Assessing the Influence of Intraoperative Core Body Temperature on Postoperative Venous Thromboembolism after Abdominal Wall Reconstruction.

Background: Venous thromboembolism (VTE) is a dangerous postoperative complication after abdominal wall reconstruction (AWR). Intraoperative core body temperature has been associated with thrombotic events in other surgical contexts. This study examines the effects of intraoperative temperature on VTE rate after AWR. Methods: A retrospective study was performed on AWR patients. Cohorts were defined by postoperative 30-day VTE. Intraoperative core body temperature was recorded as the minimum, maximum, and mean intraoperative temperatures. Study variables were analyzed with logistic regression and cutoff analysis to assess for association with VTE. Results: In total, 344 patients met inclusion criteria. Fourteen patients were diagnosed with 30-day VTE for an incidence of 4.1%. The VTE cohort had a longer median inpatient stay (8 days versus 5 days, P < 0.001) and greater intraoperative change in peak inspiratory pressure (3 mm H2O versus 1 mm H2O, P = 0.01) than the non-VTE cohort. Operative duration [odds ratio (OR) = 1.32, P = 0.01], length of stay (OR = 1.07, P = 0.001), and intraoperative PIP difference (OR = 1.18, P = 0.045) were significantly associated with 30-day VTE on univariable regression. Immunocompromised status (OR = 4.1, P = 0.023; OR = 4.0, P = 0.025) and length of stay (OR = 1.1, P < 0.001; OR = 1.1, P < 0.001) were significant predictors of 30-day VTE on two multivariable regression models. No significant associations were found between temperature metrics and 30-day VTE on cutoff point or regression analysis. Conclusions: Intraoperative core body temperature did not associate with 30-day VTE after AWR, though operative duration, length of stay, immunocompromised status, and intraoperative PIP difference did. Surgeons should remain mindful of VTE risk after AWR, and future research is warranted to elucidate all contributing factors.

Assessing the Relationship between Obesity and Trigger Point-specific Outcomes after Headache Surgery.

Background: Trigger point deactivation surgery is a safe and effective treatment for properly selected patients experiencing migraine, with 68.3%-100% experiencing symptom improvement postoperatively. However, it is still unknown why certain patients do not respond. Obesity has been shown to be associated with worsened migraine symptoms and a decreased response to select pharmacotherapies. This study aimed to determine whether obesity may also be associated with an attenuated response to surgery. Methods: A retrospective chart review was conducted to identify patients who had undergone trigger point deactivation surgery for migraine. Patients were split into obese and nonobese cohorts. Obesity was classified as a body mass index of 30 or higher per Centers for Disease Control and Prevention guidelines. Outcomes and follow-up periods were determined with respect to individual operations. Outcomes included migraine attack frequency, intensity, duration, and the migraine headache index. Differences in demographics, operative characteristics, and operative outcomes were compared. Results: A total of 62 patients were included in the study. The obese cohort comprised 31 patients who underwent 45 total operations, and the nonobese cohort comprised 31 patients who underwent 34 operations. Results from multivariable analysis showed no impact of obesity on the odds of achieving a more than 90% reduction in any individual outcome. The overall rates of improvement (≥50% reduction in any outcome) and elimination (100% reduction in all symptoms) across both cohorts were 89.9% and 65.8%, respectively. Conclusion: Obese patients have outcomes comparable to a nonobese cohort after trigger point deactivation surgery for migraine.

Patient Perceptions of Care Coordination during Neoadjuvant Therapy for Gastrointestinal Cancers: A Mixed Methods Analysis.

