Antibacterial and Antibiofilm Activity of Endophytic Alternaria sp. Isolated from Eremophila longifolia.

The threat to public health resulting from the emergence of antimicrobial resistance (AMR) is ever rising. One of the major bacterial pathogens at the forefront of this problem is methicillin-resistant Staphylococcus aureus, or MRSA, for which there is a great need to find alternative treatments. One of the most promising alternatives is endophytic fungi, which were shown to produce a vast array of bioactive compounds, including many novel antibacterial compounds. In this study, two endophytic Alternaria sp., EL 24 and EL 35, were identified from the leaves of Eremophila longifolia. Ethyl acetate (EtOAc) extracts of their culture filtrates were found to inhibit both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. The activity of each extract was shown to be greatly affected by the growth medium, with considerable reductions in minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) observed when tested in tryptic soy broth with glucose (TSBG) compared with Mueller-Hinton broth (MHB). Both extracts displayed significant (p ≤ 0.05) antibiofilm activity against all three S. aureus strains, the greatest of which was that of EL 35, which reduced biofilm formation by M180920 by 72%, while that of EL 24 resulted in a 57% reduction against ATCC 25923. Both extracts also disrupted established biofilms, of which the most effective was EL 35, which reduced the M180920 biofilm by 64%, while EL 24 also performed best against M180920, reducing biofilm by 54%. Gas chromatography-mass spectrometry (GC-MS) analysis of the EL 24 EtOAc extract revealed five known compounds. This study highlights the promise of endophytic fungi from Australian plants as a potential source of substances effective against important bacterial pathogens. Further understanding of the responsible compounds and their mechanisms could lead to the development of treatments effective against MRSA, as well as novel biofilm-resistant biomedical materials, contributing towards reducing the burden of AMR.

Exploring the Promise of Endophytic Fungi: A Review of Novel Antimicrobial Compounds.

Over the last few decades, many of the existing drugs used to treat infectious diseases have become increasingly ineffective due to the global emergence of antimicrobial resistance (AMR). As such, there is a constant demand to find new, effective compounds that could help to alleviate some of this pressure. Endophytic fungi have captured the attention of many researchers in this field, as they have displayed a vast ability to produce novel bioactive compounds, many of which possess wide-ranging antimicrobial activities. However, while highly promising, research in this area is still in its infancy. Endophytes inhabit the healthy tissues of plants asymptomatically, resulting in a mutualistic symbiosis in which the endophytes produce a plethora of bioactive compounds that support the fitness of the host plant. These compounds display great chemical diversity, representing structural groups, such as aliphatic compounds, alkaloids, peptides, phenolics, polyketides and terpenoids. In this review, the significant antimicrobial potential of endophytic fungi is detailed, highlighting their ability to produce novel and diverse antimicrobial compounds active against human, plant and marine pathogens. In doing so, it also highlights the significant contributions that endophytic fungi can make in our battle against AMR, thus providing the motivation to increase efforts in the search for new and effective antimicrobial drugs.

Mastalgia is Not An Indication for Mammogram.

BACKGROUND: Mastalgia is a common breast complaint that is worrisome to patients. This study was performed to determine if mastalgia is a sign of breast cancer and to evaluate the benefit of its work up. METHODS: Retrospective review of prospectively collected data on 8960 consecutive patients at a safety net institution from June 1, 2006 to December 31, 2020. Data on patient reported mastalgia and diagnosis of breast cancer were collected. RESULTS: 8960 patients had a mean age of 45 years. The population was predominantly underinsured, 70% Hispanic, and 16% had adequate health literacy. Approximately 31% (2820 of 8960) of patients presented with a complaint of breast pain. Of 2820 patients with breast pain, 20 (0.7%) were found to have breast cancer. The average age of patients with breast cancer was 49 years. Physical examination identified a mass in 6 patients and only 3 patients had pain limited to the side of the cancer (10 bilateral, 7 contralateral). Of 1280 patients who were under age 40 years, 88% underwent breast imaging. The Cancer Detection Rate (CDR) was 0.9 per 1000 examinations. For 950 patients age 40 to 49 years and 590 patients age 50 years and older, 98% and 99% underwent breast imaging, respectively. The CDR was 10 per 1000 examinations for age 40 to 49 and 14 per 1000 examinations for age 50 years and older. CONCLUSIONS: Mastalgia is rarely associated with breast cancer. In the absence of other findings, imaging of patients less than age 40 is not recommended. Any workup beyond routine screening mammography in age-appropriate patients, to identify the "cause" of breast pain, does not seem warranted.

