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Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery.Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded.Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis.Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p0.001). Older age at cataract diagnosis (HR =1.05, 95% confidence interval [CI] 1.04-1.06, p0.001) or at time of surgery (HR = 1.05, 95% CI 1.03-1.07, p0.001) increased fall risk, as did female sex (HR = 1.29, 95% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95% CI 1.01-1.71, p = 0.046) among nonsurgical patients.Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery.

Immunotherapy is a treatment modality that has a broad and rapidly growing range of applications to treat both chronic and acute diseases, including rheumatoid arthritis, Crohn disease, cancer, and COVID-19. Emergency physicians must be aware of the breadth of applications and be able to consider the effects of immunotherapies when patients on these treatments present to the hospital. This article provides a review of the mechanisms of action, indications for use, and potential complications of immunotherapy treatments that are relevant in the emergency care setting.

Objective To explore the association between measures of obesity and measures of trip-induced fall risk among community-dwelling older adults. Design Case-control. Setting Gait laboratory. Participants Voluntary sample of 55 community-dwelling older adults (aged ≥65y; N=55) with body mass index (BMI) of 18.84-44.68 kg/m2. Interventions Not applicable. Main Outcome Measures Measures of obesity included 6 anthropometry-based measures (BMI; thigh, hip and waist circumferences; ratio of waist-to-hip circumference; index of central obesity) and 4 dual-energy x-ray absorptiometry–based measures (percentage trunk, leg, and total fat; fat mass index). Measures of risk of tripping during overground walking included median and interquartile range of toe clearance and area under the swing phase toe trajectory. Measures of trip recovery after a laboratory-induced trip included trunk angle and angular velocity at ground contact of the first recovery step, anteroposterior distance from stepping foot to center of mass at the same instant, and step time of the first recovery step. Results Risk of tripping was associated with waist-to-hip ratio and thigh circumference. After grouping participants by waist-to-hip ratio, those with high ratios (≥0.9 cm for men and ≥0.85 cm for women) exhibited significantly greater variability in toe clearance. Trip recovery was associated with hip circumference, thigh circumference, fat mass index, and total fat. After grouping participants by fat mass index, those with high indices (>9 kg/m2 for men and >13 kg/m2 for women) exhibited less favorable trunk kinematics after a laboratory-induced trip (Cohen d=0.84). Conclusions Waist-to-hip ratio and fat mass index may more closely relate to trip-induced fall risk than BMI among community-dwelling older adults.

Introduction We present our experience developing and embedding a registry-based module for resident feedback. Methods At our institution, entering operative data into the institutional quality collaborative registry is standard practice. In February 2019, a surgical education module was embedded into the registry to capture procedure-specific resident operative assessments. Faculty engagement with the sugical education module was assessed during its first year in existence (February 2019-February 2020). Results In total, 1074 of 1269 (85%) operative assessments were completed by 27 faculty via the surgical education registry module. Median faculty engagement rate with the module following resident-assisted procedures was 91% [IQR 76%-100%]. Residents received a median of 7 operative assessments [IQR 2-19] over the study period. Conclusion By embedding a surgical education module into an existing surgical quality collaborative registry, procedure-specific operative assessments can be routinely captured.

To determine the preferences and attitudes of members of regional anesthesia societies during the COVID-19 pandemic.We distributed an electronic survey to members of the American Society of Regional Anesthesia and Pain Medicine, Regional Anaesthesia-UK, and the European Society of Regional AnaesthesiaPain Therapy. A questionnaire consisting of 19 questions was developed by a panel of experienced regional anesthesiologists and distributed by email to the participants. The survey covered the following domains: participant information, practice settings, preference for the type of anesthetic technique, the use of personal protective equipment, and oxygen therapy.The survey was completed by 729 participants from 73 different countries, with a response rate of 20.1% (729/3,630) for the number of emails opened and 8.5% (729/8,572) for the number of emails sent. Most respondents (87.7%) identified as anesthesia staff (faculty or consultant) and practiced obstetric and non-obstetric anesthesia (55.3%). The practice of regional anesthesia either expanded or remained the same, with only 2% of respondents decreasing their use compared with the pre-pandemic period. The top reasons for an increase in the use of regional anesthesia was to reduce the need for an aerosol-generating medical procedure and to reduce the risk of possible complications to patients. The most common reason for decreased use of regional anesthesia was the risk of urgent conversion to general anesthesia. Approximately 70% of the responders used airborne precautions when providing care to a patient under regional anesthesia. The most common oxygen delivery method was nasal prongs (cannula) with a surgical mask layered over it (61%).Given the perceived benefits of regional over general anesthesia, approximately half of the members of three regional anesthesia societies seem to have expanded their use of regional anesthesia techniques during the initial surge of the COVID-19 pandemic.RéSUMé: OBJECTIF: Déterminer les préférences et les attitudes des membres des sociétés d’anesthésie régionale pendant la pandémie de COVID-19. MéTHODE: Nous avons distribué un sondage électronique aux membres de l’American Society of Regional Anesthesia and Pain Medicine, de Regional Anesthesia-UK et de l’European Society of Regional AnaesthesiaPain Therapy. Un questionnaire composé de 19 questions a été élaboré par un panel d’anesthésiologistes régionaux d’expérience et distribué par courriel aux participants. Le sondage couvrait les domaines suivants : les renseignements sur les participants, les contextes de pratique, leur préférence quant au type de technique d’anesthésie, l’utilisation d’équipement de protection individuelle et l’oxygénothérapie RéSULTATS: Le sondage a été complété par 729 participants provenant de 73 pays différents, avec un taux de réponse de 20,1 % (729/3630) pour le nombre de courriels ouverts et de 8,5 % (729/8572) pour le nombre de courriels envoyés. La plupart des répondants (87,7 %) se sont identifiés comme anesthésiologistes (académique ou consultant) et pratiquaient l’anesthésie obstétricale et non obstétricale (55,3 %). Leur pratique de l’anesthésie régionale s’est étendue ou est demeurée inchangée, et seulement 2 % des répondants ont indiqué avoir diminué leur utilisation de cette pratique par rapport à la période pré-pandémique. Les principales raisons d’une augmentation de l’utilisation de l’anesthésie régionale étaient de réduire la nécessité d’une intervention médicale générant des aérosols et de réduire le risque de complications potentielles pour les patients. La raison la plus courante de diminution du recours à l’anesthésie régionale était le risque de conversion urgente à une anesthésie générale. Environ 70 % des intervenants ont utilisé des précautions en matière de propagation des aérosols lorsqu’ils procuraient des soins à un patient sous anesthésie régionale. La méthode d’administration d’oxygène la plus fréquemment utilisée était les canules nasales avec un masque chirurgical superposé (61 %). CONCLUSION: Compte tenu des avantages perçus de l’anesthésie régionale par rapport à l’anesthésie générale, environ la moitié des membres de trois sociétés d’anesthésie régionale semblent avoir élargi leur utilisation des techniques d’anesthésie régionale pendant la vague initiale de la pandémie de COVID-19.

