Analysis of schizophrenia-associated genetic markers in the HLA region as risk factors for tardive dyskinesia.

OBJECTIVES: The pathology of Tardive Dyskinesia (TD) has yet to be fully understood, but there have been proposed hypotheses for the cause of this condition. Our team previously reported a possible association of TD with the Complement Component C4 gene in the HLA region. In this study, we explored the HLA region further by examining two previously identified schizophrenia-associated HLA-region single-nucleotide polymorphisms (SNPs), namely rs13194504 and rs210133. METHODS: The SNPs rs13194504 and rs210133 were tested for association with the occurrence and severity of TD in a sample of 172 schizophrenia patients who were recruited for four studies from three different clinical sites in Canada and USA. RESULTS: The rs13194504 AA genotype was associated with decreased severity for TD as measured by Abnormal Involuntary Movement Scale (AIMS) scores (p = 0.047) but not for TD occurrence. SNP rs210133 was not significantly associated with either TD occurrence or AIMS scores. CONCLUSION: Our findings suggest that the rs13194504 AA genotype may play a role in TD severity, while SNP rs210133 may not have a major role in the risk or severity of TD.

Long-term outcomes of COVID-19 survivors with hospital AKI: association with time to recovery from AKI.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) patients who develop in-hospital acute kidney injury (AKI) have worse short-term outcomes, their long-term outcomes have not been fully characterized. We investigated 90-day and 1-year outcomes after hospital AKI grouped by time to recovery from AKI. METHODS: This study consisted of 3296 COVID-19 patients with hospital AKI stratified by early recovery (<48 hours), delayed recovery (2-7 days) and prolonged recovery (>7-90 days). Demographics, comorbidities and laboratory values were obtained at admission and up to the 1-year follow-up. The incidence of major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE), rehospitalization, recurrent AKI and new-onset chronic kidney disease (CKD) were obtained 90-days after COVID-19 discharge. RESULTS: The incidence of hospital AKI was 28.6%. Of the COVID-19 patients with AKI, 58.0% experienced early recovery, 14.8% delayed recovery and 27.1% prolonged recovery. Patients with a longer AKI recovery time had a higher prevalence of CKD (P < .05) and were more likely to need invasive mechanical ventilation (P < .001) and to die (P < .001). Many COVID-19 patients developed MAKE, recurrent AKI and new-onset CKD within 90 days, and these incidences were higher in the prolonged recovery group (P < .05). The incidence of MACE peaked 20-40 days postdischarge, whereas MAKE peaked 80-90 days postdischarge. Logistic regression models predicted 90-day MACE and MAKE with 82.4 ± 1.6% and 79.6 ± 2.3% accuracy, respectively. CONCLUSION: COVID-19 survivors who developed hospital AKI are at high risk for adverse cardiovascular and kidney outcomes, especially those with longer AKI recovery times and those with a history of CKD. These patients may require long-term follow-up for cardiac and kidney complications.

Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review.

PURPOSE: Cold-stored platelets (CSP) are an increasingly active topic of international research. They are maintained at 1-6 °C, in contrast to standard room-temperature platelets (RTP) kept at 20-24 °C. Recent evidence suggests that CSP have superior hemostatic properties compared with RTP. This narrative review explores the application of CSP in adult cardiac surgery, summarizes the preclinical and clinical evidence for their use, and highlights recent research. SOURCE: A targeted search of MEDLINE and other databases up to 24 February 2022 was conducted. Search terms combined concepts such as cardiac surgery, blood, platelet, and cold-stored. Searches of trial registries ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were included. Articles were included if they described adult surgical patients as their population of interest and an association between CSP and clinical outcomes. References of included articles were hand searched. PRINCIPAL FINDINGS: When platelets are stored at 1-6 °C, their metabolic rate is slowed, preserving hemostatic function for increased storage duration. Cold-stored platelets have superior adhesion characteristics under physiologic shear conditions, and similar or superior aggregation responses to physiologic agonists. Cold-stored platelets undergo structural, metabolic, and molecular changes which appear to "prime" them for hemostatic activity. While preliminary, clinical evidence supports the conduct of trials comparing CSP with RTP for patients with platelet-related bleeding, such as those undergoing cardiac surgery. CONCLUSION: Cold-stored platelets may have several advantages over RTP, including increased hemostatic capacity, extended shelf-life, and reduced risk of bacterial contamination. Large clinical trials are needed to establish their potential role in the treatment of acutely bleeding patients.

