Abdominal donor-site complications following autologous breast reconstruction: A multi-institutional multisurgeon study.

BACKGROUND: The deep inferior epigastric perforator (DIEP) free flap is the gold standard procedure for autologous breast reconstruction. Although breast-related complications have been well described, donor-site complications and contributing patient risk factors are poorly understood. METHODS: We examined a multi-institutional, prospectively maintained database of patients undergoing DIEP free flap breast reconstruction between 2015 and 2020. We evaluated patient demographics, operative details, and abdominal donor-site complications. Logistic regression modeling was used to predict donor-site outcomes based on patient characteristics. RESULTS: A total of 661 patients were identified who underwent DIEP free flap breast reconstruction across multiple institutions. Using logistic regression modeling, we found that body mass index (BMI) was an independent risk factor for umbilical complications (odds ratio [OR] 1.11, confidence interval [CI] 1.04-1.18, p = 0.001), seroma (OR 1.07, CI 1.01-1.13, p = 0.003), wound dehiscence (OR 1.10, CI 1.06-1.15, p = 0.001), and surgical site infection (OR 1.10, CI 1.05-1.15, p = 0.001) following DIEP free flap breast reconstruction. Further, immediate reconstruction decreases the risk of abdominal bulge formation (OR 0.22, CI 0.108-0.429, p = 0.001). Perforator selection was not associated with abdominal morbidity in our study population. CONCLUSIONS: Higher BMI is associated with increased abdominal donor-site complications following DIEP free flap breast reconstruction. Efforts to lower preoperative BMI may help decrease donor-site complications.

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.

Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism.

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common of the muscular dystrophies, affecting nearly 1 in 8000 individuals, and is a cause of profound disability. Genetically, FSHD is linked to the contraction and/or epigenetic de-repression of the D4Z4 repeat array on chromosome 4, thereby allowing expression of the DUX4 gene in skeletal muscle. If the DUX4 transcript incorporates a stabilizing polyadenylation site the myotoxic DUX4 protein will be synthesized, resulting in muscle wasting. The mechanism of toxicity remains unclear, as many DUX4-induced cytopathologies have been described, however cell death does primarily occur through caspase 3/7-dependent apoptosis. To date, most FSHD therapeutic development has focused on molecular methods targeting DUX4 expression or the DUX4 transcript, while therapies targeting processes downstream of DUX4 activity have received less attention. Several studies have demonstrated that inhibition of multiple signal transduction pathways can ameliorate DUX4-induced toxicity, and thus compounds targeting these pathways have the potential to be developed into FSHD therapeutics. To this end, we have screened a group of small molecules curated based on their reported activity in relevant pathways and/or structural relationships with known toxicity-modulating molecules. We have identified a panel of five compounds that function downstream of DUX4 activity to inhibit DUX4-induced toxicity. Unexpectedly, this effect was mediated through an mTor-independent mechanism that preserved expression of ULK1 and correlated with an increase in a marker of active cellular autophagy. This identifies these flavones as compounds of interest for therapeutic development, and potentially identifies the autophagy pathway as a target for therapeutics.

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.

Venous Thromboembolism after Deep Inferior Epigastric Perforator Flap Breast Reconstruction: Review of Outcomes After a Postoperative Prophylaxis Protocol.

BACKGROUND: Deep inferior epigastric perforator (DIEP) flap breast reconstruction is among the higher-risk patient groups for venous thromboembolism (VTE) in plastic surgery. Surgeons often opt for a patient-specific approach to postoperative anticoagulation, and the field has yet to come to a consensus on VTE chemoprophylaxis regimens. METHODS: A new chemoprophylaxis protocol was introduced starting March 2019 that involved two weeks of treatment with enoxaparin, regardless of patient risk factors. A retrospective chart review was conducted on all patients who underwent DIEP flap breast reconstruction at our institution between January 2014 and March 2020. Patients were grouped based on whether they enrolled in the new VTE protocol in the postoperative period or not. Patient demographics, prophylaxis type, and outcomes data were recorded, retrospectively. The primary outcome measure was postoperative VTE incidence. RESULTS: Risk of VTE was significantly higher in patients discharged without VTE prophylaxis compared to patients discharged with prophylaxis (3.7% vs. 0%, p = 0.03). Notably, zero patients in the VTE prophylaxis group developed a DVT or PE. Additionally, the risk of a VTE event was 25 times greater in patients with a Caprini score greater than or equal to 6 (p=0.0002). CONCLUSIONS: We demonstrate the successful implementation of a two-week VTE chemoprophylaxis protocol in DIEP flap breast reconstruction patients that significantly reduces the rate of VTE while not affecting the rate of hematoma complications.

Acceptability, Feasibility, Drug Safety, and Effectiveness of a Pilot Mass Drug Administration with a Single Round of Sulfadoxine-Pyrimethamine Plus Primaquine and Indoor Residual Spraying in Communities with Malaria Transmission in Haiti, 2018.

For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.

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.

A Novel Untethering and Duraplasty Technique for Postsurgical Tethered Spinal Cord.

Progressive post-traumatic postsurgical myelopathy (PPPM) is a known entity that can occur months to years after the initial insult. Symptomatic patients can become myelopathic and have rapid and progressive neurological decline. Surgical correction of PPPM usually involves intradural exploration and lysis of adhesions that carries the risk of further injury to the spinal cord. In this manuscript, we provide a report of a patient presenting more than 50 years after the initial resection of an intramedullary tumor. Additionally, we present and describe a novel surgical technique for managing this difficult problem and restoring normal CSF dynamics.

Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism.

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common of the muscular dystrophies, affecting nearly 1 in 8000 individuals, and is a cause of profound disability. Genetically, FSHD is linked to the contraction and/or epigenetic de-repression of the D4Z4 repeat array on chromosome 4, thereby allowing expression of the DUX4 gene in skeletal muscle. If the DUX4 transcript incorporates a stabilizing polyadenylation site the myotoxic DUX4 protein will be synthesized, resulting in muscle wasting. The mechanism of toxicity remains unclear, as many DUX4-induced cytopathologies have been described, however cell death does primarily occur through caspase 3/7-dependent apoptosis. To date, most FSHD therapeutic development has focused on molecular methods targeting DUX4 expression or the DUX4 transcript, while therapies targeting processes downstream of DUX4 activity have received less attention. Several studies have demonstrated that inhibition of multiple signal transduction pathways can ameliorate DUX4-induced toxicity, and thus compounds targeting these pathways have the potential to be developed into FSHD therapeutics. To this end, we have screened a group of small molecules curated based on their reported activity in relevant pathways and/or structural relationships with known toxicity-modulating molecules. We have identified a panel of five compounds that function downstream of DUX4 activity to inhibit DUX4-induced toxicity. Unexpectedly, this effect was mediated through an mTor-independent mechanism that preserved expression of ULK1 and correlated with an increase in a marker of active cellular autophagy. This identifies these flavones as compounds of interest for therapeutic development, and potentially identifies the autophagy pathway as a target for therapeutics.

Breast Reconstruction Trends in the Setting of Postmastectomy Radiation Therapy: Analysis of Practices among Plastic Surgeons in the United States.

Radiation is an integral part of breast cancer therapy. The ideal type and timing of breast reconstruction with relation to radiation delivery are not well established. The study aimed to identify reconstructive practices among American plastic surgeons in the setting of pre- and postmastectomy radiation. Methods: A cross-sectional survey of members of the American Society of Plastic Surgery was performed. Practice/demographic information and breast reconstruction protocols were queried. Univariate descriptive statistics were calculated, and outcomes were compared across cohorts with χ2 and Fischer exact tests. Results: Overall, 477 plastic surgeons averaging 16.3 years in practice were surveyed. With respect to types of reconstruction, all options were well represented, although nearly 60% preferred autologous reconstruction with prior radiation and 55% preferred tissue expansion followed by implant/autologous reconstruction in the setting of unknown postoperative radiation. There was little consensus on the optimal timing of reconstruction in the setting of possible postoperative radiation. Most respondents wait 4-6 or 7-12 months between the end of radiation and stage 2 implant-based or autologous reconstruction. Common concerns regarding the effect of radiation on reconstructive outcomes included mastectomy flap necrosis, wound dehiscence, capsular contracture, tissue fibrosis, and donor vessel complications. Conclusions: Despite considerable research, there is little consensus on the ideal type and timing of reconstruction in the setting of pre- and postoperative radiation. Understanding how the current body of knowledge is translated into clinical practice by different populations of surgeons allows us to forge a path forward toward more robust, evidence-based guidelines for patient care.

Pre-referral rectal artesunate: no cure for unhealthy systems.