The American Society of Anesthesiologists; All India Difficult Airway Association; European Airway Management Society; European Society of Anaesthesiology and Intensive Care; Italian Society of Anesthesiology, Analgesia, Resuscitation and Intensive Care; Learning, Teaching and Investigation Difficult Airway Group; Society for Airway Management; Society for Ambulatory Anesthesia; Society for Head and Neck Anesthesia; Society for Pediatric Anesthesia; Society of Critical Care Anesthesiologists; and the Trauma Anesthesiology Society present an updated report of the Practice Guidelines for Management of the Difficult Airway.

Epithelial cells use the process of extrusion to promote cell death while preserving a tight barrier. To extrude, a cell and its neighbors contract actin and myosin circumferentially and basolaterally to seamlessly squeeze it out of the epithelium. Recent research highlights how early apical pulsatile contractions within the extruding cell might orchestrate contraction in three dimensions so that a cell extrudes out apically. Along with apical constrictions, studies of ion channels and mathematical modeling reveal how differential contraction between cells helps select specific cells to extrude. In addition, several studies have offered new insights into pathways that use extrusion to eliminate transformed cells or cause an aberrant form of extrusion that promotes cell invasion.

Acellular cornea derived hydrogels provide significant advantages in preserving native corneal stromal keratocyte cells and endothelial cells. However, for clinical application, hydrogel physical properties need to be improved, and their role in corneal epithelial wound healing requires further investigation. In this study, an acellular porcine corneal stroma (APCS) hydrogel (APCS-gel) was successfully prepared from 20 mg/ml APCS, demonstrated optimal light transmittance and gelation kinetic properties and retained critical corneal ECM of collagens and growth factors. Compared with fibrin gel, the APCS-gel had a higher porosity ratio and faster nutrition diffusion with an accompanying improvement in the proliferation of primary rabbit corneal epithelial cells (RCECs) and stromal cells (RCSCs). These corneal cell types also displayed improved viability and cellular infiltration. Furthermore, the APCS-gel provides significant advantages in the preservation of RCECs stemness and enhancement of corneal wound healing in vitro and in vivo. After 7 days of culture, 3-4 layers of RCECs were formed on the APCS-gel in vitro, while only 1-2 layers were found on the fibrin gel. More corneal stem/progenitor cell phenotypes (K12-, p63+, ABCG2+) and proliferation phenotypes (Ki67+) were detected on the APCS-gel than fibrin gel. Using a corneal epithelial wound healing model, we also found faster reepithelization in corneas that received APCS-gel compared to fibrin gel. Additionally, our APCS-gel demonstrated better physical and biological properties when compared to Tisseel, a clinically used type of fibrin gel. In conclusion, our APCS-gel provided better corneal epithelial and stromal cell biocompatibility to fibrin gels and due to its transparency and faster gelation time could potentially be superior for clinical purposes. Statement of significance Extracellular matrix (ECM) can be used to provide tissue specific physical microstructure and biochemical cues for tissue regeneration. Here, we produced an ECM hydrogel derived from acellular porcine cornea stroma (APCS-gel) that retained critical biological characteristics of the native tissue and provided significant transparency and fast gelation time. Our data demonstrated that the APCS-gel was superior to clinically used fibrin gel, as the APCS-gel showed high porosity and permeability, better corneal stromal keratocytes infiltration, increased cellular proliferation and retention of corneal epithelial cells stemness. The APCS-gel improved corneal wound healing in vitro and in vivo. This APCS-gel may have clinical utility for corneal diseases, and the more general approach used to make this hydrogel might be used in other tissues.

Introduction Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. Methods Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p

Background and aim Infection is associated with substantial morbidity and mortality in cirrhosis, but presumably, not all infections carry the same risk of mortality. We compared outcomes of different sites of infection in a nationally representative sample of inpatients with cirrhosis. Methods We queried the Nationwide Readmissions Database for patients with cirrhosis from 2011 to 2014. Cirrhosis and infection diagnoses were identified by previously used algorithms of ICD-9 codes. The following infections were compared: urinary tract infection (UTI), pneumonia, cellulitis, spontaneous bacterial peritonitis (SBP), and Clostridium difficile infection (CDI). The primary outcome was inpatient mortality. Secondary outcomes included sepsis, any organ failure, multiple organ failures, and 30-day readmission. Outcomes were analyzed using logistic regression and included a priori covariates. Results A total of 1 798 830 weighted index admissions were identified. Infection was present in 29.2% overall-including UTI (13.7%), pneumonia (8.9%), cellulitis (5.2%), CDI (2.8%), and SBP (2.0%). Mortality was significantly higher in pneumonia (19.6%), SBP (18.6%), and CDI (17.4%) compared with cellulitis (7.6%) and UTI (11.8%). Sepsis, any, and multiple organ failures were most commonly seen in pneumonia, SBP, and CDI. Multivariable analysis demonstrated that pneumonia had the highest associated mortality (odds ratio [OR] 2.73, confidence interval [CI] 2.68-2.80) and multiple organ failures (OR 3.59, CI 3.50-3.68). Significantly increased 30-day readmission was seen only with SBP (24.9%). Conclusions Outcomes of inpatients with cirrhosis vary significantly depending on the type of infection. The severity and epidemiology of infection in cirrhosis appears to be shifting with pneumonia, not SBP, having the highest prevalence of multiple organ failures and inpatient mortality.

