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Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages. [ABSTRACT FROM AUTHOR]

Abstract In 2020, the European Commission released its Chemicals Strategy for Sustainability towards a Toxic Free Environment (CSS) as part of the European Union’s zero pollution ambition, which is a key commitment of the European Green Deal. One group of substances highlighted in the CSS is persistent, mobile and toxic and very persistent and very mobile (PMT/vPvM) substances. This article focuses on the current, broad European political landscape that applies to PMT/vPvM substances as well as looking into gaps and opportunities within this policy framework. To look at the political landscape, strategies and action plans published in the context of the European Green Deal, as well as a small number of other strategies adopted prior to the European Green Deal, were reviewed. A template was developed to identify actions related to PMT/vPvM substances and the actions were split between the following categories: “Prevent & Reduce”, “Prioritize”, and “Remediation”. Following this, opportunities and gaps were identified.The current overarching strategy governing environmental policy is the European Green Deal which aims to achieve carbon neutrality and zero pollution by 2050. The CSS is the main and most focused Green Deal strategy addressing chemical pollution and uses a hierarchy tailored to chemicals management called the Toxic Free Hierarchy. The potential sources and exposure pathways of PMT/vPvM substances which result in environmental emissions are vast. This has the resultant effect that the relevant legal framework to address PMT/vPvM substances spans policies and legislation with different aims. Broadly, these policies and legislations are related to prevention, minimization/control and remediation, as reflected by the toxic-free hierarchy. There are many gaps and opportunities in the current policy framework which have primarily arisen due to the bold ambition of the CSS and the subsequent introduction of new hazard classes for PMT/vPvM substances. One such gap is related to a lack of harmonization across European Chemicals Policy demonstrated via the Cosmetics Regulation and the Biocidal Products Regulation (BPR) which are currently not aligned. The Cosmetics Regulation does not require a re-evaluation of a substance even in light of new scientific information, whilst the BPR requires new scientific evidence to be considered. In addition, REACH (SVHC criteria) and other legislation using hazard classes for triggering risk management measures (BPR, PPPR, pharmaceutical legislation, Water Framework Directive) may be expected to be revised or are currently being revised based on the new hazard class. The regulation of PMT/vPvM substances is in its infancy. While many EU action plans exhibit gaps and opportunities for chemical regulation as a whole, only certain policies refer to PMT/vPvM substances directly. It is up to policymakers, regulators and academia to highlight those gaps and corresponding emerging windows of opportunity that reflect potential regulatory engagement. The introduction of new hazard classes for PMT/vPvM substances in the Classification, Labelling and Packaging (CLP) regulation provides a first step as these substances are identified, however, regulatory consequences need to be implemented in all other legislation in the future. This will need strong commitment from the European Commission and the EU Member States.

Port-A-Cath (port), a single-lumen, tunneled catheter, is routinely placed into the superior vena cava (SVC) for cancer patients undergoing chemotherapy. We present a case of a port placement in which variant anatomy was discovered during the fluoroscopy-guided procedure and confirmed by venogram of a persistent left-sided SVC (PLSVC). Upon further investigation into the patient's previous computed tomography (CT) scans, the diagnosis was further confirmed. Patients with PLSVC are typically asymptomatic; however, some are associated with increased congenital heart defects (CHD), which increase the risk for complications during invasive procedures. Diagnosing PLSVCs and knowing the clinical implications/complications can improve patient care; by not removing catheters unnecessarily and being prepared to treat/minimize complications.

Background: Persistent truncus arteriosus is a rare congenital cyanotic heart defect characterized by a single ventricular outflow tract. Without surgical intervention, it has a poor prognosis in infancy. Here, we report an adult female patient with uncorrected truncus arteriosus type I, who presented with acute-onset abdominal pain due to torsion of a small bowel gastrointestinal stromal tumor (GIST). Case Report: A 41-year-old woman came to our Emergency Department with acute-onset lower abdominal pain for 2 days. Congenital heart disease, truncus arteriosus, had been diagnosed at birth, and there had been no surgical intervention. Abdominal computed tomography revealed a 10×9×12-cm mixed-density mass in the pelvic capacity. Transthoracic echocardiography revealed a 33-mm ventricular septal defect. The ascending aorta originated mainly from the right ventricle, and the pulmonary artery originated from the beginning of the aorta (type I truncus arteriosus, according to Collett and Edwards classification). After a quick and detailed preoperative workup, the patient underwent tumor resection by open surgery with general anesthesia. Conclusions: This is the first case to report emergency surgery for a patient with uncorrected persistent truncus arteriosus due to torsion of a small bowel GIST. A multidisciplinary team with deep understanding of the disease entity was crucial. By considering the fixed hemodynamic and respiratory physiology, overtreatment and unrealistic goals were avoided. Eventually, the patient was discharged after being hospitalized for 2 weeks. [ABSTRACT FROM AUTHOR]

Preschool screening of attention-deficit/hyperactivity disorder (ADHD) has been found too inaccurate to be clinically useful. This may be due to the known instability of ADHD symptoms from preschool onwards, and the use of a single screening only. We hypothesized that by identifying a group of children with persistent ADHD from preschool to school age and repeating the screening, the clinical usefulness of screening would increase. This study is part of the prospective longitudinal, population-based Norwegian Mother, Father and Child Cohort Study, with a diagnostic parent interview at 3.5 years and follow-up with parent questionnaires at ages 5 and 8 years (n = 707). We identified a group classified with ADHD at all three time points (persistent ADHD). We then used the Child Behavior Checklist ADHD DSM-oriented scale at ages 3.5 and 5 years to investigate the accuracies of single- and two-stage screening at different thresholds to identify children with persistent ADHD. About 30% of the children were classified with ADHD at least once across time (at ages 3.5, 5, and/or 8 years), but only 4% (n = 30) had persistent ADHD. At all thresholds, the two-stage screening identified children with persistent ADHD more accurately than single screening, mainly due to a substantial reduction in false positives. Only a small group of children were classified with persistent ADHD from preschool to school age, underlining that future screening studies should distinguish this group from those with fluctuating symptoms when estimating screening accuracies. We recommend a two-stage screening process to reduce false positives. [ABSTRACT FROM AUTHOR]

Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS‐CoV‐2 infection in immunocompromised patients, particularly in the management of persistent SARS‐CoV‐2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti‐CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS‐CoV‐2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance. [ABSTRACT FROM AUTHOR]

Objective: To determine the predictors for chronic and/or persistent immune thrombocytopenia (ITP) among children with newly diagnosed ITP. Methods: Ours was a mixed-design study (prospective: January 2020 to March 2022 and retrospective: January 2014 to December 2019), wherein we enrolled children, aged 1 month to 18 years presenting with newly diagnosed ITP. Results: Of the 64 enrolled participants, 58 were followed up for atleast 1-year duration and 6 children were followed up for 3 to 12 months' duration. The median (IQR) age of the cohort was 8 (5, 11) years with a female preponderance (62.5%). Wet bleeding was seen in 56%; 6.25% developed intracranial bleeding. 67.2% (43/64) and 41.4% (24/58) children developed persistent and chronic ITP, respectively. Of the 34 children who achieved complete response at 12-months follow up, 21 (62%) achieved complete response by 3 months and the rest achieved complete response over the next 9 months. Development of overall response (complete or partial) at 3 and 12 months, was associated with a higher absolute lymphocyte count (ALC) at admission. The median ALC (×103/µL) at admission was 3.77 and 2.87 in children who had overall response and no response at 3 months, respectively (P = 0.03). The median ALC (×103/µL) at admission was 3.99 and 2.96 in children who had overall response and no response at 12 months, respectively (P = 0.04). Response rate was lesser in the treated group by approximately 10% compared to the non-treated group. Conclusion: The rate of chronicity and intracranial bleeding in our cohort is more than the reported rates in literature. Higher ALC was found to be associated with response. [ABSTRACT FROM AUTHOR]

Although surgical release of upper extremity nerve compression syndromes is highly effective, persistence or recurrence of symptoms and signs may occur. Thorough investigation is necessary in this situation before treatment is recommended. If the symptoms cannot be explained by other pathology than compression of the affected nerve and if conservative management has not provided improvement, reoperation may be considered. This review provides an overview of the diagnostic and surgical considerations in the revision of carpal tunnel syndrome, cubital tunnel syndrome and thoracic outlet syndrome. Level of evidence: V [ABSTRACT FROM AUTHOR]

Background: Persistent, mobile and toxic (PMT), or very persistent and very mobile (vPvM) substances are a wide class of chemicals that are recalcitrant to degradation, easily transported, and potentially harmful to humans and the environment. Due to their persistence and mobility, these substances are often widespread in the environment once emitted, particularly in water resources, causing increased challenges during water treatment processes. Some PMT/vPvM substances such as GenX and perfluorobutane sulfonic acid have been identified as substances of very high concern (SVHCs) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. With hundreds to thousands of potential PMT/vPvM substances yet to be assessed and managed, effective and efficient approaches that avoid a case-by-case assessment and prevent regrettable substitution are necessary to achieve the European Union's zero-pollution goal for a non-toxic environment by 2050. Main: Substance grouping has helped global regulation of some highly hazardous chemicals, e.g., through the Montreal Protocol and the Stockholm Convention. This article explores the potential of grouping strategies for identifying, assessing and managing PMT/vPvM substances. The aim is to facilitate early identification of lesser-known or new substances that potentially meet PMT/vPvM criteria, prompt additional testing, avoid regrettable use or substitution, and integrate into existing risk management strategies. Thus, this article provides an overview of PMT/vPvM substances and reviews the definition of PMT/vPvM criteria and various lists of PMT/vPvM substances available. It covers the current definition of groups, compares the use of substance grouping for hazard assessment and regulation, and discusses the advantages and disadvantages of grouping substances for regulation. The article then explores strategies for grouping PMT/vPvM substances, including read-across, structural similarity and commonly retained moieties, as well as the potential application of these strategies using cheminformatics to predict P, M and T properties for selected examples. Conclusions: Effective substance grouping can accelerate the assessment and management of PMT/vPvM substances, especially for substances that lack information. Advances to read-across methods and cheminformatics tools are needed to support efficient and effective chemical management, preventing broad entry of hazardous chemicals into the global market and favouring safer and more sustainable alternatives. [ABSTRACT FROM AUTHOR]

In 2020, the European Commission released its Chemicals Strategy for Sustainability towards a Toxic Free Environment (CSS) as part of the European Union's zero pollution ambition, which is a key commitment of the European Green Deal. One group of substances highlighted in the CSS is persistent, mobile and toxic and very persistent and very mobile (PMT/vPvM) substances. This article focuses on the current, broad European political landscape that applies to PMT/vPvM substances as well as looking into gaps and opportunities within this policy framework. To look at the political landscape, strategies and action plans published in the context of the European Green Deal, as well as a small number of other strategies adopted prior to the European Green Deal, were reviewed. A template was developed to identify actions related to PMT/vPvM substances and the actions were split between the following categories: "Prevent & Reduce", "Prioritize", and "Remediation". Following this, opportunities and gaps were identified.The current overarching strategy governing environmental policy is the European Green Deal which aims to achieve carbon neutrality and zero pollution by 2050. The CSS is the main and most focused Green Deal strategy addressing chemical pollution and uses a hierarchy tailored to chemicals management called the Toxic Free Hierarchy. The potential sources and exposure pathways of PMT/vPvM substances which result in environmental emissions are vast. This has the resultant effect that the relevant legal framework to address PMT/vPvM substances spans policies and legislation with different aims. Broadly, these policies and legislations are related to prevention, minimization/control and remediation, as reflected by the toxic-free hierarchy. There are many gaps and opportunities in the current policy framework which have primarily arisen due to the bold ambition of the CSS and the subsequent introduction of new hazard classes for PMT/vPvM substances. One such gap is related to a lack of harmonization across European Chemicals Policy demonstrated via the Cosmetics Regulation and the Biocidal Products Regulation (BPR) which are currently not aligned. The Cosmetics Regulation does not require a re-evaluation of a substance even in light of new scientific information, whilst the BPR requires new scientific evidence to be considered. In addition, REACH (SVHC criteria) and other legislation using hazard classes for triggering risk management measures (BPR, PPPR, pharmaceutical legislation, Water Framework Directive) may be expected to be revised or are currently being revised based on the new hazard class. The regulation of PMT/vPvM substances is in its infancy. While many EU action plans exhibit gaps and opportunities for chemical regulation as a whole, only certain policies refer to PMT/vPvM substances directly. It is up to policymakers, regulators and academia to highlight those gaps and corresponding emerging windows of opportunity that reflect potential regulatory engagement. The introduction of new hazard classes for PMT/vPvM substances in the Classification, Labelling and Packaging (CLP) regulation provides a first step as these substances are identified, however, regulatory consequences need to be implemented in all other legislation in the future. This will need strong commitment from the European Commission and the EU Member States. [ABSTRACT FROM AUTHOR]