Pre-referral rectal artesunate suppositories can save the lives of children with severe malaria if patients receive adequate post-referral care. A multi-country randomised controlled trial reporting on the efficacy of rectal artesunate informed the current WHO guidelines. In October, 2022, we reported on the findings of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, a carefully monitored roll-out of quality-assured rectal artesunate into established community-based health-care systems in DR Congo, Nigeria, and Uganda. The aim of the project was to understand the challenges involved in the successful real-world implementation of pre-referral rectal artesunate and to inform subsequent scale-up in endemic countries. In our study, we found that children treated with pre-referral rectal artesunate in routine clinical practice did not have an increased chance of survival, most likely explained by shortfalls along the continuum of care. A substantial proportion of the more than 6200 severely ill children that were followed up 28 days after treatment initiation did not receive comprehensive severe malaria care, either due to an incomplete referral to a secondary facility, or due to incomplete post-referral treatment. The observational study design allowed for a realistic assessment of the obstacles involved in implementing pre-referral rectal artesunate in settings where malaria mortality remains high. Without improving the entire continuum of care, children will continue to die from severe malaria and promising interventions will fail to meet their full potential.

Impacts of fast production of afucosylated antibodies and Fc mutants in ExpiCHO-S™ for enhancing FcγRIIIa binding and NK cell activation.

This study has employed mammalian transient expression systems to generate afucosylated antibodies and antibody Fc mutants for rapid candidate screening in discovery and early development. While chemical treatment with the fucose analogue 2-fluoro-peracetyl-fucose during transient expression only partially produced antibodies with afucosylated N-glycans, the genetic inactivation of the FUT8 gene in ExpiCHO-S™ by CRISPR/Cas9 enabled the transient production of fully afucosylated antibodies. Human IgG1 and murine IgG2a generated by the ExpiCHOfut8KO cell line possessed a 8-to-11-fold enhanced FcγRIIIa binding activity in comparison with those produced by ExpiCHO-S™. The Fc mutant S239D/S298A/I332E produced by ExpiCHO-S™ had an approximate 2-fold higher FcγRIIIa affinity than that of the afucosylated wildtype molecule, although it displayed significantly lower thermal-stability. When the Fc mutant was produced in the ExpiCHOfut8KO cell line, the resulting afucosylated Fc mutant antibody had an additional approximate 6-fold increase in FcγRIIIa binding affinity. This synergistic effect between afucosylation and the Fc mutations was further verified by a natural killer (NK) cell activation assay. Together, these results have not only established an efficient large-scale transient CHO system for rapid production of afucosylated antibodies, but also confirmed a cooperative impact between afucosylation and Fc mutations on FcγRIIIa binding and NK cell activation.

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.

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.

The fight against malaria: Diminishing gains and growing challenges.

Since the year 2000, historic reductions in malaria incidence and mortality have been driven by the widespread distribution of bed nets, drugs, and insecticides for the prevention and treatment of malaria. Scale-up of these tools has been enabled by an increase in malaria financing compounded by price reductions, yet these trends are unlikely to continue at the same rate. Rapid population growth in high-endemic areas requires procurement of more of these tools just to maintain current coverage, even as prices are likely to increase as resistance to drugs and insecticides forces shifts to newer products. Further progress toward the long-term goal of malaria eradication requires a combination of greater funding, more cost-effective resource allocation, and fundamental changes to the global malaria control strategy.

Impact of Dermal Matrix Brand in Implant-Based Breast Reconstruction Outcomes.

BACKGROUND: Implant-based reconstruction is the most common procedure for breast reconstruction after mastectomy. Acellular dermal matrix is used to provide additional coverage in subpectoral and prepectoral implant placement. In this study, the authors compared postoperative outcomes between AlloDerm (LifeCell, Branchburg, N.J.) and DermACELL (Stryker, Kalamazoo, Mich.), two acellular dermal matrix brands. METHODS: A retrospective review of implant-based breast reconstruction from 2016 to 2020 was conducted. Patient demographics and comorbidities, implant size and location, acellular dermal matrix choice, and postoperative outcomes were recorded. Primary outcomes assessed were seroma and infection compared between two acellular dermal matrix brands. Independent clinical parameters were assessed with multiple logistic regression models for the primary outcomes. RESULTS: Reconstruction was performed in 150 patients (241 breasts). Eighty-eight patients underwent expander placement with AlloDerm and 62 patients with DermACELL. There were no significant differences in patient characteristics between the two groups. There was a significantly higher incidence of seroma in the AlloDerm group in univariate (AlloDerm 21.7 percent versus DermACELL 8.2 percent, p < 0.005) and multivariate analyses ( p = 0.04; 95 percent CI, 1.02 to 6.07). Acellular dermal matrix use (regardless of type) was not associated with higher rates of infection ( p = 0.99), but body mass index was ( p = 0.004). CONCLUSIONS: Both AlloDerm and DermACELL had similar infection rates regardless of contributing risk factors. AlloDerm was found to be a risk factor for seroma formation in the postoperative period. As such, it is important to be aware of this complication when performing implant-based reconstruction with this brand of acellular dermal matrix. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Midline epigastric scars can be associated with higher umbilical complications following DIEP flap harvest.

