bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative use of tranexamic acid eliminates bleeding complications in thyroid and parathyroid surgery
Authors: Karakozis Lampros , Karageorgou Maria , Alexandrou Nikolaos , Karakozis Stavros
Published: March 2022

Introduction

Postoperative neck bleeding is a rare but life-threatening complication in thyroid and parathyroid surgery. It requires an emergency treatment algorithm to prevent asphyxia and severe brain injury. Tranexamic acid is an antifibrinolytic medication which treats or prevents excessive blood loss in a variety of clinical situations such as, major trauma, postpartum bleeding, and heavy menstruation. We studied the use of tranexamic acid to eliminate the incidence of postoperative neck hematoma.

Methods

All thyroid and parathyroid patients operated from the same surgical team were evaluated. The patients were divided in two groups: Group A before and Group B after the use of tranexamic acid. The medication was used intravenously to all Group B patients during the hemostasis control and prior the neck wound closure.

Results

A total of 1457 consecutive patients were studied from 01-01-2001 to 06-06-2021. Group A included 669 patients (620 thyroid and 49 parathyroid patients) from 01-01-2001 until 27-06-2018. Group B included 788 patients (705 thyroid and 83 parathyroid patients) from 27-06-2018 until 06-06-2021. Group A had 15 (2,24% incidence) postoperative neck hematomas and 6 of them (0,89%) required emergency surgical drainage. Group B had no postoperative bleeding episodes with the intraoperative use of tranexamic acid.

Conclusion

The use of tranexamic acid eliminates postoperative bleeding episodes in thyroid and parathyroid surgery.
Molecular testing in the diagnosis and management of thyroid malignancy: a feasibility study
Authors: Anneback Matilda , Damji Samir , Flora Rashpal , Tolley Neil , Palazzo Fausto , DiMarco Aimee
Published: March 2022

Background

NHS England’s reorganization of genomic testing has provided an opportunity to explore molecular testing as part of thyroid nodule diagnostics and the routine postoperative histology.

Aim

Routine molecular testing in an NHS service has not previously been explored. This study aims to evaluate whether (1) there is sufficient material to perform this on an FNAC in cytologically indeterminate nodules (2) what the yield is from indeterminate nodules (3) whether post-operative testing is feasible and (4) whether management is altered.

Methods

This in an ongoing feasibility study in a UK tertiary institution commenced in January 2021. Data until May in presented. Two groups are enrolled: those with indeterminate pre-operative cytology and those who have undergone thyroidectomy for malignancy. FNAC samples were sent for a routine panel including BRAFv600e, H-K-NRAS and histology for TP53, RET and NTRK in addition.

Results

Out of 30 patients with indeterminate cytology, molecular testing was requested in eight. The material was insufficient for added molecular testing in six and the panel of mutations tested was negative in two.

Thirty-one patients underwent thyroidectomy for malignancy and 11 surgical specimens underwent molecular testing. Mutations were detected in 54.5%(n=6). BRAFv600e mutation was found in four specimens with PTC, whereas NRAS mutation was detected in one Hobnail variant of PTC and one minimal invasive follicular carcinoma.

Conclusion

Addition of molecular testing to preoperative cytology was shown to require a further FNAC in a majority of cases. In postoperative specimens, molecular testing is feasible but further follow-up is required to determine whether clinical management is altered.
Parathyroid Cancer: A single centre experience of the Endocrine Surgical Care Group.
Authors: Galata' Gabriele , Hubbard Johnathan , Talat Nadia , Anscomb Natalie , Klang Patrick , Al-Lawati Ammar , Aldrees Abdulaziz , Schulte Klaus-Martin
Published: March 2022

Aim

Parathyroid Cancer is a rare condition (<3% of Primary Hyperparathyroidism). Under staging/treatment can have disastrous consequences. Risk of local recurrence, distal metastases and death is as double of those treated appropriately.

This study shows the experience of a single centre with the objective of demonstrating the importance of preoperative diagnosis, staging and initial treatment showing the difference and improved outcomes for patients appropriately treated applying the Schulte’s 3 + 3 rule.

Methods

Retrospective single centre review. The data consists of patients whom underwent oncological Parathyroidectomy between 2005 and 2020 at King’s College Hospital. SPSS software was used for analysis.

Results

38 patients were included in the study: 10 patients underwent local excision; 28 underwent oncological resection (unilateral en-bloc resection of thyroid lobe, both parathyroids and level VI lymphadenectomy). Three patients who underwent local excision elsewhere had local recurrence and were referred to our centre for further treatment. One patient with pre-operative lung metastases, underwent oncological resection had also local recurrence and died after 12 years follow up. One patient with single lung met who underwent oncological resection and excision of lung met is free of disease after 10 years. Thirty-three patients are free of disease. Average pre-operative Calcium was 3.01nmol/L, PTH 287ng/L and size 36mm.

Conclusion

Under staging/treatment showed 12-fold increase in recurrence rates. The only observed recurrence in patients that underwent initial en-bloc resection was related to advance staging/distant metastasis. This highlights the importance of recognising pre-operative indicative factors for appropriate surgical planning, reducing risk of recurrence/death.
Outcomes of surgery and treatment with selective RET TK inhibitor Selpercatinib in children with MEN2 and advanced MTC
Authors: Kurzawinski Tom , Hubbard Jonathan , Aziz Tarek Abdel , Butler Colin , Gaze Mark , Brain Caroline , Marshall Lynley , Shankar
Published: March 2022

Background

Patients with MEN2 without family history often present late with advanced MTC. Surgery is not always curative but RET tyrosine kinase pathway is a potential target for molecular treatment for progressive MTC.

