Relationship Between the Cortisol-Estradiol Phase Difference and Affect in Women.

Affective disorders impact women's health, with a lifetime prevalence of over twelve per cent. They have been correlated with reproductive cycle factors, under the regulation of hormonal circadian rhythms. In affective disorders, circadian rhythms may become desynchronized. The circadian rhythms of cortisol and estradiol may play a role in affective disorders. The purpose of this study was to explore the temporal relationship between the rhythms of cortisol and estradiol and its relationship to affect. It was hypothesized that a cortisol-estradiol phase difference (PD) exists that correlates with optimal affect. A small scale, comparative, correlational design was used to test the hypothesis. Twenty-three women were recruited from an urban university. Salivary samples were collected over a twenty-four-hour period and fitted to a cosinor model. Subjective measures of affect were collected. Relationships between the cortisol-estradiol PD and affect were evaluated using a second-degree polynomial equation. Results demonstrated a significant correlation in affect measures (p < 0.05). An optimal PD was identified for affect to be 3.6 hours. The phase relationship between cortisol and estradiol may play a role in the development of alterations in affective disorders.

A survey of blood pressure parameters after aneurysmal subarachnoid hemorrhage.

Purpose/aim: Blood pressure (BP) regulation is recommended following aneurysmal subarachnoid hemorrhage (aSAH) to prevent re-bleeding and to treat delayed cerebral ischemia. However, optimal BP thresholds are not well established. There is also variation with regard to the BP component (e.g. systolic vs. mean) that is targeted or manipulated. MATERIALS AND METHODS: An 18-question survey was distributed to physicians and advanced practitioner members of the Neurocritical Care Society. Respondents were asked which BP parameter they manipulated and what their thresholds were in different clinical scenarios. They were also asked whether they were influenced by the presence of incidental aneurysms. Answers were analyzed for differences in training background and treatment setting. RESULTS: There were 128 responses. The majority were neurointensivists (47 neurology and 37 non-neurology) and treated patients in dedicated neurointensive care units (n = 98). Systolic BP (SBP) was preferred over mean arterial pressure (MAP). Prior to aneurysm treatment, SBP limits ranged from 140 to 180 mm Hg. After aneurysm treatment, SBP limits ranged from 160 to 240 mm Hg. The maximum and minimum MAPs varied by as much as 50%. Nearly two-thirds of the respondents were influenced by the presence of incidental aneurysms. Training background influenced tolerance to BP limits with neurology-trained neurointensivists accepting higher BP limits when treating delayed ischemia ( p = .018). They were also more likely to follow SBP ( p = .018) and have a limit of 140 mm Hg prior to aneurysm treatment ( p = .001). CONCLUSIONS: There is large practice variability in BP management following aSAH. There is also uncertainty over the importance of incidental aneurysms. Further research could evaluate whether this variability has clinical significance.

STAT subtype specificity and ischemic preconditioning in mice: is STAT-3 enough?

The role of other STAT subtypes in conferring ischemic tolerance is unclear. We hypothesized that in STAT-3 deletion alternative STAT subtypes would protect myocardial function against ischemia-reperfusion injury. Wild-type (WT) male C57BL/6 mice or mice with cardiomyocyte STAT-3 knockout (KO) underwent baseline echocardiography. Langendorff-perfused hearts underwent ischemic preconditioning (IPC) or no IPC before ischemia-reperfusion. Following ex vivo perfusion, hearts were analyzed for STAT-5 and -6 phosphorylation by Western blot analysis of nuclear fractions. Echocardiography and postequilibration cardiac performance revealed no differences in cardiac function between WT and KO hearts. Phosphorylated STAT-5 and -6 expression was similar in WT and KO hearts before perfusion. Contractile function in WT and KO hearts was significantly impaired following ischemia-reperfusion in the absence of IPC. In WT hearts, IPC significantly improved the recovery of the maximum first derivative of developed pressure (+dP/dtmax) compared with that in hearts without IPC. IPC more effectively improved end-reperfusion dP/dtmax in WT hearts compared with KO hearts. Preconditioned and nonpreconditioned KO hearts exhibited increased phosphorylated STAT-5 and -6 expression compared with WT hearts. The increased subtype activation did not improve the efficacy of IPC in KO hearts. In conclusion, baseline cardiac performance is preserved in hearts with cardiac-restricted STAT-3 deletion. STAT-3 deletion attenuates preconditioning and is not associated with a compensatory upregulation of STAT-5 and -6 subtypes. The activation of STAT-5 and -6 in KO hearts following ischemic challenge does not provide functional compensation for the loss of STAT-3. JAK-STAT signaling via STAT-3 is essential for effective IPC.