RéSUMé: OBJECTIF: Les plaquettes conservées au froid (PCF) sont un sujet de recherche internationale de plus en plus populaire. Ces plaquettes sont maintenues à une température de 1-6 °C, contrairement aux plaquettes standard conservées à température ambiante (PTA), maintenues à 20­24 °C. Des données probantes récentes suggèrent que les PCF ont des propriétés hémostatiques supérieures aux PTA. Ce compte rendu narratif explore l'application de PCF en chirurgie cardiaque chez l'adulte, résume les données probantes précliniques et cliniques de leur utilisation, et met en évidence les recherches récentes. SOURCES: Une recherche ciblée dans MEDLINE et d'autres bases de données jusqu'au 24 février 2022 a été effectuée. Les termes de recherche combinaient des concepts en anglais tels que cardiac surgery, blood, platelet et cold-stored (soit chirurgie cardiaque, plaquette, et entreposage frigorifique). Des recherches dans les registres d'études ClinicalTrials.gov et le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS ont été incluses. Les articles ont été inclus s'ils décrivaient des patient·es adultes de chirurgie en tant que population d'intérêt et une association entre les PCF et les issues cliniques. Les références des articles inclus ont fait l'objet d'une recherche manuelle. CONSTATATIONS PRINCIPALES: Lorsque les plaquettes sont conservées entre 1 et 6 °C, leur taux métabolique est ralenti, préservant la fonction hémostatique pour une durée d'entreposage accrue. Les plaquettes conservées au froid ont des caractéristiques d'adhésion supérieures dans des conditions de cisaillement physiologique et des réponses d'agrégation similaires ou supérieures aux agonistes physiologiques. Les plaquettes conservées au froid subissent des changements structurels, métaboliques et moléculaires qui semblent les « amorcer ¼ pour une activité hémostatique. Bien que préliminaires, les données probantes cliniques appuient la réalisation d'études comparant les PCF aux PTA chez la patientèle présentant des saignements liés aux plaquettes, tels que les personnes bénéficiant d'une chirurgie cardiaque. CONCLUSION: Les plaquettes conservées au froid peuvent présenter plusieurs avantages par rapport aux PTA, notamment une capacité hémostatique accrue, une durée de conservation prolongée et un risque réduit de contamination bactérienne. De grands essais cliniques sont nécessaires pour établir leur rôle potentiel dans le traitement de la patientèle en hémorragie aiguë.

Profiles of Burnout and Response to the COVID-19 Pandemic Among General Surgery Residents at a Large Academic Training Program.

BACKGROUND: COVID-19 has placed demands on General Surgery residents, who are already at high risk of burnout. This study examined the pandemic's impact on burnout and wellness among General Surgery residents at a large training program. METHODS: General Surgery residents at our institution completed a survey focused on self-reported burnout, mental health, perceptions of wellness resources, and changes in activities during the pandemic. Burnout was measured using the Maslach Burnout Inventory (MBI). Unsupervised machine learning (k-means clustering) was used to identify profiles of burnout and comparisons between profiles were made. RESULTS: Of 82 eligible residents, 51 completed the survey (62% response rate). During COVID-19, 63% of residents had self-described burnout, 43% had depression, 18% acknowledged binge drinking/drug use, and 8% had anxiety. There were no significant differences from pre-pandemic levels (p all >.05). Few residents perceived available wellness resources as effective (6%). Based on MBI scores, the clustering analysis identified three clusters, characterized as "overextended", "engaged", and "ineffective". Engaged residents had the least concerning MBI scores and were significantly more likely to exercise, retain social contact during the pandemic, and had less self-reported anxiety or depression. Research residents were overrepresented in the ineffective cluster (46%), which had high rates of self-reported burnout (77%) and was characterized by the lowest personal accomplishment scores. Rates of self-reported burnout for overextended and engaged residents were 73% and 48%, respectively. CONCLUSION: Surgical residents have high rates of self-reported burnout and depression during the COVID-19 pandemic. Clusters of burnout may offer targets for individualized intervention.