Methods

Retrospective review of clinical, genetic, biochemical and imaging data of children with MEN2 who developed recurrent and progressive MTC after surgery and were treated with Selpercatinib, a selective RET TK inhibitor. The main parameters were safety, efficacy and objective treatment response.

Results

Six children (3M,3–12years,4x2B,2x2A,RET918,804) presented with palpable lymphadenopathy(5) and elevated calcitonin (median 6560ng/L,140-46850). Five had metastatic disease on imaging. All had total thyroidectomy with unilateral(2) and bilateral(2) levels 2,3,4,5,6 lymphadenectomy and resections of JV(1), RLN(2), Vagus(1). Post-operative complications included transient(3) and permanent(1) hypoparathyroidism and Horner’s syndrome(2). Two children had second surgery and one EBRT complicated by delayed oesophageal perforation and stridor requiring tracheostomy. None of the children were cured and all had disease progression evidenced by clinical deterioration, rising calcitonin and CEA(3) and worsening radiology(5). All children received Selpercatinib (92mg/m2/dose) orally twice daily. The objective clinical, radiological and biochemical response was 100% with complete resolution of all clinical symptoms (third month) and significant decrease of calcitonin and CEA within 4 weeks. Four had partial radiological response(1–3months). No child had to discontinue Selpercatinib because of a drug toxicity. Median follow up was 13 months(10–20months).

Conclusions

Children with MEN2 and advanced MTC can’t be cured by surgery and EBRT alone, but Selpercatinib has shown remarkable therapeutic efficacy with clinical, biochemical and radiological improvement and minimal toxicity.
4DCT as first line imaging during Covid pandeminc
Authors: Karamali Katerina , Salau Eniola , Das Tilak , Scoffings Daniel , Casey Ruth , Masterson Liam , Fish Brian
Published: March 2022

Aim

The Covid-19 pandemic encouraged prompt modification to clinical practice to minimise hospital attendances in an aim to minimize exposure and protection of the NHS whilst maintaining the standards of patient care. Current literature advocates that Four-Dimensional Computerised Tomography (4DCT) has equal diagnostic value as ultrasound alone or a combination of ultrasound and Sestamibi scan in the identification of abnormal parathyroid glands in the work up for surgical management of hyperparathyroidism. In response to the evolving pandemic at Addenbrookes we modified our practice and escalated 4DCT as our first line imaging. In light of this we had a unique opportunity to evaluate the diagnostic value of the currently used imaging modalities.

Methods

This is a retrospective study of 270 parathyroidectomies who underwent pre-operative 4DCT (n=270), ultrasound (n= 254) and sestamibi scan (n=253). Subsequently, we assessed the accuracy of these three modalities with the of intra-operative findings, histology, post-operative calcium and PTH.

Results

The sensitivity of the 4DCT was 77% in comparison to 43% sensitivity of the ultrasound alone. (p>0.05). The combined sensitivity of ultrasound and Sestamibi scan was found to be 69%.

Conclusion

The implementation of 4DCT as a single modality diagnostic imaging can be considered equally effective and accurate in the diagnosis of parathyroid abnormality. Implementing this would reduce the number of diagnostic tests improving the likelihood of successful operative planning and reduce financial cost.
Risk of malignancy of BTA/RCPath Thyroid cytopathology diagnostic categories in a specialist cytopathology centre
Authors: HOMER Jarrod , Bowen Alex , Enarche Alina , Rana Durgesh , Holbrook Miles , Shelton David
Published: March 2022

Aim

Fine Needle Aspiration Cytology (FNAC) remains the primary determinant of management options for a patient with a U3-5 thyroid nodule. There is significant variation in risk of malignancy (ROM) between different centres, possibly reflecting the degree of specialist reporting and interpretation of RCPath guidance. The aims of this study is to report on ROM of FNAC categories in a specialist cytopathology centre.

Methods

Consecutive thyroid FNAC results were analysed over 2 years (2017/18), all reported by dedicated cytopathologists and suspicious samples were peer reviewed. Cases suspicious for NIFTP/FVPTC were classified as Thy4. U-grade was recorded if classified during ultrasonography. Results were analysed with regard to histology available on thyroid surgery and/or clinical follow up.

Results

There were 695 samples from 567 patients. The ROM in each category was: Thy1(6%); Thy2(1%), Thy3a(13%); Thy3f(11%); Thy4(27%); Thy 5(100%). In addition, 34/86 Thy3a nodules were subject to repeat FNAC, with 19 reported as Thy2, 7 as Thy3a again, 1 as Thy3f and 2 as Thy4 on second FNAC. We found that stratification of Thy3a-3f-4 by U grade did not help with risk stratification.

Conclusions

Compared to the recent meta-analysis (Poller et al), we found a greatly reduced ROM in the Thy4 group (27% vs 79%), with smaller reductions in both Thy 3 groups in our specialised cytopathology centre. The reasons for this will be discussed. The descriptor of Thy 4 as “suspicious for malignancy” is inaccurate in our experience. Each centre should use their own figures when advising patients. Repeat FNAC for Thy3a lesions leads to >20% potentially avoiding surgery.
Re-evaluating paraganglioma surgery – towards optimising patient care
Authors: Perry Helen , Rees Aled , Scott-Coombes David , Stechman Michael
Published: March 2022

Background

Phaeochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumours of chromaffin cells that secrete catecholamines. The understanding of their aetiology and management is evolving. This study aimed to examine aspects in the management of PCC and PGL over the last decade.