Living donor liver transplantation (LDLT) is a vital tool to address the growing organ shortage in the United States caused by increasing numbers of patients diagnosed with end-stage liver disease. LDLT still only makes up a very small proportion of all liver transplantations performed each year, but there are many innovations taking place in the field that may increase its acceptance among both transplant programs and patients. These innovations include ways to improve access to LDLT, such as through nondirected donation, paired exchange, transplant chains, transplant of ABO-incompatible donors, and transplants in patients with high Model for End-Stage Liver Disease scores. Surgical innovations, such as laparoscopic donor hepatectomy, robotic hepatectomy, and portal flow modulation, are also increasingly being implemented. Policy changes, including decreasing the financial burden associated with LDLT, may make it a more feasible option for a wider range of patients. Lastly, center-level behavior, such as ensuring surgical expertise and providing culturally competent education, will help toward LDLT expansion. Although it is challenging to know which of these innovations will take hold, we are already seeing LDLT numbers improve within the past 2 years.

Transversus abdominis release (TAR) is increasingly used to address complex ventral hernias; consequently, associated complications are seen more frequently. Our hernia center has a growing experience with redo-transversus abdominis release (redo-TAR) to address large, complex hernia recurrences after failed TAR. Here, we describe our outcomes after abdominal wall reconstruction with redo-TAR. Adults undergoing elective open, redo-TAR at our institution from January 2015 to February 2021 were queried from a prospectively collected database in the Abdominal Core Health Quality Collaborative. The primary outcome was 30-day wound morbidity. Secondary outcomes were long-term composite hernia recurrence and patient-reported quality of life. Sixty-five patients underwent redo-TAR. Median age was 60 years, 50.8% were female, and median BMI 31.8 kg/m2. Median recurrent hernias were 16 cm wide by 25 cm long. Frequent mechanisms of recurrence included linea semilunaris injury (27.7%), mesh fracture (18.5%), infection (16.9%), and posterior sheath disruption (15.4%). Wound complications occurred in 33.8% and 16.9% required procedural intervention. With median clinical and PRO follow-up of 12 and 19 months, respectively, the composite hernia recurrence rate was 22.5% and patients reported significantly improved quality of life (HerQLes: median + 36.7, PROMIS: median – 9.5). Redo-TAR may be performed as a salvage procedure to reconstruct complex defects after failed TAR, however, in our center, it is associated with increased wound morbidity and fairly high composite recurrence rates. Despite this, patients report improvements in quality of life and pain. Tracking outcomes after TAR will facilitate understanding how to manage its failures.

Noninvasive ultrasound surgery can be achieved using focused ultrasound to locally affect the targeted site without damaging intervening tissues. Mechanical ablation and histotripsy use short and intense acoustic pulses to destroy the tissue via a purely mechanical effect. Here, we show that coupled with low-frequency excitation, targeted microbubbles can serve as mechanical therapeutic warheads that trigger potent mechanical effects in tumors using focused ultrasound. Upon low frequency excitation (250 kHz and below), high amplitude microbubble oscillations occur at substantially lower pressures as compared to higher MHz ultrasonic frequencies. For example, inertial cavitation was initiated at a pressure of 75 kPa for a center frequency of 80 kHz. Low frequency insonation of targeted microbubbles was then used to achieve low energy tumor cell fractionation at pressures below a mechanical index of 1.9, and in accordance with the Food and Drug Administration guidelines. We demonstrate these capabilities in vitro and in vivo. In cell cultures, cell viability was reduced to 16% at a peak negative pressure of 800 kPa at the 250 kHz frequency (mechanical index of 1.6) and to 10% at a peak negative pressure of 250 kPa at a frequency of 80 kHz (mechanical index of 0.9). Following an intratumoral injection of targeted microbubbles into tumor-bearing mice, and coupled with low frequency ultrasound application, significant tumor debulking and cancer cell death was observed. Our findings suggest that reducing the center frequency enhances microbubble-mediated mechanical ablation; thus, this technology provides a unique theranostic platform for safe low energy tumor fractionation, while reducing off-target effects.

PURPOSE: Bioactive substrates can be used therapeutically to enhance wound healing. Here, we evaluated the effect of an in-situ thermoresponsive hydrogel from decellularized porcine cornea ECM, COMatrix (COrnea Matrix), for application as an ocular surface bandage for corneal epithelial defects. METHODS: COMatrix hydrogel was fabricated from decellularized porcine corneas. The effects of COMatrix hydrogel on attachment and proliferation of human corneal epithelial cells (HCECs) were evaluated in vitro. The effect of COMatrix on the expressions of the inflammatory genes, IL-1β, TNF-α, and IL-6 was assessed by RT-PCR. The in-situ application and also repairing effects of COMatrix hydrogel as an ocular bandage was studied in a murine model of corneal epithelial wound. The eyes were examined by optical coherence tomography (OCT) and slit-lamp microscopy in vivo and by histology and immunofluorescence post-mortem. RESULTS: In vitro, COMatrix hydrogel significantly enhanced the attachment and proliferation of HCECs relative to control. HCECs exposed to COMatrix had less induced expression of TNF-α (P

Millions of young children undergo surgery and anesthesia each year, yet there is a lack of scientific consensus about the safety of anesthesia exposure for the developing brain. Also poorly understood is parental anesthesia-related decision-making and how neurotoxicity information influences their choices. The theoretical model of parental decision-making generated in this research explicates this process. Interviews with 24 mothers yielded a theoretical framework based on their narratives developed using a qualitative grounded theory analysis. Five major themes emerged from these interviews: emotional processing, cognitive processing, relationships as resources, the mother/child dyad, and the health care context. Mothers described a non-linear, iterative process; they moved fluidly through emotional and cognitive processing supported by relationships as resources and influenced by the health care context. A key element was the subtheme of the medical translator, an individual who provided context and information. The mother/child dyad grounded the model in the relationship with the child.

