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Scoring a polysomnogram is an essential skill for sleep medicine trainees to meet Accreditation Council for Graduate Medical Education Sleep Medicine Milestones. Appraisal is based on faculty evaluation rather than objective competency assessment. We developed a computer-based polysomnogram scoring curriculum, utilizing the mastery learning method, then compared achievement of competency using the new curriculum against standard institutional training.The scoring program consisted of a pretest assessment, sequential acquisition of knowledge utilizing online modules, a posttest, and competency assessment. Fellows needed to demonstrate mastery of each module before moving ahead. Competency was demonstrating ≥ 90% on interscorer reliability assessment on 5 studies (out of up to 10 attempts). Participating fellows were assigned to Mastery Learning Participants (MLP) or Traditional Learning Participants (TLP) groups and completed the program within the first 1-3 months of training.Of 87 fellows enrolled in the program, 75 participants completed the program (40 MLP and 35 TLP). Among completers, there was no difference in the proportion that achieved competency (MLP 90.0% vs TLP 97.1%;We demonstrated similar outcomes utilizing a novel, computer-based modular interactive course compared to traditional methods of teaching polysomnogram scoring. We used a mastery learning paradigm and set specific objective competency levels for this skill.Epstein LJ, Plante DT, Rosen IM. Mastery learning program to teach sleep study scoring.

The coronavirus disease 2019 (COVID-19) pandemic is a reminder that global infectious disease outbreaks are not new and they have the potential to cause catastrophic morbidity and mortality, disrupt health care delivery, demand critical decision making in the absence of scientific certainty, interrupt trainee education, inflict economic damage, and cause a spike in demand for health care services that exceeds societal capacity. In this article, we look back at how the sleep medicine community adapted to challenges imposed by the COVID-19 pandemic. To mitigate viral transmission perhaps the single most effective and efficient adaptation was the rapid adoption of telemedicine. Many additional strategies were taken up virtually overnight, including more home sleep apnea testing, reconsideration of potential risks of positive airway pressure therapy, a reduction or cessation of laboratory services, and deployment of workers to provide frontline care to infected patients. During some periods, critical shortages in essential personal protective equipment, respiratory assist devices, and even oxygen added to logistical challenges, which were exacerbated by persistent financial threats and insufficient staffing. Through ongoing innovation, resiliency, and adaptability, breakthroughs were made in assigning staff responsibilities and designing workflows, using clinical spaces, obtaining legislative support, and achieving professional society collaboration and guidance so that the missions of providing health care, teaching, and academic pursuits could continue. Here we summarize what we have learned through these critical months and highlight key adaptations that deserve to be embraced as we move forward.Khosla S, Beam E, Berneking M, et al. The COVID-19 pandemic and sleep medicine: a look back and a look ahead.

An abstract formulation of a duality principle established by Krasnoselskii is presented. Under appropriate conditions, it shall be shown that, if the solutions of a nonlinear functional equation can be obtained by finding fixed points of certain operators in possibly different Banach spaces, then these operators share some topological properties.

Neel S Vaidya,1,2 Arvin Daneshmand,3 Randy J Epstein,1,2 Parag A Majmudar,1,2 Michael W Belin,4,5 Edward C Parsons,5 Roy S Rubinfeld5– 7 1Chicago Cornea Consultants, Highland Park, IL, USA; 2Department of Ophthalmology, Rush University Medical Center, Chicago, IL, USA; 3Georgetown University Medical School, Washington, DC, USA; 4Department of Ophthalmology, University of Arizona, Tucson, AZ, USA; 5CXL Ophthalmics, LLC, Encinitas, CA, USA; 6Department of Ophthalmology, Georgetown University Medical School/Washington Hospital Cente, Washington, DC, USA; 7Re:Vision Private Practice, Rockville, MD, USACorrespondence: Neel S Vaidya, Chicago Cornea Consultants, 806 Central Ave Suite 300, Highland Park, IL, 60035, USA, Email nsv@chicagocornea.comPurpose: To assess the change in corneal pachymetry after a novel epithelium-on (EpiSmart®) corneal crosslinking procedure (CXL).Methods: Eyes treated as part of the open-label, non-controlled arm of the study “Collagen Crosslinking with Ultraviolet-A in Asymmetric Corneas” (NCT01097447) were examined at baseline, 3-, 6- and 12-months post-CXL. Thinnest pachymetry readings based on Pentacam (OCULUS GmbH, Wetzlar, Germany) were recorded.Results: A total of 101 eyes met the study inclusion criteria. Thinnest pachymetric readings at baseline averaged 451 ± 50 microns. The mean (± SD) minimum thickness was 450 ± 46 microns at 3 months, 452 ± 47 microns at 6 months, and 451 ± 48 microns at 12 months post-CXL. The changes from baseline (mean ± SE) at 3, 6, and 12 months post-CXL were − 1.2 ± 1.5 microns, 0.5 ± 1.6 microns, and 0.4 ± 1.6 microns, respectively. Student’s t-tests showed no statistically significant change in pachymetry from baseline for any exam period.Conclusion: This study demonstrated that, after EpiSmart® epithelium-on CXL, there was no substantial corneal thinning observable on Scheimpflug tomography out to 12 months.Keywords: corneal thinning, cross-linking, epithelium-on, keratoconus, pachymetry, post-surgical ectasia