Orthognathic Surgery in Older Patients: Is Age Associated With Perioperative Complications?

PURPOSE: The incidence of older patients undergoing orthognathic surgery is increasing. The purpose of this study is to evaluate the association between age and perioperative adverse outcomes in patients undergoing orthognathic surgery. METHODS: This is a retrospective cohort study of patients undergoing orthognathic surgery in the 2011 to 2019 American College of Surgeons National Surgical Quality Improvement Program databases. The primary predictor variable was age group (≥40 or <40 years). The primary outcome variable was adverse outcomes occurring within 30 days of the index operation. Descriptive, bivariate, and Firth logistic regression statistics were utilized to evaluate association between age and adverse outcomes. RESULTS: During the study period, 1,226 patients underwent an orthognathic procedure and 835 subjects were included. Of these subjects, 145 were 40 years or older (17.4%) and 690 were less than 40 years (82.6%). Subjects 40 years or older were more likely to be American Society of Anesthesiologists (ASA) classification II (P ≤ .001), ASA III (P ≤ .001), or diagnosed with obstructive sleep apnea (P ≤ .001). A total of 34 subjects experienced an adverse outcome (4.07%), though there was no significant difference in the incidence of adverse outcomes between age groups (P = .152). In bivariate analysis, hypertension on medication (P = .037), procedure type (P = .001), and segmented Le Fort I osteotomies (P = .039) were associated with adverse outcomes. After controlling for age, hypertension on medication, segmented Le Fort I osteotomies, and diagnosis of obstructive sleep apnea, isolated mandibular osteotomies were the only independent predictors of adverse outcomes (odds ratio 2.64; 95% confidence interval, 1.06 to 7.24; P = .038). Length of stay was 1.38 ± 1.43 days for the 40 years or older group compared to 1.06 ± 1.18 in the <40 group (P = .012). CONCLUSIONS: Despite higher ASA classifications, older patients did not have a significantly greater incidence of perioperative adverse outcomes including airway complications, nor was increased age associated with adverse outcomes in bivariate or multivariate analysis.

Mandibular Fracture Repair in Older Adults: Is Age Associated With Adverse Outcomes?

PURPOSE: The purpose of this study was to measure the association between age and adverse outcomes in patients undergoing open reduction internal fixation (ORIF) of mandibular fractures. METHODS: This was a retrospective cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program databases (2011 to 2019) to identify patients with mandibular fractures treated with ORIF. The primary predictor variable was age (<45 years, 45 to 54 years, 55 to 64 years, 65 to 74 years, and ≥75 years). The primary outcome variable was surgical complications. Secondary outcome variables included any complication, extended length of stay (LOS ≥95th percentile), and adverse discharge destination. Covariates included demographic, medical, and perioperative covariates. Descriptive, bivariate, and multiple logistic regression statistics were utilized to evaluate the association between age and adverse outcomes. RESULTS: During the study period, 2,843 patients underwent ORIF of a mandibular fracture, and 2,168 subjects were included. There were 1,673 subjects aged <45 years (77.2%), 240 subjects aged 45 to 54 years (11.1%), 155 subjects aged 55 to 64 years (7.10%), 53 subjects aged 65 to 74 years (2.40%), and 47 subjects aged ≥75 years (2.20%). A total of 148 subjects (6.83%) experienced a surgical complication; the incidence of surgical complications increased in a step-wise fashion with each decade of life (P ≤ .001). In bivariate analysis, subjects aged 65 to 74 years were more likely to experience extended LOS (P = .004), whereas subjects aged ≥75 years were more likely to have an extended LOS (P ≤ .001) and an adverse discharge destination (P ≤ .001). In multivariate analysis, age 65 to 74 years was an independent predictor of any complication (P = .032, 95% confidence interval [CI] = 1.08 to 5.37), extended LOS (P = .001, 95% CI = 1.72 to 8.79), and adverse discharge destination (P = .050, 95% CI = 1.00 to 14.4), whereas age ≥75 years was an independent predictor of surgical complications (P = .043, 95% CI = 1.03 to 6.68), any complication (P = .018, 95% CI = 1.20 to 6.75), extended LOS (P = .001, 95% CI = 2.35 to 12.3), and an adverse discharge destination (P ≤ .001, 95% CI = 3.01 to 33.2). CONCLUSIONS: The elderly are at increased risk of adverse outcomes with step-wise increases in the odds of select outcomes with increasing age.