Chlorhexidine is an antimicrobial agent widely used for infection prevention in medical settings. Nevertheless, allergic reactions ranging from mild to severe have been reported following its use. In this review, we analyzed all case reports published between the introduction of chlorhexidine and the end of 2019 for allergic responses associated with the use of medical devices and or other medical products containing chlorhexidine (CHX) to ascertain the prevalence of severe CHX allergic reactions and what practices might best mitigate those risks.In total, 77 publications containing 124 reported cases of allergic reactions were grouped into 3 product categories, catheters, semisolids, and fluid products. The country, type of reaction, route of sensitization, allergy confirmation, and intervention or mitigation was extracted for each case. Overall, 30 cases were associated with catheters, 46 cases were associated with semisolid products, and 48 cases were associated with the use of other medical products. Severe cases were managed with intravenous fluids, steroids, and epinephrine (adrenaline). None of the reported cases were fatal. The allergy risks can be mitigated by better warning and training clinicians and by recording and screening patient histories for CHX presensitization from prior exposure. For patients undergoing pre-use blood tests, IgE antibody screens can also be performed. Finally, as a precaution in the event a rare severe allergic reaction occurs, procedure carts and rooms can be prestocked with injectable epinephrine and other rapidly acting anti-inflammatory medications.

Introduction Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB. Results Of the NVAF population (n = 466,991), 33.4% (n = 155,959) had multimorbidity, including 36,921 apixaban, 10,248 dabigatran, 45,509 rivaroxaban, and 63,281 warfarin patients. Compared to warfarin, apixaban and rivaroxaban were associated with a lower risk of stroke/SE (hazard ratio [HR] 0.63, 95% CI 0.54–0.74; HR 0.70, 95% CI 0.64–0.77, respectively). Apixaban and dabigatran were associated with a lower risk of MB (HR 0.61, 95% CI 0.56–0.67; HR 0.75, 95% CI 0.66–0.86, respectively) and rivaroxaban was associated with a higher risk of MB (HR 1.06, 95% CI 1.01–1.12) compared to warfarin. Conclusions Among patients with NVAF and six or more comorbid conditions, NOACs were associated with varying risk of stroke/SE and MB compared to warfarin and to each other. Rather than a “one drug fits all” approach, our results may be useful for appropriate OAC treatment for multimorbid patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01724-8.

Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1–3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases, including cancer1,5. The mechanisms that drive cell extrusion remain incompletely understood. Here, to analyse cell extrusion by Caenorhabditis elegans embryos3, we conducted a genome-wide RNA interference screen, identified multiple cell-cycle genes with S-phase-specific function, and performed live-imaging experiments to establish how those genes control extrusion. Extruding cells experience replication stress during S phase and activate a replication-stress response via homologues of ATR and CHK1. Preventing S-phase entry, inhibiting the replication-stress response, or allowing completion of the cell cycle blocked cell extrusion. Hydroxyurea-induced replication stress6,7 triggered ATR–CHK1- and p53-dependent cell extrusion from a mammalian epithelial monolayer. We conclude that cell extrusion induced by replication stress is conserved among animals and propose that this extrusion process is a primordial mechanism of cell elimination with a tumour-suppressive function in mammals. A cell-cycle checkpoint triggers the extrusion of both nematode and mammalian cells experiencing replication stress.

We present long-term combined results of two clinical trials implementing R-MACLO-IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM-MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM-MCL2 ClinicalTrials.gov identifier NCT00878254) received rituximab (375 mg/m2 IV weekly × 4, repeated every 6 months for 3 years). Considering all 44 patients, 41 (93.2%) achieved complete response (CR), two (4.5%) partial response (PR), and one (2.3%) was not evaluated for response. With a median follow up of 7.2 years (range < 1 month to 16 years), the 5-year progression-free survival (PFS) was 55.6% (95% CI: 38.9%-69.4%) and median PFS 7.9 years (95% CI: 3.7-11 years). The 5-year OS was 83.3% (95% CI: 68.1%-91.7%) and median OS was not reached. Patients with blastic variant (n = 6) had a 5-year PFS and OS of 20.8% and 60%, respectively. Myelosuppression was the most common adverse event during immunochemotherapy. Long-term treatment-related mortality was 6.8%. Note, R-MACLO-IVAM followed by maintenance therapy is an effective regimen to induce long-term remission in MCL without need for consolidation with ASCT.

Corneal wound healing depends on extracellular matrix (ECM) and topographical cues that modulate migration and proliferation of regenerating cells. In our study, silk films with either flat or nanotopography patterned parallel ridge widths of 2000, 1000, 800 nm surfaces were combined with ECMs which include collagen type I (collagen I), fibronectin, laminin, and Poly-d-Lysine to accelerate corneal wound healing. Silk films with 800 nm ridge width provided better cell spreading and wound recovery than other size topographies. Coating 800 nm patterned silk films with collagen I proves to optimally further increased mouse and rabbit corneal epithelial cells growth and wound recovery. This enhanced cellular response correlated with redistribution and increase in size and total amount of focal adhesion. Transcriptomics and signaling pathway analysis suggested that silk topography regulates cell behaviors via actin nucleation ARP-WASP complex pathway, which regulate filopodia formation. This mechanism was further explored and inhibition of Cdc42, a key protein in this pathway, delayed wound healing and decreased the length, density, and alignment of filopodia. Inhibition of Cdc42 in vivo resulted in delayed re-epithelization of injured corneas. We conclude that silk film nanotopography in combination with collagen I constitutes a better substrate for corneal wound repair than either nanotopography or ECM alone.

