Tyrosine Sulfation at Antibody Light Chain CDR-1 Increases Binding Affinity and Neutralization Potency to Interleukine-4.

Structure and function of therapeutic antibodies can be modulated by a variety of post-translational modifications (PTM). Tyrosine (Tyr) sulfation is a type of negatively charged PTM that occurs during protein trafficking through the Golgi. In this study, we discovered that an anti-interleukin (IL)-4 human IgG1, produced by transiently transfected HEK293 cells, contained a fraction of unusual negatively charged species. Interestingly, the isolated acidic species exhibited a two-fold higher affinity to IL-4 and a nearly four-fold higher potency compared to the main species. Mass spectrometry (MS) showed the isolated acidic species possessed an +80-Dalton from the expected mass, suggesting an occurrence of Tyr sulfation. Consistent with this hypothesis, we show the ability to control the acidic species during transient expression with the addition of Tyr sulfation inhibitor sodium chlorate or, conversely, enriched the acidic species from 30% to 92% of the total antibody protein when the IL-4 IgG was co-transfected with tyrosylprotein sulfotransferase genes. Further MS and mutagenesis analysis identified a Tyr residue at the light chain complementarity-determining region-1 (CDRL-1), which was sulfated specifically. These results together have demonstrated for the first time that Tyr sulfation at CDRL-1 could modulate antibody binding affinity and potency to a human immune cytokine.

Pre-referral rectal artesunate is no "magic bullet" in weak health systems.

Severe malaria is a potentially fatal condition that requires urgent treatment. In a clinical trial, a sub-group of children treated with rectal artesunate (RAS) before being referred to a health facility had an increased chance of survival. We recently published in BMC Medicine results of the CARAMAL Project that did not find the same protective effect of pre-referral RAS implemented at scale under real-world conditions in three African countries. Instead, CARAMAL identified serious health system shortfalls that impacted the entire continuum of care, constraining the effectiveness of RAS. Correspondence to the article criticized the observational study design and the alleged interpretation and consequences of our findings.Here, we clarify that we do not dispute the life-saving potential of RAS, and discuss the methodological criticism. We acknowledge the potential for confounding in observational studies. Nevertheless, the totality of CARAMAL evidence is in full support of our conclusion that the conditions under which RAS can be beneficial were not met in our settings, as children often failed to complete referral and post-referral treatment was inadequate.The criticism did not appear to acknowledge the realities of highly malarious settings documented in detail in the CARAMAL project. Suggesting that trial-demonstrated efficacy is sufficient to warrant large-scale deployment of pre-referral RAS ignores the paramount importance of functioning health systems for its delivery, for completing post-referral treatment, and for achieving complete cure. Presenting RAS as a "magic bullet" distracts from the most urgent priority: fixing health systems so they can provide a functioning continuum of care and save the lives of sick children.The data underlying our publication is freely accessible on Zenodo.

Analysis of Complications in Patients With a History of Cannabis Use and Tobacco Use Undergoing Implant-Based Breast Reconstruction.

BACKGROUND: There is limited information regarding the perioperative effects of marijuana in breast reconstructive surgeries. OBJECTIVES: The objective of this study was to explore the association between a history of cannabis use and postoperative complications in the setting of implant-based breast reconstruction. METHODS: Two databases, TriNetX and PearlDiver, were queried for patients undergoing implant-based breast reconstruction. Patients were divided into 4 groups based on active ICD-10 diagnostic codes: (1) cannabis use only, (2) tobacco use only, (3) cannabis and tobacco use, and (4) neither cannabis nor tobacco use. Associations with postoperative complications were analyzed with a logistic regression test. RESULTS: TriNetX search revealed that 327 patients had an active diagnosis of cannabis use only and 1118 had an active diagnosis of tobacco use only. Patients in the cannabis only cohort had a significantly increased risk of developing surgical site infection. Patients in the tobacco only cohort had significantly increased risk of developing wound dehiscence, need for debridement, and surgical site infection. The PearlDiver search included 472 patients who had an active diagnosis of both cannabis and tobacco use and 17,361 patients with a diagnosis of tobacco use only. Patients with a diagnosis of cannabis and tobacco use had a significantly increased risk of developing postoperative complications including surgical site infection, wound dehiscence, need for incision and drainage, and debridement. CONCLUSIONS: Patients undergoing implant-based breast reconstruction with an active diagnosis of cannabis with or without tobacco use were at increased risk of developing postoperative complications, and the risk was even higher in patients using both tobacco and cannabis.

Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study.

BACKGROUND: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. METHODS: An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. RESULTS: Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35-6.92 and aOR=2.16, 95% CI 1.11-4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45-0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). CONCLUSIONS: Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov : NCT03568344.

Environmentally sustainable practices in global health research and higher education institutions: Lessons from consultation with the TropEd Global Health institutions.

OBJECTIVE: To examine how global health institutions are reducing the greenhouse gas emissions from their own operations and analyse the facilitators and barriers to achieving decarbonisation goals. METHODS: We reviewed the sustainability goals and implementation plans of 10 global health universities from the 'TropEd' network. We systematically collected information from institutional websites and annual reports. Through online interviews, 11 key informants validated the information from 9 of the institutions and shared their opinions regarding what factors are helping their institutions decarbonise and what factors are hindering progress. RESULTS: 4/10 institutions sampled have a sustainability strategy and implementation plan, only 3/10 have specific decarbonisation goals, and 3/10 are reporting on progress. 5/10 institutions reported that they are in the process of determining emission reduction targets. CONCLUSION: This paper identifies common success factors that facilitate decarbonisation as well as common challenges and how they are being tackled, and makes recommendations on sustainability efforts in academic institutions.

Using Hawkes Processes to model imported and local malaria cases in near-elimination settings.

Developing new methods for modelling infectious diseases outbreaks is important for monitoring transmission and developing policy. In this paper we propose using semi-mechanistic Hawkes Processes for modelling malaria transmission in near-elimination settings. Hawkes Processes are well founded mathematical methods that enable us to combine the benefits of both statistical and mechanistic models to recreate and forecast disease transmission beyond just malaria outbreak scenarios. These methods have been successfully used in numerous applications such as social media and earthquake modelling, but are not yet widespread in epidemiology. By using domain-specific knowledge, we can both recreate transmission curves for malaria in China and Eswatini and disentangle the proportion of cases which are imported from those that are community based.

How long is the last mile? Evaluating successful malaria elimination trajectories.

BACKGROUND: Many national malaria programmes have set goals of eliminating malaria, but realistic timelines for achieving this goal remain unclear. In this investigation, historical data are collated on countries that successfully eliminated malaria to assess how long elimination has taken in the past, and thus to inform feasible timelines for achieving it in the future. METHODS: Annual malaria case series were sought for 56 successful elimination programmes through a non-systematic review. Up to 40 years of annual case counts were compiled leading up to the first year in which zero locally acquired or indigenous cases were reported. To separate the period over which effective elimination efforts occurred from prior background trends, annual case totals were log transformed, and their slopes evaluated for a breakpoint in linear trend using the segmented package in R. The number of years from the breakpoint to the first year with zero cases and the decline rate over that period were then calculated. Wilcox-Mann-Whitney tests were used to evaluate whether a set of territory characteristics were associated with the timelines and decline rates. RESULTS: Case series declining to the first year with zero cases were compiled for 45/56 of the candidate elimination programmes, and statistically significant breakpoints were identified for 42. The median timeline from the breakpoint to the first year with zero local cases was 12 years, over which cases declined at a median rate of 54% per year. Prior to the breakpoint, the median trend was slightly decreasing with median annual decline of < 3%. Timelines to elimination were fastest among territories that lacked land boundaries, had centroids in the Tropics, received low numbers of imported cases, and had elimination certified by the World Health Organization. CONCLUSION: The historical case series assembled here may help countries with aspirations of malaria elimination to set feasible milestones towards this goal. Setting goals for malaria elimination on short timescales may be most appropriate in isolated, low importation settings, such as islands, while other regions aiming to eliminate malaria must consider how to sustainably fund and maintain vital case management and vector control services until zero cases are reached.

Structure-function relationships of the soluble form of the antiaging protein Klotho have therapeutic implications for managing kidney disease.