What factors differentiate dentigerous cysts from other pericoronal lesions?

OBJECTIVE: To evaluate the histopathologic outcomes of pericoronal radiolucencies and identify factors predictive of diagnosis. STUDY DESIGN: A retrospective cohort study of 258 patients with 280 radiolucent pericoronal lesions undergoing treatment at our institution between 2005 and 2019. The primary predictor variable was lesion size (≥2 cm and <2 cm). The primary outcome variable was histopathologic diagnosis (dentigerous cyst vs other pathologic entity). Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between clinical and radiographic variables and histopathologic diagnosis. RESULTS: The study sample was composed of 258 patients with 280 histopathologic specimens. There were 218 dentigerous cysts (77.9%) and 62 other pathologic entities (22.1%). Lesions ≥2 cm were 3.20 times more likely to be diagnosed as a nondentigerous cyst pathologic entity (P ≤ .001). After adjusting for jaw (maxilla vs mandible), pain, history of infection, cortical perforation, expansion, and multiple lesions, younger age (P ≤ .001, odds ratio [OR] = 0.950, 95% confidence interval [CI] = 0.929-0.972) and lesion size as a continuous variable (P = .007, OR = 1.06, 95% CI = 1.02-1.11) were independent predictors of other pathologic entities. CONCLUSIONS: The majority of pericoronal radiolucent lesions were dentigerous cysts. Younger age and larger lesions were independent predictors of other pathologic entities.

Algorithmic Approach to Antibiotic Prophylaxis for Traumatic Craniomaxillofacial Injuries.

ABSTRACT: Prophylactic antibiotics are commonly used in the management of traumatic injuries to the maxillofacial complex, yet there are no set guidelines for when and when not to prescribe. The purpose of this review is to present the evidence for antibiotic prophylaxis in different clinical scenarios and to propose algorithms to facilitate the decision making process with the ultimate goal of improving antibiotic prescribing practices. A number of databases were searched using a wide range of keywords to ensure the topic was fully encapsulated. The review is divided into 3 sections: soft tissue trauma, maxillofacial fractures, and ballistic injuries. The algorithms were constructed using the current evidence as well as pathophysiologic principles, especially when there were insufficient studies. This review found the literature on antibiotic prophylaxis to be highly varied and not standardized. Creating an algorithm for providers to follow will help to set a standard of care and decrease the misuse of antibiotics.

Lemierre Syndrome: Unusual Presentation With Superior Ophthalmic Vein Thrombosis.

ABSTRACT: Lemierre syndrome (LS) is a rare, but serious condition most commonly associated with oropharyngeal bacterial infection. Infection results in thrombophlebitis of the internal jugular vein and its tributaries. It usually affects previously healthy young adults. The authors report an unusual case of an elderly patient with penicillin allergy who developed Lemierre syndrome from an odontogenic infection (Streptococcus intermedius) resistant to clindamycin. She developed thrombosis of the internal jugular vein and superior ophthalmic vein resulting in visual changes. Treatment required incision and drainage, intravenous antibiotics and anticoagulation. Antibiotics were tailored to culture and sensitivities after testing response to a beta-lactam. With antibiotic resistance increasing, investigation of penicillin allergies is warranted for severe head and neck infections.

Re-evaluating if observation continues to be the best management of idiopathic granulomatous mastitis.

BACKGROUND: The presentation of idiopathic granulomatous mastitis can mimic breast cancer. Therefore, awareness of the condition is important for surgeons. The current series is the largest in a US population. METHODS: Retrospective chart review of patients treated at a county, safety-net hospital in Arizona. Cases were identified from January 2006 to January 2019. Sociodemographic information, clinical history, management, and outcomes were collected. RESULTS: There were 145 occurrences of idiopathic granulomatous mastitis among 120 women. Most of the patients (92%) were of Hispanic ethnicity and born outside (87%) of the United States. The average age was 35 years. Nearly all patients (95%) were parous, with an average of 3 pregnancies. Most (88%) presented with a palpable mass, and more than half (54%) of these masses were painful. Six patients had prolactinomas or hyperprolactinemia, 11 patients were pregnant, and 5 were postpartum. Early in the time period studied, 6 patients underwent excision of the masses. The remaining 114 underwent planned observation after biopsy confirmation of the diagnosis. Two patients were lost to follow-up, and the other 112 patients with idiopathic granulomatous mastitis resolved spontaneously. Nineteen had more than 1 episode. Average time to resolution was 5 months (range 0-20). Adjusted log-normal regression analysis found that later age of first live birth was associated with greater time to resolution (P < .01). CONCLUSION: Idiopathic granulomatous mastitis is a self-limited, benign condition that waxes and wanes and eventually resolves without resection. After diagnosis, medications are unnecessary, and operations can be limited to drainage procedures for fluid collections.

Awareness of residents' technical ability can affect margin status in breast conserving operations.

PURPOSE: The current study was performed to determine if awareness of the potential affect of residents could affect margin status. METHODS: Retrospective review of all patients who underwent lumpectomy from July 2006 to May 2017 was evaluated. The effect of surgical residents' participation and their technical ability was evaluated to determine the effect on margin status. Logistic regression analysis was performed to determined factors which affect margin status. RESULTS: Of 444 patients, 14% of patients had positive margins. The positive margin rate was lower during the second time period after the effect of technical ability of the residents was known 12% versus 19% (p = 0.10). Greater participation by the attending surgeon (32% vs. 21%) occurred in the second time period. In multivariate logistic regression analysis, operations done by residents with satisfactory technical skills or attending surgeon were less likely to have positive margins than those done by residents with unsatisfactory technical skills (OR 0.19, 95% CI 0.10-0.38; p = 0.0001). With mean follow-up of 48 months, 1.4% had local recurrences as a first event. CONCLUSIONS: Technically ability of residents appears to affect margin status after lumpectomy. Increased intervention by the attending surgeon can improve this outcome.

Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study.

Acute kidney injury (AKI) after severe burns is historically associated with a high mortality. Over the past two decades, various modes of renal replacement therapy (RRT) have been used in this population. The purpose of this multicenter study was to evaluate demographic, treatment, and outcomes data among severe burn patients treated with RRT collectively at various burn centers around the United States. After institutional review board approval, a multicenter observational study was conducted. All adult patients aged 18 or older, admitted with severe burns who were placed on RRT for acute indications but not randomized into a concurrently enrolling interventional trial, were included. Across eight participating burn centers, 171 subjects were enrolled during a 4-year period. Complete data were available in 170 subjects with a mean age of 51 ± 17, percent total body surface area burn of 38 ± 26% and injury severity score of 27 ± 21. Eighty percent of subjects were male and 34% were diagnosed with smoke inhalation injury. The preferred mode of therapy was continuous venovenous hemofiltration at a mean delivered dose of 37 ± 19 (ml/kg/hour) and a treatment duration of 13 ± 24 days. Overall, in hospital, mortality was 50%. Among survivors, 21% required RRT on discharge from the hospital while 9% continued to require RRT 6 months after discharge. This is the first multicenter cohort of burn patients who underwent RRT reported to date. Overall mortality is comparable to other critically ill populations who undergo RRT. Most patients who survive to discharge eventually recover renal function.