Simple Summary: Persistent infection with high-risk HPV is the main cause of cervical cancer. However, the changes in epigenetics and viral load (VL) during persistent HPV infection are not well understood. This study selected individuals with a persistent HPV infection but without developing high-grade cervical lesions, analyzed the changes in PAX1/JAM3 methylation and VL according to the duration of HPV infection, and found that in women with HPV infections persisting for more than 3 years, there is a notable increase in the methylation levels of PAX1/JAM3, which could be used as cumulative evidence of persistent HPV infection before the occurrence of precancerous lesions. HPV infection persisting for more than 3 years is more likely to be associated with vaginal lesions, and HPV VL could be used as an indicative biomarker for concurrent cervical–vaginal lesions, which might be helpful to provide a clinical perspective for monitoring and intervention of individuals with persistent HPV infection. The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People's Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical–vaginal lesions, especially for HPV other than 16/18 genotypes. [ABSTRACT FROM AUTHOR]

Persistent pneumothorax is a life-threatening complication that can occur after congenital cardiac surgery. Traditional treatment such as chest tube drainage may not be effective in managing this condition. This study presents a new minimally invasive method for treating persistent pneumothorax using platelet-rich plasma–fibrin glue (PRP–FG). The method has been successful in treating postoperative chylothorax in previous studies, and its use has decreased morbidity, mortality, and hospital stay in chylothorax patients. Ten patients with persistent pneumothorax following cardiothoracic surgery (3 TAPVC, 2 d-TGA, 2 VSD + IAA,1 TRUNCUS + TAPVC, 1 VSD + COA, 1 GLENN), who did not respond to conservative management, underwent treatment with PRP–FG. Follow-up was done for a period of 1–4 years. The age and diagnoses of pneumothorax after surgery were 85.5 ± 36.0 days and 62.4 ± 34.3 h, respectively. Persistent pneumothorax of 8 patients (80%) was cured completely after PRP–FG injection. PRP–FG therapy was failed in two patients who died. All cured patients had a normal life without any complications during follow-up. After PRP–FG injection, 3 patients stopped bubbling at one-time injection, 3 patients stopped bubbling at two-time injection, and 2 patients stopped bubbling at three-time injection. Two patients died during treatment; in these cases, one-time injections were done which was not successful. Persistent pneumothorax after congenital–cardiac surgery can be treated successfully with PRP–FG. This bedside minimal-invasive procedure may significantly decrease the morbidity and mortality rate. Further research is needed to confirm the efficacy of this promising treatment through multicentre clinical trials. [ABSTRACT FROM AUTHOR]

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, including their polymicrobial biofilms, and, moreover, kills S. aureus persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for S. aureus after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy—including ability to reduce persistent and resistant microbial populations—farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges. [ABSTRACT FROM AUTHOR]

Chronic hand eczema (CHE) is persistent inflammatory dermatitis that may significantly affect the quality of life, with psychosocial effects, impact on school, work, and leisure activities, influence on socioeconomic status, and high health care costs. Pediatric-CHE (P-CHE) has a high prevalence yet has not been extensively studied in children and adolescents. There is minimal published data on P-CHE in North America, and no specific management guidelines. Limited prevalence data show broad ranges (0.9%-4.4%) in preschool and school children, with 1 study stating up to 10.0% 1-year prevalence for ages 16 to 19 years. Atopic dermatitis and allergic contact dermatitis appear important in the pathogenesis of this disease process, although there is limited pediatric data assessing disease associations and no standardized methodology for evaluating this disorder. Given the potential life-changing consequences of P-CHE, further research into this disease process is warranted to help generate best therapeutic practices and minimize this disease process' morbidity in adulthood.

AimsNo prior study has been adequately powered to evaluate real-world safety outcomes in those receiving adjunctive ablation lesions beyond pulmonary vein isolation (PVI). We sought to evaluate characteristics and in-hospital complications among patients undergoing PVI with and without adjunctive lesions.Methods and resultsPatients in the National Cardiovascular Data Registry AFib Ablation Registry undergoing first-time atrial fibrillation (AF) ablation between 2016 and 2020 were identified and stratified into paroxysmal (PAF) and persistent AF, and separated into PVI only, PVI + cavotricuspid isthmus (CTI) ablation, and PVI + adjunctive (superior vena cava isolation, coronary sinus, vein of Marshall, atypical atrial flutter lines, other). Adjusted odds of adverse events were calculated using multivariable logistic regression. A total of 50 937 patients [PAF: 30 551 (60%), persistent AF: 20 386 (40%)] were included. Among those with PAF, there were no differences in the adjusted odds of complications between PVI + CTI or PVI + adjunctive when compared with PVI only. Among persistent AF, PVI + adjunctive was associated with a higher risk of any complication [3.0 vs. 4.5%, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.07-1.58] and major complication (0.8 vs. 1.4%, OR 1.56, 95% CI 1.10-2.21), while no differences were observed in PVI + CTI compared with PVI only. Overall, there was high heterogeneity in adjunctive lesion type, and those receiving adjunctive lesions had a higher comorbidity burden.ConclusionAdditional CTI ablation was common without an increased risk of complications. Adjunctive lesions other than CTI are commonly performed in those with more comorbidities and were associated with an increased risk of complications in persistent AF, although the current analysis is limited by high heterogeneity in adjunctive lesion set type.