Methods

Patients undergoing surgery for PCC/PGL over an eleven-year period were studied using a prospectively maintained database and electronic hospital clinical portal. Appropriate statistics were then employed.

Results

Sixty-nine patients underwent surgery (35 female, median age 52 years (12–82) to treat 57 PCC (inc. 2 bilateral) and 14 PGLs (inc. 2 recurrences). Although PCC and PGL patients were matched for gender and tumour-size, those with PGL were younger (median 40 (12–75) versus 54 (23–82), p = 0.044). PGL patients were also more likely to have a genetic abnormality identified (58.3% versus 16.1%, p = 0.002) and to have a malignant tumour (38.5% vs 6.8%, p = 0.002). Peri-operative blockade regimes were similar, but PGLs more frequently had an open procedure (42.9% vs 5.3% p<0.001). However, when laparoscopic surgery was undertaken, the conversion rate was not significantly different (PGL: 7.1%, PCC 5.2% p = 0.785). Distant and local recurrences were more common in the paraganglioma group (PGL: 25.0%, PCC 1.8%, p=0.002).

Conclusions

PGLs represent an even rarer subset of an already rare tumour-type. Access to multi-disciplinary specialists and appropriate decision-making are critical. High incidence of inherited disease, increased malignancy and recurrence rates along with the increased operative complexity favour greater use of open surgery and specialised follow-up to ascertain recurrence, as well as access to high quality genetic counselling services.
The putative oncogenic role of WDTC1 in colorectal cancer
Authors: Wang Xiaoyu , Cai Qiuyin , Ping Jie , Diaz-Zabala Hector , Xia Yumin , Guo Xingyi
Published: March 2022

Microsatellite instability (MSI) is detected in approximately 15% of colorectal cancers (CRCs). WD40 and tetratricopeptide repeats 1 (WDTC1) is frequently mutated in MSI CRC, indicating that it may contribute to CRC development. However, the functional evidence of the role of WDTC1 in CRC development remains unknown. Herein, we conducted in vitro assays to examine the function of WDTC1 using knockdown experiments in three CRC cell lines, SW480, CACO2, and LoVo. We provided strong evidence that silencing WDTC1 significantly suppressed cell proliferation, migration, and invasion consistently in all three CRC cell lines. To evaluate the potential role of WDTC1 in regulating CRC-related genes, we conducted RNA sequencing after 24 and 48 h in SW480 cells after treating WDTC1-siRNA and its vehicle control cells. Differential gene expression analysis identified 44 (42 downregulated and 2 upregulated) and 16 (all downregulated) genes, at time points of 24 and 48 h, respectively, whereas 15 downregulated genes were commonly detected at both time points. The ingenuity pathways analysis suggested that the most significant enrichments associated with cancer function and upstream regulator ATM/ATR were observed for these commonly observed genes. We further verified differential gene expression of eight cancer-related genes, ARHGEF12, GSTP1, FNDC3A, TMTC3, RTN4, RRM2, UHMK1, and PTPRF, using RT-PCR in all three cell lines. Our findings provided additional insight into the oncogenic role of WDTC1 in CRC development.
Post-vaccination analysis of anti-spike antibody responses in kidney transplant recipients with and without COVID-19 infection in a tertiary care centre, India
Authors: Jasuja Sanjiv , Jha Vivekanand , Sagar Gaurav , Bahl Anupam , Verma Shalini , Jasuja Neharita , Kaur Jasmeet
Published: March 2022

Background

To investigate the anti-spike antibody response to vaccination in kidney transplant recipients (KTRs) previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as compared with KTRs with no history of coronavirus disease 2019 (COVID-19) from India.

Methods

SARS-CoV-2 spike immunoglobulin (Ig) G antibody response was measured in 105 post-COVID-19 KTRs with PCR-confirmed SARS-CoV-2 infection who received either no vaccination (cohort 1), a single dose (cohort 2) or two doses (cohort 3) of vaccine and compared with 103 two-dose vaccinated COVID-19-naïve KTRs with no history of COVID-19 (cohort 4).

Results

Out of 103 COVID-19-naïve two-dose vaccinated KTRs, <50% became seropositive with anti-spike antibody titres >50 arbitrary unit/mL subsequent to complete vaccination, the seroconversion rate being comparable in subjects receiving CovishieldTM versus CovaxinTM vaccines. However, the seropositive KTRs vaccinated with CovishieldTM had higher anti-spike antibody titres as compared with those who received CovaxinTM. We observed higher anti-SARS-CoV-2 spike antibody levels in post-COVID-19 KTRs after one dose of vaccine as compared with COVID-19-naïve two-dose vaccinated KTRs. Importantly, the second dose in post-COVID-19 KTRs did not significantly increase anti-spike antibody levels compared with the single-dose recipients.

