Evaluation of the Safety of Uninterrupted Warfarin Anticoagulation With Tranexamic Acid in Total Joint Arthroplasty.

BACKGROUND: The continuation of long-term warfarin therapy is gaining acceptance in minor surgeries but maintaining therapeutic international normalized ratio (INR) values among patients during major orthopedic procedures raises concern. While bridging therapy with low-molecular-weight heparin is currently recommended for patients receiving anticoagulation, few studies have evaluated the safety of continuing warfarin during total joint arthroplasty. This study evaluated the safety and efficacy of continuous warfarin anticoagulation through total joint arthroplasty with and without prophylactic tranexamic acid (TXA). MATERIALS AND METHODS: We conducted a retrospective, matched-pair analysis of two experimental groups of patients who underwent primary total hip arthroplasty or total knee arthroplasty performed by a single surgeon. Our first experimental group, warfarin plus TXA (warfarin+TXA), consisted of 21 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) and who received prophylactic TXA. Our second experimental group, warfarin without TXA (warfarin-TXA), consisted of 40 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) without prophylactic TXA. RESULTS: The percent change in hemoglobin value after surgery, red blood cells transfused, surgical site infections, bleeding complications, and thrombotic complications were similar between both experimental and control groups. When comparing the historical group with the warfarin+TXA group, the addition of TXA resulted in a statistical decrease in mean red blood cells transfused and estimated blood loss, with no statistically significant increase in complications. CONCLUSION: Many factors must be considered when choosing perioperative thromboembolic prophylaxis for arthroplasty candidates with medical comorbidities requiring long-term anticoagulation. This study presents data indicating that it could be safe and effective to continue therapeutic warfarin while using prophylactic TXA. [Orthopedics. 202x;4x(x):xx-xx.].

The association of hernia-specific and procedural risk factors with early complications in ventral hernia repair: ACHQC analysis.

BACKGROUND: Many surgical risk assessment tools emphasize patient-specific risk factors. Our objective was to use a hernia-specific database to assess risk factors of complications in ventral hernia repair (VHR) focusing on hernia-specific and procedural factors. METHODS: The ACHQC database was queried for elective VHR in adults from 2012 to 2023. Primary outcome was overall 30-day complications. Multivariable logistic regression was used for analysis. RESULTS: 41,526 VHR were included. The rate of 30-day complications was 18%, surgical site infection 3%, surgical site occurrence requiring procedural intervention 4%, readmission 4%, reoperation 2%, and mortality 0.2%. Multivariable analysis demonstrated that BMI, ASA, frailty, COPD, anticoagulants, defect width, incisional and recurrent hernias, presence of stoma or prior mesh, prior abdominal wall infection, non-clean wound, operative time, open approach and myofascial release were associated with 30-day complications (OR â€‹= â€‹1.01-1.66). Preoperative chlorhexidine, bowel preparation and fascial closure were associated with lower complication risk (OR â€‹= â€‹0.70-0.89). CONCLUSION: Hernia and procedural risk factors are associated with early complications following elective VHR. These factors need to be included in surgical risk assessment tools, to supplement patient-specific factors.

The Joint Awareness Score: A Shortened, Simplified, Improved Alternative to the Forgotten Joint Score.

Background: The Forgotten Joint Score (FJS) is a 12-question patient-reported outcomes measure created to measure a patient's awareness of their artificial joint. The FJS has attained wide usage, though it is not without weaknesses. Our patients report that the semantics of the English translation are flawed and that the 5 answer options for each question are poorly differentiated. Additionally, the FJS will result in no score if 3 or more questions are unanswered. This prompted the development of an alternative patient-reported outcomes measure, the Joint Awareness Score (JAS), that builds upon the core concept of joint awareness underlying the FJS, but that is easier to understand and shorter to complete. We completed an exploratory, pilot study to evaluate this outcomes instrument. Our hypothesis is that the JAS will correlate strongly with the FJS and could be used as a substitute. Methods: Knee arthroplasty patients in a prospective registry were administered the FJS and the JAS. Internal consistency and correlation were calculated with Cronbach's alpha and Pearson's correlation coefficient, respectively. Results: This study included 174 patients. Cronbach's alpha for FJS was 0.97 for 6 months and 0.97 for 12 months, whereas JAS was 0.89 at 6 months and 0.85 at 12 months. Pearson correlation comparing FJS and JAS at 6 months was 0.88 (95% confidence interval: 0.83, 0.92) and 0.86 (95% confidence interval: 0.78, 0.92) at 12 months. Conclusions: The Joint Awareness Score is a new patient-reported outcomes measure that is a substitute for the FJS, with half the number of questions, improved semantics, and simplified answers.