Long-term survival in elderly women receiving chemotherapy for non-metastatic breast cancer: a population-based analysis.

BACKGROUND: Older women are poorly represented in trials evaluating chemotherapy for breast cancer (BC). This study aimed to describe survival and associated factors among elderly women receiving chemotherapy for non-metastatic BC. METHODS: This was a population-based cohort study including women ≥ 70 years old diagnosed with invasive, non-metastatic BC from 2010 to 2017 in SEER. Among those who received chemotherapy, overall survival (OS) was determined using Kaplan-Meier curves and hazard ratios were reported with 95% confidence intervals (CIs). Adjustment was made for available confounders. Co-morbidity is not available in SEER. BC-specific survival (BCSS) and subdistribution hazard ratios were determined using competing risks analysis. RESULTS: The cohort consisted of 109,239 women aged 70+, of whom 17,961 (16%) received chemotherapy. Chemotherapy patients were younger (median 73.0 years vs. 77.0), had more advanced disease (25% stage III vs. 5.2%), and were more likely to receive mastectomy (50% vs. 33%). Among chemotherapy patients, 5-year OS was 77.8% (95% CI 76.9-78.6%), and for women 80+ was 60.2% (95% CI 57.5-63.1%). More recent diagnoses, no previous history of cancer, and receipt of radiotherapy were all associated with improved BCSS. Conversely, older age, higher tumour grade, advanced stage, and human epidermal growth factors receptor (HER)2 negative tumours were associated with worse BCSS. 56% of deaths were due to BC, and women aged 80+ had worse BCSS compared to those aged 70-79 (adjusted sdHR 1.62, 95% CI 1.43-1.84). CONCLUSIONS: Elderly women with advanced disease can achieve good survival after chemotherapy for non-metastatic BC. Those with HER2+ disease have superior survival, reinforcing benefit in this population.

Longitudinal prediction of hospital-acquired acute kidney injury in COVID-19: a two-center study.

BACKGROUND: To investigate the temporal characteristics of clinical variables of hospital-acquired acute kidney injury (AKI) in COVID-19 patients and to longitudinally predict AKI onset. METHODS: There were 308 hospital-acquired AKI and 721 non-AKI (NAKI) COVID-19 patients from Stony Brook Hospital (New York, USA) data, and 72 hospital-acquired AKI and 303 NAKI COVID-19 patients from Tongji Hospital (Wuhan, China). Demographic, comorbidities, and longitudinal (3 days before and 3 days after AKI onset) clinical variables were used to compute odds ratios for and longitudinally predict hospital-acquired AKI onset. RESULTS: COVID-19 patients with AKI were more likely to die than NAKI patients (31.5% vs 6.9%, adjusted p < 0.001, OR = 4.67 [95% CI 3.1, 7.0], Stony Brook data). AKI developed on average 3.3 days after hospitalization. Procalcitonin was elevated prior to AKI onset (p < 0.05), peaked, and remained elevated (p < 0.05). Alanine aminotransferase, aspartate transaminase, ferritin, and lactate dehydrogenase peaked the same time as creatinine, whereas D-dimer and brain natriuretic peptide peaked a day later. C-reactive protein, white blood cell and lymphocyte showed group differences - 2 days prior (p < 0.05). Top predictors were creatinine, procalcitonin, white blood cells, lactate dehydrogenase, and lymphocytes. They predicted AKI onset with areas under curves (AUCs) of 0.78, 0.66, and 0.56 at 0, - 1, and - 2 days prior, respectively. When tested on the Tongji Hospital data, the AUCs were 0.80, 0.79, and 0.77, respectively. CONCLUSIONS: Time-locked longitudinal data provide insight into AKI progression. Commonly clinical variables reasonably predict AKI onset a few days prior. This work may lead to earlier recognition of AKI and treatment to improve clinical outcomes.

