sizeable HA on Valsalva (OR = 1.04, 95% CI = 1.01-1.08; P = 0.02), LAM avulsion (OR = 2.87, 95% CI = 1.32-6.25; P = 0.008), and enterocele (OR = 2.70, 95% CI = 1.12-6.50; P = 0.03) emerged as independent predictors of failed pessary fittings.

Conclusions:

Younger age, LAM avulsion, enterocele, and sizeable HA on Valsalva proved independently predictive of failed pessary fittings in women with symptomatic POP.
Safety of intraocular pressure measurement using air-puff tonometer after implantable collamer lens implantation
Authors: Shen Yang , Chen Xun , Xian Yiyong , Wang Xuanqi , Wang Xiaoying , Zhou Xingtao
Published: January 2022

Purpose:

To determine the safety of intraocular pressure (IOP) measurement using a noncontact tonometer in patients who have undergone implantable collamer lens (ICL) implantation.

Setting:

Eye, Ear, Nose, and Throat Hospital.

Design:

Prospective study.

Methods:

64 eyes of 33 patients (aged 28.4 ± 5.2 years) scheduled for ICL implantation were enrolled. The anterior segment parameters and vault were obtained using an anterior segment analyzer. A noncontact air-puff tonometer was used preoperatively and at 1 day and 1 week postoperatively to assess corneal biomechanical properties and IOP. The Corvis ST was used to evaluate the distance between the corneal endothelial layer and iris (E-Iris Dist) and the distance between the corneal endothelial layer and ICL (E-ICL Dist) when the cornea was deformed by the airflow.

Results:

The mean anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) decreased significantly postoperatively (all P values <.001). The E-ICL Dist values measured 1 day and 1 week postoperatively were similar (P = .107). However, a contact between the corneal endothelium and ICL was detected in 2 eyes when the cornea was deformed to the highest concavity. The 1-day postoperative vault, ACV, ACA, and preoperative stress–strain index contributed significantly (P = .001, P = .023, P = .010, and P = .019, respectively) to determine the distance. The mean E-iris Dist values decreased significantly at 1 day and 1 week postoperatively (P < .001). The 1-week postoperative vault and ACD contributed significantly (P = .025 and P = .039, respectively) to determine the E-Iris Dist value.

Conclusions:

Excessively high vault, shallow ACD, narrow ACA, low ACV, and soft cornea are associated with a lower E-ICL distance and thus may be risk factors for a contact between the corneal endothelium and ICL during IOP measurement. Although there is no proof that the contact may cause any risks to the endothelium, noncontact air-puff tonometry should be avoided in eyes predicted by the study model to be at risk of this occurring. Contact IOP measurements using Goldmann applanation tonometers or dynamic contour tonometers may be alternate methods of IOP measurements in extreme cases.
The intensive care management of acute ischaemic stroke
Authors: Sharma Deepak , Smith Martin
Published: January 2022

Purpose of review

To discuss recent advances in the critical care management of acute ischaemic stroke patients and highlight controversies and consensus.

Recent findings

Intravenous thrombolysis and endovascular thrombectomy are standard of care reperfusion therapies that have revolutionized the management of acute ischaemic stroke and transformed outcomes for patients. They can now be delivered in extended time windows and to those previously ineligible for intervention based on advanced neuroimaging criteria. Secondary systemic insults, such as hypo- and hypertension, hyperthermia or hyperglycaemia, which can extend the area of ischaemia must also be prevented or corrected to minimize infarct progression. Meticulous blood pressure management is of central importance, particularly in patients that have undergone reperfusion therapies. Neurological deterioration can occur because of infarct extension, haemorrhagic transformation or worsening cerebral oedema. Transcranial Doppler ultrasonography allows bedside, noninvasive evaluation of cerebral haemodynamics and is increasingly used in acute stroke triage, management and recovery prediction. The management of acute ischaemic stroke raises several ethical issues, and shared decision making is essential to ensure outcomes that are compatible with an individual patient's expectations.