Conclusions

Our data present that in KTRs with previous SARS-CoV-2 infection, a single dose of vaccine (CovishieldTM) may be effective in mounting an optimal immune response. In contrast, COVID-19-naïve two-dose vaccinated KTRs respond poorly (<50%) to the current recommendation of a two-dose regimen in India.
Geospatiotemporal and causal inference study of cannabis and other drugs as risk factors for female breast cancer USA 2003–2017
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: March 2022

Breast cancer (BC) is the commonest human cancer and its incidence (BC incidence, BCI) is rising worldwide. Whilst both tobacco and alcohol have been linked to BCI genotoxic cannabinoids have not been investigated. Age-adjusted state-based BCI 2003–2017 was taken from the Surveillance Epidemiology and End Results database of the Centers for Disease Control. Drug use from the National Survey of Drug Use and Health, response rate 74.1%. Median age, median household income and ethnicity were from US census. Inverse probability weighted (ipw) multivariable regression conducted in R. In bivariate analysis BCI was shown to be significantly linked with rising cannabis exposure {β-est. = 3.93 [95% confidence interval 2.99, 4.87], P = 1.10 × 10−15}. At 8 years lag cigarettes:cannabis [β-est. = 2660 (2150.4, 3169.3), P = 4.60 × 10−22] and cannabis:alcoholism [β-est. = 7010 (5461.6, 8558.4), P = 1.80 × 10−17] were significant in ipw-panel regression. Terms including cannabidiol [CBD; β-est. = 16.16 (0.39, 31.93), P = 0.446] and cannabigerol [CBG; β-est. = 6.23 (2.06, 10.39), P = 0.0034] were significant in spatiotemporal models lagged 1:2 years, respectively. Cannabis-liberal paradigms had higher BCI [67.50 ± 0.26 v. 65.19 ± 0.21/100 000 (mean ± SEM), P = 1.87 × 10−11; β-est. = 2.31 (1.65, 2.96), P = 9.09 × 10−12]. 55/58 expected values >1.25 and 13/58 >100. Abortion was independently and causally significant in space–time models. Data show that exposure to cannabis and the cannabinoids Δ9-tetrahydrocannabinol, CBD, CBG and alcoholism fulfil quantitative causal criteria for BCI across space and time. Findings are robust to adjustment for age and several known sociodemographic, socio-economic and hormonal risk factors and establish cannabinoids as an additional risk factor class for breast carcinogenesis. BCI is higher under cannabis-liberal legal paradigms.
Global burden of rheumatic heart disease and its association with socioeconomic development status, 1990–2019
Authors: Lv Meina , Jiang Shaojun , Liao Dongshan , Lin Zhi , Chen Haiyu , Zhang Jinhua
Published: March 2022

Aims

Rheumatic heart disease (RHD) remains an important health issue, yet global attention to RHD is diminishing. This study aimed to investigate the global burden of RHD and its relationship with socioeconomic development status.

Methods and results

Data were obtained from the Global Burden of Disease (GBD) 2019 database. Incidence, prevalence, disability-adjusted life years (DALYs), and mortality numbers and rates for RHD were extracted and stratified by sex, level of socio-demographic index (SDI), country, and territory. In addition, the burden of RHD was compared across age groups. From 1990 to 2019, the age-standardized incidence and prevalence rates of RHD increased by 14.4% (11.2–17.0%) and 13.8% (11.0–16.0%), respectively. Incidence and prevalence rates showed an increasing trend in low SDI and low-middle SDI locations, while high-middle SDI and high SDI locations showed a decreasing trend. The age-standardized DALYs and mortality rates of RHD decreased by 53.1% (46.4–60.0) and 56.9% (49.8–64.7%), and this downward trend was more prominent in high-middle SDI and middle SDI locations. In addition, the age of incidence and prevalence rates were concentrated between 5–24 years and 15–49 years, predominantly in poor regions, and RHD appeared to be more common in women than in men.

Conclusion

The burden of RHD is negatively correlated with socioeconomic development status. In particular, the burden of RHD among children, adolescents, and women of childbearing age in poorer regions requires more attention. Policymakers should use the 2019 GBD data to guide cost-effective interventions and resource allocation for RHD.
The Validity and Reliability of Retrospective Measures of Childhood Socioeconomic Status in the Health and Retirement Study: Evidence From the 1940 U.S. Census
Authors: Warren John Robert , Lee Mark , Osypuk Theresa L
Published: March 2022

Objectives

Retrospective measures of childhood socioeconomic status (SES) in cohort studies of aging that first observe people late in life—such as the Health and Retirement Study (HRS)—are widely used. However, their measurement validity and reliability are unknown. We assess the reliability and validity of the HRS’s retrospective measures of parental education and childhood family finances.

Methods

We use records for 6,343 HRS sample members who were children in 1940 that have been linked to records from the complete-count 1940 U.S. Census. We assess interrater reliability by comparing (a) retrospective reports of childhood SES collected from sample members in the 1992–2018 HRS to (b) prospective measures of parallel concepts collected from HRS sample members’ parents in the 1940 Census. We assess predictive validity by comparing the results of analyses that model later-life outcomes as a function of childhood SES as measured both prospectively and retrospectively.

Results

Interrater reliabilities of retrospective measures of parental education are high; however, the same is not true of the retrospective measure of childhood family finances. Both retrospective and prospective measures of childhood SES are predictive of later-life outcomes, and with similar strengths and directions of associations for most outcomes.