Temporary Abdominal Closure Combined With an Irrigating System Utilizing Hypochlorous Acid Solution to Decrease Abdominal Mucopurulence.

Introduction: Leaving the abdominal cavity open is a well-described and frequently utilized technique in the treatment of severe intra-abdominal sepsis. Irrigation through a negative pressure wound therapy device is a technique employed to assist in the closure of wounds as well as the reduction of bacterial contamination. Furthermore, hypochlorous acid has been found to be safe and effective in microorganismal elimination from extremity wounds. There is no literature regarding the infusion of hypochlorous solution into the abdominal cavity for intra-abdominal sepsis or mucopurulent abscesses or biofilm. Objectives: A 47-year-old man with granulomatosis polyangiitis was started on weekly rituximab. After 4 infusions, skin sloughing, ultimately diagnosed as toxic epidermal necrolysis, developed. During the hospital course, he developed sepsis and bowel perforation necessitating an exploratory laparotomy. The abdomen was left open with a temporary abdominal closure using the Abthera open abdomen negative wound therapy device; however, the abdomen remained infected with visually diffuse, thickening mucopurulence despite multiple washouts. Therefore, a VAC Vera-Flo irrigation device was combined with the Abthera open abdomen negative wound therapy device and cyclical irrigation of hypochlorous acid. After 72 hours, the purulence visually was improved and no adverse events were recorded with the placement of intra-abdominal hypochlorous acid. Conclusions: The combination of two medical devices for the intra-abdominal instillation of irrigation is considered "off-label use" from the manufacturer's recommendations. In addition, the repeated instillation of hypochlorous acid solution has not been described but was noted to have visually decreased the contaminated effluent within the intra-abdominal fluid.

A Novel Approach To Sealing The Denuded Dermis of the Abdominal Wall With A Negative Pressure Wound Device After A Decompressive Laparotomy.

The open abdomen is a well-known technique that is applied in a wide variety of clinical situations, including treatment of abdominal compartment syndrome, damage control laparotomy, and severe intraabdominal sepsis. Disease states such as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis or extensive deep partial and/or full-thickness torso burns involving the abdomen often result in a complete epidermal and partial dermal loss. When ABThera Open Abdomen Negative Pressure Wound Therapy is attempted in these patients, the exposed subcutaneous tissue rarely allows for an adequate seal between the adhesive barrier and the denuded skin. This is because successful placement of negative pressure wound therapy device necessitates having a dry epidermal surface allowing the adhesive tape to actually adhere. The ABThera Open Abdomen Negative Pressure Wound Therapy visceral protective layer was placed over the exposed bowel, followed by the blue perforated foam interface and then the adhesive barrier drape. Over the top of the "less-than-air-tight" adhesive barrier drape was placed a standard isolation transport bowel bag, which was stapled to the dermis, but outside of the previously placed adhesive barrier drape's diameter to "bolster" the adhesive barrier drape, only allowing the suction tube to extend inferiorly. This ABThera Open Abdomen Negative Pressure Wound Therapy ABNPWT held suction, even during multiple adjacent dressing changes, despite the exposed dermis. This case report reveals a unique approach that solves the issue of inadequate seal due to extensive burns to the torso and has significant benefit in burn and wound care practices.

High-volume hemofiltration in adult burn patients with septic shock and acute kidney injury: a multicenter randomized controlled trial.

BACKGROUND: Sepsis and septic shock occur commonly in severe burns. Acute kidney injury (AKI) is also common and often results as a consequence of sepsis. Mortality is unacceptably high in burn patients who develop AKI requiring renal replacement therapy and is presumed to be even higher when combined with septic shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood purification technique would be beneficial in this population. METHODS: We conducted a multicenter, prospective, randomized, controlled clinical trial to evaluate the impact of HVHF on the hemodynamic profile of burn patients with septic shock and AKI involving seven burn centers in the United States. Subjects randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while control subjects were managed in standard fashion in accordance with local practices. RESULTS: During a 4-year period, a total of nine subjects were enrolled for the intervention during the ramp-in phase and 28 subjects were randomized, 14 each into the control and HVHF arms respectively. The study was terminated due to slow enrollment. Ramp-in subjects were included along with those randomized in the final analysis. Our primary endpoint, the vasopressor dependency index, decreased significantly at 48 hours compared to baseline in the HVHF group (p = 0.007) while it remained no different in the control arm. At 14 days, the multiple organ dysfunction syndrome score decreased significantly in the HVHF group when compared to the day of treatment initiation (p = 0.02). No changes in inflammatory markers were detected during the 48-hour intervention period. No significant difference in survival was detected. No differences in adverse events were noted between the groups. CONCLUSIONS: HVHF was effective in reversing shock and improving organ function in burn patients with septic shock and AKI, and appears safe. Whether reversal of shock in these patients can improve survival is yet to be determined. TRIAL REGISTRATION: Clinicaltrials.gov NCT01213914 . Registered 30 September 2010.

Retroperitoneal Necrotizing Fasciitis from Fournier's Gangrene in an Immunocompromised Patient.

INTRODUCTION: Necrotizing fasciitis (NF) is a devastating soft tissue disease causing fulminant clinical deterioration, and extension into the retroperitoneum has a high mortality rate. This disease process demands a strong clinical suspicion for early identification which must be coupled with frequent wide surgical debridements and intravenous antibiotics for improved outcomes. Various clinical risk factors may render a weakness in the patient's immune status including diabetes mellitus, chronic renal failure, obesity, and autoimmune disorders, such as a human immunodeficiency virus (HIV) infection. CASE REPORT: A 55-year-old male presented with hypotension requiring a large intravenous fluid resuscitation and vasopressors. He was diagnosed with the human immunodeficiency virus upon presentation. A computerized tomographic scan revealed air and fluid in the perineum and pelvis, ascending into the retroperitoneum. Multiple surgical debridements to his perineum, deep pelvic structures, and retroperitoneum were completed. After colostomy placement, antibiotic administration, and wound care, he was closed using split-thickness skin grafting. CONCLUSION: NF is a sinister and fulminant disease requiring prompt diagnosis and surgical intervention. The best chance for survival occurs with emergent surgical debridement and appropriate intravenous antibiotics. While retroperitoneal NF is consistent with uniformly poor outcomes, patients are best treated in an American Burn Association-verified burn center.

Lemons in the Arizona Sunshine: The Effects of Furocoumarins Leading to Phytophotodermatitis and Burn-like Injuries.

INTRODUCTION: Phytophototoxic dermatitis is a strong phototoxic reaction to ultraviolet A (UV-A) radiation exposure after cutaneous contact with citrus fruit containing furocoumarins, leading to skin injury. At the Arizona Burn Center (Phoenix, AZ), the majority of these injuries are managed in the outpatient setting. CASE REPORT: The authors present a pediatric admission for burn-like injuries following prolonged cutaneous exposure to lemons while playing in the Arizona sunshine. A 7-year-old girl playing in her backyard squeezed lemon juice onto her skin while in the hot Arizona sunshine; within 24 hours, the child experienced pain, erythema, and blistering to multiple areas of her skin. She was admitted to the authors' burn center for wound care and pain control. She had scattered first-degree and second-degree burn-like lesions to her face, neck, and chest as well as bilateral forearms, hands, lower extremities, and feet. After blister debridement, appropriate dressing care, and pain medication, the patient was discharged home after 4 days of hospitalization with appropriate clinical follow-up. CONCLUSIONS: Burn-like lesions caused by furocoumarins after cutaneous absorption and UV-A exposure are known clinical entities in Arizona. The sequential progression from erythema to blisters equivalent to second-degree burn-like lesions to cutaneous hyperpigmentation is a well-described clinical triad. Meticulous wound care and pain control for the treatment of these burn-like lesions are essential as is the need for the wound care specialist to be well versed on this topic to quickly identify the etiology of the injury, thereby avoiding misdiagnosing the patient with nonaccidental traumatic injuries.