A bundle of medical, endovascular and surgical strategies implemented by a multidisciplinary team working to locally agreed protocols can improve long-term stroke outcomes.
How to manage traumatic brain injury without invasive monitoring?
Authors: Godoy Daniel A. , Rabinstein Alejandro A.
Published: January 2022

Purpose of review

Severe traumatic brain injury (TBI) is an extremely serious health problem, especially in low–middle income countries (LMICs). The prevalence of severe TBI continues to increase in LMICs. Major limitations in the chain of care for TBI patients are common in LMICs including suboptimal or nonexistent prehospital care, overburdened emergency services, lack of trained human resources and limited availability of ICUs. Basic neuromonitoring, such as intracranial pressure, are unavailable or underutilized and advanced techniques are not available.

Recent findings

Attention to fundamental principles of TBI care in LMICs, including early categorization, prevention and treatment of secondary insults, use of low-cost technology for evaluation of intracranial bleeding and neuromonitoring, and emphasis on education of human resources and multidisciplinary work, are particularly important in LMICs. Institutional collaborations between high-income and LMICs have developed evidence focused on available resources. Accordingly, an expert group have proposed consensus recommendations for centers without availability of invasive brain monitoring.

Severe TBI is very prevalent in LMIC and neuromonitoring is often not available in these environments. When intracranial pressure monitors are not available, careful attention to changes on clinical examination, serial imaging and noninvasive monitoring techniques can help recognize intracranial hypertension and effectively guide treatment decisions.
Enteral feeding, even when the gut does not feel very good?
Authors: Reintam Blaser Annika , Hiesmayr Michael
Published: January 2022

Purpose of review

To summarize knowledge on the gut function in relation to enteral nutrition.

Recent findings

The gut is certainly suffering during critical illness but our understanding of the exact mechanisms involved is limited. Physicians at bedside are lacking tools to identify how well or bad the gut is doing and whether the gut is responding adequately to critical illness. Sensing nutrition as a signal is important for the gut and microbiome. Enteral nutrition has beneficial effects for the gut perfusion and function. However, early full enteral nutrition in patients with shock was associated with an increased number of rare but serious complications.

Whenever synthesizing knowledge in physiology and available evidence in critically ill, we suggest that enteral nutrition has beneficial effects but may turn harmful if provided too aggressively. Contraindications to enteral nutrition are listed in recent guidelines. For patients with gastrointestinal dysfunction but without these contraindications, we suggest considering early enteral nutrition as a signal to the gut and to the body rather than an energy and protein provision. With this rationale, we think that low dose of enteral nutrition could and probably should be provided also when the gut does not feel very good. Understanding the feedback from the gut in response to enteral nutrition would be important, however, monitoring tools are currently limited to clinical assessment only.
Enterohormone therapy for short bowel syndrome
Authors: Verbiest Astrid , Wauters Lucas , Vanuytsel Tim
Published: January 2022

Purpose of review

Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL.

Recent findings

During the first years following extensive surgery, spontaneous structural and functional intestinal changes take place which stimulate a more efficient nutrient and fluid absorption in the remaining bowel. Given their potential role in the ileal braking mechanism, enterohormones, such as glucagon-like peptide (GLP)-2, GLP-1, and peptide YY (PYY), promote an accelerated adaptation or hyperadaptation. While the exact role of GLP-1 and PYY in SBS is still being explored, GLP-2 analogs have clearly shown to be effective in improving outcome in SBS.