Two patients with delayed sleep-wake phase disorder (DSWPD) demonstrated improvement in sleep quality and duration, reduction in symptoms, and elimination of the need for hypnotic or stimulant medications after changing their sleep schedules in response to the coronavirus disease 2019 (COVID-19) pandemic lockdown work schedule changes. These cases highlight the impact of work schedules on patient health and raise questions about approaches to workplace schedule requirements postpandemic. CITATION: Epstein LJ, Cai A, Klerman EB, Czeisler CA. Resolving delayed sleep-wake phase disorder with a pandemic: two case reports. J Clin Sleep Med. 2022;18(1):315–318.

Background and Objective Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The “Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults” (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. Methods This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006–2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. Results In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. Conclusions Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00901-2.

PURPOSE Predicting short-term mortality in patients with advanced cancer remains challenging. Whether digitalized clinical text can be used to build models to enhance survival prediction in this population is unclear. MATERIALS AND METHODS We conducted a single-centered retrospective cohort study in patients with advanced solid tumors. Clinical correspondence authored by oncologists at the first patient encounter was extracted from the electronic medical records. Machine learning (ML) models were trained using narratives from the derivation cohort, before being tested on a temporal validation cohort at the same site. Performance was benchmarked against Eastern Cooperative Oncology Group performance status (PS), comparing ML models alone (comparison 1) or in combination with PS (comparison 2), assessed by areas under receiver operating characteristic curves (AUCs) for predicting vital status at 11 time points from 2 to 52 weeks. RESULTS ML models were built on the derivation cohort (4,791 patients from 2001 to April 2017) and tested on the validation cohort of 726 patients (May 2017-June 2019). In 441 patients (61%) where clinical narratives were available and PS was documented, ML models outperformed the predictivity of PS (mean AUC improvement, 0.039, P < .001, comparison 1). Inclusion of both clinical text and PS in ML models resulted in further improvement in prediction accuracy over PS with a mean AUC improvement of 0.050 ( P < .001, comparison 2); the AUC was > 0.80 at all assessed time points for models incorporating clinical text. Exploratory analysis of oncologist's narratives revealed recurring descriptors correlating with survival, including referral patterns, mobility, physical functions, and concomitant medications. CONCLUSION Applying ML to oncologists' narratives with or without including patient's PS significantly improved survival prediction to 12 months, suggesting the utility of clinical text in building prognostic support tools.

Objective: Menopause is associated with an increased prevalence of sleep difficulties. We evaluated the economic burden of sleep disturbances among working midlife women. Methods: This retrospective, longitudinal cohort study collected data from the US Study of Women's Health Across the Nation (SWAN) database of women age 42-52 years at enrollment. We assessed the association between sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) and workplace productivity (employment [yes/no] and work hours/wk) for women who were employed at the baseline visit and had ≥1 follow-up visit. We estimated overall economic burden by multiplying changes in productivity by median age-specific hourly US wages. Each woman's data were compared from visit to visit and were excluded after the first observed unemployment. Regression analysis was used to estimate associations between changes in sleep and changes in workplace productivity while controlling for relevant characteristics that varied over time. Results: The analysis included 2,489 working women (19,707 visits); 31% became unemployed during follow-up. Risk of unemployment was 31% higher for women with versus without new-onset sleep disturbances (P = 0.0474). Onset of sleep disturbances was associated with a 0.44-0.57 hours/wk reduction in work time (not significant). Using the more conservative reduction (0.44 h), sleep problems were associated with an annual loss of $517 to $524 per woman and $2.2 billion/yr in lost productivity among women age 42-64 nationwide. Conclusions: New-onset sleep problems in midlife women are associated with significant increases in risk of unemployment and ∼$2 billion/yr in lost productivity nationwide. Video Summary:.