Background Diabetes mellitus (DM) is common in patients with cirrhosis and is associated with increased risk of infection. Aim To analyze the impact of uncontrolled DM on infection and mortality among inpatients with advanced cirrhosis. Methods This study utilized the Nationwide Inpatient Sample from 1998 to 2014. We defined advanced cirrhosis using a validated ICD-9-CM algorithm requiring a diagnosis of cirrhosis and clinically significant portal hypertension or decompensation. The primary outcome was bacterial infection. Secondary outcomes included inpatient mortality stratified by elderly age (age≥70). Multivariable logistic regression analyzed outcomes. Results 906,559 (29.2%) patients had DM and 109,694 (12.1%) were uncontrolled. Patients who had uncontrolled DM were younger, had less ascites, but more encephalopathy. Bacterial infection prevalence was more common in uncontrolled DM (34.2% vs. 28.4%, OR 1.33, 95% CI 1.29–1.37, p Conclusions Uncontrolled DM is associated with increased risk of infection, and when combined with elderly age is associated with increased risk of inpatient mortality. Glycemic control is a modifiable target to improve morbidity and mortality in patients with advanced cirrhosis.

Aims: Childhood cancer survival is suboptimal inmost low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' Materials and methods: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. Results: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. Conclusions: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. in many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. in some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients. (C) 2020 The Royal College of Radiologists. Published by Elsevier Ltd.Y, IAEAInternational Atomic Energy Agency [E3.30.31], This study was funded through the IAEA Coordinated Research Project E3.30.31: Paediatric radiation oncology practice in low and middle income countries: a pattern of care study by the International Atomic Energy Agency.

Abstinence in patients with alcohol‐associated liver disease (ALD) reduces mortality. Most predictors of relapse are not quantifiable, preventing objective analysis of relapse risk and targeted intervention to improve clinical outcomes. We prospectively enrolled patients with ALD from November 2016 to December 2019 and administered a survey with two previously published scales to assess insight into alcohol‐use disorder (Hanil Alcohol Insight Scale [HAIS]) and social support (Community Assessment Inventory Scale [CAIS]). Relapse was assessed using surveys and metabolite testing. Unadjusted and prespecified adjusted regression analyses identified predictors of relapse. We enrolled 81% of eligible patients (n = 136), of whom 58 had follow‐up data available at the time of analysis. Over a median follow‐up of 1 year (interquartile range: 0.5‐1.4), 10 patients relapsed (17%). Patients who relapsed were more likely to continue drinking despite either a diagnosis of liver disease or a decompensating event, and were less likely to have been transplanted (all P < 0.05). In unadjusted regression, the HAIS and the “support inside the home” subcategory of the CAIS were predictive of relapse, with odds ratio (OR) = 0.84 (95% confidence interval 0.72‐0.97) and 0.85 (0.74‐0.97). In adjusted regression, the HAIS was no longer significant, with adjusted OR = 0.70 (0.49‐1.00, P = 0.05), whereas the “support inside the home’ subcategory of CAIS remained significant, with adjusted OR = 0.69 (0.51‐0.92, P = 0.01). Conclusions: Risk factors for relapse in patients with ALD were identified and quantified prospectively, suggesting opportunities to objectively identify patients at risk for relapse as well as to intervene to prevent relapse.

The coronavirus disease 2019 (COVID-19) disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often results in severe hypoxemia requiring airway management. Because SARS-CoV-2 virus is spread via respiratory droplets, bag-mask ventilation, intubation, and extubation may place health care workers (HCW) at risk. While existing recommendations address airway management in patients with COVID-19, no guidance exists specifically for difficult airway management. Some strategies normally recommended for difficult airway management may not be ideal in the setting of COVID-19 infection. To address this issue, the Society for Airway Management (SAM) created a task force to review existing literature and current practice guidelines for difficult airway management by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. The SAM task force created recommendations for the management of known or suspected difficult airway in the setting of known or suspected COVID-19 infection. The goal of the task force was to optimize successful airway management while minimizing exposure risk. Each member conducted a literature review on specific clinical practice section utilizing standard search engines (PubMed, Ovid, Google Scholar). Existing recommendations and evidence for difficult airway management in the COVID-19 context were developed. Each specific recommendation was discussed among task force members and modified until unanimously approved by all task force members. Elements of Appraisal of Guidelines Research and Evaluation (AGREE) Reporting Checklist for dissemination of clinical practice guidelines were utilized to develop this statement. Airway management in the COVID-19 patient increases HCW exposure risk. Difficult airway management often takes longer and may involve multiple procedures with aerosolization potential, and strict adherence to personal protective equipment (PPE) protocols is mandatory to reduce risk to providers. When a patient's airway risk assessment suggests that awake tracheal intubation is an appropriate choice of technique, and procedures that may cause increased aerosolization of secretions should be avoided. Optimal preoxygenation before induction with a tight seal facemask may be performed to reduce the risk of hypoxemia. Unless the patient is experiencing oxygen desaturation, positive pressure bag-mask ventilation after induction may be avoided to reduce aerosolization. For optimal intubating conditions, patients should be anesthetized with full muscle relaxation. Videolaryngoscopy is recommended as a first-line strategy for airway management. If emergent invasive airway access is indicated, then we recommend a surgical technique such as scalpel-bougie-tube, rather than an aerosolizing generating procedure, such as transtracheal jet ventilation. This statement represents recommendations by the SAM task force for the difficult airway management of adults with COVID-19 with the goal to optimize successful airway management while minimizing the risk of clinician exposure.