PURPOSE: Effective cancer care coordination (CCC) is an integral component of health care delivery and critical to achieving optimal oncologic outcomes. Neoadjuvant therapy (NT), the delivery of multimodality therapy prior to surgery, is inherently complex and multidisciplinary, but CCC during NT is poorly understood. The objective of this study was to characterize patient perceptions of CCC during NT using a mixed methods approach. METHODS: This study is a cross-sectional analysis of patients with gastrointestinal cancers receiving NT who participated in a prospective longitudinal cohort study evaluating their real-time experience using a customized smartphone application. Patients completed the Cancer Care Coordination Questionnaire for Patients (CCCQ-P), a 20-item validated measure of care coordination quality, six weeks after initiating NT. Items were scored on a 5-point Likert scale, and subsections on communication (13 questions) and navigation (7 questions) were calculated with higher scores signifying better CCC. Univariate linear regression was used to calculate the impact of fragmented care and other factors on perceived CCC. Semi-structured interviews were conducted among a convenience sample of patients (n = 5); transcribed interviews were then coded using an inductive approach. RESULTS: Among 82 participants, mean age was 61 years old, 68% were male, and mean number of comorbidities was 1.68. Overall (mean 76.6 out of 100), communication subsection (48.6 out of 65), and navigation subsection (28.0 out of 35) CCCQ-P scores suggested overall positive perceptions of care coordination. Qualitative analysis of patient interviews highlighted the need for coordination among physicians before communicating the plan to patients as well as the importance of providers communicating plans in verbal and written form. CONCLUSIONS: Successful completion of NT requires significant care coordination between patients and healthcare professionals. Yet, in this cross-sectional analysis of patients on a prospective cohort study, patient perceptions of CCC during NT were overall positive. Future research should focus on optimizing other aspects of care delivery in order to improve outcomes of NT.

Quality of Life and Real-time Patient Experience During Neoadjuvant Therapy: A Prospective Cohort Study.

OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.

Reducing hospital admissions in patients with malignant pleural effusion: a quality improvement study.

BACKGROUND: Malignant pleural effusions (MPE) can cause severe dyspnoea leading to greater than 125 000 hospitalisations per year and cost greater than US$5 billion per year in the USA. Timely insertion of tunnelled pleural catheters (TPCs) is associated with fewer inpatient days and emergency department visits. We conducted a quality improvement study to reduce hospital admissions of patients with MPE. METHODS: Key stakeholders were surveyed, including thoracic and breast oncology teams, general pulmonary and interventional pulmonology (IP) to help identify the underlying causes and solutions. Our preintervention group consisted of 51 patients who underwent TPC placement by our IP service. In our first intervention, we reviewed referrals for MPE with the scheduling team and triaged them based on urgency. In the second intervention, we added a follow-up phone call 1 week after the initial thoracentesis performed by IP to assess for the recurrence of symptoms. RESULTS: Demographic and clinical characteristics were summarised across the three groups. We evaluated the rate ratio (RR) of admissions in the intervention groups with the multivariable Poisson regression and adjusted for race, gender and cancer. Compared with the preintervention group, intervention I showed trends towards a 41% lower hospital admission rate (RR 0.59 (0.33-1.07), p=0.11). Compared with the preintervention group, intervention II showed trends towards a 40% lower hospital admission rate (RR 0.6 (0.36-0.99), p=0.07). The results did not reach statistical significance. Exploratory comparisons in readmission rates between interventions I and II showed no difference (RR 0.89 (0.43-1.79), p=0.75). CONCLUSIONS: Both interventions showed trends toward fewer hospital readmissions although they were not statistically significant. Larger-size prospective studies would be needed to demonstrate the continued effectiveness of these interventions.

Severe obesity is associated with increased migraine severity and frequency: A retrospective cohort study.

Migraine headaches and obesity are both prevalent disorders, resulting in a high socioeconomic burden. To better understand the relationship between obesity and migraine, the aim of this study was to investigate the association between migraine severity, metabolic syndrome and estrogen-associated variables. A retrospective analysis of adult patients with refractory migraine seen by our senior author (J.E.J.) was performed. Patient demographics and migraine characteristics, including migraine intensity, duration, and number of headaches per month were collected from medical records. Migraine headache index (MHI) was calculated by multiplying frequency, intensity and duration of headaches. Weight and height were used to calculate body mass index (BMI) and these were divided per Center for Disease Control (CDC) classifications. Univariate linear regression models were used to evaluate associations. Patients (n = 223) were predominantly female (78%) with a mean age of 44 years at presentation. Patients with a BMI higher than 40 (class 3 obesity) had a higher MHI (p = 0.01) and experienced a higher number of migraines per month (p = 0.007), compared to patients with a healthy BMI, respectively. Migraine frequency was found to be significantly higher in post-menopausal women compared to pre-menopausal women (p = 0.02). No other significant associations were found. This study found that severe obesity (BMI > 40) is associated with increased migraine severity and frequency. Post-menopausal patients are also found to have increased migraine frequency, which could be explained by the estrogen-withdrawal hypothesis. Future studies are needed to evaluate the outcomes of individuals with obesity after nerve deactivation surgery.