The human TMPRSS2 gene is pathogenetically implicated in both coronaviral lung infection and prostate cancer, suggesting its potential as a drug target in both contexts. SARS-COV-2 spike polypeptides are primed by the host transmembrane TMPRSS2 protease, triggering virus fusion with epithelial cell membranes followed by an endocytotic internalisation process that bypasses normal endosomal activation of cathepsin-mediated innate immunity; viral co-opting of TMPRSS2 thus favors microbial survivability by attenuating host inflammatory responses. In contrast, most early hormone-dependent prostate cancers express TMPRSS2:ERG fusion genes arising from deletions that eliminate the TMPRSS2 coding region while juxtaposing its androgen-inducible promoter and the open reading frame of ERG, upregulating pro-inflammatory ERG while functionally disabling TMPRSS2. Moreover, inflammatory oxidative DNA damage selects for TMPRSS2:ERG-fused cancers, whereas patients treated with antiinflammatory drugs develop fewer of these fusion-dependent tumors. These findings imply that TMPRSS2 protects the prostate by enabling endosomal bypass of pathogens which could otherwise trigger inflammation-induced DNA damage that predisposes to TMPRSS2:ERG fusions. Hence, the high oncogenic selectability of TMPRSS2:ERG fusions may reflect a unique pro-inflammatory synergy between androgenic ERG gain-of-function and fusogenic TMPRSS2 loss-of-function, cautioning against the use of TMPRSS2-inhibitory drugs to prevent or treat early prostate cancer.

Objectives To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). Methods This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). Results We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P Conclusions One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.

The aim of this study was to assess changes in visual acuity after epithelium-on ("epi-on") corneal crosslinking after a diagnosis of keratoconus.Subjects with corneal ectatic diseases were enrolled in a prospective, randomized, controlled, open-label, multicenter trial. Subjects were randomized to 1 of 3 treatment groups and treated with an epi-on crosslinking system including riboflavin/sodium iodide and pulsed UVA exposure (EpiSmart® , CXL Ophthalmics, Encinitas, CA). The UVA treatment groups were 2.4 J/cm2 over 20 minutes, 3.6 J/cm2 over 20 minutes, and 3.6 J/cm2 over 30 minutes. The primary end point was logarithm of the minimum angle of resolution corrected distance visual acuity (CDVA). Secondary end points were logarithm of the minimum angle of resolution uncorrected distance visual acuity (UCVA), maximum corneal curvature (Kmax), and minimum corneal thickness. Data were assessed 6 and 12 months post-operatively, using t-tests for differences from baseline.Two thousand two hundred twenty-eight subjects were treated with epi-on crosslinking. One thousand nine hundred twenty-two subjects had a diagnosis of keratoconus; other treated eyes had postsurgical and other ectasias. At 6 and 12 months, the subjects with keratoconus demonstrated significant improvements in CDVA, UCVA, and Kmax; minimum corneal thickness was unchanged. One hundred ninety-five subjects (8.7%) reported at least 1 adverse event (AE). A mild corneal epithelial defect was reported in 31 cases (1.4%) and was the only AE reported in1% of subjects. There were no serious AEs related to the treatment.EpiSmart® epi-on crosslinking resulted in mean improvements in CDVA, UCVA, and Kmax at both 6 and 12 months and an excellent safety and efficacy profile in subjects with keratoconus, with few significant side effects. Differences between UVA treatment groups were not significant.

The aim of this retrospective analysis is to determine the most frequently prescribed medications for the treatment of NREM parasomnias and evaluate reported outcomes. We performed a retrospective chart review of all patients with NREM parasomnia diagnosed within Brigham and Women’s Hospital (BWH) clinics examining the date of diagnosis, date of starting therapy, comorbidities, type of medication prescribed, and the reported change in symptoms or side effects at follow-up visits. From 2012 to 2019, 110 patients (59 females, 51 male) at BWH clinics received a diagnosis of NREM parasomnia, including sleepwalking and night terrors. The mean age was 44. Comorbidities included obstructive sleep apnea (OSA) (46%), periodic limb movement syndrome (PLMS) (13%), insomnia (19%), Restless leg syndrome (RLS) (9%), epilepsy (4%), and REM behavior disorder (RBD) (9%). Initial treatment strategies include behavioral and safety counseling only (34%), pharmacological treatment (29%), treatment of any comorbidity (28%), and combined treatment of any of the above (9%). Improvement was reported with: treatment of OSA (n = 23 52% reported improvement), melatonin (n = 8, improvement reported by 88%.,benzodiazepine (n = 7, improvement reported by 57%). Treating comorbid conditions is a frequent treatment strategy, often associated with symptom improvement. The pharmacologic treatment most commonly included melatonin and benzodiazepines. Comprehensive management should include behavioral and safety recommendations, assessment of comorbid conditions, and individually tailored pharmaceutical treatment.

BackgroundEvaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). MethodsUsing previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. ResultsThe ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. ConclusionThis review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

Intragenic CpG dinucleotides are tightly conserved in evolution yet are also vulnerable to methylation-dependent mutation, raising the question as to why these functionally critical sites have not been deselected by more stable coding sequences. We previously showed in cell lines that altered exonic CpG methylation can modify promoter start sites, and hence protein isoform expression, for the human TP53 tumor suppressor gene. Here we extend this work to the in vivo setting by testing whether synonymous germline modifications of exonic CpG sites affect murine development, fertility, longevity, or cancer incidence. We substituted the DNA-binding exons 5–8 of Trp53, the mouse ortholog of human TP53, with variant-CpG (either CpG-depleted or -enriched) sequences predicted to encode the normal p53 amino acid sequence; a control construct was also created in which all non-CpG sites were synonymously substituted. Homozygous Trp53-null mice were the only genotype to develop tumors. Mice with variant-CpG Trp53 sequences remained tumor-free, but were uniquely prone to dental anomalies causing jaw malocclusion (p < .0001). Since the latter phenotype also characterises murine Rett syndrome due to dysfunction of the trans-repressive MeCP2 methyl-CpG-binding protein, we hypothesise that CpG sites may exert non-coding phenotypic effects via pre-translational cis-interactions of 5-methylcytosine with methyl-binding proteins which regulate mRNA transcript initiation, expression or splicing, although direct effects on mRNA structure or translation are also possible.

While newborns and children with hearing loss are routinely offered genetic testing, adults are rarely clinically tested for a genetic etiology. One clinically actionable result from genetic testing in children is the discovery of variants in syndromic hearing loss genes. EYA4 is a known hearing loss gene which is also involved in important pathways in cardiac tissue. The pleiotropic effects of rare EYA4 variants are poorly understood and their prevalence in a large cohort has not been previously reported. We investigated cardio-auditory phenotypes in 11,451 individuals in a large biobank using a rare variant, genome-first approach to EYA4. We filtered 256 EYA4 variants carried by 6737 participants to 26 rare and predicted deleterious variants carried by 42 heterozygotes. We aggregated predicted deleterious EYA4 gene variants into a combined variable (i.e. “gene burden”) and performed association studies across phenotypes compared to wildtype controls. We validated findings with replication in three independent cohorts and human tissue expression data. EYA4 gene burden was significantly associated with audiometric-proven HL (p = $${5.43\times 10}^{-5})$$ , Mobitz Type II AV block (p = $${2.16\times 10}^{-5}$$ ) and the syndromic presentation of HL and primary cardiomyopathy (p = 0.0194). Analyses on audiogram, echocardiogram, and electrocardiogram data validated these associations. Prior reports have focused on identifying variants in families with severe or syndromic phenotypes. In contrast, we found, using a genotype-first approach, that gene burden in EYA4 is associated with more subtle cardio-auditory phenotypes in an adult medical biobank population, including cardiac conduction disorders which have not been previously reported. We show the value of using a focused approach to uncover human disease related to pleiotropic gene variants and suggest a role for genetic testing in adults presenting with hearing loss.