The fortuitously discovered antiaging membrane protein αKlotho (Klotho) is highly expressed in the kidney, and deletion of the Klotho gene in mice causes a phenotype strikingly similar to that of chronic kidney disease (CKD). Klotho functions as a co-receptor for fibroblast growth factor 23 (FGF23) signaling, whereas its shed extracellular domain, soluble Klotho (sKlotho), carrying glycosidase activity, is a humoral factor that regulates renal health. Low sKlotho in CKD is associated with disease progression, and sKlotho supplementation has emerged as a potential therapeutic strategy for managing CKD. Here, we explored the structure-function relationship and post-translational modifications of sKlotho variants to guide the future design of sKlotho-based therapeutics. Chinese hamster ovary (CHO)- and human embryonic kidney (HEK)-derived WT sKlotho proteins had varied activities in FGF23 co-receptor and ß-glucuronidase assays in vitro and distinct properties in vivo Sialidase treatment of heavily sialylated CHO-sKlotho increased its co-receptor activity 3-fold, yet it remained less active than hyposialylated HEK-sKlotho. MS and glycopeptide-mapping analyses revealed that HEK-sKlotho is uniquely modified with an unusual N-glycan structure consisting of N,N'-di-N-acetyllactose diamine at multiple N-linked sites, one of which at Asn-126 was adjacent to a putative GalNAc transfer motif. Site-directed mutagenesis and structural modeling analyses directly implicated N-glycans in Klotho's protein folding and function. Moreover, the introduction of two catalytic glutamate residues conserved across glycosidases into sKlotho enhanced its glucuronidase activity but decreased its FGF23 co-receptor activity, suggesting that these two functions might be structurally divergent. These findings open up opportunities for rational engineering of pharmacologically enhanced sKlotho therapeutics for managing kidney disease.

The Art of M. Michael Cohen, Jr.

This article describes Dr. M. Michael Cohen, Jr.'s passion for art and music. His two sons share family memories and photos. Dr. Cohen developed a keen interest in the visual arts, collecting lithographs, enjoying many art exhibits, and conducting original research on Picasso's art. His interest in faces formed a central connection between his professional life and his artistic interest. His love of music began as a young boy. Classical music and opera were the soundtrack to his creative pursuits. He enjoyed sharing music with his family immensely, especially opera performances.

High-risk, recurrent and oligometastatic prostate cancer: recent developments on the role of radiation.

PURPOSE OF REVIEW: Although a standard of care in the treatment of organ-confined prostate cancer, use of radiation for treatment in the high-risk, metastatic and salvage settings is evolving rapidly. RECENT FINDINGS: Recent clinical trials have explored the role of increased treatment for high-risk disease with the addition of adjuvant chemotherapy and expanded the role of radiation in settings previously reserved for systemic therapy. Addition of adjuvant chemotherapy for high-risk prostate cancer is controversial and recent evidence is discussed that continues to refine the patient population for further evaluation. Evidence recently published demonstrates that for patients with low burden metastatic disease and those with oligometastatic disease may have a survival benefit with radiation treatment to all sites of known disease. Finally, reirradiation after prior radiotherapy-based treatment offers a potential salvage option for patients with locally recurrent prostate cancer. SUMMARY: As treatment paradigms evolve for prostate cancer, recent evidence continues to demonstrate benefit for the use of local therapy, both in patients with organ-confined disease and, more increasingly, in those with limited metastatic or locally recurrent disease. Further work is needed to identify subgroups of patients who may benefit from available treatment escalation approaches.

Choosing Between Mastectomy and Breast-Conserving Therapy: Is Patient Distress an Influencing Factor?