Discussion

Researchers who rely on retrospective indicators of childhood SES from the HRS should be aware of their measurement properties. They are measured with error, and that error modestly attenuates estimates of their associations with later-life outcomes. However, prospective and retrospective measures of childhood SES have similar predictive validity. These findings should reassure researchers who rely on retrospective measures of childhood SES in the HRS and similarly designed surveys.
Promoting Social Connection in Dementia Caregivers: A Call for Empirical Development of Targeted Interventions
Authors: Van Orden Kimberly A , Heffner Kathi L
Published: March 2022

Social connection is an understudied target of intervention for the health of individuals providing care for a family member with Alzheimer’s disease and related dementias (ADRD). To guide future research, we discuss considerations for interventions to promote social connection, with a particular focus on reducing loneliness: (a) include caregiver perspectives in designing and delivering interventions; (b) adapt to stages of dementia; (c) consider caregiving demands, including the use of brief interventions; (d) specify and measure mechanisms of action and principles of interventions; (e) consider dissemination and implementation at all stages of research. With support from the National Institute on Aging for a Roybal Center for Translational Research in the Behavioral and Social Sciences of Aging, we are developing a portfolio of mechanism-informed and principle-driven behavioral interventions to promote social connection in ADRD caregivers that can be flexibly applied to meet a diverse set of needs while maximizing resources and reducing demands on caregivers.
Reformed but not converted: Paolo Sarpi, the English mission in Venice and conceptions of religious change
Authors: Davies Eloise
Published: March 2022

Taking as its starting point the well-known English effort to ‘convert’ Venice to Protestantism in the wake of the Venetian Interdict controversy (1606–7), this article explores the ways in which early modern conceptions of conversion varied according to context. Drawing on evidence relating to Venice, England, Ireland and the Jesuit missions to China, it traces how divergent understandings of religious change shaped – and were shaped by – confessional controversy. The idea of ‘conversion’ posed particular conceptual difficulties as a description of inter-confessional transfer, and this article probes the implications of these difficulties for religious and political debate.
The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Authors: Sheehan Jessica L , Jacob Janson , Berinstein Elliot M , Greene-Higgs LaVana , Steiner Calen A , Berry Sameer K , Shannon Carol , Cohen-Mekelburg Shirley A , Higgins Peter D R , Berinstein Jeffrey A
Published: March 2022

Background

Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited.

Methods

A systematic search was completed using PubMed, Embase, the Cochrane Library, and Scopus through May of 2020. The exposure of interest was any opioid medication prescribed by a healthcare provider. Outcomes included readmissions rate, hospitalization, hospital length of stay, healthcare costs, emergency department visits, outpatient visits, IBD-related surgeries, and IBD-related medication utilization. Meta-analysis was conducted on study outcomes reported in at least 4 studies using random-effects models to estimate pooled relative risk (RR) and 95% confidence interval (CI).

Results

We identified 1969 articles, of which 30 met inclusion criteria. Meta-analysis showed an association between opioid use and longer length of stay (mean difference, 2.25 days; 95% CI, 1.29-3.22), higher likelihood of prior IBD-related surgery (RR, 1.72; 95% CI, 1.32-2.25), and higher rates of biologic use (RR, 1.38; 95% CI, 1.13-1.68) but no difference in 30-day readmissions (RR, 1.17; 95% CI, 0.86-1.61), immunomodulator use (RR, 1.13; 95% CI, 0.89-1.44), or corticosteroid use (RR, 1.36; 95% CI, 0.88-2.10) in patients with IBD. On systematic review, opioid use was associated with increased hospitalizations, healthcare costs, emergency department visits, outpatient visits, and polypharmacy.

Discussion

Opioids use among patients with IBD is associated with increased healthcare utilization. Nonopioid alternatives are needed to reduce burden on the healthcare system and improve patient outcomes.
An Example of a Singular Integral and a Weight
Authors: Honzík Petr
Published: March 2022

Sharp weighted inequalities were recently proved for several classical operators in Harmonic analysis, however for the rough singular integral the sharp result remains open. The best bound so far was found by Hytönen, Roncal and Tapiola in [2]. For $A_2$ weight, it is quadratic, meaning $\|T_\Omega f\|_{L^2_{\omega }}\leq C [\omega ]_2^2 \|f\|_{L^2_{\omega }}.$ The authors also conjectured that the best bound is linear. We provide example of $A_2$ weights $\omega _n$, test functions $f_n$ and rough singular integrals $$ \begin{align*} & T_{\Omega_n}(f)(x)=\textrm{p.v.} \int_{\mathbb R^2} |y|^{-2} \Omega_n(y/|y|)f(x-y) dy, \end{align*}$$where $\Omega _n $ is a function in $L^\infty (\mathbb S^{1})$ with norm $1$ and vanishing integral such that $$ \begin{align*} &\|T_{\Omega_n} f_n\|_{L^2_{\omega_n}}\geq C [\omega_n]_2^{3/2} \|f_n\|_{L^2_{\omega_n}}\end{align*}$$and $[\omega _n]_2\approx n,$ disproving the conjecture.
Tertiary syphilis mimicking metastatic rectal cancer
Authors: Smith Matthew J , Ong Meydene , Maqbool Abrar
Published: March 2022

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. Tertiary syphilis, a late-stage multi-visceral complication of the disease is characterized by its diversity of clinical manifestations. Here, we present the first documented case of tertiary syphilis that clinically and radiologically mimicked primary rectal cancer with hepatic metastasis.
Psychobiotics in diet: significance and applications of neuroactive and psychoactive microbial metabolites
Authors: Giri Rajat , Sharma Rakesh Kumar
Published: March 2022

The brain governs psychiatric behavior of an individual by regulating certain neuroactive compounds produced within the body. These might also be produced by the microbes present in the gut, along with certain probiotic strains: the psychobiotics. A healthy diet including psychobiotics plays an important role in neurological functioning by producing a number of psychoactive compounds. Health benefits of probiotic microorganisms to the host and their psychoactive metabolites involved in the alternation of brain functioning are summarized in this article. The effect of diet on gut microbiota is highlighted, along with the possibility of probiotic bacteria as psychobiotics in the treatment or prevention of mental health–related disorders. The psychobiotic formulations seem to be a step toward precision probiotics development.
Polypharmacy, Potentially Inappropriate Medications, and Drug-Drug Interactions in Vulnerable Older Adults With Advanced Cancer Initiating Cancer Treatment
Authors: Ramsdale Erika , Mohamed Mostafa , Yu Veronica , Otto Ethan , Juba Katherine , Awad Hala , Moorthi Kiran , Plumb Sandy , Patil Amita , Vogelzang Nicholas , Dib Elie , Mohile Supriya
Published: March 2022

Purpose

Polypharmacy is prevalent in older adults starting cancer treatment and associated with potentially inappropriate medications (PIM), potential drug-drug interactions (DDI), and drug-cancer treatment interactions (DCI). For a large cohort of vulnerable older adults with advanced cancer starting treatment, we describe patterns of prescription and nonprescription medication usage, the prevalence of PIM, and the prevalence, severity, and type of DDI/DCI.