A superconducting joint for multi-filamentary Bi2Sr2Ca2Cu3O10+ δ (Bi2223) tape, which has applications in nuclear magnetic resonance and magnetic resonance imaging, has been developed based on incongruent melting and multi-junction methods. In this study, the critical current limit, optimal oxygen annealing conditions, and reproducibility of this joint are experimentally evaluated. The results indicate that the critical current limit of the joint at 77 K is determined by that of the tape. The critical current limit was estimated to be about 40 A. Additional oxygen annealing after heat treatment below 1143 K. appears to have no effect on the critical current, and that above 1153 K slightly increases the critical current. It is found that the multi-junction method effectively increases the reproducibility of obtaining a high critical current. To obtain a high critical current at 77 K, the highest temperature in the joint creation process should be lowered to near the incongruent melting temperature of Bi2223 (about 1133 K in air). Two Bi2223 coils, each with one joint (four junctions), were prepared and their persistent current at 77 K was tested. A persistent current of above 20 A was measured with a resistance of about 10 pΩ. [ABSTRACT FROM AUTHOR]

Post-mastectomy pain syndrome (PMPS) is a type of chronic postsurgical pain that can be severe, debilitating and frequently encountered in clinical practice. Multiple studies have focused on prevention, identifying risk factors and treating this condition. Nonetheless, PMPS remains a complex condition to treat effectively. In this case report, we describe the use of percutaneous electrical nerve stimulation in a breast cancer patient who experienced PMPS refractory to conventional treatments. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Initial antibiotics for true Staphylococcus epidermidis bacteremia include vancomycin or linezolid, but if bacteremia persists, consideration should be made for salvage combination therapy regimes such as daptomycin with ceftaroline. [ABSTRACT FROM AUTHOR]

Carpal tunnel release (CTR) is the most performed surgery of the upper extremity. It is effective but not without complications. This state-of-the-art review covers most common intra- and postoperative complications after CTR. As endoscopic carpal tunnel release (ECTR) has developed over time, severe complications, such as nerve lesions, have diminished. ECTR still has a higher risk on transient nerve lesions. Open CTR on the other hand has a higher incidence of wound-related problems, including scar tenderness, irrespective of incision used. Most complications, such as pillar pain and infection, are ill-defined in the literature, leaving the exact incidence unknown and proposing challenges in treatment. The same is true for failure of treatment. Optimizing the length and location of incisions has played a vital role in reducing intra- and postoperative complications in CTR. It is expected that technical advances, such as ultrasound-guided percutaneous carpal tunnel release, will continue to play a role in the future. Level of evidence: V. [ABSTRACT FROM AUTHOR]

Background and Objectives: Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods: This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results: In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00–1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm2/m2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm2/m2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm2/m2 (HR 4.28, 95% CI 1.50–12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions: In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed. [ABSTRACT FROM AUTHOR]

ABSTRACT A comprehensive pangenomic approach was employed to analyze the genomes of 75 type II methylotrophs spanning various genera. Our investigation revealed 256 exact core gene families shared by all 75 organisms, emphasizing their crucial role in the survival and adaptability of these organisms. Additionally, we predicted the functionality of 12 hypothetical proteins. The analysis unveiled a diverse array of genes associated with key metabolic pathways, including methane, serine, glyoxylate, and ethylmalonyl-CoA (EMC) metabolic pathways. While all selected organisms possessed essential genes for the serine pathway, Methylooceanibacter marginalis lacked serine hydroxymethyltransferase (SHMT), and Methylobacterium variabile exhibited both isozymes of SHMT, suggesting its potential to utilize a broader range of carbon sources. Notably, Methylobrevis sp. displayed a unique serine-glyoxylate transaminase isozyme not found in other organisms. Only nine organisms featured anaplerotic enzymes (isocitrate lyase and malate synthase) for the glyoxylate pathway, with the rest following the EMC pathway. Methylovirgula sp. 4MZ18 stood out by acquiring genes from both glyoxylate and EMC pathways, and Methylocapsa sp. S129 featured an A-form malate synthase, unlike the G-form found in the remaining organisms. Our findings also revealed distinct phylogenetic relationships and clustering patterns among type II methylotrophs, leading to the proposal of a separate genus for Methylovirgula sp. 4M-Z18 and Methylocapsa sp. S129. This pangenomic study unveils remarkable metabolic diversity, unique gene characteristics, and distinct clustering patterns of type II methylotrophs, providing valuable insights for future carbon sequestration and biotechnological applications.IMPORTANCEMethylotrophs have played a significant role in methane-based product production for many years. However, a comprehensive investigation into the diverse genetic architectures across different genera of methylotrophs has been lacking. This study fills this knowledge gap by enhancing our understanding of core hypothetical proteins and unique enzymes involved in methane oxidation, serine, glyoxylate, and ethylmalonyl-CoA pathways. These findings provide a valuable reference for researchers working with other methylotrophic species. Furthermore, this study not only unveils distinctive gene characteristics and phylogenetic relationships but also suggests a reclassification for Methylovirgula sp. 4M-Z18 and Methylocapsa sp. S129 into separate genera due to their unique attributes within their respective genus. Leveraging the synergies among various methylotrophic organisms, the scientific community can potentially optimize metabolite production, increasing the yield of desired end products and overall productivity.

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. MAIN OUTCOME MEASURES: Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year 2. RESULTS: Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P = 0.002), and was 65.0 and 67.4, respectively (P = 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P = 0.006) and change (4.3 vs. 8.1; P = 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P = 0.004) and changes (2.4 vs. 7.1; P = 0.009). Predominantly persistent intraretinal fluid through year 2 was associated with a higher 2-year risk of scar development (adjusted hazard ratio = 1.49; P = 0.03). CONCLUSIONS: Approximately one quarter of eyes had PP-IRF through year 2. Predominantly persistent intraretinal fluid through year 1 was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA. Predominantly persistent intraretinal fluid through year 2 was independently associated with worse long-term VA and scar development.

Pascal Owusu-Agyemang,1,2 Lei Feng,3 Juan P Cata1,2 1Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA; 3Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Pascal Owusu-Agyemang, Department of Anesthesiology and Perioperative Medicine, the University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0401, Houston, TX, 77030, USA, Tel + 1 832 465 8964, Email poagyemang@mdanderson.orgPurpose: Sustained opioid use is a well-known complication after surgery. Our objective was to determine whether there is any association between a patient’s race or ethnicity and the sustained use of opioids in the year following surgery. Opioid use over the initial 3, 6, and 12 postoperative months was categorized as “sustained early”, persistent, and chronic, respectively.Patients and Methods: Single-institution retrospective study of adults (≥ 18 years) who had undergone open abdominal surgery for cancer. Multivariable logistic regression was used to evaluate the association between race/ethnicity and opioid use.Results: Of the 3523 patients included in the study, 2543 (72.2%) were non-Hispanic (NH) White, 476 (13.5%) were Hispanic or Latino, 262 (7.4%) were NH-Black, 186 (5.3%) were Asian, and 56 (1.6%) belonged to other racial or ethnic groups. The overall rates of sustained early, persistent, and chronic opioid use were 15.9%, 7.1%, and 2.6%, respectively. In the multivariable analysis, patient race/ethnicity was associated with sustained early postoperative opioid use (p-value=0.037), with Hispanics/Latinos having significantly higher odds than NH-Whites (OR = 1.382 [95% CI: 1.057– 1.808]; p = 0.018). However, neither persistent nor chronic opioid use was associated with race/ethnicity (p = 0.697 and p = 0.443, respectively).Conclusion: In this retrospective study of adults who had undergone open abdominal surgery, patient race/ethnicity was not consistently associated with the development of sustained opioid use over the first 12 postoperative months.Keywords: race, ethnicity, persistent, chronic, opioids, cancer

Background: Approximately 50%–90% of children with immediate‐type cow's milk allergy (CMA) acquire tolerance by pre‐school age. We aimed to investigate the acquisition rate of CMA tolerance in children aged 6–12 years. Methods: We included children with CMA who persisted until the age of 6. Tolerance was defined as passing an oral food challenge with 200 mL of unheated cow's milk (CM) or consuming 200 mL of CM without symptoms, whereas persistent CMA was defined as fulfilling neither of these criteria by 12 years old. Children receiving oral immunotherapy (OIT) were excluded from the primary analysis. Risk factors associated with persistent CMA were assessed using Cox regression analysis. Results: Of 80 included children, 30 (38%) had previous CM anaphylaxis, and 40 (50%) had eliminated CM completely from their diet. The median CM‐specific immunoglobulin E (sIgE) level at 6 years old was 12.0 kUA/L. Tolerance was acquired by 25 (31%) and 46 (58%) children by the age of 9 and 12 years, respectively. At baseline, persistent CMA was associated with higher CM‐sIgE levels (hazard ratio 2.29, 95% confidence interval 1.41–3.73, optimal cutoff level 12.7 kUA/L), previous CM anaphylaxis (2.07, 1.06–4.02), and complete CM elimination (3.12, 1.46–6.67). No children with CMA who had all three risk factors (n = 14) acquired tolerance. Conclusion: Except for OIT patients, more than half of children with CMA at 6 years old acquired tolerance by 12 years old. Children with CMA who have the risk factors are less likely to acquire tolerance. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate the prevalence of headaches and back pain after regional anesthesia compared to general anesthesia. Methods: Cross-sectional studies involving 100 patients who were admitted at Department of Anesthesia, Mamata Medical College, Khammam and had undergone CS were included in the study. Results: Our study was made up of 100 participants who have done a CS under the two types of anesthesia. Mean age of patients was 30.5 with a SD of 6.80. Youngest individual was 17 years old while the oldest was 50 years old. Mean height was 162.38 cm, shortest patient was 130 cm while the longest was 160. Average weight was 73 kg, biggest weight was 104 kg while the smallest weight was 50 kg. Mean BMI values were 28.32 kg/m², largest BMI value was 38.66 kg/m² while the smallest value was 22.04 kg/m². As for the most commonly used anesthesia type, spinal anesthesia was the most common with 79 (79%) patients, while general anesthesia was used only in 21 (21%) patients Fentanyl was the most common anesthetic used in surgery, it was used in 15 (15%) patients followed by fentanyl with dolozal/peptidin, which was used in 12 (12%) patients. As for analgesics used after surgery, intravenous paracetamol was the most commonly used (24 patients, 24%), followed by sodium diclofinac and ketozor (2 patients, 2%). There was also no correlation between occurrence of headache and anesthesia type, as patients who had headaches and undergone general surgery. Conclusion: Our study has shown that there's no link between the anesthetic procedure and occurrence of back pain and headaches, even though most of the participants have gotten regional anesthesia. [ABSTRACT FROM AUTHOR]

Key Clinical Message Initial antibiotics for true Staphylococcus epidermidis bacteremia include vancomycin or linezolid, but if bacteremia persists, consideration should be made for salvage combination therapy regimes such as daptomycin with ceftaroline.

The continued spread of African swine fever (ASF) in Eurasia remains a global problem for the world pig industry. The disease is characterized by high mortality (up to 100 %) and acute course - domestic and wild animals die within the first two weeks after infection. However, active surveillance on ASF in Eastern Europe had been showing regular detection of seropositive susceptible animals, especially among wild boar populations which may indicate chronic, asymptomatic infection and even the survival of individual animals. At the same time, the persistence of the virus in the wild boar population creates constant risks of sporadic outbreaks of ASF in infected areas, and the infection can become endemic. The aim of the study was a systematic review of the available data on seroprevalence among wild boars in relation to the possible establishment of ASF endemicity in Eurasia. In these animals, there was a change in the dynamics of the disease, which is manifested by self-sustaining cycles of infection. Seropositive wild boars are being found in the Baltic countries, Hungary, Poland, Romania, Slovakia, and Russia. Seroprevalence rates among wild boars hunted in ASF-infected areas of European countries range from 0.3 to 3.8 %. In the Baltic countries, the number of seropositive samples from wild boars exceeds the number of samples positive for ASF virus in polymer chain reaction (PCR). A similar trend persists in those regions where the ASF virus has been present for a long time (Poland, Lithuania, Latvia, Estonia), which may indicate the endemic nature of ASF. In the Russian Federation, ASF-endemic territories in the wild have not yet been registered, although isolated cases of seropositive wild boars have been detected in some regions since 2013. In the future, in order to understand the dynamics of the disease in the wild, it is necessary to conduct a comprehensive diagnosis of the ASF virus genome and antibodies in wild boar samples, which eventually will allow choosing the right strategy to combat ASF.

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, including their polymicrobial biofilms, and, moreover, kills S. aureus persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for S. aureus after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy—including ability to reduce persistent and resistant microbial populations—farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges.

The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People’s Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical–vaginal lesions, especially for HPV other than 16/18 genotypes.

Nawara Sakpuwadol, Sarawin Harnchoowong, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Poonkiat Suchonwanit, Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand, Tel +66-2-2011141, Fax +66-2-201-1211 Ext 4, Email poonkiat@hotmail.comAbstract: Pretibial pruritic papular dermatitis (PPPD) is a distinctive skin disorder in response to persistent pretibial manipulation. Clinically, it manifests as multiple discrete, pruritic, flesh-colored-to-erythematous papules and plaques confined to the pretibial area. The histological hallmark of PPPD comprises irregular epidermal psoriasiform hyperplasia with parakeratosis and spongiosis, dermal fibrosis, and lymphohistiocytic infiltration. Due to its rarity and underrecognition, the prevalence and standard treatment of the disease have yet to be well elucidated. Here, we present a case of PPPD in a 60-year-old female presenting with numerous pruritic, erythematous-to-brownish papules and plaques on bilateral pretibial areas for 1.5 years. The lesions were significantly improved after 1 month of additional treatment with oral pentoxifylline. In this report, we aim to raise awareness in recognizing PPPD since it manifests unique clinical, dermoscopic, and histological features, representing pretibial skin’s response to chronic rubbing. In addition, we proposed a novel effective therapy for the disease using pentoxifylline.Keywords: persistent, pruritus, rubbing, shin, varicosity, venous insufficiency

Resetting in stochastic systems is defined in different ways. In this research, a 1D non-Markovian random walk is considered. In this process, the reset changes the dynamics in a way where the random walker, after losing its memory, goes back to a fixed point in space and starts again. In this study we investigate time evolution and also the long-time limit of displacement moments in the presence of resetting. Our calculations in the long-time limit show that the probability distribution function for displacement reaches a steady-state. On the other hand, this distribution never gets to a Gaussian form for any values of the resetting rate. We will show that, in contrast to the case where the process does not undergo resetting, the moments accumulate to finite values. This is confirmed by doing Monte Carlo simulations.

AIM: To describe a case of aqueous misdirection complicated by subsequent persistent choroidal effusions following implantation of a Preserflo MicroShunt (PMS) device to treat advanced closed angle glaucoma. METHODS: A 67-year-old caucasian female with advanced primary angle-closure glaucoma on four medications with an intraocular pressure (IOP) of 26 mm Hg was listed for a PMS insertion with mitomycin C (MMC). RESULTS: Past ocular history was significant for pseudophakia and previous yttrium aluminum garnet (YAG) peripheral iridotomy. Surgery was uneventful but on the first postoperative day, she developed aqueous misdirection complicated by subsequent development of persistent uveal effusions. Conventional treatment strategies including atropine drops, YAG hyaloidotomy and choroidal effusion drainage proved ineffective. A combination of oral steroids and pars plana vitrectomy (PPV) along with an irido-zonulo-hyloidectomy (IZH) proved efficacious. CONCLUSION: To the best of the author's knowledge, this is the first published case of aqueous misdirection complicated with the presence of significant, unresolving choroidal effusions, highlighting the possibility and sequelae of comorbid pathology in nanophthalmic eyes.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been responsible for the initiation of the global pandemic since 2020. The virus spreads through contaminated air particles, fomite, and surface-contaminated porous (i.e., paper, wood, and masks) and non-porous (i.e., plastic, stainless steel, and glass) materials. The persistence of viruses on materials depends on porosity, adsorption, evaporation, isoelectric point, and environmental conditions, such as temperature, pH, and relative humidity. Disinfection techniques are crucial for preventing viral contamination on animated and inanimate surfaces. Currently, there are few effective methodologies for preventing SARS-CoV-2 and other coronaviruses without any side effects. Before infection can occur, measures must be taken to prevent the persistence of the coronavirus on the surfaces of both porous and non-porous inanimate materials. This review focuses on coronavirus persistence in surface materials (inanimate) and control measures. Viruses are inactivated through chemical and physical methods; the chemical methods particularly include alcohol, chlorine, and peroxide, whereas temperature, pH, humidity, ultraviolet irradiation (UV), gamma radiation, X-rays, ozone, and non-thermal, plasma-generated reactive oxygen and nitrogen species (RONS) are physical methods. [ABSTRACT FROM AUTHOR]