Preoperative carbohydrate loading before colorectal surgery: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Preoperative carbohydrate loading has been introduced as a component of many enhanced recovery after surgery programs. Evaluation of current evidence for preoperative carbohydrate loading in colorectal surgery has never been synthesized. METHODS: MEDLINE, Embase, and CENTRAL were searched until May 2021. Randomized controlled trials (RCTs) comparing patients undergoing colorectal surgery with and without preoperative carbohydrate loading were included. Primary outcomes were changes in blood insulin and glucose levels. A pairwise meta-analysis was performed using inverse variance random effects. RESULTS: The search yielded 3656 citations, from which 12 RCTs were included. In total, 387 patients given preoperative carbohydrate loading (47.2% female, age: 62.0 years) and 371 patients in control groups (49.4% female, age: 61.1 years) were included. There was no statistical difference for blood glucose and insulin levels between both patient groups. Patients receiving preoperative carbohydrate loading experienced a shorter time to first flatus (SMD: - 0.48 days, 95% CI: - 0.84 to - 0.12, p = 0.008) and stool (SMD: - 0.50 days, 95% CI: - 0.86 to - 0.14, p = 0.007). Additionally, length of stay was shorter in the preoperative carbohydrate loading group (SMD: - 0.51 days, 95% CI: - 0.88 to - 0.14, p = 0.007). There was no difference in postoperative morbidity and patient well-being between both groups. CONCLUSIONS: Preoperative carbohydrate loading does not significantly impact postoperative glycemic control in patients undergoing colorectal surgery; however, it may be associated with a shorter length of stay and faster return of bowel function. It merits consideration for inclusion within colorectal enhanced recovery after surgery protocols.

In-hospital predictors of post-stroke depression for targeted initiation of Selective Serotonin Reuptake Inhibitors (SSRIs).

BACKGROUND: Although SSRIs are no longer widely prescribed for post-stroke motor recovery, fluoxetine demonstrated beneficial effects on post-stroke depression (PSD). Given the potential side effects of SSRIs, targeted initiation among individuals at highest risk for PSD warrants consideration. While previous studies have identified stroke severity and psychiatric history as factors associated with PSD, its predictability remains unknown. In this study, we investigate inpatient predictive factors to better identify individuals who might derive the most benefit from targeted initiation of SSRIs. METHODS: We performed a retrospective analysis of a prospectively-collected registry of adult patients presenting with acute ischemic stroke to a tertiary referral urban academic comprehensive stroke center between 2016-2020. Patients were seen 4-6 weeks post-discharge and administered the PHQ-9 (Patient Health Questionnaire-9) to screen for PSD (PHQ-9 ≥ 5). Demographics, history of depression, stroke severity, and inpatient PHQ-9 scores were abstracted. Logistic regression was used to determine factors associated with PSD and an ROC analysis determined the predictability of PSD in the inpatient setting. RESULTS: Three hundred seven individuals were administered the PHQ-9 at follow-up (mean age 65.5 years, 52% female). History of depression (OR = 4.11, 95% CI: 1.65-10.26) and inpatient PHQ-9 score (OR = 1.17, 95% CI: 1.06-1.30) were significantly associated with PSD. Stroke severity, marital status, living alone, employment, and outpatient therapy were not associated with PSD. The ROC curve using a positive inpatient PHQ-9 achieved an area under the curve (AUC) of 0.65 (95% CI: 0.60-0.70), while the AUC was 0.72 (95% CI: 0.66-0.77) after adding history of depression. CONCLUSIONS: History of depression and a positive inpatient PHQ-9 appear to be most strongly predictive of long-term PSD. Initiating SSRIs only in those individuals at highest risk for PSD may help reduce the burden of stroke recovery in this targeted population while minimizing adverse side effects.