Laparoscopic Toupet fundoplication: a safe and effective anti-reflux option in lung transplant recipients.

BACKGROUND: Fundoplication is known to improve allograft outcomes in lung transplant recipients by reducing retrograde aspiration secondary to gastroesophageal reflux disease, a modifiable risk factor for chronic allograft dysfunction. Laparoscopic Nissen fundoplication has historically been the anti-reflux procedure of choice, but the procedure is associated with discernable rates of postoperative dysphagia and gas-bloat syndrome. Laparoscopic Toupet fundoplication, an alternate anti-reflux surgery with lower rates of foregut complications in the general population, is the procedure of choice on our institution's lung transplant protocol. In this work, we evaluated the efficacy and safety of laparoscopic Toupet fundoplication in our lung transplant recipients. METHODS: A prospective case series of 44 lung transplant recipients who underwent laparoscopic Toupet fundoplication by a single surgeon between September 2018 and November 2020 was performed. Preoperative and postoperative results from 24-h pH, esophageal manometry, gastric emptying, and pulmonary function studies were collected alongside severity of gastroesophageal reflux disease and other gastrointestinal symptoms. RESULTS: Median DeMeester score decreased from 25.9 to 5.4 after fundoplication (p < 0.0001), while percentage of time pH < 4 decreased from 7 to 1.1% (p < 0.0001). The severity of heartburn and regurgitation were also reduced (p < 0.0001 and p = 0.0029 respectively). Overall, pulmonary function, esophageal motility, gastric emptying, severity of bloating, and dysphagia were not significantly different post-fundoplication than pre-fundoplication. Patients with decreasing rates of FEV1 pre-fundoplication saw improvement in their rate of change of FEV1 post-fundoplication (p = 0.011). Median follow-up was 32.2 months post-fundoplication. CONCLUSIONS: Laparoscopic Toupet fundoplication provides objective pathologic acid reflux control and symptomatic gastroesophageal reflux improvement in lung transplant recipients while preserving lung function and foregut motility. Thus, laparoscopic Toupet fundoplication is a safe and effective antireflux surgery alternative in lung transplant recipients.

Fertility Preservation Knowledge, Attitudes, and Self-Reported Behaviors of Resident Physicians.

Purpose: Fertility preservation (FP) and family building are important considerations for quality survivorship for young cancer patients. Resident physicians across all specialties encounter reproductive-aged cancer patients. The purpose of this study was to assess resident physicians' attitudes and awareness about FP with the goal to identify specific educational gaps to direct future training. Methods: The Institutional Review Board (IRB)-approved anonymous online survey was sent to resident physicians across specialties at three separate academic-affiliated campuses in one state. The survey consisted of three sections: awareness about FP options and knowledge about referral placement, attitudes and comfort levels discussing FP, and practices regarding FP. Data were collected in Qualtrics and analyzed by resident specialty, age, level of training, and gender. Statistical analyses were conducted with Prism. Results: Obstetrics and gynecology residents and fellows were significantly more aware of FP options in cancer patients than their counterparts in other specialties. Postgraduate year (PGY 3) residents and beyond were more aware of at least one male and one female FP option compared with PGY 1 and 2 residents. Of importance, we found that the majority of resident physicians are aware of FP options and the referral process, but they are uncomfortable discussing these techniques with their patients. Conclusion: To provide better education for patients, focus should be on outpatient educational activities for both the health care provider and the patient to facilitate conversation about FP.

The effect of smoking status on inguinal hernia repair outcomes: An ACHQC analysis.

BACKGROUND: Smoking has been shown to negatively affect surgical outcomes, so smoking cessation prior to elective operations is often recommended. However, the effects of smoking status on inguinal hernia repair outcomes have not been extensively studied. Hence, we investigated the association between smoking status and short-term adverse outcomes following inguinal hernia repair. METHODS: Abdominal Core Health Quality Collaborative database was queried for elective, clean inguinal hernia repairs, excluding those with concomitant procedures or where length of stay > 30 days. The resulting cohort was divided into three groups: current smokers, former smokers, and never smokers. Baseline patient, hernia, operative characteristics, and 30-day outcomes were compared. Multivariable logistic regression was used to evaluate the association between smoking status and overall and wound complications. RESULTS: 19,866 inguinal hernia repairs were included (current smokers = 2239, former smokers = 4064 and never smokers = 13,563). Current smokers and former smokers, compared to never smokers, had slightly higher unadjusted rates of overall complication rates (9% and 9% versus 7%, p = 0.003) and surgical site occurrences/infection (6% and 6% versus 4%, p < 0.001). However, on multivariable analysis, compared to current smokers, neither the rates of overall complications nor surgical site occurrences were significantly different in former smokers (OR = 0.93, 95% CI [0.76, 1.13] and OR = 0.92, 95% CI [0.73, 1.17]) and never smokers (OR = 0.99, 95% CI [0.83, 1.18] and OR = 0.86, 95% CI [0.70,1.06]) respectively. CONCLUSIONS: Smoking status is not associated with short-term adverse outcomes following inguinal hernia repair. Mandating smoking cessation does not appear necessary to prevent short-term adverse outcomes.

Fluid Overload Precedes and Masks Cryptic Kidney Injury in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective cohort study. SETTING: Quaternary care PICU. PATIENTS: Seven hundred twenty intubated children with ARDS between 2011 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily fluid balance, urine output (UOP), and creatinine for days 1-7 of ARDS were retrospectively abstracted. A subset of patients had angiopoietin 2 (ANGPT2) quantified on days 1, 3, and 7. Patients were classified as AKI by Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 then grouped by timing of AKI onset (early if days 1-3 of ARDS, late if days 4-7 of ARDS, persistent if both) for comparison of PICU mortality and ventilator-free days (VFDs). A final category of "Cryptic AKI" was used to identify subjects who met KDIGO stage 2/3 criteria only when creatinine was adjusted for FO. Outcomes were compared between those who had Cryptic AKI identified by FO-adjusted creatinine versus those who had no AKI. Conventionally defined AKI occurred in 26% of patients (early 10%, late 3%, persistent 13%). AKI was associated with higher mortality and fewer VFDs, with no differences according to timing of onset. The Cryptic AKI group (6% of those labeled no AKI) had higher mortality and fewer VFDs than patients who did not meet AKI with FO-adjusted creatinine. FO, FO-adjusted creatinine, and ANGPT2 increased 1 day prior to meeting AKI criteria in the late AKI group. CONCLUSIONS: AKI was associated with higher mortality and fewer VFDs in pediatric ARDS, irrespective of timing. FO-adjusted creatinine captures a group of patients with Cryptic AKI with outcomes approaching those who meet AKI by traditional criteria. Increases in FO, FO-adjusted creatinine, and ANGPT2 occur prior to meeting conventional AKI criteria.

The Impact of Limited Language Proficiency in Screening for Breast Cancer.

BACKGROUND: The prevalence of a culturally diverse population in the United States continues to grow. Nevertheless, the national impact of limited English proficiency (LEP) in breast cancer screening is still unknown. METHODS: A retrospective review of the 2015 sample of the National Health Interview Survey database was performed. The cohort included women with and without LEP between 40 and 75 years. We evaluated differences in screening rates, baseline, socioeconomic, access to healthcare, and breast cancer risk factors with univariate and multivariate regression analyses. RESULTS: The prevalence of LEP was 5.7% (N = 1825, weighted counts 3936,081). LEP women showed a statistically significant lower rate of overall screening mammograms (78% vs. 90%), fewer benign lumps removed (6.4% vs. 17%) and lower rates of access to healthcare variables. They showed a higher rate of nonprivate insurance and living below the poverty line, a lower rate of hormone replacement therapy (1.8% vs. 5.6%), older menarche (12.97 vs. 12.75) and a higher rate of current menstruation (36% vs. 24). LEP women were associated with a lower probability of having a screening mammogram in multivariate analysis (OR: 0.67, 95% CI: 0.51-0.87). When LEP was subdivided into Spanish and "other" languages, Spanish speakers were associated with a lower probability of a screening mammogram (OR 0.67, 95% CI 0.49-0.90) while controlling for the same covariates. CONCLUSION: The results from our study showed that LEP women are associated with a lower probability of having a screening mammogram. Particularly, the Spanish speakers were found as a vulnerable subgroup.

When is a lipoma not a lipoma? Case report presenting a lipoblastoma-like tumor of the gluteal cleft in an older gentleman with literature review.

INTRODUCTION AND IMPORTANCE: Lipoblastoma-like tumors are rare tumors that can be confused with lipoblastomas and liposarcomas but have distinct characteristics. This tumor has previously been identified in the vulva of females, and recently in isolated cases of young males. Given its rarity, we present an instance of this tumor in an older man, demonstrating that this pathology is not limited to a specific age or sex, and surgeons and pathologists must be aware of it in their differential. CASE PRESENTATION: A 58-year-old male presented for evaluation of an enlarging mass in his right gluteal cleft. Prior to referral for surgical evaluation, the patient underwent an ultrasound-guided biopsy of the mass. Histologically, the tumor was a low-grade cellular spindle cell neoplasm in a fibrous to myxoid stroma. Immunohistochemical and molecular workup ruled out several malignant mesenchymal neoplasms, including myxoid liposarcoma, dedifferentiated liposarcoma, melanoma, low-grade fibromyxoid sarcoma, and sarcomatoid carcinoma. The patient initially declined surgery, but the mass continued to grow, and excision was chosen given the uncertain pathology. The tumor was resected with negative margins and histologically characterized as a "lipoblastoma-like lesion", with features of a myxoid liposarcoma and spindle cell lipoma. Seven months post-resection, there were no signs of recurrence or metastasis. CLINICAL DISCUSSION: Despite radiologic and pathologic similarities to malignant lipomatous tumors, lipoblastoma-like tumors are benign and have a good prognosis. CONCLUSIONS: Clinicians should be aware of this entity despite its rarity as resection with negative margins is curative and may be needed to rule out more aggressive tumors.

Outcomes are Better With a Medial-Stabilized vs a Posterior-Stabilized Total Knee Implanted With Kinematic Alignment.

BACKGROUND: There is no consensus whether a posterior-stabilized (PS) total knee device is superior to a more congruent, cruciate-substituting, medial-stabilized device (MS). This study compared the clinical outcomes of these devices. The primary hypothesis was that the clinical outcomes would be better in the MS group implanted with kinematic alignment. METHODS: This prospective, randomized, single-center Level 1 study compared the outcomes of 99 patients who received a PS device and 101 patients who received an MS device implanted with kinematic alignment. Institutional Review Board approval and informed consent were obtained. Clinical and radiographic assessments were performed preoperatively, 6 weeks, 6 months, and annually. RESULTS: All subjects reached the minimum follow-up of 2 years. There were no statistically significant differences in demographic characteristics, preoperative scores, or alignment (preoperative or postoperative). Tourniquet time was 7.24% longer for the PS group (40.28 min vs 37.56 min, P < .0086). There were significant differences between groups for the 1-year and 2-year Knee Society scores, Forgotten Joint Score, and ROM; in every case favoring the MS group. The FJS was 68.3 in the MS group at 2 years and 58.3 in the PS group (P = .02). The maximum flexion at 2 years was 132° in the MS group and 124° in the PS group (P < .0001). CONCLUSION: The clinical outcomes of the MS group at 1 and 2 years were better. At the minimum 2-year follow-up, the results demonstrate the superiority of the medial-stabilized device in terms of multiple clinical outcomes. LEVEL OF EVIDENCE: I.

Spinal Tuberculosis Secondary to Intravesical Bacille Calmette-Guerin Treatment for Bladder Cancer.

Intravesical administration of bacille Calmette-Guérin (BCG) is an important component of the gold standard in treating non-muscle invasive bladder cancer (NMIBC). However, complications of this treatment include infections caused by the dissemination of Mycobacterium bovis. We present a case of a 62-year-old man who had been treated with intravesical BCG for bladder cancer and developed an M. bovis infection of his vertebral column. About four months after completing the BCG treatment, he developed an acute onset of severe upper thoracic radicular back pain, with radiation anteriorly to his sternum. Examination revealed the presence of early myelopathy. After other causes were ruled out, he was diagnosed with the infection four months later. He was investigated for the pain, with resulting imaging identifying an erosive ventral epidural mass at the T4-T5 levels causing cord compression. The patient underwent a transthoracic procedure to evacuate the paraspinal mass lesion and obtain a diagnostic biopsy, followed by a posterolateral decompression of the lesion and posterior instrumented stabilization. Pathology resulted in the identification of a granuloma with a single acid-fast bacillus (AFB) from the paraspinal abscess, thus being diagnostic of a mycobacterial granuloma with paraspinal involvement. We subsequently performed an extensive review of current literature, looking at articles on spinal osteomyelitis following intravesical BCG treatment of bladder cancer. We identified 26 documented cases in English literature. We present our case report with a good outcome at 24 months, resolving with appropriate chemotherapy. Additionally, we completed a systematic review of the literature and discuss this infrequent iatrogenic pathology. Our report reveals the good response to targeted therapy in the case of osteomyelitis at other skeletal sites and that practitioners caring for these patients maintain a high degree of suspicion in the workup of these patients. Early identification and treatment can appropriately treat osteomyelitis with good long-term outcomes.

Timing and Clinical Significance of Fluid Overload in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Fluid overload is associated with worse outcomes in adult and pediatric acute respiratory distress syndrome. However, the time-course of fluid overload and its relationship to outcome has not been described. We aimed to determine the relationship between the timing of fluid overload and outcomes over the first 7 days after acute respiratory distress syndrome onset in children. DESIGN: Retrospective cohort study. SETTING: Single tertiary care PICU. PATIENTS: Intubated children with acute respiratory distress syndrome between 2011 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily and cumulative total fluid intake, total output, urine output, and fluid balance were collected for each 24-hour period from days 1 to 7 after acute respiratory distress syndrome onset. We tested the association between daily cumulative fluid metrics with PICU mortality and probability of extubation by 28 days using multivariable logistic and competing risk regression, respectively. In a subset of children, plasma was collected on day 1 and day 3 of acute respiratory distress syndrome and angiopoietin-2 quantified. Of 723 children with acute respiratory distress syndrome, 132 died (18%). In unadjusted analysis, nonsurvivors had higher cumulative fluid balance starting on day 3. In multivariable analysis, a positive cumulative fluid balance on days 5 through 7 was associated with increased mortality. Higher cumulative fluid balance on days 4 to 7 was associated with lower probability of extubation. Elevated angiopoietin-2 on day 1 predicted early (within 3 d) fluid overload greater than or equal to 10%, and elevated angiopoietin-2 on day 3 predicted late (between days 4 and 7) fluid overload. CONCLUSIONS: Fluid overload after day 4 of acute respiratory distress syndrome, but not before, was associated with worse outcomes. Higher angiopoietin-2 predicted subsequent fluid overload. Our results suggest that future interventions aimed at managing fluid overload may have differential efficacy depending on when in the time-course of acute respiratory distress syndrome they are initiated.

Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease.

BACKGROUND: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. OBJECTIVES: We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. METHODS: Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. RESULTS: Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. CONCLUSION: These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.

Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease that is known to be, at least in part, genetically determined. Mutations in caspase recruitment domain-containing protein 14 (CARD14) have been shown to result in various forms of psoriasis and related disorders. OBJECTIVE: We aimed to identify rare DNA variants conferring a significant risk for AD through genetic and functional studies in a cohort of patients affected with severe AD. METHODS: Whole-exome and direct gene sequencing, immunohistochemistry, real-time PCR, ELISA, and functional assays in human keratinocytes were used. RESULTS: In a cohort of patients referred with severe AD, DNA sequencing revealed in 4 patients 2 rare heterozygous missense mutations in the gene encoding CARD14, a major regulator of nuclear factor κB (NF-κB). A dual luciferase reporter assay demonstrated that both mutations exert a dominant loss-of-function effect and result in decreased NF-κB signaling. Accordingly, immunohistochemistry staining showed decreased expression of CARD14 in patients' skin, as well as decreased levels of activated p65, a surrogate marker for NF-κB activity. CARD14-deficient or mutant-expressing keratinocytes displayed abnormal secretion of key mediators of innate immunity. CONCLUSIONS: Although dominant gain-of-function mutations in CARD14 are associated with psoriasis and related diseases, loss-of-function mutations in the same gene are associated with a severe variant of AD.

Distribution of Late-Onset Neonatal Sepsis Pathogens Differs in Inpatient and Outpatient Settings.

OBJECTIVE: We sought to examine pathogen distribution and clinical presentation of late-onset sepsis (LOS) at an urban tertiary care center. STUDY DESIGN: We performed a retrospective review of all culture-confirmed cases of LOS presenting to our institution from 2013 to 2017. Medical records were evaluated for demographic information, sepsis risk factors, encounter location, and clinical outcome. RESULTS: We identified 97 cases of LOS, with a median age at diagnosis of 25 days. The most common pathogens were Escherichia coli (22.7%), Staphylococcus aureus (17.5%), coagulase-negative staphylococci (12.4%), and Enterococcus faecalis (12.4%). Infections due to E. coli predominated in the outpatient setting (44%), whereas S. aureus and Gram-negative organisms other than E. coli were more frequently isolated from inpatients (21 and 24%, respectively). Gram-positive organisms were more common in infants delivered through cesarean section (p = 0.002) and were associated with more complications (p = 0.03). Escherichia coli LOS presented at an earlier age than S. aureus (15 vs. 32 days; p = 0.04). Of the 15 cases of meningitis, 40% did not have a positive blood culture. CONCLUSION: Pathogen distribution in our population was different from those previously reported, with a higher prevalence of S. aureus. Encounter location and age at presentation varied significantly by pathogen.

Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second-line switches in Swaziland.

INTRODUCTION: As antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource-constrained settings report significant shortfalls. METHODS: From a public sector HIV programme in rural Swaziland, we evaluated the VL cascade of adults (≥18 years) on ART from the time of the first elevated VL (>1000 copies/mL) between January 2013 and June 2014 to treatment switching by December 2015. We additionally described HIV drug resistance for patients with virological failure. We used descriptive statistics and Kaplan-Meier estimates to describe the different steps along the cascade and regression models to determine factors associated with outcomes. RESULTS AND DISCUSSION: Of 828 patients with a first elevated VL, 252 (30.4%) did not receive any enhanced adherence counselling (EAC). Six hundred and ninety-six (84.1%) patients had a follow-up VL measurement, and the predictors of receiving a follow-up VL were being a second-line patient (adjusted hazard ratio (aHR): 0.72; p = 0.051), Hlathikhulu health zone (aHR: 0.79; p = 0.013) and having received two EAC sessions (aHR: 1.31; p = 0.023). Four hundred and ten patients (58.9%) achieved VL re-suppression. Predictors of re-suppression were age 50 to 64 (adjusted odds ratio (aOR): 2.02; p = 0.015) compared with age 18 to 34 years, being on second-line treatment (aOR: 3.29; p = 0.003) and two (aOR: 1.66; p = 0.045) or three (aOR: 1.86; p = 0.003) EAC sessions. Of 278 patients eligible to switch to second-line therapy, 120 (43.2%) had switched by the end of the study. Finally, of 155 successfully sequenced dried blood spots, 144 (92.9%) were from first-line patients. Of these, 133 (positive predictive value: 92.4%) had resistance patterns that necessitated treatment switching. CONCLUSIONS: Patients on ART with high VLs were more likely to re-suppress if they received EAC. Failure to re-suppress after counselling was predictive of genotypically confirmed resistance patterns requiring treatment switching. Delays in switching were significant despite the ability of the WHO algorithm to predict treatment failure. Despite significant progress in recent years, enhanced focus on quality care along the VL cascade in resource-limited settings is crucial.