Methods

This secondary analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment (University of Rochester Cancer Center [URCC] 13059; PI: Mohile). PIM were categorized using 2019 Beers criteria and Screening Tool of Older Persons’ Prescriptions. Potential DDI/DCI were evaluated using Lexi-Interact Online. Medication classification followed the World Health Organization Anatomical Therapeutic Chemical system. Bivariate associations were evaluated between sociodemographic and geriatric assessment (GA) measures and medication measures. Chord diagrams and network analysis were used to understand and describe DDI/DCI.

Results

Among 718 patients (mean age 77.6 years), polypharmacy (≥5 medications), excessive polypharmacy (≥10 medications), and ≥1 PIM were identified in 61.3%,14.5%, and 67.1%, respectively. Cardiovascular medications were the most prevalent (47%), and nonprescription medications accounted for 26% of total medications and 40% of PIM. One-quarter of patients had ≥1 potential major DDI not involving cancer treatment, and 5.4% had ≥1 potential major DCI. Each additional medication increased the odds of a potential major DDI and DCI by 39% and 12%, respectively. Polypharmacy and PIM are associated with multiple GA domains.

Conclusion

In a cohort of vulnerable older adults with advanced cancer starting treatment, polypharmacy, PIM, and potential DDI/DCI are very common. Nonprescription medications are frequently PIMs and/or involved in potential DDI/DCI.
Moving Publicness Forward: Merging Moulton and Merritt’s Frameworks to Examine Managed Care Organizations
Authors: Varkey Sapna
Published: March 2022

Publicness work focuses on the unique characteristics that make an organization more, or less, public, and dates back to the late 70s. Despite the range of publicness research that exists, the characteristics explored remain largely unchanged. However, merging Merritt’s (2019) primary influences that make an organization public and Moulton’s (2009) realized publicness frameworks provides the structure necessary to explore a broader conceptualization of organizational publicness. This study pushes theory forward by considering aspects of publicness beyond political authority-specific characteristics and uses behavioral health managed care organizations (MCOs) as the tool for exploration. This work outlines propositions, offers metrics that can be used in future studies, and explores how the framework can be valuable and what it might reveal in organizational settings beyond MCOs.
Molecular Manipulations and Intestinal Stem Cell-Derived Organoids in Inflammatory Bowel Disease
Authors: Boye Theresa Louise , Steenholdt Casper , Jensen Kim Bak , Nielsen Ole Haagen
Published: March 2022

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states. Recent developments in patient-derived epithelial intestinal stem cell (ISC) organoid technologies have opened exciting new therapeutic opportunities to potentially attain molecular healing by combining stem cell therapy with molecular manipulations using (epi)drugs and/or CRISPR/Cas9 genome editing. Here, we are the first to discuss the possibility for phenotypic, genotypic, and epigenetic restoration via molecular manipulations and stem cell therapy in IBD from a clinical perspective.
Quantifying rates of HIV-1 flow between risk groups and geographic locations in Kenya: A country-wide phylogenetic study
Authors: Nduva George M , Otieno Frederick , Kimani Joshua , Wahome Elizabeth , McKinnon Lyle R , Cholette Francois , Majiwa Maxwell , Masika Moses , Mutua Gaudensia , Anzala Omu , Graham Susan M , Gelmon Larry , Price Matt A , Smith Adrian D , Bailey Robert C , Baele Guy , Lemey Philippe , Hassan Amin S , Sanders Eduard J , Esbjörnsson Joakim
Published: March 2022

In Kenya, HIV-1 key populations including men having sex with men (MSM), people who inject drugs (PWID) and female sex workers (FSW) are thought to significantly contribute to HIV-1 transmission in the wider, mostly heterosexual (HET) HIV-1 transmission network. However, clear data on HIV-1 transmission dynamics within and between these groups are limited. We aimed to empirically quantify rates of HIV-1 flow between key populations and the HET population, as well as between different geographic regions to determine HIV-1 ‘hotspots’ and their contribution to HIV-1 transmission in Kenya. We used maximum-likelihood phylogenetic and Bayesian inference to analyse 4058 HIV-1 pol sequences (representing 0.3 per cent of the epidemic in Kenya) sampled 1986–2019 from individuals of different risk groups and regions in Kenya. We found 89 per cent within-risk group transmission and 11 per cent mixing between risk groups, cyclic HIV-1 exchange between adjoining geographic provinces and strong evidence of HIV-1 dissemination from (i) West-to-East (i.e. higher-to-lower HIV-1 prevalence regions), and (ii) heterosexual-to-key populations. Low HIV-1 prevalence regions and key populations are sinks rather than major sources of HIV-1 transmission in Kenya. Targeting key populations in Kenya needs to occur concurrently with strengthening interventions in the general epidemic.
Iron deficiency anemia in pregnancy
Authors: Igbinosa Irogue , Berube Caroline , Lyell Deirdre J.
Published: March 2022

Purpose of review

Anemia in pregnancy is associated with increased maternal and neonatal morbidity. There is increasing awareness amongst obstetricians about the need to screen for iron deficiency anemia (IDA), as well as growing literature on diagnosis and treatment. This review aims to summarize causes, consequences, treatment, and evaluation of IDA in pregnancy.