Whereas spontaneous intestinal adaptation improves the nutritional status of SBS patients to a certain extent, GLP-2 analogs can further decrease parenteral support needs through hyperadaptation. There are, however, other promising candidates on the horizon that – alone or in combination – could possibly establish additional disease-modifying effects.
The role of endocrine-disrupting phthalates and bisphenols in cardiometabolic disease: the evidence is mounting
Authors: Lucas Andrew , Herrmann Susan , Lucas Michaela
Published: January 2022

Purpose of review

There is substantive and accumulating evidence that endemic exposure to plastic-associated chemicals (PACs) contribute to the pathophysiology of metabolic conditions, like obesity, diabetes, and heart disease. The consequences of this endemic exposure in inducing a pro-inflammatory state in adipose tissues as a critical link between exposure and disease is reviewed.

Recent findings

In general, PACs are classified as nonpersistent in vivo because of their rapid metabolism to easily excreted forms. The parental chemicals, however, are typically lipophilic, with the potential to bioaccumulate. Recent data from selected association studies suggest exposure to PACs drive predisease states like obesity and inflammation of the adipose tissues. A range of experimental studies are discussed with a focus on biological mechanisms that are susceptible to the influence of PACs and which may promote metabolic disease, the detection of PACs within susceptible tissues and biological effects that are detectable at doses that correspond to real-life exposures to these chemicals.

If we hypothesize the toxic pressure from chronic exposure to PACs will progress disease processes, then individuals with comprehensively characterized indicators of premetabolic disease could undergo trials of quantifiable interventions to reduce exposure to PACs to test if the trajectory of disease-associated analytes, is altered.
Mucosal immunity in primary sclerosing cholangitis: from the bowel to bile ducts and back again
Authors: Liaskou Evaggelia , Quraishi Mohammed Nabil , Trivedi Palak J.
Published: January 2022

Purpose of review

In this article, we provide a contemporary overview on PSC pathogenesis, with a specific focus on the role of mucosal immunity.

Recent findings

The extent of enteric dysbiosis in PSC has been extensively quantified, with evidence of reduced bacterial diversity and enrichment of species capable of driving lymphocyte recruitment from the gut to the liver. Integrative pathway-based analysis and metagenomic sequencing indicate a reduction in butyrate-producing species, near absence of bacteria that activate the nuclear bile acid receptor FXR, and depletion of species that regulate the synthesis of vitamin B6 and branched-chain amino acids. Immunotyping of the cellular inflammatory infiltrate has identified a population of intrahepatic naive T cells, with tendency to acquire a Th17 polarisation state, paralleled by heightened responses to pathogen stimulation. Moreover, the search for antigen specificity has revealed the presence of overlapping nucleotide clonotypes across the gut and liver, highlighting the ability to recognize a common pool of epitopes bearing structural similarities across afflicted sites.

Understanding the complex mechanisms that underpin mucosal immune responses between the liver and gut will help identify new druggable targets in PSC, centring on gut microbial manipulation, bile acid therapies, and restoration of immune homeostasis.
Bile acids, bile pigments and colorectal cancer risk
Authors: Kuhls Stephanie , Osswald Annika , Ocvirk Soeren
Published: January 2022

Purpose of review

The gut microbial co-metabolism of bile-derived compounds (e.g. bile acids and bile pigments) affects colorectal cancer (CRC) risk. Here, we review recent findings with focus on selected novel aspects of bile-associated effects with interesting but unclear implications on CRC risk.

Recent findings

Numerous studies demonstrated novel biotransformation of bile acids by gut bacteria (e.g. microbial conjugation of bile acids), resulting in diverse bile acid compounds that show complex interactions with host receptors (e.g. FXR, TGR5). In addition, YAP-associated signalling in intestinal epithelial cells is modulated via bile acid receptor TGR5 and contributes to colonic tumorigenesis. Finally, studies indicate that serum levels of the bile pigment bilirubin are inversely associated with CRC risk or intestinal inflammation and that bilirubin affects gut microbiota composition.