Objective Neonatal hyperthyroidism may be caused by a permanent non-autoimmune genetic disorder or, more frequently, by maternally transmitted high serum TRAb levels. Variable thyroid dysfunction may be observed in this second context. We aimed to evaluate the prevalence of neonatal non-autoimmune hyperthyroidism and of the different types of thyroid function in neonates with a high risk of hyperthyroidism due to maternal Graves’ disease (GD). Design and methods This observational cohort study included all neonates identified in the database of a single academic pediatric care center, over a period of 13 years, as having non-autoimmune hyperthyroidism or an autoimmune disorder with high TRAb levels (above 6 IU/L) transmitted by their mothers. Patients were classified as having neonatal hyperthyroidism, hypothyroidism, or euthyroidism with a permanent or transient disorder. Results Two of the 34 consecutive neonates selected (6%) had permanent non-autoimmune hyperthyroidism due to germline (n = 1) or somatic (n = 1) mutations of the TSH receptor gene. The patients with high serum TRAb levels at birth had transient hyperthyroidism (n = 23), hypothyroidism (primary n = 2, central n = 3) or persistent euthyroidism (n = 4). Conclusion These original findings highlight the need for careful and appropriate monitoring of thyroid function in the long term, not only for the rare patients with non-autoimmune neonatal hyperthyroidism, but also for repeat monitoring during the first month of life in neonates with maternally transmitted high TRAb levels, to ensure the early identification of thyrotoxicosis in more than two thirds of cases and to detect primary or central hypothyroidism, thereby potentially decreasing associated morbidity.

Equity in access is one of the core goals of the Organ Procurement and Transplant Network (OPTN). However, disparities in liver transplantation have been described since the passage of the National Organ Transplant Act, which established OPTN in the 1980s. During the past few decades, several efforts have been made by the United Network for Organ Sharing (UNOS) to address disparities in liver transplantation with notable improvements in many areas. Nonetheless, disparities have persisted across insurance type, sex, race/ethnicity, geographic area, and age. African Americans have lower rates of referral to transplant centers, females have lower rates of transplantation from the liver waiting list than males, and public insurance is associated with worse posttransplant outcomes than private insurance. In addition, pediatric candidates and older adults have a disadvantage on the liver transplant waiting list, and there are widespread regional disparities in transplantation. Given the large degree of inequity in liver transplantation, there is a tremendous need for studies to propose and model policy changes that may make the liver transplant system more just and equitable.

Background: Concussion subtypes are typically organized into commonly affected symptom areas or a combination of affected systems, an approach that may be flawed by bias in conceptualization or the inherent limitations of interdisciplinary expertise.Objective: The purpose of this study was to determine whether a bottom-up, unsupervised, machine learning approach, could more accurately support concussion subtyping.Methods: Initial patient intake data as well as objective outcome measures including, the Patient-Reported Outcomes Measurement Information System (PROMIS), Dizziness Handicap Inventory (DHI), Pain Catastrophizing Scale (PCS), and Immediate Post-Concussion Assessment and Cognitive Testing Tool (ImPACT) were retrospectively extracted from the Advance Concussion Clinic's database. A correlation matrix and principal component analysis (PCA) were used to reduce the dimensionality of the dataset. Sklearn's agglomerative clustering algorithm was then applied, and the optimal number of clusters within the patient database were generated. Between-group comparisons among the formed clusters were performed using a Mann-Whitney U test.Results: Two hundred seventy-five patients within the clinics database were analyzed. Five distinct clusters emerged from the data when maximizing the Silhouette score (0.36) and minimizing the Davies-Bouldin score (0.83). Concussion subtypes derived demonstrated clinically distinct profiles, with statistically significant differences (p < 0.05) between all five clusters.Conclusion: This machine learning approach enabled the identification and characterization of five distinct concussion subtypes, which were best understood according to levels of complexity, ranging from Extremely Complex to Minimally Complex. Understanding concussion in terms of Complexity with the utilization of artificial intelligence, could provide a more accurate concussion classification or subtype approach; one that better reflects the true heterogeneity and complex system disruptions associated with mild traumatic brain injury.

Antiseptic wound ointments are widely used to treat dermal wounds that are microbially contaminated. Polygalacturonic acid (PG)+caprylic acid (CAP) is a novel combination that has been shown to eradicate biofilms. We developed a novel PG+CAP ointment and compared the biofilm eradication capability and cytotoxicity of PG+CAP with that of commercially available antiseptic wound ointments. We used a well-established biofilm model to quantitatively assess the eradication of organisms following exposure to the wound ointments for 2 hours. PG+CAP ointment completely eradicated Candida albicans, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus biofilms, whereas MediHoney, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BZK) ointments failed to eradicate all biofilms within 2 hours. We assessed cytotoxicity by exposing L-929 fibroblasts to extracts of each ointment; Trypan blue exclusion was used to assess cell viability, and Alamar blue conversion was used to assess metabolic function. After exposure to PG+CAP and MediHoney, fibroblast viability was 96.23% and 95.23%, respectively (Trypan blue), and was comparable to untreated cells (98.77%). PHMB and BZK showed reduced viability (83.25% and 77.83%, respectively, p < 0.05 ). Metabolic activity results followed a similar pattern. Cytotoxicity of PG+CAP ointment towards erythrocytes was comparable to saline. PG+CAP ointment seems to be safe and can rapidly eradicate microbial biofilm; thus, PG+CAP ointment merits further in vivo testing as a potential antimicrobial wound ointment.

We have developed a personalized vaccine in which patientderived leukemia cells are fused to autologous dendritic cells, evoking a polyclonal T-cell response against shared antigens and neoantigens. We postulated that the dendritic cell/acute myeloid leukemia fusion vaccine would demonstrate synergy with checkpoint blockade by expanding tumor antigen-specific lymphocytes that would provide a critical substrate for checkpoint blockade-mediated activation. Using an immunocompetent murine leukemia model, we examined the immunological response to and therapeutic efficacy of vaccination in conjunction with checkpoint blockade with respect to leukemia engraftment, disease burden, survival and the induction of tumor-specific immunity. Mice treated with checkpoint blockade alone had rapid progression of leukemia and only a modest extension of survival. Vaccination with dendritic cell/acute myeloid leukemia fusions resulted in the expansion of tumor-specific lymphocytes and disease eradication in a subset of animals, while the combination of vaccination and checkpoint blockade induced a fully protective tumor-specific immune response in all treated animals. Vaccination followed by checkpoint blockade resulted in upregulation of genes regulating activation and proliferation in memory and effector T cells. Long-term survivors exhibited increased T-cell clonal diversity and were resistant to subsequent tumor challenge. The combination of dendritic cell/acute myeloid leukemia fusion vaccine and checkpoint blockade treatment offers unique synergy, inducing durable activation of leukemia-specific immunity, protection from lethal tumor challenge and the selective expansion of tumor-reactive clones.