IntroductionAt the early epicentre of the COVID-19 crisis in the USA, our institution saw a surge in the demand for inpatient consultations for areas impacted by COVID-19 (eg, infectious diseases, nephrology, palliative care) and shortages in personal protective equipment (PPE). We aimed to provide timely specialist input for consult requests during the COVID-19 pandemic by implementing an Inpatient eConsult Programme.MethodsWe used the reach, effectiveness, adoption, implementation and maintenance implementation science framework and run chart analysis to evaluate the reach, adoption and maintenance of the Inpatient eConsult Programme compared with traditional in-person consults. We solicited qualitative feedback from frontline physicians and specialists for programme improvements.ResultsDuring the study period, there were 46 available in-person consult orders and 21 new eConsult orders. At the peak of utilisation, 42% of all consult requests were eConsults, and by the end of the study period, utilisation fell to 20%. Qualitative feedback revealed subspecialties best suited for eConsults (infectious diseases, nephrology, haematology, endocrinology) and influenced improvements to the ordering workflow, documentation, billing and education regarding use.DiscussionWhen offered inpatient eConsult requests as an alternative to in-person consults in the context of a surge in patients with COVID-19, frontline physicians used eConsult requests and decreased use of in-person consults. As the demand for consults decreased and PPE shortages were no longer a major concern, eConsult utilisation decreased, revealing a preference for in-person consultations when possible.ConclusionsLessons learnt can be used to develop and implement inpatient eConsults to meet context-specific challenges at other institutions.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count

Summary Background Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy. Methods We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years. Findings We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0–75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8–90·9), for 3 years was 97·3% (95·2–98·6), and for 5 years was 98·6% (97·6–100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3–95·9), for 3 years was 97·8% (96·6–99·3), and for 5 years was 96·6% (94·0–98·9). Interpretation These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach. Funding European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d’HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.

The optimal method of fixation of acute Lisfranc injuries is yet to be established. We aim to systematically review the literature to identify the impact of fixation method on postoperative functional outcomes. A systematic review was undertaken using the PRISMA framework to identify all studies reporting postoperative functional outcomes in patients who underwent open-reduction internal fixation of acute Lisfranc injuries. Studies reporting outcomes of numerous fixation methods were divided into fixation subcohorts. Studies comparing bridge plate with transarticular screw fixation were included for meta-analysis, conducted using a random-effects model. Seventeen studies (20 subcohorts) with 462 patients were included. Mean patient age was 29.6 (rang, 15-81) years. Mean follow-up was 38.7 (range 11 to 287) months. American Academy of Orthopaedic Surgeons midfoot score (AOFAS-MF) was the most frequently reported functional outcome (16/20 subcohorts). Overall weighted mean AOFAS-MF was 76.3 ± 9.4 for all cases, with 74.2 ± 9.4 for transarticular screws and 79.2 ± 8.3 for bridge plates. The mean difference between screw and plate was not statistically significant (mean difference = 5.0, 95% confidence interval, -4.8 – 14.8, p = .3). A single study reported AOFAS-MF mean of 92 using suture button fixation. Meta-analysis of the 2 available comparative studies revealed higher postoperative AOFAS-MF with bridge plate fixation (pooled standardized mean difference, 0.51; 95% confidence interval, 0.15-0.87, p = .006). There is scarcity of literature examining the impact of fixation method on postoperative functional outcomes in acute Lisfranc injuries. A small number of studies have reported superior functional outcomes with use of bridge plate fixation. Further evidence is needed to ascertain which injuries are best managed with each fixation method or whether 1 fixation construct is universally superior.

Invasive fungal diseases (IFDs) are common in patients with acute myeloid leukemia (AML), but no recent data on incidence without antifungal prophylaxis are available. We evaluated the incidence of IFDs in patients with AML undergoing induction chemotherapy at Stanford University Hospital from 2012 to 2017, for up to 12 weeks after induction. We also analyzed factors associated with IFD development. Thirty-six of 240 patients (13%) developed at least one proven or probable IFD. Seventy-eight percent of the proven or probable IFDs were due toiCandida/ioriAspergillus/ispecies. Infection due toiFusarium/iandiMucorales/iwas uncommon. Absolute neutrophil count (ANC) oflt;500 µL/L at the start of induction was associated with an increased risk of IFD. One hundred and eighty-seven patients (78%) were started on systemic antifungal drugs, even without microbiologic evidence of an IFD. IFDs remain frequent in AML patients undergoing induction chemotherapy without antifungal prophylaxis.