Corrigendum: Germline hypomorphic CARD11 mutations in severe atopic disease.

This corrects the article DOI: 10.1038/ng.3898.

Germline hypomorphic CARD11 mutations in severe atopic disease.

Few monogenic causes for severe manifestations of common allergic diseases have been identified. Through next-generation sequencing on a cohort of patients with severe atopic dermatitis with and without comorbid infections, we found eight individuals, from four families, with novel heterozygous mutations in CARD11, which encodes a scaffolding protein involved in lymphocyte receptor signaling. Disease improved over time in most patients. Transfection of mutant CARD11 expression constructs into T cell lines demonstrated both loss-of-function and dominant-interfering activity upon antigen receptor-induced activation of nuclear factor-κB and mammalian target of rapamycin complex 1 (mTORC1). Patient T cells had similar defects, as well as low production of the cytokine interferon-γ (IFN-γ). The mTORC1 and IFN-γ production defects were partially rescued by supplementation with glutamine, which requires CARD11 for import into T cells. Our findings indicate that a single hypomorphic mutation in CARD11 can cause potentially correctable cellular defects that lead to atopic dermatitis.

Indication for Lower Extremity Revascularization and Hospital Profiling of Readmissions.

BACKGROUND: Surgical readmissions are common, costly, and the focus of national quality improvement efforts. Given the relatively high readmission rates among vascular patients, pay-for-performance initiatives such as Medicare's Hospital Readmissions Reduction Program (HRRP) have targeted vascular surgery for increased scrutiny in the near future. Yet, the extent to which institutional case mix influences hospital profiling remains unexplored. We sought to evaluate whether higher readmission rates in vascular surgery are a reflection of worse performance or of treating sicker patients. METHODS: This retrospective observational cohort study of the national Medicare population includes 479,047 beneficiaries undergoing lower extremity revascularization (LER) in 1,701 hospitals from 2005 to 2009. We employed hierarchical logistic regression to mimic Center for Medicare and Medicaid Services methodology accounting for age, gender, preexisting comorbidities, and differences in hospital operative volume. We estimated 30-day risk-standardized readmission rates (RSRR) for each hospital when including (1) all LER patients; (2) claudicants; or (3) high-risk patients (rest pain, ulceration, or tissue loss). We stratified hospitals into quintiles based on overall RSRR for all LERs and examined differences in RSRR for claudicants and high-risk patients between and within quintiles. Next, we evaluated differences in case mix (the proportion of claudicants and high-risk patients treated) across quintiles. Finally, we simulated differences in the receipt of penalties before and after adjusting for hospital case mix. RESULTS: Readmission rates varied widely by indication: 7.3% (claudicants) vs. 19.5% (high risk). Even after adjusting for patient demographics, length of stay, and discharge destination, high-risk patients were significantly more likely to be readmitted (odds ratio 1.76, 95% confidence interval 1.71-1.81). The Best hospitals (top quintile) under the HRRP treated a much lower proportion of high-risk patients compared with the Worst hospitals (bottom quintile) (20% vs. 56%, P < 0.001). In the absence of case-mix adjustment, we observed a stepwise increase in the proportion of hospitals penalized as the proportion of high-risk patients treated increased (35-60%, P < 0.001). However, after case-mix adjustment, there were no differences between quintiles in the proportion of hospitalized penalized (50-46%, P = 0.30). CONCLUSION: Our findings suggest that the differences in readmission rates following LER are largely driven by hospital case mix rather than true differences in quality.