7 b Scores from 5 to 17 are considered positive as indicated in the ESCD patch test guideline.[1] Six weeks after patch testing, the patient presented with a pruritic papulovesicular reaction on sites of the positive patch test reactions to doxepin hydrochloride tablet 0.01 pet. and 0.01% aq. (Figure 2A-C). Patch testing with doxepin in aqua and strong/extreme positive patch test reactions to doxepin even at 0.01% in pet. and aq. were other unique features. Keywords: allergic contact dermatitis; aqua; case report; deposition; dilution series; doxepin; long-lasting; patch test; persistent; skin accumulation EN allergic contact dermatitis aqua case report deposition dilution series doxepin long-lasting patch test persistent skin accumulation 209 212 4 08/04/23 20230901 NES 230901 Doxepin is a tricyclic antidepressant drug with potent H1- and H2-antihistaminic properties. [Extracted from the article]

Objective: To investigate the correlation between various co-morbidities of COVID-19 patients with persistent PCR positivity in hospitalized patients. Study Design: Prospective Observational. Setting: Nishtar Medical University, Multan COVID Isolation Wards, and ICU. Period: 15 September 2020 to 14 September 2021. Material & Methods: The study sample included 162 hospitalized patients who underwent COVID-19 PCR testing at admission, 4 weeks, and 8 weeks, and their comorbidities data were collected. Multiple regression analysis was performed to determine the relationship between co-morbidities and COVID-19 PCR positivity. Results: Among 162 patients, seventy-nine (48.8%) were male and the mean age of the patients was 53.46±15.81 years. Out of 162 patients, 70 (43.2%) tested positive for COVID-19, while 92 (56.8%) tested negative. Among 70 patients who had positive PCR, 45(64.28%) patients had prolonged positive PCR (at 4 weeks) and out of 45, 29 (64.45%) again remained positive at 8 weeks. While carrying out the multiple linear regression, the results indicated that the presence of hypertension, diabetes, and lung disease was positively associated with persistent COVID-19 PCR positivity (at 4 and 8 weeks). However, no significant association was found between persistent COVID-19 PCR positivity and liver disease, malignancy, and ischemic heart disease. Conclusion: The study highlights the importance of considering co-morbidities like diabetes, hypertension, and lung disease, in predicting persistent COVID-19 PCR positivity in hospitalized patients. Further research is needed to confirm these findings and investigate the underlying mechanisms of these associations. [ABSTRACT FROM AUTHOR]

Individuals with prolonged or frequent episodes account for a disproportionate share of the burden of depression. However, there are surprisingly few data on whether individuals at risk for developing chronic–intermittent depression (CID) as opposed to briefer, infrequent depressive episodes (time-limited depression [TLD]) can be distinguished before their first depressive episode. We followed a community sample of 465 never-depressed females on five occasions from age 14 to 20 years and examined whether 18 preonset clinical and psychosocial variables prospectively predicted CID. The CID group accounted for 40% of depressed cases but 84% of the cumulative time depressed in the sample. Participants with CID (n = 60) exhibited significantly higher preonset levels of 16 of the 18 risk factors than the never-depressed group (n = 315). The TLD group (n = 90) had significantly higher preonset levels of nine risk factors than never-depressed participants. Finally, the CID group had significantly higher levels of nine risk factors than the TLD group, five of which were similar in TLD and never-depressed participants. These findings indicate that differences between CID and TLD are evident before onset and suggest that the liability to CID may be both greater than, and somewhat different from, the liability to TLD. Moreover, they suggest that individuals at risk for a malignant course of depression can be targeted for prevention and early intervention. General Scientific Summary: A minority of individuals with a chronic–intermittent course account for a disproportionate share of the burden of depression. However, there are few data on whether they can be distinguished from individuals who will develop more time-limited depressions (TLDs) before the onset of the disorder. We identified a number of preonset variables that distinguished individuals who later developed chronic–intermittent depression (CID) from those who developed TLD. Moreover, individuals who developed TLD did not differ from those who remained depression-free on some of these predictors, suggesting that the liability to CID may be both stronger and somewhat different than the liability to TLD. [ABSTRACT FROM AUTHOR]

Study Design.: Prospective pharmacoepidemiologic study. Objective.: To investigate clinical and sociodemographic factors associated with persistent opioid use in the years following spine surgery among patients with persistent opioid use preceding lumbar spine surgery. Summary of Background Data.: It is unknown whether successful spine surgery leads to a cessation of preoperative persistent opioid use. Materials and Methods.: Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked for patients operated for degenerative lumbar spine disorders between 2007 and 2017. The primary outcome measure was persistent opioid use in the second year after surgery. Functional disability was measured with the Oswestry Disability Index (ODI). Factors associated with persistent opioid use in the year before, and two years following, surgery were identified using multivariable logistic regression analysis. The variables included in the analysis were selected based on their demonstrated role in prior studies. Results.: The prevalence of persistent opioid use was 8.7% in the year before surgery. Approximately two-thirds of patients also met the criteria for persistent opioid use the second year after surgery. Among patients who did not meet the criteria for persistent opioid use the year before surgery, 991 (3.3%) patients developed persistent opioid use in the second year following surgery. The strongest association was exhibited by high doses of benzodiazepines in the year preceding surgery (OR 1.7, 95% CI 1.26 to 2.19, P <0.001). Among patients without persistent opioid use, the most influential factor associated with new-onset persistent opioid use in the second year after surgery was the use of high doses of benzodiazepines (OR 1.8, 95% CI 1.26 to 2.44, P <0.001), high doses of z -hypnotics (OR 2.6, 95% CI 2.10 to 3.23, P <0.001) and previous surgery at the same lumbar level (OR 1.37, 95% CI 1.11 to 1.68, P =0.003). Conclusion.: A substantial proportion of patients reported sustained opioid use after surgery. Patients with persistent opioid use before surgery should be supported to taper off opioid treatment. Special efforts appear to be required to taper off opioid use in patients using high doses of benzodiazepines. Level of Evidence.: 2; Prospective observational study. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent/persistent primary hyperparathyroidism in patients who have undergone previous parathyroidectomy is a challenging condition. Imaging is important for localizing the parathyroid adenoma for re-exploration and 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) seems ideal for this purpose. Aim: This prospective study attempted to ascertain the utility of 18F-FCH PET/CT as an investigation in preoperative localization of abnormal parathyroid tissue in recurrent/persistent primary hyperparathyroidism while comparing it with 99mTc-Sestamibi dual-phase scintigraphy with early single-photon emission CT (SPECT)/CT and neck ultrasonography (USG). Methods: Twenty patients with biochemical features of recurrent/persistent primary hyperparathyroidism were enrolled into this study. They underwent neck USG, 99mTc-Sestamibi dual-phase scintigraphy with early SPECT/CT and 18F-FCH PET/CT for localization of parathyroid lesions. Six patients underwent surgical resection of the detected lesions, 3 were awaiting surgery, and 11 were managed conservatively. One patient died due to COVID. Results: The calculated positive predictive values on a per-lesion basis of neck USG, 99mTc-sestamibi scintigraphy and early SPECT/CT and 18F-FCH PET/CT in the cohort of the 5 operated patients were 75% (3/4), 71.4% (5/7), and 71.4% (5/7), respectively. On a per-patient basis, the lesion detection rate was 100% for 99mTc-sestamibi scan and FCH PET (5/5) and 80% on neck USG (4/5). Conclusion: 18F-FCH PET/CT is a highly accurate imaging modality for the detection of parathyroid lesions in patients with recurrent/persistent primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