Characterizing treatment burden during neoadjuvant therapy for patients with gastrointestinal cancer: A mixed methods analysis.

INTRODUCTION: Neoadjuvant therapy (NT) is increasingly used before surgery for patients with gastrointestinal (GI) cancers. Treatment burden is a patient-centered measure defined as the work of being a patient and characterizes the impact of medical treatment on one's functioning and well-being. While treatment burden has previously been studied in chronic diseases and cancer survivorship, the treatment burden of undergoing NT is unknown. METHODS: All patients enrolled in a prospective cohort study evaluating the real-time experience of NT for GI cancers completed either the Patient Experience with Treatment and Self-management (PETS) survey, a 46-item validated measure of treatment burden, or the mini-PETS questionnaire. PETS subsections were scored on a 5-point Likert scale and then standardized on a 100-point scale (a higher number means more treatment burden). Semistructured interviews were conducted among a convenience sample of patients (n = 5); qualitative data were coded and then analyzed using an integrated approach. RESULTS: Among 126 participants, the mean age was 59 years old, 61% were male, and the mean number of comorbidities was 1.57. The most common cancers were colorectal (46%) and pancreatic (28%). The mean length of NT treatment was 3.7 months and 80.2% of patients underwent surgical resection following NT. The highest standardized treatment burden scores were observed in healthcare services (44 ± 15), social limitations (44 ± 26), exhaustion (41 ± 23), and medical expenses (40 ± 18) whereas the lowest scores were reported in medication use (19 ± 16) and interpersonal challenges (19 ± 17). Commonly experienced emotional symptoms were feeling worn out (43%) or frustrated (32%). No significant differences were observed in mean treatment burden subscores between patients who underwent surgery versus those who did not. Qualitative analysis of treatment burden during NT identified common themes of impact on normal life activities, challenges with healthcare access, impact on relationships, and significant physical and emotional symptoms. CONCLUSIONS: NT is associated with a significant treatment burden, particularly in the domains of accessing healthcare services, social limitations, and exhaustion. Given the increasing use of NT for GI cancers, novel patient-centered approaches are needed to improve quality of life and ensure the completion of multimodality therapy.

Fall Prevention With the Smart Socks System Reduces Hospital Fall Rates.

BACKGROUND: Falls of inpatients are common in hospitals. Existing fall prevention measures do not work consistently. PURPOSE: To determine whether Smart Socks reduce fall rates in fall risk patients at a major academic health center's neurological and neurosurgical based units. METHODS: A prospective study was conducted that provided fall risk patients with Smart Socks and no other fall prevention system. Data collected included duration of Smart Socks wearing, number of alarms, response times, and patient-days. RESULTS: A total of 569 fall risk patients were included for 2211.6 patient-days. There were 4999 Smart Socks alarms, but none of the patients fell. We observed a lower fall rate, of 0 per 1000 patient-days, for patients wearing Smart Socks than the historical fall rate of 4 per 1000 patient-days. The median nurse response time was 24 seconds. CONCLUSIONS: The Smart Socks reduced fall rates of fall risk patients included in the study.

Efficacy of PECS block in addition to multimodal analgesia for postoperative pain management in patients undergoing outpatient elective breast surgery: A retrospective study.

Background: Pectoralis nerve blocks (PECS) have been shown in numerous studies to be a safe and effective method to treat postoperative pain and reduce postoperative opioid consumption after breast surgery. However, there are few publications evaluating the PECS block effectiveness in conjunction with multimodal analgesia (MMA) in outpatient breast surgery. This retrospective study aims to evaluate the efficacy of PECS's blocks on perioperative pain management and opioid consumption. Methods: We conducted a retrospective study to assess the efficacy of preoperative PECS block in addition to preoperative MMA (oral acetaminophen and/or gabapentin) in reducing opioid consumption in adult female subjects undergoing outpatient elective breast surgery between 2015 and 2020. A total of 228 subjects were included in the study and divided in two groups: PECS block group (received PECS block + MMA) and control Group (received only MMA). The primary outcome was to compare postoperative opioid consumption between both groups. The secondary outcome was intergroup comparisons of the following: postoperative nausea and vomiting (PONV), incidence of rescue antiemetic medication, PACU non-opioid analgesic medication required, length of PACU stay and the incidence of 30-day postoperative complications between both groups. Results: Two hundred and twenty-eight subjects (n = 228) were included in the study. A total of 174 subjects were allocated in the control group and 54 subjects were allocated in the PECS block group. Breast reduction and mastectomy/lumpectomy surgeries were the most commonly performed procedures (48% and 28%, respectively). The total amount of perioperative (intraoperative and PACU) MME was 27 [19, 38] in the control group and 28.5 [22, 38] in the PECS groups (p = 0.21). PACU opioid consumption was 14.3 [7, 24.5] MME for the control group and 17 [8, 23] MME (p = 0.732) for the PECS group. Lastly, the mean overall incidence of postsurgical complications at 30 days was 3% (N = 5), being wound infection, the only complication observed in the PECS groups (N = 2), and hematoma (N = 2) and wound dehiscence (N = 1) in the control group. Conclusion: PECS block combined with MMA may not reduce intraoperative and/or PACU opioid consumption in patients undergoing outpatient elective breast surgery.