Recent Findings

National guidelines provide varying guidance on diagnosis and treatment of IDA in pregnancy. Serum ferritin is a helpful adjunct for the diagnosis of IDA. Oral iron remains an option for treatment; absorption is improved with every other day dosing and is effective for patients able to tolerate. Emerging studies on modern generations of intravenous (IV) iron demonstrate shorter infusion times and improved safety profiles. Notably, recent UK guidelines provide consideration for universal IV iron supplementation for treatment of anemia beyond 34 weeks of pregnancy.

Iron, in dietary, oral, and IV forms, has been found effective in resolving anemia in pregnancy. Pregnant people with IDA in the third trimester are more likely to benefit from IV iron. Future studies designed and powered to assess maternal and perinatal morbidity indicators and blood transfusion rates can strengthen recommendations.
Development and Structure of an Accurate Machine Learning Algorithm to Predict Inpatient Mortality and Hospice Outcomes in the Coronavirus Disease 2019 Era
Authors: Chi Stephen , Guo Aixia , Heard Kevin , Kim Seunghwan , Foraker Randi , White Patrick , Moore Nathan
Published: March 2022

Background:

The coronavirus disease 2019 (COVID-19) pandemic has challenged the accuracy and racial biases present in traditional mortality scores. An accurate prognostic model that can be applied to hospitalized patients irrespective of race or COVID-19 status may benefit patient care.

Research Design:

This cohort study utilized historical and ongoing electronic health record features to develop and validate a deep-learning model applied on the second day of admission predicting a composite outcome of in-hospital mortality, discharge to hospice, or death within 30 days of admission. Model features included patient demographics, diagnoses, procedures, inpatient medications, laboratory values, vital signs, and substance use history. Conventional performance metrics were assessed, and subgroup analysis was performed based on race, COVID-19 status, and intensive care unit admission.

Subjects:

A total of 35,521 patients hospitalized between April 2020 and October 2020 at a single health care system including a tertiary academic referral center and 9 community hospitals.

Results:

Of 35,521 patients, including 9831 non-White patients and 2020 COVID-19 patients, 2838 (8.0%) met the composite outcome. Patients who experienced the composite outcome were older (73 vs. 61 y old) with similar sex and race distributions between groups. The model achieved an area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.88, 0.91) and an average positive predictive value of 0.46 (0.40, 0.52). Model performance did not differ significantly in White (0.89) and non-White (0.90) subgroups or when grouping by COVID-19 status and intensive care unit admission.

Conclusion:

A deep-learning model using large-volume, structured electronic health record data can effectively predict short-term mortality or hospice outcomes on the second day of admission in the general inpatient population without significant racial bias.
Caregiver Burden in Caregivers of Children With Special Health Care Needs and Association With Chronic Pain
Authors: Camelo Castillo Wendy , Onasanya Oluwadamilola , dosReis Susan , Hogans Beth , Reeves Gloria
Published: March 2022

Background/Objectives:

Chronic noncancer pain (CNCP) affects millions of individuals in the United States but evidence of its prevalence among caregivers of children with special health care needs is sparse. We sought to estimate the prevalence of CNCP and its association with caregiver burden, in a nationally representative sample.

Methods:

Retrospective cross-sectional study using pooled Medical Expenditure Panel Survey data for 2010–2015. Within interviewed households, family groups consisting of at least 1 parent and 1 child (0–17 y) were identified. CNCP was identified by one or more International Classification of Diseases, Ninth Revision (ICD-9)-CM codes utilizing previously published approaches. Level of caregiver burden was defined using a validated screener questionnaire identifying children with high burden of care (ie, special health care needs), for example, high or low burden. We estimated prevalence of CNCP as a function of caregiver burden, as well as the association of risk factors with CNCP, including parent sociodemographic features, clinical diagnoses, and family level characteristics.

Results:

We identified 46,525 caregivers of whom 3.6% reported experiencing high caregiving burden. The prevalence of CNCP was 25.5% and 14.0% among parents with high compared with low caregiving burden, respectively. Odds of CNCP were higher among parents with high compared to those with lower caregiver burden (odds ratio=1.29, 95% confidence interval=1.06–1.55). Being obese, experiencing disability, and having a mental health diagnosis were associated with higher odds of CNCP.