BACKGROUND: Breast-conserving therapy (BCT) offers oncologic outcomes similar to those of mastectomy, yet many patients, when provided the option, choose mastectomy. This study aimed to evaluate the relationship between patient-reported distress and surgical decisions and to determine factors predictive of choosing BCT versus mastectomy. METHODS: Patients with newly diagnosed breast cancer deemed candidates for BCT who completed a distress screen at their initial visit to an academic institution between 2016 and 2019 were retrospectively reviewed. This screening tool captures distress in emotional, social, health, and practical domains on a scale of 0 to 10. The distress scores were compared against surgical decisions using nonparametric Wilcoxon rank-sum tests. Patient factors associated with surgical choice were analyzed using chi-square, Fisher's exact, and Student's t tests. A two-sided p value lower than 0.05 was considered significant. RESULTS: Of 506 patients deemed eligible for BCT, 430 (85%) chose BCT and 76 (15%) pursued mastectomy. The distress levels did not differ significantly between the surgical options. The patients who underwent mastectomy were on the average younger (50.7 vs 60.4 years; p < 0.0001), presented with palpable masses (p < 0.0001), had stage 0, 2, or 3 versus stage 1 disease (p < 0.0001), sought consultation for second opinions (19.7% vs 8.6%; p = 0.0032), received neoadjuvant chemotherapy (31.6% vs 16.3%; p = 0.0016), or had deleterious gene mutations (21.1% vs 5.1%; p < 0.0001). CONCLUSIONS: Distress was not associated with the pursuit of surgical treatment. Rather, younger age, search for a second opinion, and a palpable mass present at presentation were associated with more aggressive surgical decisions. Understanding factors that influence surgical decision-making is critical in guiding informed decisions that reflect patient values.

Phonon counting and intensity interferometry of a nanomechanical resonator.

In optics, the ability to measure individual quanta of light (photons) enables a great many applications, ranging from dynamic imaging within living organisms to secure quantum communication. Pioneering photon counting experiments, such as the intensity interferometry performed by Hanbury Brown and Twiss to measure the angular width of visible stars, have played a critical role in our understanding of the full quantum nature of light. As with matter at the atomic scale, the laws of quantum mechanics also govern the properties of macroscopic mechanical objects, providing fundamental quantum limits to the sensitivity of mechanical sensors and transducers. Current research in cavity optomechanics seeks to use light to explore the quantum properties of mechanical systems ranging in size from kilogram-mass mirrors to nanoscale membranes, as well as to develop technologies for precision sensing and quantum information processing. Here we use an optical probe and single-photon detection to study the acoustic emission and absorption processes in a silicon nanomechanical resonator, and perform a measurement similar to that used by Hanbury Brown and Twiss to measure correlations in the emitted phonons as the resonator undergoes a parametric instability formally equivalent to that of a laser. Owing to the cavity-enhanced coupling of light with mechanical motion, this effective phonon counting technique has a noise equivalent phonon sensitivity of 0.89 ± 0.05. With straightforward improvements to this method, a variety of quantum state engineering tasks using mesoscopic mechanical resonators would be enabled, including the generation and heralding of single-phonon Fock states and the quantum entanglement of remote mechanical elements.

Telehealth: Could It Be an Avenue to Microvascular Breast Reconstruction for Patients with Geographical Barriers?

BACKGROUND: All women undergoing a mastectomy have the right to reconstruction. However, many women do not receive reconstruction and many more are not aware of all the reconstructive options available to them. Travel distance to a center that provides reconstruction and subsequent follow-up may be a contributing factor to this disparity especially among those who seek microsurgical options. Telehealth, which provides patients with remote video consultations and decreases the travel burden, may be a solution to optimize the accessibility of breast reconstruction for these patients. The purpose of this study was to discuss the efficacy and reliability of telehealth to overcome geographic barriers. METHODS: Patients who received breast reconstruction and participated in video telehealth visits between February and May 2020 were included in this study. Patient demographics, comorbidities, and clinical outcomes were collected. Video telehealth encounters were reviewed to determine specific concerns and questions discussed during these encounters. RESULTS: A total of 235 breast reconstruction surgery patient encounters were recorded for 4 plastic surgeons who offer microsurgical breast reconstruction. Eighty-eight patients (37.4%) were seen as telehealth visits, 20 (22.7%) of which were new patient visits. Eight (9.09%) patients were microsurgical breast reconstruction candidates and 25 (28.4%) were following-up after microsurgical breast reconstruction. The majority of telehealth visits included normally healing wounds in the postoperative patient. CONCLUSION: Telehealth provides an avenue for premastectomy consultation, second opinion visits, and postoperative follow-up for patients who have geographical barriers precluding them from reaching plastic surgeons who perform all types of breast reconstruction.

Effects of Intravenous Tranexamic Acid During Rhytidectomy: A Randomized, Controlled, Double-Blind Pilot Study.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent shown to decrease intraoperative bleeding, reduce transfusions, and improve outcomes across multiple specialties. Within plastic surgery, initial reports are encouraging but formal studies are lacking. OBJECTIVES: The aim of this study was to determine whether intravenous (IV) TXA has any effect on intraoperative bleeding or postoperative sequelae in patients undergoing a deep-plane facelift. METHODS: This is a prospective, randomized, double-blind, case series in a private practice surgery center. The participants were 44 patients undergoing rhytidectomy with the senior authors (R.A.G. or M.J.G). The treatment group received a 1-g dose of IV TXA prior to skin incision and the same dose 4 hours later (vs saline). Bleeding was rated mild, moderate, or severe. Postoperative ecchymosis and edema were subjectively evaluated by patient and surgeon and scores were aggregated for analysis. RESULTS: The TXA group showed decreased intraoperative bleeding but this difference did not reach statistical significance. Postoperative ecchymosis/edema ratings were lower for patients who received TXA, including a statistically significant decrease in surgeon-rated bruising. TXA resulted in a statistically significant decrease in postoperative collections in this study and no major complications occurred. CONCLUSIONS: TXA is a safe, low-cost addition to any existing surgical protocol and may lead to fewer surgical sequelae and improved satisfaction. Although we did not observe a dramatically different intraoperative experience, postoperative bruising and collections were significantly reduced. TXA acid may have great value in the management of patients undergoing rhytidectomy and its use warrants further study.

Revisiting the Relationship Between Hospital Case Volume and Outcomes in Abdominally Based Free Flap Breast Reconstruction.

BACKGROUND: Increased operative volume has been associated with benefits in patient outcomes for a variety of surgical procedures. In autologous abdominally based breast reconstruction, however, there are few studies assessing the association between procedure volume and patient outcomes. The objectives of this study are to evaluate the associations between abdominal-based free flap breast reconstruction and patient outcomes. METHODS: The 2013-2014 Healthcare Cost and Utilization Project National Inpatient Sample was queried for all female patients with a diagnosis of breast cancer who underwent mastectomy and immediate abdominally based breast reconstruction (deep inferior epigastric perforator or transverse rectus abdominus muscle free flaps). Outcomes included occurrence of major or surgical site in-hospital complications, hospital cost, and length of stay (LOS). High-volume (HV) hospitals were defined as the 90th percentile of annual case volume or higher (>18 cases/y). Multivariate regressions and generalized linear modeling with gamma log-link function were performed to access the outcomes associated with HV hospitals. RESULTS: Overall, 7145 patients at 473 hospitals were studied; of these, 42.4% of patients were treated at HV hospitals. There were significant differences in unadjusted major complications (2.1% vs 4.3%; P < 0.001) and unadjusted surgical site complications (3.5% vs 6.1%; P < 0.001) between HV and non-HV hospitals. After adjustments for clinical and hospital characteristics, patients treated at HV hospitals were less likely to experience a major complication (odds ratio, 0.488; 95% confidence interval, 0.353-0.675; P < 0.001) or surgical site complication (odds ratio, 0.678; 95% confidence interval, 0.519-0.887; P = 0.005). There was no difference in inpatient cost between HV and non-HV hospitals ($26,822 vs $26,295; marginal cost, $528; P = 0.102); however, HV hospitals had a shorter LOS (4.31 vs 4.40 days; marginal LOS, -0.10 days; P = 0.005). CONCLUSIONS: Hospitals that perform a larger volume of immediate abdominal-based breast reconstructions after mastectomy, when compared with those that perform a lower volume of these procedures, seem to have an associated lower rate of major complications and a shorter LOS. However, these same HV centers demonstrate no decrease in costs. Further research is needed to understand how these HV centers can reduce hospital costs.

"Remarkable solutions to impossible problems": lessons for malaria from the eradication of smallpox.

BACKGROUND: Malaria elimination and eventual eradication will require internationally coordinated approaches; sustained engagement from politicians, communities, and funders; efficient organizational structures; innovation and new tools; and well-managed programmes. As governments and the global malaria community seek to achieve these goals, their efforts should be informed by the substantial past experiences of other disease elimination and eradication programmes, including that of the only successful eradication programme of a human pathogen to date: smallpox. METHODS: A review of smallpox literature was conducted to evaluate how the smallpox programme addressed seven challenges that will likely confront malaria eradication efforts, including fostering international support for the eradication undertaking, coordinating programmes and facilitating research across the world's endemic countries, securing sufficient funding, building domestic support for malaria programmes nationally, ensuring strong community support, identifying the most effective programmatic strategies, and managing national elimination programmes efficiently. RESULTS: Review of 118 publications describing how smallpox programmes overcame these challenges suggests eradication may succeed as a collection of individual country programmes each deriving local solutions to local problems, yet with an important role for the World Health Organization and other international entities to facilitate and coordinate these efforts and encourage new innovations. Publications describing the smallpox experience suggest the importance of avoiding burdensome bureaucracy while employing flexible, problem-solving staff with both technical and operational backgrounds to overcome numerous unforeseen challenges. Smallpox's hybrid strategy of leveraging basic health services while maintaining certain separate functions to ensure visibility, clear targets, and strong management, aligns with current malaria approaches. Smallpox eradication succeeded by employing data-driven strategies that targeted resources to the places where they were most needed rather than attempting to achieve mass coverage everywhere, a potentially useful lesson for malaria programmes seeking universal coverage with available tools. Finally, lessons from smallpox programmes suggest strong engagement with the private sector and affected communities can help increase the sustainability and reach of today's malaria programmes. CONCLUSIONS: It remains unclear whether malaria eradication is feasible, but neither was it clear whether smallpox eradication was feasible until it was achieved. To increase chances of success, malaria programmes should seek to strengthen programme management, measurement, and operations, while building flexible means of sharing experiences, tools, and financing internationally.

Strengthening surveillance systems for malaria elimination: a global landscaping of system performance, 2015-2017.

BACKGROUND: Surveillance is a core component of an effective system to support malaria elimination. Poor surveillance data will prevent countries from monitoring progress towards elimination and targeting interventions to the last remaining at-risk places. An evaluation of the performance of surveillance systems in 16 countries was conducted to identify key gaps which could be addressed to build effective systems for malaria elimination. METHODS: A standardized surveillance system landscaping was conducted between 2015 and 2017 in collaboration with governmental malaria programmes. Malaria surveillance guidelines from the World Health Organization and other technical bodies were used to identify the characteristics of an optimal surveillance system, against which systems of study countries were compared. Data collection was conducted through review of existing material and datasets, and interviews with key stakeholders, and the outcomes were summarized descriptively. Additionally, the cumulative fraction of incident infections reported through surveillance systems was estimated using surveillance data, government records, survey data, and other scientific sources. RESULTS: The landscaping identified common gaps across countries related to the lack of surveillance coverage in remote communities or in the private sector, the lack of adequate health information architecture to capture high quality case-based data, poor integration of data from other sources such as intervention information, poor visualization of generated information, and its lack of availability for making programmatic decisions. The median percentage of symptomatic cases captured by the surveillance systems in the 16 countries was estimated to be 37%, mostly driven by the lack of treatment-seeking in the public health sector (64%) or, in countries with large private sectors, the lack of integration of this sector within the surveillance system. CONCLUSIONS: The landscaping analysis undertaken provides a clear framework through which to identify multiple gaps in current malaria surveillance systems. While perfect systems are not required to eliminate malaria, closing the gaps identified will allow countries to deploy resources more efficiently, track progress, and accelerate towards malaria elimination. Since the landscaping undertaken here, several countries have addressed some of the identified gaps by improving coverage of surveillance, integrating case data with other information, and strengthening visualization and use of data.

Racial disparities in postmastectomy breast reconstruction: National trends in utilization from 2005 to 2014.