Ventricular arrhythmias and sudden death events following acalabrutinib initiation.

Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large-cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence of VAs. The primary-endpoint was incident VA development (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). Probability-scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as function of time-on-therapy were calculated. Weighted average observed incidence rates were compared with expected population rates using relative-risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1063 person-years of follow-up, there were 8 cases of incident-VAs, including 6 in those without coronary disease (CAD) or heart failure (HF) and 1 sudden-death; median time-to-event 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100 000 person years compared with a reported incidence of 48.1 among similar-aged non-BTKi-treated subjects (relative risk, 8.2; P < .001; AER, 346). Outside of age, no cardiac or electrocardiographic variables associated with VA development. Collectively, these data suggest VAs may be a class-effect of BTKi therapies.

Impact of a pharmacist-led tacrolimus management protocol in the outpatient setting.

BACKGROUND: Clinical pharmacists are often used to make recommendations regarding tacrolimus therapy in the post transplant setting.Therapeutic drug monitoring (TDM) of tacrolimus after transplant is based on trough levels in the setting of predetermined institutional immunosuppression goals. To evaluate time within therapeutic range (TTR) of tacrolimus the Rosendaal method can be utilized. OBJECTIVE: Our study aimed to compare objective therapeutic drug monitoring outcomes after the implementation of a pharmacist driven tacrolimus management protocol (postprotocol initiation) with previous management by providers (preprotocol initiation). PRACTICE DESCRIPTION: The Ohio State University Wexner Medical Center (OSUWMC) is a 700-bed academic medical center in Columbus, OH. On average, OSUWMC completes more than 300 kidney transplants each year. There are 6 abdominal transplant pharmacists (including one postgraduate year 2 transplant pharmacy resident) that rotate through the inpatient and outpatient setting. PRACTICE INNOVATION: A pharmacist-led tacrolimus management protocol in kidney transplant recipients was initiated in October 2018 at our institution, which enabled pharmacists to dose and adjust tacrolimus in the outpatient setting in accordance with prespecified goals. EVALUATION METHODS: This single-center retrospective analysis included adult kidney transplant recipients on de novo tacrolimus. Patient's tacrolimus levels were evaluated for 6 months after transplant. The mean tacrolimus percent TTR and the median coefficient of variation (CV) were calculated and compared in postprotocol initiation group (n = 85) with preprotocol initiation group (n = 39). TTR was calculated using the Rosendaal method. RESULTS: There was no statistically significant difference between the preprotocol initiation and postprotocol initiation group mean TTR (59.6% vs. 60.5%, P = 0.723), mean CV from 0-3 months after transplant (36.3 vs. 36.0, P = 0.900), and mean CV from at least 3-6 months after transplant (24.5 vs. 22.7, P = 0.351). Rejection rates, development of donor-specific antibodies, and renal function were similar between groups. CONCLUSION: Based on our findings, transplant pharmacists were equally as effective at maintaining tacrolimus percent TTR and CV in the designated kidney transplant recipients included in the management protocol compared with primary management by other transplant providers. The delegation of tacrolimus management to clinical pharmacists is a viable alternative to primary management by outpatient practitioners.

Hypertension and incident cardiovascular events after next-generation BTKi therapy initiation.