BACKGROUND: Umbilical complications can be relatively common after breast reconstruction with deep inferior epigastric perforator (DIEP) flaps. The medial umbilical ligaments and the ligamentum teres hepatis can be the sole blood supply to the umbilicus after a DIEP flap harvest. Prior incisions along the epigastric midline may disrupt the ligamentum teres hepatis. In this retrospective study, we assess the influence of previous midline epigastric scars on umbilical complications after DIEP flap harvest. METHODS: All patients who underwent breast reconstruction with DIEP flaps were identified at an academic institution over six years. Relevant sociodemographic and clinicopathologic factors were reviewed in the electronic medical records. Univariate and multivariate analyses were performed to determine the role of clinical variables to predict the chance of umbilical complications. RESULTS: A total of 243 patients met inclusion criteria, with 39 patients (16%) having prior surgery utilizing midline epigastric incisions. Twenty-one patients had umbilical complications. No significant difference in patient characteristics was found between patients with and without prior midline epigastric scars. Patients with a history of previous midline epigastric scars had a higher rate of umbilical complications (20.5% vs. 6.4%, p < 0.01). Bilateral medial row perforator-based DIEP flap harvest was also related to a higher rate of umbilical complications (18.4% vs. 6.2% p < 0.01). CONCLUSION: Previous midline epigastric scars are associated with higher rates of umbilical complications after DIEP flap harvest. Bilateral medial row perforator-based DIEP flap harvest exacerbates the rate of umbilical complications and should be avoided in patients with prior midline epigastric incision whenever possible.

Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda.

The key to reducing malaria deaths in highly endemic areas is prompt access to quality case management. Given that many severe cases occur at peripheral level, rectal artesunate (RAS) in the form of suppositories was developed in the 1990s, allowing for rapid initiation of life-saving antimalarial treatment before referral to a health facility with full case management capabilities. One randomized controlled trial published in 2009 showed a protective effect of RAS pre-referral treatment against overall mortality of 26%, but with significant differences according to study sites and length of referral. Two important issues remained unaddressed: (1) whether the mortality impact of RAS observed under controlled trial conditions could be replicated under real-world circumstances; and (2) clear operational guidance for the wide-scale implementation of RAS, including essential health system determinants for optimal impact. From 2018 to 2020, the Community Access to Rectal Artesunate for Malaria (CARAMAL) project was conducted as a large-scale observational implementation study in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda (registered on ClinicalTrials.gov as NCT03568344). CARAMAL aimed to provide high-quality field evidence on the two issues above, in three remote settings with high malaria endemicity. A number of complementary study components were implemented. The core of the CARAMAL study was the Patient Surveillance System (PSS), which allowed tracking of cases of severe febrile illness from first contact at the periphery to a referral health facility, and then on to a Day 28 visit at the home of the patient. Community and provider cross-sectional surveys complemented the PSS. Here we describe in some detail RAS implementation, as well as the key CARAMAL study components and basic implementation experience. This manuscript does not intend to present key study results, but provides an extensive reference document for the companion papers describing the impact, referral process, post-referral treatment and costing of the RAS intervention.

Using observed incidence to calibrate the transmission level of a mathematical model for Plasmodium vivax dynamics including case management and importation.

In this work, we present a simple and flexible model for Plasmodium vivax dynamics which can be easily combined with routinely collected data on local and imported case counts to quantify transmission intensity and simulate control strategies. This model extends the model from White et al. (2016) by including case management interventions targeting liver-stage or blood-stage parasites, as well as imported infections. The endemic steady state of the model is used to derive a relationship between the observed incidence and the transmission rate in order to calculate reproduction numbers and simulate intervention scenarios. To illustrate its potential applications, the model is used to calculate local reproduction numbers in Panama and identify areas of sustained malaria transmission that should be targeted by control interventions.