Background and Objectives: Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods: This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results: In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00–1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm2/m2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm2/m2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm2/m2 (HR 4.28, 95% CI 1.50–12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions: In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed.

Introduction: Though autologous blood patch (ABP) pleurodesis is widely used in adults, its use in children is uncommon, with only one reported in a neonate thus far. Here, we report a late-preterm neonate with persistent air leak and concurrent Aspergillus infection, who was successfully treated with ABP, and we review the literature on pleurodesis. Case report: A late-preterm baby girl born at 35 weeks of gestation was referred with respiratory distress since birth. She required intubation and high-frequency oscillatory ventilation (HFOV) as she did not respond to conventional ventilation. On day 2 of life (D2), she developed left pneumothorax and, on D3, right pneumothorax, requiring intercostal chest tube drains (ICDs). The child was extubated on D14, and the right ICD was removed on D18. However, the left pneumothorax persisted. Computerized tomography revealed right-sided consolidation and pneumatoceles, and persistent left pneumothorax. ABP was done on D23 and D25, with resolution of pneumothorax and removal of ICD on D27. Concurrently, pleural fluid cultures done on D16, D23 and D25 grew Aspergillus terreus, which was treated with voriconazole. The child is well at 3 months follow-up. Conclusion: ABP for persistent pneumothorax is a safe, easy and inexpensive bedside procedure. Though its therapeutic role is well established in adults and older children, its use in neonates, especially in preemies, is less explored. The results are satisfactory, and it may be a feasible alternative to surgery when used in select neonates.

Background: Diarrheal disease is heterogeneous, including watery diarrhea (WD) and dysentery, some cases of which become persistent diarrhea (PD). Changes in risk over time necessitate updated knowledge of these syndromes in sub-Saharan Africa. Methods: The Vaccine Impact on Diarrhea in Africa (VIDA) study was an age-stratified, case-control study of moderate-to-severe diarrhea among children <5 years old in The Gambia, Mali, and Kenya (2015–2018). We analyzed cases with follow-up of about 60 days after enrollment to detect PD (lasting ≥14 days), examined the features of WD and dysentery, and examined determinants for progression to and sequelae from PD. Data were compared with those from the Global Enteric Multicenter Study (GEMS) to detect temporal changes. Etiology was assessed from stool samples using pathogen attributable fractions (AFs), and predictors were assessed using χ2 tests or multivariate regression, where appropriate. Results: Among 4606 children with moderate-to-severe diarrhea, 3895 (84.6%) had WD and 711 (15.4%) had dysentery. PD was more frequent among infants (11.3%) than in children 12–23 months (9.9%) or 24–59 months (7.3%), P =.001 and higher in Kenya (15.5%) than in The Gambia (9.3%) or Mali (4.3%), P <.001; the frequencies were similar among children with WD (9.7%) and those with dysentery (9.4%). Compared to children not treated with antibiotics, those who received antibiotics had a lower frequency of PD overall (7.4% vs 10.1%, P =.01), and particularly among those with WD (6.3% vs 10.0%; P =.01) but not among children with dysentery (8.5% vs 11.0%; P =.27). For those with watery PD, Cryptosporidium and norovirus had the highest AFs among infants (0.16 and 0.12, respectively), while Shigella had the highest AF (0.25) in older children. The odds of PD decreased significantly over time in Mali and Kenya while increasing significantly in The Gambia. Conclusions: The burden of PD endures in sub-Saharan Africa, with nearly 10% of episodes of WD and dysentery becoming persistent. This report updates our knowledge of the risk factors and etiology associated with persistent diarrhea and dysentery. We demonstrate that both persistent and bloody diarrhea remain serious problems with distinct etiology, presentation, and outcomes among sub-Saharan African infants. [ABSTRACT FROM AUTHOR]

Pre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD patients, we identified a de novo missense variant, PBX1:c.551G>C p.R184P, in a patient with tetralogy of Fallot with absent pulmonary valve and extra-cardiac phenotypes. Functional analysis of this variant by creating a CRISPR-Cas9 gene-edited mouse model revealed multiple congenital anomalies. Congenital heart defects (persistent truncus arteriosus and ventricular septal defect), hypoplastic lungs, hypoplastic/ectopic kidneys, aplastic adrenal glands and spleen, as well as atretic trachea and palate defects were observed in the homozygous mutant embryos at multiple stages of development. We also observed developmental anomalies in a proportion of heterozygous embryos, suggestive of a dominant mode of inheritance. Analysis of gene expression and protein levels revealed that although Pbx1 transcripts are higher in homozygotes, amounts of PBX1 protein are significantly decreased. Here, we have presented the first functional model of a missense PBX1 variant and provided strong evidence that p.R184P is disease-causal. Our findings also expand the phenotypic spectrum associated with pathogenic PBX1 variants in both humans and mice.