BACKGROUND: Post-market analyses revealed unanticipated links between first-generation Bruton's tyrosine kinase inhibitor (BTKi) therapy, ibrutinib, and profound early hypertension. Yet, whether this is seen with novel selective second (next)-generation BTKi therapy, acalabrutinib, is unknown. METHODS: Leveraging a large cohort of consecutive B cell cancer patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence and ramifications of new or worsened hypertension [systolic blood pressure (SBP) ≥ 130 mmHg] after acalabrutinib initiation. Secondary endpoints were major cardiovascular events (MACE: arrhythmias, myocardial infarction, stroke, heart failure, cardiac death) and disease progression. Observed incident hypertension rates were compared to Framingham heart-predicted and ibrutinib-related rates. Multivariable regression and survival analysis were used to define factors associated with new/worsened hypertension and MACE, and the relationship between early SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of acalabrutinib-related hypertension was assessed. RESULTS: Overall, from 280 acalabrutinib-treated patients, 48.9% developed new/worsened hypertension over a median of 41 months. The cumulative incidence of new hypertension by 1 year was 53.9%, including 1.7% with high-grade (≥ 3) hypertension. Applying the JNC 8 cutoff BP of ≥ 140/90 mmHg, the observed new hypertension rate was 20.5% at 1 year, > eightfold higher than the Framingham-predicted rate of 2.4% (RR 8.5, P < 0.001), yet 34.1% lower than ibrutinib (12.9 observed-to-expected ratio, P < 0.001). In multivariable regression, prior arrhythmias and Black ancestry were associated with new hypertension (HR 1.63, HR 4.35, P < 0.05). The degree of SBP rise within 1 year of treatment initiation predicted MACE risk (42% HR increase for each + 5 mmHg SBP rise, P < 0.001). No single antihypertensive class prevented worsened acalabrutinib-related hypertension. CONCLUSIONS: Collectively, these data suggest that hypertension may be a class effect of BTKi therapies and precedes major cardiotoxic events.

Impact of Dose Intensity on Pathologic Complete Response Rate in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Docetaxel, Carboplatin, Trastuzumab and Pertuzumab (TCHP).

BACKGROUND: Neoadjuvant chemotherapy is the cornerstone treatment for locally advanced breast cancer. Balancing toxicity and efficacy are a common concern of patients treated with chemotherapy. OBJECTIVE: The objective of this study was to determine the impact of dose intensity on pathologic complete response (pCR) at the time of surgery in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. PATIENTS AND METHODS: A retrospective, single-center review was conducted on patients with HER2+ breast cancer who received neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) followed by definitive surgery. RESULTS: A total of 159 patients were included in the analysis; pCR was obtained in 66 patients (42%). There was no statistically significant difference between the mean dose intensity of each of the individual agents in TCHP and pCR rates. The mean overall dose intensity of docetaxel, carboplatin, trastuzumab and pertuzumab was 90.5%, 90.9%, 97.5%, and 93.9%, respectively. Although higher chemotherapy dose intensity (> 85%) was associated with higher pCR rates, no statistically significant difference was found compared with chemotherapy dose intensity < 85%. The TCHP regimen was difficult to tolerate; 104 patients (65%) required a dose reduction or dose delay during treatment due to toxicity. CONCLUSION: The TCHP regimen, which combines chemotherapy and HER2-directed therapy is effective at obtaining pCR in patients with locally advanced HER2+ breast cancer. These results suggest that the dose intensity of the individual agents did not have a significant impact on pCR rates. Given these findings, providers may be more comfortable allowing dose reductions for greater patient tolerability without sacrificing efficacy.

Bladder Management With Chronic Indwelling Catheter is Associated with Elevated Mortality in Patients with Spinal Cord Injury.

OBJECTIVE: To evaluate the impact of bladder management method, specifically chronic indwelling catheter (IndC), on survival in patients with spinal cord injury (SCI) in Spinal Cord Injury Model System database. METHODS: Spinal Cord Injury Model System is a multicenter longitudinal database since 1970 with >40,000 patients with SCI. Adult patients (>18 at the time of injury) were screened. Patients who died within 1 year of injury and had 2 or more changes in method of bladder management, or reported normal volitional void were excluded. Outcome of interest was death from nonpulmonary, nonwound related sepsis (NPNWS). Left truncation cox regression method using age as the time-scale was used to calculate hazard ratios. RESULTS: A total of 13,616 patients were included. Comparison was performed between "IndC" group (n = 4872; 36.1%) vs "Other" (n = 8744; 63.9%). After adjusting for age and change in bladder management method, "IndC" is associated with elevated NPNWS mortality (2.10; 95% confidence interval 1.72-2.56, P < .001). Multivariable analysis, adjusting for age at injury, gender, race, education, insurance status, etiology of SCI, injury level, neurologic impairment level, and change in bladder management method, showed IndC was associated with significantly higher risk of death from NPNWS compared to other methods of bladder management. CONCLUSION: In a large cohort of SCI patients, bladder management with IndC is predictive of significantly propagated NPNWS related mortality compared to other methods of bladder management. While identifying IndC is an independent mortality risk factor, a better understanding of the underlying mechanisms could inform strategies to improve neurourological care and survival after SCI.