Diagnostic Accuracy of Ankle-Brachial Pressure Index Compared with Doppler Arterial Waveforms for Detecting Peripheral Arterial Disease: A Systematic Review.

GENERAL PURPOSE: To present the results of a research study evaluating the diagnostic accuracy of the ankle-brachial pressure index (ABPI) compared with that of Doppler arterial waveforms (DAWs) to detect peripheral arterial disease (PAD). TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing education activity, the participant will:1. Summarize the evidence the authors considered when comparing the diagnostic accuracy of the ABPI with that of Doppler arterial waveforms to detect PAD.2. Select the characteristics of the participants in the studies the authors analyzed.3. Identify the results of the authors' study comparing the diagnostic accuracy of the ABPI with that of Doppler arterial waveforms to detect PAD.4. Distinguish the authors' conclusions about the advantages of using Doppler arterial waveforms to detect PAD.

Although the ankle-brachial pressure index (ABPI) is a useful tool for the noninvasive assessment of peripheral arterial disease (PAD), it has several limitations necessitating alternative noninvasive diagnostic tools. This study assesses the diagnostic accuracy of ABPI compared with Doppler arterial waveforms (DAWs) to detect PAD. The authors searched Embase and MEDLINE for original studies that reported sensitivities and specificities for both the ABPI and DAW. Four studies were included representing 657 patients (58.8% men) with a mean age of 63.4 years. The authors detected overall higher sensitivities using DAW compared with ABPI but higher specificities with ABPI compared with DAW. In conclusion, because of the higher sensitivity and lower specificity of DAW compared with ABPI, the authors recommend DAW as a potential screening tool for PAD. To confirm these results, larger sample sizes and comparative trials with homogeneous reference standards and patient populations are required. In addition, DAW is not easily documented for everyday bedside practice in the community. With COVID-19 restrictions, an audible handheld Doppler signal may act as a reproducible equivalent to DAW and thus facilitate timely, safe application of compression therapy at point-of-care.

Drugs associated with development of porokeratosis: A systematic review.

Porokeratosis is a rare disorder characterized by atrophic macules or patches, with a well-defined ridge-like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug-induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug-induced porokeratosis in MEDLINE and Embase in June 2020. After full-text review, 25 studies were included for analysis. We identified 26 patients with drug-induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large-scale studies are required to confirm our findings and further explore the pathogenesis for drug-induced porokeratosis.

Schizophrenia-associated gene dysbindin-1 and tardive dyskinesia.

Tardive dyskinesia (TD) is a potentially irreversible movement disorder observed following long-term antipsychotic exposure. Its cause is unknown; however, a genetic component has been supported by studies of affected families. Dysbindin-1, encoded by the dystrobrevin-binding protein 1 DTNBP1 gene, has been associated with schizophrenia and is potentially involved in dopamine neurotransmission through its regulation of dopamine release and dopamine D2 receptor recycling, making it a candidate for investigation in TD. We investigated common variants across the DTNBP1 gene in our schizophrenia/patients with schizoaffective disorder of European ancestry. We found a number of DTNBP1 three-marker haplotypes to be associated with TD occurrence and TD severity (p < 0.05). These preliminary findings, if replicated in larger independent samples, would suggest that drugs targeting dysbindin-1 may be an option in the prevention and treatment of TD.

The Incidence and Prevalence of Uveitis in Psoriasis: A Systematic Review and Meta-Analysis.