Bile acids and bile pigments have multiple effects on intestinal microbe-host interactions, which may collectively modulate long-term CRC risk of the host.
Influenza vaccines: where we are, where we are going
Authors: Khalil Nadim , Bernstein David I.
Published: January 2022

Purpose of review

Influenza vaccines are the most useful strategy for preventing influenza illness, especially in the setting of the COVID-19 pandemic. For the coming year (2021/2022) all vaccines will be quadrivalent and contain two influenza A strains [(H1N1)pdm09-like and (H3N2)-like viruses] and two influenza B strains (Victoria lineage-like and Yamagata lineage-like viruses). However, the currently licensed have suboptimal efficacy due to the emergence of new strains and vaccine production limitations. In this review, we summarize the current recommendations as well as new advancements in influenza vaccinations.

Recent findings

Recent advances have been aimed at moving away from egg-based vaccines and toward cell culture and recombinant vaccines. This removes egg adaptations that decrease vaccine efficacy, removes the reliance on egg availability and decreases the time necessary to manufacture vaccines. However, even more radical changes are needed if we are to reach the ultimate goal of a universal vaccine capable of providing long-lasting protection against all or at least most influenza strains. We discuss various strategies, including using more stable influenza antigens such as the hemagglutinin stalk and internal proteins as well as new adjuvants, new vaccine formulations, and DNA/RNA-based vaccines that are currently being developed.

The currently available vaccines have suboptimal efficacy and do not provide adequate protection against drifted and shifted strains. Thus, the development of a universal influenza vaccine that induces long-lasing immunity and protects against a broad range of strains is crucial.
First intention high-frequency jet ventilation for periviable infants
Authors: Elgin Timothy G. , Stanford Amy H. , Klein Jonathan M.
Published: January 2022

Purpose of review

Ventilation of periviable infants born at 22–23 weeks gestation remains a challenge in neonatology. This review highlights the evidence surrounding the use of first intention high-frequency jet ventilation (HFJV) in infants born near the limits of viability with a review of pulmonary fetal development and a focused overview of HFJV strategies including an in-depth analysis of the management strategies used in the initial randomized trials.

Recent findings

A paucity of recent trials exists, with no randomized control trials assessing the use of first intention HFJV performed in the last 25 years. A retrospective observational cohort trial of the use of HFJV for infants born at less than 750 g has been recently published demonstrating the efficacy of HFJV for this population even with 2.0-mm endotracheal tubes.

The lack of recent randomized trials contributes to the controversy surrounding the use of first intention HFJV. Although new research is needed in the area, this review includes the ventilation strategy of an experienced center with a focus on the use of first intention HFJV for the care of premature infants born less than 24 weeks gestation.
Risk of Human Immunodeficiency Virus Acquisition Among High-Risk Heterosexuals With Nonviral Sexually Transmitted Infections: A Systematic Review and Meta-Analysis
Authors: Barker Erin K. , Malekinejad Mohsen , Merai Rikita , Lyles Cynthia M. , Sipe Theresa Ann , DeLuca Julia B. , Ridpath Alison D. , Gift Thomas L. , Tailor Amrita , Kahn James G.
Published: January 2022

Background

Nonviral sexually transmitted infections (STIs) increase risk of sexually acquired human immunodeficiency virus (HIV) infection. Updated risk estimates carefully scrutinizing temporality bias of studies are needed.

Methods

We conducted a systematic review (PROSPERO CRD42018084299) of peer-reviewed studies evaluating variation in risk of HIV infection among high-risk heterosexuals diagnosed with any of: Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, Treponema pallidum, and/or Trichomonas vaginalis. We searched PubMed, Web of Science, and Embase databases through December 2017 and included studies where STIs and HIV were assessed using laboratory tests or medical examinations and where STI was diagnosed before HIV. After dual screening, data extraction, and risk of bias assessment, we meta-analytically pooled risk ratios (RRs).

Results

We found 32 eligible studies reporting k = 97 effect size estimates of HIV acquisition risk due to infection with one of the abovementioned STIs. Most data were based on women engaged in sex work or other high-risk occupations in developing countries. Many studies did not measure or adjust for known confounders, including drug injection and condom use, and most were at medium or high risk of bias because of the potential for undetected HIV infection to have occurred before STI infection. Human immunodeficiency virus acquisition risk increased among women infected with any pathogen; the effect was greatest for women infected with Mycoplasma genitalium (RR, 3.10; 95% confidence interval [CI], 1.63–5.92; k = 2) and gonorrhea (RR, 2.81; 95% CI, 2.25–3.50; k = 16) but also statistically significant for women infected with syphilis (RR, 1.67; 95% CI, 1.23–2.27; k = 17), trichomonas (RR, 1.54; 95% CI, 1.31–1.82; k = 17), and chlamydia (RR, 1.49; 95% CI, 1.08–2.04; k = 14). For men, data were space except for syphilis (RR, 1.77; 95% CI, 1.22–2.58; k = 5).

Conclusion

Nonviral STI increases risk of heterosexual HIV acquisition, although uncertainty remains because of risk of bias in primary studies.
NF2-mutated Renal Carcinomas Have Common Morphologic Features Which Overlap With Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma
Authors: Paintal Ajit , Tjota Melissa Y. , Wang Peng , Fitzpatrick Carrie , Wanjari Pankhuri , Stadler Walter M. , Gallan Alexander J. , Segal Jeremy , Antic Tatjana
Published: January 2022

Genetic alterations involving NF2 occur at low frequencies in renal cell carcinoma across all of the major histologic subtypes and have been associated with adverse outcomes. To better characterize tumors harboring these alterations, we identified 14 cases with NF2 mutations that had been previously diagnosed as papillary renal cell carcinoma; renal cell carcinoma, unclassified; or translocation associated renal cell carcinoma. These tumors were characterized by a tubulopapillary architecture, sclerotic stroma, microscopic coagulative necrosis, and psammomatous calcifications. All the cases displayed eosinophilic cytology as well as a high nuclear grade (World Health Organization/International Society of Urological Pathology [WHO/ISUP] grade 3 to 4) in all but 1 case. A subset of cases shared features with the recently described biphasic hyalinizing psammomatous renal cell carcinoma. Next-generation sequencing demonstrated mutations involving NF2 gene in all cases. In 10 cases, this was paired with the loss of chromosome 22. Additional mutations involving PBRM1 were found in 5 cases that were associated with a more solid growth pattern. Eight patients presented with metastatic disease including all 5 with PBRM1 mutations. Despite the aggressive disease course seen in many of the patients in our series, 2 patients exhibited a dramatic response to immunotherapy. Our results support the existence of a distinct group of cases of renal cell carcinoma characterized by distinct although admittedly nonspecific morphology, an aggressive disease course, and NF2 mutations, often paired with the loss of chromosome 22.
Lymphocyte-Rich Spindle Cell Thymoma
Authors: Suster David , Mackinnon Alexander Craig , Pihan German , Everts Robin , Suster Saul
Published: January 2022

A study of 80 cases of spindle cell thymoma in which the spindle cell component was overshadowed by massive numbers of stromal lymphocytes is presented. The patients were 38 women and 42 men, aged 8 to 81 years (mean=54 y). All tumors presented as an anterior mediastinal mass; 5 patients had myasthenia gravis and one had Good syndrome. The tumors were well-circumscribed, encapsulated, and measured 2.9 to 26.0 cm in greatest diameter (mean=7.3 cm). Using modified Masaoka staging, 66 tumors were stage I, 10 were stage IIa, 2 were stage III and 1 was stage IV. Histologically the tumors were characterized by a predominant lymphocytic population admixed with scattered small spindle epithelial cells. The neoplastic spindle cells in these tumors demonstrated 2 major growth patterns: in 33 cases, the tumors were exclusively composed of dense sheets of lymphocytes containing scattered spindle cells resembling a lymphocyte-rich thymoma (WHO type B1); in the remaining cases the tumors showed admixtures of a predominantly lymphocytic component with areas that were lymphocyte-poor and contained a pure spindle cell population similar to WHO type A. Immunohistochemical stains and electron microscopy corroborated the spindle cell morphology in both types. The GTF2I p.L424H variant was identified in 53 of 63 (84%) cases analyzed. Clinical follow-up in 27 cases showed that most of the tumors behaved in an indolent manner. Our study expands the spectrum of spindle cell thymoma by demonstrating the existence of cases that are predominantly composed of lymphocyte-rich elements and lack areas with a pure (lymphocyte poor) spindle cell morphology.
HPV51-associated Leiomyosarcoma
Authors: Williams Erik A. , Montesion Meagan , Lincoln Vadim , Tse Julie Y. , Hiemenz Matthew C. , Mata Douglas A. , Shah Bhamini B. , Shoroye Adebowale , Alexander Brian M. , Werth Adrienne J. , Foley-Peres Kathleen , Milante Riza R. , Ross Jeffrey S. , Ramkissoon Shakti H. , Williams Kevin Jon , Adhikari Laura J. , Zuna Rosemary E. , LeBoit Philip E. , Lin Douglas I. , Elvin Julia A.
Published: January 2022

Inactivating mutations in tumor suppressor genes TP53 and RB1 are considered central drivers in leiomyosarcomas (LMSs). In high-risk human papillomavirus (HPV)-related tumors, a similar functional outcome is achieved through oncoproteins E6 and E7, which inactivate the p53 and RB1 proteins, respectively. Here, we hypothesized that HPV infection could provide an alternative mechanism for tumorigenesis in a subset of TP53/RB1-wildtype LMS. We evaluated tumor samples from 2585 consecutive unique patients carrying a diagnosis of gynecologic or soft tissue LMS. Tumor DNA and available RNA were analyzed by hybrid-capture-based next-generation sequencing/comprehensive genomic profiling of 406 genes and transcripts (FoundationOneHeme). Of the initial 2585 cases, we excluded 16 based on the presence of molecular alterations that are considered defining for sarcomas other than LMS. In the remaining 2569 cases, we searched for LMS that were TP53/RB1-wildtype (n=486 of 2569; 18.9%). We also searched LMS tumors for HPV sequences that we then classified into genotypes by de novo assembly of nonhuman sequencing reads followed by alignment to the RefSeq database. Among TP53/RB1-wildtype LMS, we identified 18 unique cases harboring HPV sequences. Surprisingly, most (n=11) were HPV51-positive, and these 11 represented all HPV51-positive tumors in our entire LMS database (n=11 of 2569; 0.4%). The absence of genomic alterations in TP53 or RB1 in HPV51-positive LMS represented a marked difference from HPV51-negative LMS (n=2558; 0% vs. 72% [P<0.00001], 0% vs. 53% [P=0.0002]). In addition, compared with HPV51-negative LMS, HPV51-positive LMS were significantly enriched for genomic alterations in ATRX (55% vs. 24%, P=0.027) and TSC1 (18% vs. 0.6%, P=0.0047). All HPV51-positive LMS were in women; median age was 54 years at surgery (range: 23 to 74 y). All known primary sites were from the gynecologic tract or adjacent anogenital area, including 5 cases of vaginal primary site. Histology was heterogeneous, with evaluable cases showing predominant epithelioid (n=5) and spindle (n=5) morphology. In situ hybridization confirmed the presence of high-risk HPV E6/E7 mRNA in tumor cells in three of three evaluable cases harboring HPV51 genomic sequences. Overall, in our pan-LMS analysis, HPV reads were identified in a subset of TP53/RB1-wildtype LMS. For all HPV51-associated LMS, the striking absence of any detectable TP53 or RB1 mutations and predilection for the female lower reproductive tract supports our hypothesis that high-risk HPV can be an alternative tumorigenic mechanism in this distinct class of LMS.