Additional therapeutic options are needed for relapsed and refractory multiple myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 50–77]) and a median of four prior regimens (range: 2–14); 85% had refractory disease (lenalidomide [80%]; bortezomib [75%]; lenalidomide and bortezomib [50%]). Patients received a median of six cycles (range: 1–74) of panobinostat (10 or 15 mg), lenalidomide 15 mg, bortezomib 1 mg/m2, and dexamethasone 20 mg (pano-RVd). Median follow-up was ~14 months. Six dose-limiting toxicities were reported (mostly hematological); maximum tolerated dose of panobinostat (primary endpoint) was 10 mg. Most common adverse events (AEs) were diarrhea (60%) and peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of patients and included decreased neutrophil (45%), platelet (25%) and white blood cell (25%) counts, anemia (25%) and hypophosphatemia (25%). No treatment-related discontinuations or mortality occurred. In evaluable patients (n = 18), overall response rate was 44%, and clinical benefit rate was 61%. Median duration of response was 9.2 months; progression-free survival was 7.4 months; overall survival was not reached. Pano-RVd proved generally well-tolerated and demonstrated potential to overcome lenalidomide and/or bortezomib resistance.

Background The AMPLIFY trial found significantly lower major bleeding (MB) and similar recurrent venous thromboembolism (VTE) risks associated with apixaban vs warfarin among patients with VTE. Objectives To compare MB, clinically-relevant non-major (CRNM) bleeding, and recurrent VTE risks among clinically-relevant subgroups of newly diagnosed elderly patients with VTE prescribed apixaban vs warfarin. Methods US Medicare patients prescribed apixaban or warfarin within 30 days post-VTE encounter were identified. Propensity score matching (PSM) was used to control for patient characteristics. Cox models were used to assess MB, CRNM bleeding, and recurrent VTE. Subgroup analyses were conducted for index VTE encounter type, index VTE diagnosis type, index VTE etiology, sex, and frailty. Results Post-PSM, 11,363 matched pairs of patients prescribed apixaban or warfarin were identified. Apixaban had lower MB (Hazard Ratio [HR]:0.76; 95% CI:0.64–0.91) and similar recurrent VTE risks (HR:1.04; 95% CI:0.75–1.43) vs warfarin. No significant interactions were observed between treatment and index VTE encounter type, index VTE diagnosis type, or sex for risk of MB, CRNM bleeding, or recurrent VTE. Significant interactions: frail patients prescribed apixaban had a 15% lower, while non-frail patients prescribed apixaban had 32% lower CRNM bleeding risk vs those prescribed warfarin. Patients with provoked VTE prescribed apixaban trended toward a higher, while those with unprovoked VTE trended toward a lower risk of recurrent VTE vs patients prescribed warfarin. Conclusions Apixaban was associated with significantly lower risks of MB and CRNM bleeding, and similar risk of recurrent VTE as compared with warfarin across the overall population and most subgroups.

Background/aimsTo determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4–11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages.MethodsRetrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points.ResultsA total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%.ConclusionWe found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.

Background: Vitamin D deficiency is common in HIV population and has been associated with increased comorbidity risk and poor immunologic status. Objective: To evaluate the effect of protease inhibitor lopinavir/ritonavir monotherapy on changes in serum 25-hydroxyvitamin D [25(OH)D] over 48 weeks. Methods: Thirty-four treatment-naïve HIV individuals initiating lopinavir/ritonavir monotherapy and receiving clinical care from private practice in Houston, Texas, were included. Serum 25-hydroxyvitamin D levels from stored plasma samples collected from IMANI-2 pilot study at both baseline and 48 weeks were analyzed using LC-MS assays. Mean 25(OH)D at baseline and 48 weeks were compared using paired t-tests. Linear regression analysis was used to evaluate factors associated with changes in 25(OH)D. Logistic regression analyses were used to determine the effect of vitamin D status and covariates on CD4 cell count recovery. Results: Mean 25(OH)D was significantly higher at 48 weeks (26.3 ng/mL (SD + 14.9); p=0.0003) compared to baseline (19.8 ng/mL (SD +12.1), with fewer individuals having vitamin D deficiency (41.2%) and severe deficiency (11.8%). Both body mass index and baseline CD4 cell count were significant independent covariates associated with 25(OH)D changes over 48 weeks. Baseline vitamin D status did not affect CD4 cell count recovery. However, in a 24-week multivariate analysis, current tobacco use was significantly associated with a decreased odds of CD4 cell count recovery (AOR 0.106, 95% CI 0.018-0.606; p=0.012). Conclusion: Individuals treated with lopinavir/ritonavir monotherapy had significantly higher 25(OH)D after 48 weeks. Current tobacco users had significantly diminished CD4 cell count recovery after starting treatment, warranting further clinical investigation.

Objective Congenital diarrheal disorders (CDDs) are a group of rare diseases among which some present as inherited disorders of intestinal electrolyte transportation: congenital chloride diarrhea (CCD) and congenital sodium diarrhea (CSD) with prenatal manifestations, mainly polyhydramnios, leading to premature delivery. Affected neonates present with watery stools, sometimes mistaken as urine, leading to a misdiagnosis of Bartter syndrome. The aim of this study was to study the value of a prenatal biochemical pattern in the case of suspected CDD. Methods We retrospectively studied 12 amniotic fluids of CDD-affected fetuses prenatally suspected and confirmed after birth. Digestive enzymes, proteins and electrolytes were assayed and showed abnormal biochemical patterns. Results The 12 infants (8 CCD- and 4 CSD-affected) were born prematurely with a normal birth weight. Electrolytes and the Bartter index were normal for all cases. Amniotic fluid enzyme patterns were abnormal: anal leakage for 9, as expected, but vomiting of bile was observed for 3 infants, for whom an occlusive syndrome required surgery, and thereafter severe complications appeared with a poor prognosis. Conclusion Amniotic fluid biochemical patterns differentiate CDD from Bartter syndrome. If a vomiting bile pattern is observed, postnatal management should take into account the hypothesis of a most severe complication. This article is protected by copyright. All rights reserved.