BACKGROUND: The systemic effects and comorbidities of psoriasis include ocular disorders, such as uveitis. Patients with psoriatic arthritis in particular have been demonstrated to have an elevated risk for developing uveitis. Presently, the risk of uveitis in psoriasis has yet to be fully elucidated and this systematic review seeks to address this gap. OBJECTIVE: To examine the prevalence and incidence of uveitis in psoriasis patients compared to non-psoriasis patients. METHODS: We conducted a systematic review search on MEDLINE, Embase, and CENTRAL electronic databases with no lower limit on year of publication. RESULTS: Fourteen articles met our inclusion criteria, with a total of 234 143 psoriasis subjects. Two studies found that participants with severe psoriasis were at a greater risk of uveitis than those with mild psoriasis. A random-effects meta-analysis of the 3 studies, which reported risk of incidence of uveitis in psoriasis patients compared to non-psoriasis controls, found a pooled risk ratio of 1.29 (95% CI, 1.10-1.51), indicating an increased risk of uveitis in psoriasis. Three studies compared risk of uveitis in psoriatic arthritis with psoriasis-only participants, all finding that psoriatic arthritis was associated with a greater risk of uveitis. CONCLUSIONS: In summary, our findings suggest that psoriasis is associated with an increased risk of uveitis, with or without psoriatic arthritis.

BiGG Models: A platform for integrating, standardizing and sharing genome-scale models.

Genome-scale metabolic models are mathematically-structured knowledge bases that can be used to predict metabolic pathway usage and growth phenotypes. Furthermore, they can generate and test hypotheses when integrated with experimental data. To maximize the value of these models, centralized repositories of high-quality models must be established, models must adhere to established standards and model components must be linked to relevant databases. Tools for model visualization further enhance their utility. To meet these needs, we present BiGG Models (http://bigg.ucsd.edu), a completely redesigned Biochemical, Genetic and Genomic knowledge base. BiGG Models contains more than 75 high-quality, manually-curated genome-scale metabolic models. On the website, users can browse, search and visualize models. BiGG Models connects genome-scale models to genome annotations and external databases. Reaction and metabolite identifiers have been standardized across models to conform to community standards and enable rapid comparison across models. Furthermore, BiGG Models provides a comprehensive application programming interface for accessing BiGG Models with modeling and analysis tools. As a resource for highly curated, standardized and accessible models of metabolism, BiGG Models will facilitate diverse systems biology studies and support knowledge-based analysis of diverse experimental data.

Incidence, characteristics, and risk factors of new liver disorders 3.5 years post COVID-19 pandemic in the Montefiore Health System in Bronx.

PURPOSE: To determine the incidence of newly diagnosed liver disorders (LD) up to 3.5-year post-acute COVID-19, and risk factors associated with new LD. METHODS: We analyzed 54,699 COVID-19 patients and 1,409,547 non-COVID-19 controls from March-11-2020 to Jan-03-2023. New liver disorders included abnormal liver function tests, advanced liver failure, alcohol and non-alcohol related liver disorders, and cirrhosis. Comparisons were made with ambulatory non-COVID-19 patients and patients hospitalized for other lower respiratory tract infections (LRTI). Demographics, comorbidities, laboratory data, incomes, insurance status, and unmet social needs were tabulated. The primary outcome was new LD at least two weeks following COVID-19 positive test. RESULTS: Incidence of new LD was not significantly different between COVID-19 and non-COVID-19 cohorts (incidence:1.99% vs 1.90% p>0.05, OR = 1.04[95%CI: 0.92,1.17], p = 0.53). COVID-19 patients with new LD were older, more likely to be Hispanic and had higher prevalence of diabetes, hypertension, chronic kidney disease, and obesity compared to patients without new LD. Hospitalized COVID-19 patients had no elevated risk of LD compared to hospitalized LRTI patients (2.90% vs 2.07%, p>0.05, OR = 1.29[0.98,1.69], p = 0.06). Among COVID-19 patients, those who developed LD had fewer patients with higher incomes (14.18% vs 18.35%, p<0.05) and more with lower incomes (21.72% vs 17.23%, p<0.01), more Medicare and less Medicaid insurance, and more patients with >3 unmet social needs (6.49% vs 2.98%, p<0.001) and fewer with no unmet social needs (76.19% vs 80.42%, p<0.001). CONCLUSIONS: Older age, Hispanic ethnicity, and obesity, but not COVID-19 status, posed increased risk for developing new LD. Lower socioeconomic status was associated with higher incidence of new LD.