Conclusions:

Chronic pain is more common among caregivers with high caregiver burden. Our findings highlight the need to further explore the nature and impact of risk factors on caregiver health and disability.
Parashewanella hymeniacidonis sp. nov., isolated from marine sponge (Hymeniacidon sinapium)
Authors: Kim Soo-Bin , Park Jin-Sook
Published: March 2022

A flagella bacterium, designated strain 202IG2-18T was isolated from a marine sponge Hymeniacidon sinapium from Ulleung-do in the Republic of Korea. Cells were Gram-stain-negative, motile, aerobic, rod-shaped and non-pigmented. The strain was able to grow at pH 5.5–9.5 (optimum, pH 7.5), in the presence of 1–5 % (w/v) NaCl (optimum, 3 %, w/v) and at 18–30 °C (optimum, 30 °C). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 202IG2-18T belonged to the family

Shewanellaceae

, and was most closely related to [

Shewanella

] irciniae NRRL B-41466T (97.9 %), followed by

Parashewanella tropica

KCCM 43304T (97.1 %),

Parashewanella curva

KCTC 62318T (96.3 %) and

Parashewanella spongiae

KCTC 22492T (96.2 %). The predominant fatty acids were iso-C15 : 0 (25.7 %), C17 : 1
 ω8c (13.5 %), summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c, 12.7 %), iso-C13 : 0 (10.4 %) and C16 : 0 (9.6 %). The only detected respiratory quinone was ubiquinone Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unidentified glycolipids, two unidentified aminophospholipids, an unidentified phospholipid and an unidentified aminolipid. The G+C content of the genomic DNA was 39.8 mol%. The average nucleotide identity values compared to all other related species was below 72.8 % and digital DNA–DNA hybridization values were 21.1–22.3 %, all below the threshold for bacterial species delineation. Phenotypic, phylogenetic, genomic and chemotaxonomic characteristics showed that strain 202IG2-18T represents a novel species of the genus

Parashewanella

, for which the name Parashewanella hymeniacidonis sp. nov. is proposed. The type strain is 202IG2-18T (=KACC 22256T=LMG 32203T).
Hymenobacter armeniacus sp. nov. and Hymenobacter montanus sp. nov., two radiation-resistant bacteria from soil
Authors: Park Yuna , Chang Yoonjee , Kim Myung Kyum
Published: March 2022

Two bacterial strains, designated BT189T and BT664T, were isolated from soil sampled in the Republic of Korea. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strains BT189T and BT664T belonged to the genus

Hymenobacter

, family

Hymenobacteraceae

(order

Cytophagales

). The 16S rRNA genes of the two strains shared a sequence similarity of 93.7 %. The closely related species of strain BT189T were

Hymenobacter rubidus

DG7BT (97.1 % 16S rRNA similarity) and

Hymenobacter terrae

DG7AT (96.7 %). The closest related species to strain BT664T were

Hymenobacter sedentarius

DG5BT (95.3 %) and

Hymenobacter terrenus

MIMtkLc17T (95.2 %). The genome sizes of strains BT189T and BT664T were 5 285 287 and 5 475 357 bp, respectively. The genomic DNA G+C contents of strains BT189T and BT664T were 63.2 and 59.3 mol%, respectively. The main fatty acids of strain BT189T were iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1 
ω6c/C16 : 1 
ω7c), and those of strain BT664T were iso-C15 : 0, C16 : 1
 ω5c and summed feature 3 (C16 : 1 
ω6c/C16 : 1 
ω7c). The main polar lipid in both strains was phosphatidylethanolamine and the predominant respiratory quinone was MK-7, supporting the affiliation of these strains with the genus

Hymenobacter

. Based on the results of biochemical, chemotaxonomic and phylogenetic analyses, two novel species, Hymenobacter armeniacus BT189T (=KCTC 72341T=NBRC 114843T) and Hymenobacter montanus BT664T (KACC 21967T=NBRC 114856T), are proposed.
Microbe Profile: Legionella pneumophila - a copycat eukaryote
Authors: Hilbi Hubert , Buchrieser Carmen
Published: March 2022

Legionella pneumophila

is an environmental bacterium that parasitizes aquatic protozoa and uses the same processes to infect humans. The facultative intracellular pathogen causes a life-threatening pneumonia with possible systemic complications. The co-evolution with protozoa is reflected in an armoury of bacterial effectors, and many of these type IV-secreted proteins have likely been acquired by interdomain horizontal gene transfer (HGT) from hosts. The unique features of

L. pneumophila

are the largest bacterial effector repertoire known to date, subversion of virtually all eukaryotic signalling pathways and acquisition of eukaryotic enzyme activities used to manipulate the host cell to the pathogen’s advantage.
Genomic surveillance of SARS-CoV-2 in a university community: insights into tracking variants, transmission, and spread of Gamma (P.1) variant
Authors: Ciubotariu Ilinca I. , Dorman Jack , Perry Nicole M. , Gorenstein Lev , Kattoor Jobin J. , Fola Abebe A. , Zine Amy , Hendrix G. Kenitra , Wilkes Rebecca P. , Kitchen Andrew , Carpi Giovanna
Published: March 2022

Using a combination of data from routine surveillance, genomic sequencing, and phylogeographic analysis we tracked the spread and introduction events of SARS-CoV-2 variants focusing on a large university community. Here, we sequenced and analyzed 677 high-quality SARS-CoV-2 genomes from positive RNA samples collected from Purdue University students, faculty, and staff who tested positive for the virus between January 2021 and May 2021, comprising an average of 32% of weekly cases across the time frame. Our analysis of circulating SARS-CoV-2 variants over time revealed periods when Variant of Concern (VOC) Alpha (B.1.1.7) and Iota (B.1.526) reached rapid dominance and documented that VOC Gamma (P.1) was increasing in frequency as campus surveillance was ending. Phylodynamic analysis of Gamma genomes from campus alongside a subsampling of >20,000 previously published P.1 genomes revealed ten independent introductions of this variant into the Purdue community, predominantly from elsewhere in the United States, with introductions from within the state of Indiana and from Illinois, and possibly Washington and New York, suggesting a degree of domestic spread. We conclude that a robust and sustained active and passive surveillance program coupled with genomic sequencing during a pandemic offers important insights into the dynamics of pathogen arrival and spread in a campus community and can help guide mitigation measures.