Risk Factors Associated with Suboptimal Tobramycin Levels in the Medical Intensive Care Unit.

BACKGROUND: Optimal aminoglycoside dosing in critically ill patients represents a challenge for practitioners, especially in the medical intensive care unit (MICU). MICU patients exhibit altered pharmacokinetics due to pathophysiological changes the body undergoes in critical illness, leading to possible treatment failure. The literature surrounding optimal dosing and therapeutic drug monitoring strategies of aminoglycosides in MICU patients is scarce and conflicting. Additionally, only a few studies have investigated risk factors for suboptimal pharmacokinetic target obtainment. Currently, no definitive risk factors have been identified to predict suboptimal aminoglycoside target obtainment in MICU patients. OBJECTIVE: The objective of this study was to determine risk factors for suboptimal pharmacokinetic target obtainment in patients receiving tobramycin in the MICU. METHODS: This single-center, retrospective cohort study included patients 18-89 years old who received at least one 7 mg/kg tobramycin dose in the MICU from January, 1 2015 to September, 30 2020. Patients also had to have at least two detectable drug levels obtained at least one half-life apart following the first tobramycin dose. The primary outcome was to determine the incidence of optimal pharmacokinetic target obtainment, defined as a tobramycin maximum concentration (Cmax) ≥ 10 mcg/ml, and to identify the risk factors for suboptimal (Cmax < 10 mcg/mL) pharmacokinetic target obtainment, in MICU patients. Secondary outcomes were compared between suboptimal and optimal target obtainment in patients with culture confirmed gram-negative infection susceptible to tobramycin. These secondary outcomes included all-cause in-hospital mortality, ICU length of stay (LOS), hospital LOS, and vasopressor duration in those with shock. RESULTS: A total of 230 patients were included in this retrospective study. For the primary outcome, 187 (81.3%) patients achieved optimal target obtainment. Through multivariate logistic regression, female sex and serum albumin < 2.5 g/dL were identified as independent risk factors for suboptimal target obtainment; [OR = 2.14; 95% CI (1.05-4.37), p = 0.037], [OR = 2.50; 95% CI (1.21-5.19), p = 0.014], respectively. Fifty-four (23%) patients had culture-confirmed gram-negative infections susceptible to tobramycin and were included in the subgroup analysis. Of these 54 patients, 11 (20.4%) did not achieve optimal target concentrations. In patients with culture-confirmed gram-negative infection, there was no difference between patients with optimal target obtainment and suboptimal target obtainment in ICU LOS, hospital LOS, all-cause mortality, or vasopressor duration in those with shock. CONCLUSIONS: Among patients receiving their first dose of tobramycin in the MICU, 81.3% obtained an optimal serum concentration. Female sex and serum albumin < 2.5 g/dL were identified as risk factors for suboptimal target obtainment; however, further research is warranted to assess the utility of using these two covariates as risk factors for more aggressive dosing in critically ill MICU patients.

Resection Status Does Not Impact Recurrence in Well-Differentiated Liposarcoma of the Extremity.

BACKGROUND: Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status. METHODS: A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS. RESULTS: 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection. DISCUSSION: In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Assessment of Leptomeningeal Carcinomatosis Diagnosis, Management and Outcomes in Patients with Solid Tumors Over a Decade of Experience.

OBJECTIVE: Leptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS). MATERIALS AND METHODS: We performed a single-institution retrospective study (registration #: OSU2016C0053) of 153 patients diagnosed with LMC treated at The Ohio State University, Comprehensive Cancer Center, (OSUCCC)-James between January 1, 2010 and December 31, 2015. RESULTS: Median age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status ≤1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months). CONCLUSION: Despite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC.