Perioperative Safety of Combined Augmentation-Mastopexy: An Evaluation of National Database.

INTRODUCTION: The safety of combined augmentation-mastopexy is controversial. This study evaluates a national database to analyze the perioperative safety of combined augmentation-mastopexy to either augmentation or mastopexy alone. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients undergoing augmentation mammaplasty and mastopexy from 2005 to 2018. The patients were divided into the following groups: group I, augmentation; group II, mastopexy; group III, combined augmentation-mastopexy. Baseline characteristics and outcomes were compared. Outcomes were 30-day complications, reoperation, and readmission. RESULTS: We found 5868 (74.2%) augmentation only, 1508 (19.1%) mastopexy only and 534 (6.6%) combined augmentation-mastopexy cases. Mean operative time was highest among the combined group at 129 minutes compared with 127 minutes for mastopexy alone and 66 minutes for augmentation alone (P < 0.01). Rates of any complications and readmission were different among groups (0.8% vs 2.5% vs 1.5% respectively, P < 0.01 and 0.7% vs 1.5% vs 1.5% respectively, P = 0.049), whereas reoperation was not statistically different (1.2% vs 1.4% vs 1.5%, P = 0.75). The incidence of dehiscence (0.6%; P < 0.01) was highest in the combined group. Multivariable logistic regression analysis did not reveal an increased odds of complications, reoperation, or readmission with combined augmentation-mastopexy. CONCLUSIONS: An evaluation of the nationwide cohort suggests that combined augmentation-mastopexy is a safe procedure in the perioperative period.

Morbidity Associated With Structural Graft Use in Paramedian Forehead Flap.

INTRODUCTION: Paramedian forehead flap for nasal reconstruction may involve the use of a structural graft. The authors hypothesized that the use of structural grafts with paramedian forehead flap is associated with an increased risk of 30-day complications. METHODS: This is a retrospective study of the American College of Surgeon (ACS) National Surgical Quality Improvement Program (NSQIP). We identified all patients undergoing paramedian forehead flap reconstruction from 2007 through 2018 using Current Procedural Terminology code 15731. Patients who had structural graft harvested at the time of paramedian forehead flap were identified using Current Procedural Terminology codes. Groups were defined based on the use of structural grafts. Propensity score matching was performed using preoperative and intraoperative characteristics to produce matched cohorts. The authors further stratified individual graft types to identify differential risks associated with each. Logistic regression was then used to determine whether the use of structural grafts was associated with increased risk for 30-day complications. RESULTS: The authors identified 1198 patients with paramedian forehead flap reconstruction, of whom 325 (27.1%) required structural grafts. Propensity score matching 1:1 yielded 247 patients in each of the matched cohorts. Overall 30-day complications (4.5% versus 5.3%), wound related complications (3.2% versus 4.1%), systemic complications (1.2% versus 2%), unplanned reoperation (6.5% versus 3.2%), and unplanned readmission (6.6% versus 10.2%) were similar between the 2 groups (P > 0.05). Subgroup analysis of different graft types showed that costochondral graft was associated with increased wound related complications (0.9% versus 8.3%, P = 0.03). The odds of having wound related complications with the use of costochondral graft was OR = 5.3, CI = 1.5-18.8, P = 0.02. CONCLUSIONS: Although the use of structural grafts does not increase risk of overall 30-day complications, there is an increased risk of wound related complications associated with the use of costochondral and rib grafts.

Idiopathic Calcinosis Cutis of the Hand.

Calcinosis cutis is a disease process characterized by calcified lesions in the skin. Although there are five subtypes of calcinosis, idiopathic calcinosis cutis is a rare disease process with no clear etiology. It has been described in many parts of the body; however, there are only five reported cases specifically involving the hands. We describe the presentation and successful treatment of a case of idiopathic calcinosis cutis in a 65-year-old man with lesions on his bilateral hands. We believe that surgical excision of symptomatic lesions is a safe and effective treatment for idiopathic calcinosis cutis of the hands.

Acellular Piscine Dermis for Pediatric Hand Burn Reconstruction.

Pediatric hand burns are difficult to treat, with thin tissue with critical structures close to the skin and the small scale of the anatomy of children's hands. Additionally, pediatric burns can be challenging due to the concern for donor-site morbidity and the paucity of donor sites when reconstructing these wounds. In this report, we discuss the successful application of a piscine-derived acellular dermal matrix in a 13-month-old child with deep partial thickness and full-thickness burns to the right upper extremity. She had excellent long term cosmetic results and function by 3 years postoperatively, including full extension and flexion of all digits in her right hand.

Geographic Trends in the Neurosurgery Match During the COVID-19 Pandemic.

In the present article, the impact of the COVID-19 pandemic on geographical trends in the neurosurgery match in successfully matched applicants was analyzed. A cross-sectional analysis for the years from 2017 to 2021 was performed. Successful applicants' region, state, and medical school were compared with the location of their matched residency program. The number of applicants matching at a residency program within the same region or state as their home medical school or their own medical school was then evaluated. One hundred fifteen neurosurgery residency programs and 1066 successfully matched applicants were included in the analysis. When comparing 2021 with previous years, no significant change in the percentage of applicants matching at their home region (43.1% vs 49.7%, P = .09), home state (25.1% vs 26.3%, P = .69), or home program (19.9% vs 18.7%, P = .70) was found. The COVID-19 pandemic did not significantly affect geographic trends during the neurosurgery match in 2021. This is of note as the COVID-19 pandemic significantly affected the match in other competitive specialties, including plastic surgery, dermatology, and otolaryngology. Despite limited away rotations, it is possible that neurosurgery programs did not change their applicant selection criteria and implemented systems to virtually interact with applicants outside of their local region.

Preoperative Frailty Risk in Cranioplasty Patients: Risk Analysis Index Predicts Adverse Outcomes.

Cranioplasty is a common surgical procedure used to repair cranial defects, and it is associated with significant morbidity and mortality. Although frailty is a strong predictor of poor postoperative outcomes across surgical specialties, little is known about frailty's impact on cranioplasty outcomes. This study examined the association between frailty and cranioplasty by comparing the effect of the Risk Analysis Index-Administrative (RAI-A) and the Modified Frailty Index-5 (mFI-5) on cranioplasty outcomes. Methods: The National Surgical Quality Improvement Program was queried for patients undergoing cranioplasty between 2012 and 2020. Receiver operating characteristics and multivariable analyses were used to assess the relationship of postoperative outcomes and the RAI-A, mFI-5, and increasing patient age. Results: There were 2864 included study patients with a median age of 57 years (IQR, 44-67), and a higher proportion of patients were women (57.0%) and White (68.5%). The RAI-A had a more robust predictive ability for 30-day mortality (C-Statistic, 0.741; 95% confidence interval (CI), 0.678-0.804) compared with mFI-5 (C-Statistic, 0.574; 95% CI, 0.489-0.659) and increasing patient age (C-Statistic, 0.671; 95% CI, 0.610-0.732). On multivariable analyses, frailty was independently associated with mortality and other poor postoperative outcomes (P < 0.05). Conclusions: The RAI-A demonstrated superior discrimination than the mFI-5 and increasing patient age in predicting mortality. Additionally, the RAI-A showed independent associations with nonhome discharge and postoperative complications (CDII, CDIIIb, and CDIV). The high rates of operative morbidity (5.0%-36.5%) and mortality (0.4%-3.2%) after cranioplasty highlight the importance of identifying independent risk factors for poor cranioplasty outcomes.

Botulinum Toxin A for the Treatment of Sympathomimetic Pressor-Induced Digital Hand Ischemia in the Critically Ill Intensive Care Unit Patient.

Vasopressor-induced ischemia of the hand, while relatively rare, is a severe complication in critically ill intensive care unit (ICU) patients requiring high concentrations of sympathomimetic pressors and often results in digit necrosis and amputation. Currently, there are no widely accepted approaches for treating this cause of peripheral digital ischemia. Case reports have demonstrated that reducing the concentration of vasopressors that patients are given may reverse the progression of ischemic events prior to necrosis. While this approach is at odds with the principle of "life over limb," it demonstrates that digit necrosis can be reversed, resulting in improved outcomes. Here, we present a therapeutic strategy for treating digital limb ischemia in the septic ICU patient without the need to lower systemic vasopressor dose by using locally injected botulinum toxin A into ischemic hands.

Orphan Applicants in Plastic Surgery: Where Do Medical Students Without an Affiliated Residency Program Match?

Background: The number of resident positions in integrated plastic surgery residencies are relatively few and highly sought after. Medical students interested in plastic surgery as a career are faced with the challenge of deciding where to apply for these highly competitive spots. This sense of keen competition means students are often applying to almost all available programs across the country with the idea of increasing their chance of successfully matching. Previous research has shown that exposure to specialty programs in medical school portends enhanced success in residency matches. This study focuses on medical students who come from schools without plastic surgery residencies-orphans-and the characteristics of those who successfully matched into integrated plastic surgery programs. Methods: This study evaluated trends in successfully matched applicants in integrated plastic surgery residencies from 2016-2021 by looking at applicants' medical school type, presence of plastic surgery residency associated with the medical school, and geographic region. Geographic region of residency programs, medical school of applicants, and national quality ranking of medical schools were correlated with applicant demographics. The data were tabulated and analyzed utilizing chi-square analysis. Results: Orphans who graduated from allopathic medical schools without an affiliated integrated plastic surgery residency program comprised 24.4% of successfully matched applicants, whereas those with affiliated integrated residency programs comprised 72.2%. However, at the top quartile of prestige-rated residency programs, these orphan applicants only comprised 17.4% of residents. Of all medical school applicants, 18.2% matched at a residency program affiliated with their medical school (P = 0.04). Annually, 1 to 3 osteopathic medical school graduates and 3 to 9 international medical graduates matched, representing less than 1 and 4%, respectively, of all matched applicants; these applicants had the least successful match rates. Conclusions: There continues to be a modest number of successfully matched integrated plastic surgery residents who are graduates of allopathic medical schools with no affiliated residency program but disproportionately fewer at the top quartile institutions. There are also very few osteopathic and international medical school graduates who match, which has seen no significant change over the last 6 years.

Successful upper extremity limb salvage using cellular- and tissue-based products in a patient with uncontrolled diabetes.

INTRODUCTION: Uncontrolled diabetes causes dysfunction in all stages of wound healing, including greatly delayed wound closure owing to impaired angiogenesis. CTPs play an important role in advanced wound care, especially in complex diabetic wounds. The 3 categories of CTP are ECMs, amniotic tissues, and composite products that combine living cells and a collagen matrix. These products are available as xenografts or allografts, or as bioengineered products. ECMs provide a biological scaffold to facilitate wound healing, and these tend to modulate the wound environment and become incorporated into the wound bed. CASE REPORT: A right-hand dominant female with uncontrolled type 2 diabetes presented with a complex nonhealing wound of the right upper extremity; the patient was treated with CTPs after surgical intervention (incision and drainage of the abscess, open carpal tunnel release, forearm fasciotomy, and excisional debridement) for a deep forearm abscess. Exposed critical structures included flexor tendons and the median nerve. The patient received a single application of a meshed dermal regeneration template, an application of minimally processed human umbilical cord membrane, and an application of acellular fish skin, resulting in successful wound reconstruction and improved function of the right upper extremity. CONCLUSION: To the authors' knowledge, this is the first described use of acellular fish skin in the setting of upper extremity reconstruction.

COVID-19 and the Otolaryngology Match: An Increase in Applicants Remaining Close to Home.

INTRODUCTION: Otolaryngology residency remains one of the most competitive surgical subspecialties to apply for with a 63% match rate in 2021. This is a difficult and stressful process for applicants in any given year, and it was even further complicated by restrictions mandated by coronavirus disease 2019 (COVID-19) protections. Analyzing geographical trends in successfully matched applicants provides prospective applicants and programs with helpful information about how previous trends were affected by the pandemic as we look toward future match cycles. METHODS: The medical schools of 1,587 successfully matched applicants from 2017-2021 were identified and compared to the 116 otolaryngology residency programs. Successful applicants' medical school state and region were then compared to the location of their matched residency program state and region. From this, we evaluated the number of applicants matching at the residency program affiliated with their medical school or at a residency program within the same state or region as their home medical school. RESULTS: A significant increase in the percentage of applicants matching at their home program and within their home state (p < 0.001) occurred in 2021 when compared to previous years. Applicants matching within their home region was not found to increase significantly (p = 0.43) in 2021 compared to previously. The regions with the greatest increase in the percentage of applicants matching to their home programs were the Northeast and Midwest (12% increase), while the Midwest had the largest increase in percentage of applicants matching within their home state (15%). CONCLUSION: The COVID-19 pandemic significantly affected the otolaryngology match in 2021 with applicants and programs alike choosing to stay closer to home with their residency match selections. Overall, regional location remains a major determinant of future residency location for otolaryngology applicants, and this did not change significantly during 2021, but applicants matched more frequently at their home medical school program. It is anticipated that the match process will be similar in 2022 given the ongoing pandemic, so the importance of home program and region will likely be emphasized again.

The Impact of COVID-19 on the Orthopaedic Surgery Residency Match.

Introduction Matching into an orthopaedic surgery residency program presents a challenging accomplishment for applicants to achieve in any given year. Due to the profound changes to the application process caused by the coronavirus disease 2019 (COVID-19) pandemic it was theorized that there would be a change in the number of graduates matching close to their home medical school region, state, and program. Methods Orthopaedic surgery residency program Web sites and social media accounts were accessed to elucidate current resident data, including graduates' medical school, and geographical location of their school. Chi-square analysis was performed to identify trends in current residents matching within their home program, state, and region associated with the 2021 orthopaedic match. These numbers were compared with previous year's successful applicants. Results In 2021, a significant 4.4% ( p =0.02) increase in successful matches within applicants' home states occurred (33.4% vs. 37.8%) and home programs ( p <0.001) when compared with previous years (21.2% vs. 27.4%). However, in 2021, there was no significant change in home region matching ( p =0.56) with 60% of successful matches occurring in home regions. This was statistically consistent with what was observed in previous years (61.4%). Conclusion The COVID-19 pandemic was associated with restrictions in travel and interview options resulting in a significant increase in the number of orthopaedic applicants who matched into their home program, or at programs in their home state compared with previous years. Although no statistically significant regional change occurred during the 2021 match, it remains the leading predictor of where successful applicants will match. With many unknowns related to the upcoming match cycles it is important for applicants and programs to have a general idea of recent trends and outcomes to best focus their efforts, especially if diversity and minority inclusion are considered in highly competitive specialties like orthopaedic surgery.

Successful Prepectoral Breast Reconstruction in a Patient With Systemic Sclerosis.

Patients with connective tissue diseases have been shown to be at higher risk for complications after surgery. In this report, we describe a case of a patient with long-standing, stable systemic sclerosis (SS), diagnosed approximately 28 years ago, who underwent nipple-sparing mastectomy and immediate reconstruction with prepectoral tissue-expander placement. She subsequently had uneventful implant-based reconstruction with adjunctive fat grafting. To our knowledge, this is the first reported case of implant-based prepectoral reconstruction after mastectomy in a patient with SS.

Surface Area Graphic Evaluation (SAGE) Diagram Documentation in Burn Patients: Room for Quality Improvement.

Background The first step in the management of burn patients is an accurate estimation of the total body surface area (TBSA) involvement. Depending on which, burns are categorized as major (>20%) and minor (<20%). This then dictates fluid resuscitation and level of care. At the University of New Mexico Burn Center, we use Surface Area Graphic Evaluation (SAGE) diagramming to objectively estimate the body surface area involvement. We hypothesized patients undergoing SAGE documentation will have better outcomes.  Methods This is a retrospective study of 320 consecutive patients from 2014-2018 at the University of New Mexico Burn Center. Only patients treated surgically were included. We recorded patient demographics, comorbidities, and burn details. The primary measure of interest was SAGE documentation and the secondary measure of interest was outcomes associated with it. Results We found that a SAGE diagram was only documented for a minority of patients (40%). After comparing patients in the SAGE group vs. No SAGE group, we found that the patients were the same in both groups with regards to demographics, comorbidities, and burn characteristics. The use of a SAGE diagram did not appear to be a significant predictor of complications, including surgical site infections, graft loss, donor site complications, postoperative pneumonia, urinary tract infections, deep vein thrombosis, or myocardial infarction (p=0.254). Conclusion Only a minority of patients get a SAGE diagram documented. However, our study did not find any improved outcomes with the use of a SAGE diagram. There is a need for prospective studies to validate the utility of SAGE diagramming in predicting adverse outcomes in major burns.

Anomalous Presentation of Venous Malformations in an Adolescent Male.

Venous malformations (VMs) may manifest clinically in a broad spectrum. Most VMs are sporadic with previous studies reporting less than 1.2% to be inherited. Conversely, multifocal lesions, such as glomuvenous malformations (GVMs), which have glomus cells in their vascular walls, have been reported to have a frequency of inheritance of 63.8%. Both VMs and GVMs may occur due to sporadic mutation and must be differentiated clinically because this will dictate their proper treatment. Sporadic GVMs involve skin and subcutis, with bluish-purple coloration, are painful to compression, and have no radiographic evidence of phleboliths. Previous studies have demonstrated that VMs are almost always associated with a single lesion that is nontender to compression and are often able to be diagnosed by the presence of phleboliths on radiographic imaging. We present a case of a 14-year-old right-hand-dominant male who presented with two distinct VMs on the dorsum of the right index finger at the proximal and middle phalanges. A previously biopsied lesion overlying the ipsilateral olecranon, which was reported as a possible glomus tumor versus vascular malformation, was present as well. Based on history, physical examination, multicentric presentation, and radiographic findings, the presumptive diagnosis was that the lesions were GVMs. However, after surgical excision and histopathologic examination, the lesions were determined to be VMs because of the absence of glomus cells. Due to the difference in treatment modalities for VMs and GVMs, the ability to accurately diagnose these lesions clinically is essential. This case represents an anomalous presentation of multiple venous malformations occurring in two distinct locations in a 14-year-old boy.

Evaluating the Integrated Plastic Surgery Residency Match During the Novel Coronavirus Pandemic.

The COVID-19 pandemic had significant impacts on medical education and on the 2021 Match. Visiting student rotations at locations other than students' home institutions were cancelled and residency interviews were hosted virtually. This study evaluated the impact that COVID-19 had on the 2021 Match including residency programs matching applicants from within their own institution as well as from within the same region. The sex of matched applicants in the Match cycles was analyzed as well. Data were collected from residency program websites, social media accounts, and communication with current residents. Data were tabulated and chi-square analysis was performed. The overall difference in matched internal candidates pre-/post-pandemic was determined to be statistically significant (8.3% increase; p = 0.004). The Midwest was determined to exhibit a significant increase for matching residents from medical schools in the same region (15.6% increase; p = 0.04). Female applicants were also determined to be significantly more likely to match into integrated plastic surgery programs in 2021. COVID-19 significantly impacted the 2021 Match with an increased number of programs selecting internal candidates, matched female applicants, and regional selectivity, especially in the Midwest. It is our hope that applicants, programs, and the plastic surgery community will use this information to continue to improve the residency selection process in the future.

Botulinum Toxin A Salvage of Ischemic Hand Trauma.

Posttraumatic hand injuries from crush injury, infusion, or iatrogenic vascular cannulation can cause ischemic finger damage that can progress to necrosis and digital amputation. Botulinum toxin type A (Botox) improves blood flow in chronic vasospastic disorders of the hand. Botox's efficacy in salvaging ischemic loss in digits in acute traumatic and iatrogenic injury has not been previously reported. From February of 2015 to December of 2016, 11 patients at a Level I trauma center (West Virginia University) presented to the hand surgery service with early ischemic injury and vascular compromise to hand and fingers as a result of crush, direct drug injection, or proximal arterial injury from drug injection or catheterization. Before 2015, all patients with vascular compromise were treated with standard protocol. After January of 2016, patients were treated with additional injection of 80 to 100 U of Botox into the palm and wrist. Before administration of Botox, six patients with vascular compromise of one or more fingers were treated with a conservative protocol and 83 percent had amputation of necrotic digits. After January of 2016, five patients with ischemia were treated with Botox into the palm and proximal arteries. All Botox-treated digits were preserved (100 percent salvage). Pain scores were lower in Botox-treated fingers. We conclude that (1) in the acute traumatic vascular hand injury, early Botox injection markedly increases digital salvage; (2) direct nerve effects after Botox injections improve postinjury pain scores; and (3) early use of Botox in finger injuries is our standard approach to impending ischemia in the hand.

Temporary Use of Acellular Dermal Matrix in Upper Extremity Salvage.

Wound coverage of exposed vascular bypasses after acute limb revascularization may not be immediately possible, while delay may create a hostile environment for the bypass graft. The use of negative-pressure wound therapy may not be possible because of extrinsic compression. Temporary use of acellular dermal matrix can help salvage upper extremity. We present 2 patients with brachial artery transection secondary to blunt trauma, who had revascularization with interposition saphenous vein grafts. We used acellular dermal matrix as temporary coverage for the exposed arterial bypass grafts to allow for patient stabilization, serial debridement, and demarcation of the surrounding tissues before definitive coverage. Additionally, the use of negative-pressure wound therapy caused diminished pulses in the bypass graft, creating the need for reliable temporary coverage. The acellular dermal matrix dressing was left in place until definitive closure was possible. Both patients underwent successful wound coverage with fasciocutaneous flaps without disruption, thrombosis, or infection of the bypass grafts. Follow-up at 6 months demonstrated good healing and excellent function. The use of the acellular dermal matrix provides temporary coverage of vital structures until definitive reconstruction can be performed.

Pollicization of Long Finger After Traumatic Amputation of Thumb and Index Finger.

We present a 51-year-old male who sustained a traumatic amputation with a saw of the right thumb, index finger, and carpal bones back to the radius. The amputated digits were mangled and not suitable for replantation. We performed pollicization of the long finger which helped restore a more functional hand. In select situations, this reconstructive option has the advantages of being a single-stage procedure with limited donor site morbidity and no need for microsurgical anastomosis.

The life-cycles of skin replacement technologies.

INTRODUCTION: Skin Replacement Technologies (SRTs) emerged as skin alternatives for burns, large excisions or trauma. The original publications represent the available knowledge on a subject and can be modeled as a logistic S-curve which depicts the technology's evolution life-cycle. The Technology Innovation Maturation Evaluation (TIME) model was previously introduced to study the life-cycles of biotechnologies. METHODS: PubMed database was searched 1900-2015 to review relevant publications. All skin replacement or regeneration products on the US market were included. The TIME model was applied to assess evolutionary patterns for each technology. RESULTS AND DISCUSSION: Three SRT clusters were identified: processed biologics technologies (PBT), extracellular matrix technologies (EMT), and cell-based technologies (CBT). Publications on EMTs and CBTs start decades after PBTs, however, are greater in number and follow an ascending trend. PBTs reached a plateau, suggesting near-senescence. The CBT curve was non-logarithmic and the TIME model could not be applied. The technology initiation point (Ti) for PBTs was 1939 and the establishment point (Te) 1992. For EMT, Ti was 1966 and Te 2010. Sixty-one products were identified (49 EMTs, 7 CBTs, 5 PBTs). PBTs appeared 11 years after Te and EMTs four years prior Te. Thirty-seven products in the EMT category, and one in the PBT category, were developed before Te. The most common FDA regulatory mechanism for SRT was found to be 510(k) followed by HCT/P 361. CONCLUSION: Innovation is an indicator of the evolution of technology. The number of publications can be used as a metric of this evolution and the fact that the SRT field falls under such pattern demonstrates that SRT is an innovation-based industry. EMT is the most efficient cluster. Few products from SRT registered a commercial success, and from those that did, those technologies were generally found to be part of the most productive cluster, 1st in concept, conceptually simple, easily regulated and produced, cost and clinically efficient, reimbursable, able to solve a specific problem efficiently, had a platform technology design that allowed for further innovation and adaptation for other uses and, as found by application of the TIME model, appear prior to technology establishment.

Successful management of sternomanubrial joint septic arthritis with pectoralis muscle flap closure: a case series.

Primary infection of the sternomanubrial joint (SMJ) is extremely rare. We present four consecutive cases who were all treated with SMJ resection (partial sternectomy), bilateral partial 2nd rib resection and immediate placement of temporary wound vacuum therapy followed by pectoralis major muscle flap closure. Average patient age was 35.5 years with male predominance (75%). All patients had intravenous drug use as underlying risk factor along with concomitant viral infections Hep C (75%) and HIV (25%). MSSA was identified in resection cultures in 75% of the patients. Delayed bilateral PMFC was achieved in all patients (average post-resection day 5). Response to treatment was excellent with no recurrent infections, no complications and zero 30-day mortalities. Our experience represents the largest reported case series in adults and would suggest that aggressive surgical resection followed by PMFC would appear to be the preferred treatment for all patients with SMJ infection.