An enterocutaneous fistula (ECF) with an associated large hernia defect poses a significant challenge for the reconstructive surgeon. We aim to describe operative details and 30-day outcomes of elective hernia repair with an ECF when performed by surgeons participating in the Abdominal Core Health Quality Collaborative (ACHQC). Patients undergoing concomitant hernia and ECF elective repair were identified within the ACHQC. Outcomes of interest were operative details and 30-day rates of surgical site infections (SSI), surgical site occurrences requiring procedural intervention (SSOPI), medical complications, and mortality. 170 patients were identified (mean age 60 years, 52.4% females, mean BMI 32.3 kg/m2). 106 patients (62%) had small-bowel ECFs, mostly managed with resection without diversion. 30 patients (18%) had colonic ECFs, which were managed with resection without diversion (14%) or resection with diversion (6%). 100 (59%) had a prior mesh in place, which was removed in 90% of patients. Hernias measured 14 cm ± 7 in width, and 68 (40%) had a myofascial release performed (41 TARs). Mesh was placed in 115 cases (68%), 72% as a sublay, and more frequently of biologic (44%) or permanent synthetic (34%) material. 30-day SSI was 18% (37% superficial, 40% deep), and 30-day SSOPI was 21%. 19 patients (11%) were re-operated: 8 (8%) due to a wound complication and 4 (2%) due to a missed enterotomy. Two infected meshes were removed, one biologic and one synthetic. Surgeons participating in the ACHQC predominantly resect ECFs and repair the associated hernias with sublay mesh with or without a myofascial release. Morbidity remains high, most closely related to wound complications, as such, concomitant definitive repairs should be entertained with caution.

BACKGROUND AND OBJECTIVE: To provide an updated estimate of incidence and prevalence of the foremost retinal diseases in the U.S. PATIENTS AND METHODS: Retrospective study of the Vestrum Health Database evaluating eyes with diagnoses of wet or dry age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), branch or central retinal vein occlusion (BRVO; CRVO) from January 2014 to December 2019 across 58 retina practices. RESULTS: Of the 3,086,791 eyes examined, 490,881 (15.9%) had dry AMD, 294,041 (9.5%) wet AMD, 270,703 (8.8%) DME, 254,690 (8.3%) DR without DME, 73,617 (2.4%) BRVO, and 50,670 (1.6%) CRVO. Dry AMD had the highest incidence. These diseases comprised 61.0% of total prevalence and 54.3% of incidence among patients at the retina practices analyzed. CONCLUSIONS: Based on a diverse database, these diseases comprised the majority of U.S. retina practice cases, with increasing annual incidences. AMD is the most common diagnosis, then diabetic eye disease. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:29–36.]

Aim and objective To compare the arresting caries effectiveness of two different silver nanoparticle (AgNP) concentrations of nano-silver fluoride (NSF), namely 400 and 600 ppm. The hypothesis is that in posterior primary teeth with occlusal and approximal active dentin carious lesions, NSF 600's effectiveness will be higher than that of the NSF 400 solution over a 6-month follow-up period. Materials and methods This was a double-blind randomized clinical trial (RCT) conducted in the city of Recife, Brazil. A total of 337 children aged 5-7 years who attended the University of Pernambuco Dental School's clinics were examined. A single-blinded investigator conducted the examinations and treatment of the children. After baseline examination and recording of the dmft index, children were allocated to one of two study groups (NSF 600-intervention and NSF 400-positive control). In both groups, each tooth received two drops of NSF and treatments were performed only once in 6 months. The follow-up examinations were visual and tactile, performed in 30, 90, and 180 days to determine the activity of caries. The carious lesions that were not arrested in 30 days were recorded and referred for restorative treatment. Results The NSF 600 showed higher rate of success in arresting caries (72.7%, p = 0.025) compared with NSF 400 (56.5%). Conclusion The higher rate of success of NSF 600 can be explained by the higher concentration of AgNPs. Clinical significance Nano-silver fluoride has emerged as an excellent alternative to silver diamine fluoride (SDF), as it adds a high antibacterial effect to better esthetic results. Treatment is simple, non-invasive, and incurs low cost. It is ideal for use in community-based programs to increase the access to dental care without staining teeth black like other silver products. How to cite this article Arnaud M, Junior PCM, Lima MGS, et al. Nano-silver Fluoride at Higher Concentration for Caries Arrest in Primary Molars: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2021;14(2):207-211.

Objective: The objective of our study was to assess the utility of sequential fetal urine analysis in severe lower urinary tract obstruction (LUTO) when selecting cases suitable for vesicoamniotic shunting. Material and Methods: This was a retrospective cohort study of cases of severe LUTO treated in our fetal medicine center from 1994 to 2013. Two fetal bladder samples were taken 24–48 h apart to assess renal function. A vesicoamniotic shunt was inserted in case of improvement in urinary biochemistry between the 2 samples. We assessed perinatal morbidity and mortality and renal function at 5 years. Results: Among a total of 26 LUTO cases with sequential urine analysis, 5 showed normal urinary biochemistry, 13 were abnormal, and 8 improved between the 2 samples. These 8 cases underwent vesicoamniotic shunt placement, leading to the birth of 6/8 (75%) live infants, 5/6 (83%) of whom had normal renal function at 5 years. The 5 cases with normal biochemistry occasioned 2 neonatal deaths and 3 children with normal renal function at 5 years. Elective termination of pregnancy was requested by parents for the fetuses exhibiting abnormal biochemistry. Conclusion: An improvement in urinary biochemistry between 2 sequential fetal bladder punctures in severe LUTO could be an effective criterion in the selection of candidates for vesicoamniotic shunting. However, the benefit of a shunt in fetuses with normal amniotic fluid remains to be evaluated in clinical trials.