Long-term outcomes of hospitalized patients with SARS-CoV-2/COVID-19 with and without neurological involvement: 3-year follow-up assessment.

BACKGROUND: Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. METHODS AND FINDINGS: Patients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves. CONCLUSIONS: Patients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.

Risk of Venous Thromboembolism With Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk-Enriched Rheumatoid Arthritis Patients.

OBJECTIVE: The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. METHODS: Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. RESULTS: Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. CONCLUSION: Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.

Metabolomic and genetic architecture of gestational diabetes subtypes.

AIMS/HYPOTHESIS: Physiological gestational diabetes mellitus (GDM) subtypes that may confer different risks for adverse pregnancy outcomes have been defined. The aim of this study was to characterise the metabolome and genetic architecture of GDM subtypes to address the hypothesis that they differ between GDM subtypes. METHODS: This was a cross-sectional study of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study who underwent an OGTT at approximately 28 weeks' gestation. GDM was defined retrospectively using International Association of Diabetes and Pregnancy Study Groups/WHO criteria, and classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity) or insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion). Metabolomic analyses were performed on fasting and 1 h serum samples in 3463 individuals (576 with GDM). Genome-wide genotype data were obtained for 8067 individuals (1323 with GDM). RESULTS: Regression analyses demonstrated striking differences between the metabolomes for insulin-deficient or insulin-resistant GDM compared to those with normal glucose tolerance. After adjustment for covariates, 33 fasting metabolites, including 22 medium- and long-chain acylcarnitines, were uniquely associated with insulin-deficient GDM; 23 metabolites, including the branched-chain amino acids and their metabolites, were uniquely associated with insulin-resistant GDM; two metabolites (glycerol and 2-hydroxybutyrate) were associated with the same direction of association with both subtypes. Subtype differences were also observed 1 h after a glucose load. In genome-wide association studies, variants within MTNR1B (rs10830963, p=3.43×10-18, OR 1.55) and GCKR (rs1260326, p=5.17×10-13, OR 1.43) were associated with GDM. Variants in GCKR (rs1260326, p=1.36×10-13, OR 1.60) and MTNR1B (rs10830963, p=1.22×10-9, OR 1.49) demonstrated genome-wide significant association with insulin-resistant GDM; there were no significant associations with insulin-deficient GDM. The lead SNP in GCKR, rs1260326, was associated with the levels of eight of the 25 fasting metabolites that were associated with insulin-resistant GDM and ten of 41 1 h metabolites that were associated with insulin-resistant GDM. CONCLUSIONS/INTERPRETATION: This study demonstrates that physiological GDM subtypes differ in their metabolome and genetic architecture. These findings require replication in additional cohorts, but suggest that these differences may contribute to subtype-related adverse pregnancy outcomes.

Measuring context-response associations that drive habits.

People achieve important life outcomes of health, financial security, and productivity by repeating operant behavior. To identify whether such operants reflect goal pursuit or habit, the present research introduces a new paradigm that yields objective measures of learning and controls for the motivations of goal pursuit. In two experiments, participants practiced a sequential task of making sushi and then completed a test of the strength of cue-response (habit) associations in memory. Finally, they repeated the sushi task without instructions while under cognitive load (designed to impede deliberation about goals). As predicted, greater task practice yielded stronger cue-response associations, which in turn promoted task success. Practice did not improve performance by enhancing goal intentions or other task motivations. We conclude that repetition facilitates performance by creating mental associations that automatically activate practiced, habitual responses upon perception of recurring context cues.

Maternal Nativity and Preterm Birth.