BACKGROUND: Evidence of racial disparities in the receipt of postmastectomy breast reconstruction is well documented. The objective of this study was to describe trends in racial disparities overall and by reconstructive technique. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify women who underwent mastectomy and/or breast reconstruction from 2005 to 2014. Patient demographics were recorded, and cases were grouped by reconstructive status and technique. Trends were assessed with the Cochran-Armitage test and the index of disparity. RESULTS: Over the study period, 92,960 postmastectomy patients were identified (77,049 white women, 10,396 black women, 4939 Asian women, and 576 Native American women), of whom 46,931 underwent reconstruction. Of these, 7692 women underwent autologous reconstructions (3913 free flaps and 3696 pedicled flaps). From 2005 to 2014, receipt of breast reconstruction by postmastectomy patients rose from 33.2% to 60.0%, receipt of autologous reconstruction by patients who underwent breast reconstruction fell from 30.4% to 15.9%, and receipt of free-flap reconstruction by patients who underwent autologous reconstruction rose from 15.0% to 70.8%. These trends were significant in all racial subgroups (P < .001), except for Native Americans (P = .269). The index of disparity decreased from 51.4% to 22.6% for overall receipt of breast reconstruction, decreased from 10.7% to 7.0% for tissue expander and implant-based reconstruction, increased from 18.0% to 27.3% for autologous reconstruction, and decreased from 66.7% to 4.3% for free-flap reconstruction. CONCLUSIONS: The use of postmastectomy breast reconstruction is steadily rising in the United States. Racial disparities persist, but progress has been made. Further efforts are needed to reduce racial disparities. Cancer 2018;124:2774-2784. © 2018 American Cancer Society.

Does industry funding mean more publications for subspecialty academic plastic surgeons?

BACKGROUND: Conflict of interest among physicians in the context of private industry funding led to the introduction of the Physician Payments Sunshine Act in 2010. This study examined whether private industry funding correlated with scholarly productivity in the respective subspecialties of plastic surgery and the wider academic plastic surgery community. MATERIALS AND METHODS: Full-time plastic surgeons and their academic attributes were identified via institutional websites. Fellowship-trained individuals were segregated into subspecialties of microsurgery, craniofacial surgery, hand surgery, esthetic surgery, and burn surgery. The Center for Medicare and Medicaid Services Open Payment database was used to extract industry funding information. Each individual's bibliometric data were then collected through Scopus to determine the correlation between selected surgeon characteristics, academic productivity, and industry funding. RESULTS: Nine hundred and thirty-five academic plastic surgeons were identified, with 532 having defined subspecialty training. Academic bibliometrics among subspecialty surgeons were comparable among the five groups with esthetic and craniofacial surgeons displaying a preponderance of attaining more industry funding (P = 0.043) and career publications respectively, with the latter not attaining statistical significance (P = 0.12). Overall, research-specific funding (P = 0.014) and higher funding amounts (P < 0.0001) correlated with higher Hirsch indices in tandem with higher academic rank. A funding level of $2000 appeared to be the approximate cutoff above which scholastic productivity became apparent. CONCLUSIONS: Our study demonstrated in detail the association between industry funding and academic bibliometrics in academic plastic surgery of every subspecialty. Even at modest amounts, industry support, especially when research designated, positively influenced research and therefore, academic output.

Surgical site infection in immediate breast reconstruction: Does chemotherapy timing make a difference?

BACKGROUND AND OBJECTIVES: We aim to analyze the impact of chemotherapy timing on surgical site infections (SSI) after immediate breast reconstruction (IBR). METHODS: A retrospective review of patients undergoing IBR between 2010 and 2015 was performed. Patients were divided into four groups: those with neoadjuvant chemotherapy only, adjuvant chemotherapy only, both adjuvant and neoadjuvant, and those with no chemotherapy. Outcomes of interest included SSI and timing of post-operative SSI. RESULTS: A total of 949 reconstructions were performed over the study period. Subgroup breakdown was as follows: A total of 56 (5.9%) neoadjuvant only, 173 (18.2%) adjuvant only, 18 (1.9%) both, and 702 (74.0%) none. Overall infection rates were 10.7%, 10.4%, 22.2%, and 6.1% in the four groups, respectively (P = 0.015). On multivariate analysis, no significant differences were observed when comparing presence or absence of chemotherapy in the overall reconstruction cohort or when subgrouped by reconstruction modality-autologous or alloplastic. There were no significant differences in time from neoadjuvant chemotherapy to surgery date noted between patients who developed a post-operative SSI and those who did not (4.40 ± 1.58 vs 4.72 ± 1.39 weeks; P = 0.517). CONCLUSION: Chemotherapy timing did not increase the odds of surgical site infections in patients undergoing immediate breast reconstruction.