Biologic therapies associated with development of palmoplantar pustulosis and palmoplantar pustular psoriasis: a systematic review.

BACKGROUND: Palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) are chronic inflammatory skin conditions characterized by eruptions of sterile pustules on the palms and/or soles. Biologic use has been associated with PPP and PPPP development in the literature. OBJECTIVES: To identify PPP and PPPP associated with biologics and summarize reported treatments and outcomes. METHODS: We systematically searched in MEDLINE and Embase for articles that reported PPP or PPPP during biologic treatment. After a full-text review, 53 studies were included for analysis. RESULTS: We identified 155 patients with PPP/PPPP onset during biologic treatment, with a mean age of 44.1 years and a female preponderance (71.6%). The most frequently reported biologics were adalimumab (43.9%) and infliximab (33.3%). IL-17 inhibitors, secukinumab (7.6%) and brodalumab (1.5%), were reported only in association with PPPP. Overall, 58.8% of patients had complete remission (CR) in 3.6 months and 23.5% had partial remission (PR) in 3.7 months. The most common treatments that led to CR were topical corticosteroids (n = 16) and biologic switching (n = 8). CONCLUSIONS: Clinicians should anticipate PPP or PPPP as potential drug reactions to biologics such as adalimumab and infliximab. Large-scale studies are required to confirm our findings and further explore the pathogenesis for biologic-associated PPP and PPPP.

Incidence of new-onset in-hospital and persistent diabetes in COVID-19 patients: comparison with influenza.

BACKGROUND: This study investigated the incidences and risk factors associated with new-onset persistent type-2 diabetes during COVID-19 hospitalization and at 3-months follow-up compared to influenza. METHODS: This retrospective study consisted of 8216 hospitalized, 2998 non-hospitalized COVID-19 patients, and 2988 hospitalized influenza patients without history of pre-diabetes or diabetes in the Montefiore Health System in Bronx, New York. The primary outcomes were incidences of new-onset in-hospital type-2 diabetes mellitus (I-DM) and persistent diabetes mellitus (P-DM) at 3 months (average) follow-up. Predictive models used 80%/20% of data for training/testing with five-fold cross-validation. FINDINGS: I-DM was diagnosed in 22.6% of patients with COVID-19 compared to only 3.3% of patients with influenza (95% CI of difference [0.18, 0.20]). COVID-19 patients with I-DM compared to those without I-DM were older, more likely male, more likely to be treated with steroids and had more comorbidities. P-DM was diagnosed in 16.7% of hospitalized COVID-19 patients versus 12% of hospitalized influenza patients (95% CI of difference [0.03,0.065]) but only 7.3% of non-hospitalized COVID-19 patients (95% CI of difference [0.078,0.11]). The rates of P-DM significantly decreased from 23.9% to 4.0% over the studied period. Logistic regression identified similar risk factors predictive of P-DM for COVID-19 and influenza. The adjusted odds ratio (0.90 [95% CI 0.64,1.28]) for developing P-DM was not significantly different between the two viruses. INTERPRETATION: The incidence of new-onset type-2 diabetes was higher in patients with COVID-19 than influenza. Increased risk of diabetes associated with COVID-19 is mediated through disease severity, which plays a dominant role in the development of this post-acute infection sequela. FUNDING: None.