Importance: Preterm birth is a major contributor to neonatal morbidity and mortality, and considerable differences exist in rates of preterm birth among maternal racial and ethnic groups. Emerging evidence suggests pregnant individuals born outside the US have fewer obstetric complications than those born in the US, but the intersection of maternal nativity with race and ethnicity for preterm birth is not well studied. Objective: To determine if there is an association between maternal nativity and preterm birth rates among nulliparous individuals, and whether that association differs by self-reported race and ethnicity of the pregnant individual. Design, Setting, and Participants: This was a nationwide, cross-sectional study conducted using National Center for Health Statistics birth registration records for 8 590 988 nulliparous individuals aged 15 to 44 years with singleton live births in the US from 2014 to 2019. Data were analyzed from March to May 2022. Exposures: Maternal nativity (non-US-born compared with US-born individuals as the reference, wherein US-born was defined as born within 1 of the 50 US states or Washington, DC) in the overall sample and stratified by self-reported ethnicity and race, including non-Hispanic Asian and disaggregated Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Pacific Islander, Vietnamese, and other Asian), non-Hispanic Black, Hispanic and disaggregated Hispanic subgroups (Cuban, Mexican, Puerto Rican, and other Hispanic), and non-Hispanic White. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks of gestation) and the secondary outcome was very preterm birth (<32 weeks of gestation). Results: Of 8 590 988 pregnant individuals included (mean [SD] age at delivery, 28.3 [5.8] years in non-US-born individuals and 26.2 [5.7] years in US-born individuals; 159 497 [2.3%] US-born and 552 938 [31.2%] non-US-born individuals self-identified as Asian or Pacific Islander, 1 050 367 [15.4%] US-born and 178 898 [10.1%] non-US-born individuals were non-Hispanic Black, 1 100 337 [16.1%] US-born and 711 699 [40.2%] non-US-born individuals were of Hispanic origin, and 4 512 294 [66.1%] US-born and 328 205 [18.5%] non-US-born individuals were non-Hispanic White), age-standardized rates of preterm birth were lower among non-US-born individuals compared with US-born individuals (10.2%; 95% CI, 10.2-10.3 vs 10.9%; 95% CI, 10.9-11.0) with an adjusted odds ratio (aOR) of 0.90 (95% CI, 0.89-0.90). The greatest relative difference was observed among Japanese individuals (aOR, 0.69; 95% CI, 0.60-0.79) and non-Hispanic Black individuals (aOR, 0.74; 0.73-0.76) individuals. Non-US-born Pacific Islander individuals experienced higher preterm birth rates compared with US-born Pacific Islander individuals (aOR, 1.15; 95% CI, 1.04-1.27). Puerto Rican individuals born in Puerto Rico compared with those born in US states or Washington, DC, also had higher preterm birth rates (aOR, 1.07; 95% CI, 1.03-1.12). Conclusions and Relevance: Overall preterm birth rates were lower among non-US-born individuals compared with US-born individuals. However, there was substantial heterogeneity in preterm birth rates across maternal racial and ethnic groups, particularly among disaggregated Asian and Hispanic subgroups.

Different roles of interpersonal trust and institutional trust in motivating older adults to receive COVID-19 vaccines in Singapore.

Since the approvals of several vaccines against COVID-19 by the World Health Organization, a large body of research has studied the determinants of individuals' intention to be vaccinated against COVID-19 in a variety of societies. Vaccine intention is a complex construct rooted in the social context that informs the decision-making process. The underlying reasons for older adults' intention to receive the vaccination is even more important to health authorities in societies with large proportions of older adults. In this paper, we interview 27 women over age 55 in Singapore about their COVID-19 vaccine decision-making. Using a social-ecological framework of trust, we identify factors at both individual and institutional levels that build or undermine trust and underlie older women's decisions to receive COVID-19 vaccinations in an authoritarian regime. Findings show that both interpersonal trust and institutional trust contribute to vaccine uptake, however, trust can also contribute to delays in vaccination. Moreover, a sizable minority of respondents report that they were vaccinated not because of institutional trust, but because they felt compelled to do so. The results shed light on directions for future vaccination campaigns.

Pazopanib elicits remarkable response in metastatic porocarcinoma: a functional precision medicine approach.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

Concordance of the ACR TI-RADS Classification With Bethesda Scoring and Histopathology Risk Stratification of Thyroid Nodules.

Importance: Although most thyroid nodules are benign, 10% to 15% of them harbor cancer. Thyroid ultrasonography is useful for risk stratification of nodules, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) classification provides recommendations for fine-needle aspiration cytology (FNAC) based on objective ultrasonographic features of these nodules. Objective: To validate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology. Design, Setting, and Participants: This retrospective cohort study was performed to evaluate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology and was conducted in Singapore General Hospital Outpatient Otolaryngology clinic in March 2021 to May 2021. Data analysis was performed in May 2021. Main Outcomes and Measures: Results were deemed concordant when ACR TI-RADS recommendations aligned with Bethesda scores. Conversely, results were classified as nonconcordant with Bethesda scores and/or histopathology results when nodules that were recommended for FNAC yielded benign results or nodules that were not recommended for FNAC yielded malignant results. Results: A total of 446 patients (370 women [83%]; mean [range] age, 60 [24-89] years) who underwent ultrasonography of the thyroid and ultrasonography-guided thyroid FNACs were identified. A total of 492 of 630 nodules (78.1%) were benign on FNAC (Bethesda II). Score 3 ACR TI-RADS nodules yielded the highest negative predictive values: 94.6% (95% CI, 92.9%-95.9%; P < .001) compared with Bethesda scoring and 100.0% (95% CI, 15.8%-100.0%; P = .003) compared with histopathology. Score 4 or 5 ACR TI-RADS nodules yielded positive predictive values of 2.8% and 16.2%, respectively, compared with Bethesda scoring and 6.1% and 66.7%, respectively, compared with histopathology. Small (<1.5 cm) ACR TI-RADS nodules of scores of 4 and 5 that were not recommended for FNAC yielded a malignant risk of 5.7% and 25.0% on Bethesda 5 and 6, respectively. On surgical excision, 5 of 46 (10.9%) ACR TI-RADS 4 nodules and 15 of 21 (71.4%) of ACR TI-RADS 5 nodules were confirmed to be malignant. Among nodules initially not recommended for FNAC, histopathology-proven cancer was found in 4 of 13 (30.7%) and 3 of 6 (50.0%) of nodules, respectively. Conclusions and Relevance: These findings suggest that ACR TI-RADS score 3 nodules have a low risk of cancer and should be considered for FNAC only if nodules are 2.5 cm or larger. Patients with small (<1.5 cm) ACR TI-RADS 4 and 5 nodules should be appropriately counseled for FNAC to exclude cancer.

Pearls & Oy-sters: Whole-Genome Sequencing in Critically Ill Neurologic Patient Leads to Diagnosis With Treatment Implications.

Many adult patients with a history of seizures and global developmental delay do not have an identified etiology for their epilepsy. Rapid whole-genome sequencing (rWGS) can be used to identify a genetic etiology in critically ill patients to provide actionable interventions. In this case, a 27-year-old patient with a history of epilepsy, global developmental delay, and intellectual disability presented with altered mental status and new abnormal movements. The patient acutely declined over the course of 24-48 hours of presentation, including nonconvulsive status epilepticus leading to intubation for airway protection, 2 episodes of ventricular tachycardia requiring synchronized cardioversion, and 1 episode of supraventricular tachycardia. The patient was found to be in metabolic crisis. Metabolic workup and rapid whole-genome sequencing were sent. Patient was treated with 10% dextrose in normal saline and a mitochondrial cocktail. She received treatment with ammonia scavengers and hemodialysis with resolution of metabolic crisis. rWGS found a homozygous pathogenic variant in TANGO2 and a de novo pathogenic variant in KCNQ1, ultimately leading to the creation of a metabolic emergency protocol and implantable cardioverter defibrillator placement. This case highlights the use of rWGS in an acutely ill patient leading to actionable interventions. It also highlights the utility and importance of genetic sequencing in reevaluation of adult neurologic patients.

The ENCODE Imputation Challenge: a critical assessment of methods for cross-cell type imputation of epigenomic profiles.

A promising alternative to comprehensively performing genomics experiments is to, instead, perform a subset of experiments and use computational methods to impute the remainder. However, identifying the best imputation methods and what measures meaningfully evaluate performance are open questions. We address these questions by comprehensively analyzing 23 methods from the ENCODE Imputation Challenge. We find that imputation evaluations are challenging and confounded by distributional shifts from differences in data collection and processing over time, the amount of available data, and redundancy among performance measures. Our analyses suggest simple steps for overcoming these issues and promising directions for more robust research.

Lung Cancer Screening Penetration in an Urban Underserved County.

PURPOSE: To compare residential geography, sex, socioeconomic status (SES), and race/ethnicity of patients screened at Montefiore's Lung Cancer Screening Program with those of patients diagnosed with lung cancer, assessing whether screening efforts are appropriately focused. METHODS: This retrospective cohort study involved patients within a multisite urban medical center undergoing lung cancer screening or diagnosed with lung cancer from January 1, 2015 to December 31, 2019. Inclusion criteria were residence within the Bronx, NY and age between 55 and 80 years. Institutional review board approval was obtained. Data were analyzed using the Wilcoxon two-sample t test and χ2. RESULTS: The cohorts comprised 1568 (50.3%) women and 1551 (49.7%) men (mean age 65.6 ± 6.16). The Southeast Bronx had the most diagnosed lung cancers (29.96%) and screenings (31.22%). Sex did not significantly differ (p = 0.053). Cancer and screening cohorts were from impoverished neighborhoods with mean SES of - 3.11 ± 2.78 and - 3.44 ± 2.80 (p < 0.01). The lower tier SES neighborhoods demonstrated more patients in the screening cohort than cancer cohort (p = 0.01). Both cohorts included a majority of Hispanic patients, although race/ethnicity differed significantly (p = 0.01). Lower SES neighborhoods showed no significant difference in race/ethnicity between cancer and screening cohorts (p = 0.262). CONCLUSION: Though statistically significant differences were found between cohorts, likely due to sample size, few clinically meaningful differences were found, implying our lung cancer screening program was effective in reaching the desired population. Demographics-based programs should be considered in global efforts to screen vulnerable populations.

Chronic Hypertension in Pregnancy: A Lens Into Cardiovascular Disease Risk and Prevention.

Hypertension is a major, modifiable risk factor for cardiovascular disease (CVD) in the United States. Over the past decade, the prevalence of chronic hypertension (CHTN) during pregnancy has nearly doubled with persistent race- and place-based disparities. Blood pressure elevations are of particular concern during pregnancy given higher risk of maternal and fetal morbidity and mortality, as well as higher lifetime risk of CVD in birthing individuals with CHTN. When identified during pregnancy, CHTN can, therefore, serve as a lens into CVD risk, as well as a modifiable target to mitigate cardiovascular risk throughout the life course. Health services and public health interventions that equitably promote cardiovascular health during the peripartum period could have an important impact on preventing CHTN and reducing lifetime risk of CVD. This review will summarize the epidemiology and guidelines for the diagnosis and management of CHTN in pregnancy; describe the current evidence for associations between CHTN, adverse pregnancy outcomes, and CVD; and identify opportunities for peripartum care to equitably reduce hypertension and CVD risk throughout the life course.

The Role of Physician-Directed Duplex after Brachial Plexus Block in Arteriovenous Fistula Creation.

BACKGROUND: Best practice guidelines for dialysis access creation emphasize distal sites and autogenous tissue before more proximal sites and synthetic shunts. Pre-operative vein mapping is a useful modality to evaluate optimal access location; however, vein size is often underestimated secondary to patient hypovolemia, room temperature, and basal vascular tone. Supraclavicular brachial plexus blocks (BPB) are routinely performed to provide surgical anesthesia but also have known vasodilatory effects. Although many surgeons use both techniques, most do not repeat vein mapping after BPB to re-evaluate targets after block-mediated vasodilation. Therefore, we evaluated whether the role of physician-directed vein mapping after BPB resulted in more favorable access creations. METHODS: All patients who underwent primary ipsilateral access creation with physician-directed post-block duplex between 2017 and 2018 were evaluated. Vein mapping was reviewed for "theoretical access location" using the criterion of >2.5 mm vessels. Fistula preference was analogous to current indications with the following order of preference: wrist radiocephalic, forearm radiocephalic, brachiocephalic, brachiobasilic, and finally prosthetic graft. RESULTS: Forty-three patients met inclusion criteria. In total, physician-directed duplex after regional block resulted in the creation of higher preference accesses than predicted in 62.8% of patients. In 34.9% the access was at the predicted level and only 2.3% were at a lower preference. Furthermore, there were no differences in the maturation rates between accesses placed at higher preference locations than predicted compared to those at expected sites (74% vs. 79%, P = 0.38). The overall revision rate for higher preference access was 22.2% compared to 23.1% for equal/lower preference accesses. Of those accesses that failed, 83.3% of new accesses were created at the original theoretical location while 17.7% required placement of a lower preference access. CONCLUSIONS: Physician-directed ultrasound after BPB allows for identification of more preferential targets for access creation compared to pre-operative vein mapping. For access created at more preferential locations than pre-operatively predicted prior to BPB, there was no difference in maturation rates compared to those created at the theoretical vein mapping location.

Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate.

INTRODUCTION: The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA). METHODS: Patients aged ≥ 18 years with active RA and an inadequate response to MTX received open-label tofacitinib modified-release 11 mg once daily plus MTX for 24 weeks. In the double-blind MTX withdrawal phase, those who had achieved CDAI LDA (≤ 10) at week 24 were randomised 1:1 to receive tofacitinib monotherapy or continued tofacitinib plus MTX. Efficacy analyses were performed in subgroups defined by whether remission and/or LDA had been achieved at week 24 with: Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)], Routine Assessment of Patient Index Data 3 (RAPID3), CDAI and Simplified Disease Activity Index (SDAI); or DAS28-4[C-reactive protein(CRP)] < 2.4/ < 2.6/ < 2.9/ ≤ 3.2. RESULTS: Five hundred and thirty patients received treatment in the double-blind MTX withdrawal phase. Proportions of patients achieving each disease activity criterion at week 24 varied by metric. Across disease activity metrics [excluding DAS28-4(ESR) remission], 58-89% of patients per group, and numerically more patients receiving tofacitinib plus MTX, achieved the same criterion at week 48 as at week 24. Differences between groups in least squares mean change from baseline (Δ) DAS28-4(ESR) from week 24-48 favoured tofacitinib plus MTX (nominal p values < 0.05). RAPID3 and DAS28-4(CRP) estimated a higher proportion of patients with acceptable disease state versus DAS28-4(ESR), CDAI remission and SDAI remission. CONCLUSION: Response rates at the beginning of the double-blind phase varied across metrics. A consistent trend towards higher response rates with tofacitinib plus MTX was observed across metrics after randomisation, with nominal differences in DAS28-4(ESR) responses. Compared with continued combination therapy, MTX withdrawal did not lead to a clinically meaningful reduction in the response to tofacitinib. DAS28-4(CRP) and RAPID3 were the least stringent metrics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02831855.

Heart-Kidney Transplantation in a Transgender Woman.

We describe the care of a transgender woman with heart failure who underwent heart-kidney transplantation. Perioperative management of hormone therapy, considerations for future gender-affirming surgeries, and psychosocial aspects of care are discussed. Interdisciplinary collaboration is essential in the treatment of patients with advanced heart failure in the setting of gender-affirming therapies. (Level of Difficulty: Advanced.).

Stress, mindfulness, and systemic lupus erythematosus: An overview and directions for future research.

Although the pathogenesis of autoimmunity is not fully understood, it is thought to involve genetic, hormonal, immunologic, and environmental factors. Stress has been evaluated as a potential trigger for autoimmunity and disease flares in patients with systemic lupus erythematosus (SLE). The physiologic changes that occur with stress involve numerous catecholamines, hormones, and cytokines that communicate intricately with the immune system. There is some evidence that these systems may be dysregulated in patients with autoimmune disease. Mindfulness-based techniques are practices aimed at mitigating stress response and have been shown to improve quality of life in general population. This review will discuss pathophysiology of chronic stress as it relates to SLE, evidence behind mindfulness-based practices in these patients, and directions for future research.

Utilizing Telemedicine and Modified Fibrosis Staging Protocols to Maintain Treatment Initiation and Adherence Among Hepatitis C Patients During the COVID-19 Pandemic.

The COVID-19 pandemic exacerbated the decline in Hepatitis C Virus (HCV) screening and treatment globally in part due to lockdowns and restrictions at healthcare centers. The goal of this retrospective cohort study was to assess the effectiveness of an updated workflow implemented at Boston Medical Center (BMC) HCV clinics. Revised workflow incorporated appointments via telemedicine, transitioning to blood test-based fibrosis scoring, and delivering medication by mail to mitigate the lack of in-person services. We compared 2 cohorts of patients who attended at least the initial intake appointment at BMCHCV clinics: 170 before the pandemic and 133 after the pandemic. Outcome variables included treatment starts, fibrosis lab tests completed, appointment attendance, and SVR achievement. Proportions for outcome variables were compared between groups by use of χ2 and 2-sample t-tests where appropriate. Our results showed a 14.43% decrease in completing fibrosis scoring tests (P-value: <.001) and a 15.21% decrease in medication initiation (P-value: <.001) among the patients who initiated care during the pandemic (modified workflow group). Furthermore, we found a 18.56% decrease in sustained virologic response (SVR) among the modified workflow group when compared to the controls. Overall, these results align with current trends of patients' decreasing engagement in HCV care but show higher retention than other published data. Furthermore, these figures support how appointments via telemedicine, transitioning to blood test-based fibrosis scoring, and medication delivery by mail can serve as tools to increase access to HCV care and successful HCV treatment completion even after COVID restrictions are lifted.