Declining Intensive Care Unit Mortality of COVID-19: A Multi-Center Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) mortality has waned significantly over time; however, factors contributing towards this reduction largely remain unidentified. The purpose of this study was to evaluate the trend in mortality at our large tertiary academic health system and factors contributing to this trend. METHODS: This is a retrospective cohort study of intensive care unit (ICU) patients diagnosed with COVID-19 between March and August 2020 admitted across 14 hospitals in the Philadelphia area. Collected data included demographics, comorbidities, admission risk of mortality score, laboratory values, medical interventions, survival outcomes, hospital and ICU length of stay (LOS) and discharge disposition. Chi-square (χ2) test, Fisher exact test, Cochran-Mantel-Haenszel method, multinomial logistic regression models, independent sample t-test, Mann-Whitney U test and one-way analysis of variance (ANOVA) were used. RESULTS: A total of 1,204 patients were included. Overall mortality was 39%. Mortality declined significantly from 46% in March to 14% in August 2020 (P < 0.05). The most common underlying comorbidities were hypertension (60.2%), diabetes mellitus (44.7%), dyslipidemia (31.6%) and congestive heart failure (14.7%). Hydroxychloroquine (HCQ) use was more commonly associated with the patients who died, while the use of remdesivir, tocilizumab, steroids and duration of these medications were not significantly different. Peak values of ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and D-dimer levels were significantly higher in patients who died (P < 0.05). The mean hospital LOS was significantly longer in the patients who survived compared to the patients who died (18 vs. 12, P < 0.05). CONCLUSIONS: The mortality of patients admitted to our ICU system significantly decreased over time. Factors that may have contributed to this may be the result of a better understanding of COVID-19 pathophysiology and treatments. Further research is needed to elucidate the factors contributing to a reduction in the mortality rate for this patient population.

Does platelet administration affect mortality in elderly head-injured patients taking antiplatelet medications?

A significant portion of patients sustaining traumatic brain injury (TBI) take antiplatelet medications (aspirin or clopidogrel), which have been associated with increased morbidity and mortality. In an attempt to alleviate the risk of increased bleeding, platelet transfusion has become standard practice in some institutions. This study was designed to determine if platelet transfusion reduces mortality in patients with TBI on antiplatelet medications. Databases from two Level I trauma centers were reviewed. Patients with TBI 50 years of age or older with documented preinjury use of clopidogrel or aspirin were included in our cohort. Patients who received platelet transfusions were compared with those who did not to assess outcome differences between them. Demographics and other patient characteristics abstracted included Injury Severity Score, Glasgow Coma Scale, hospital length of stay, and warfarin use. Three hundred twenty-eight patients comprised the study group. Of these patients, 166 received platelet transfusion and 162 patients did not. Patients who received platelets had a mortality rate of 17.5 per cent (29 of 166), whereas those who did not receive platelets had a mortality rate of 16.7 per cent (27 of 162) (P = 0.85). Transfusion of platelets in patients with TBI using antiplatelet therapy did not reduce mortality.

Risk factors for relapse of ventilator-associated pneumonia in trauma patients.

BACKGROUND: Our goal was to define risk factors for ventilator-associated pneumonia (VAP) relapse and examine the implications, if any, for initial therapy in trauma patients. METHODS: Trauma patients cared for in the surgical intensive care unit during a 48-month period with confirmed VAP recurrence were evaluated. Recurrent VAP was defined as a positive quantitative culture (> or = 10(4) colony-forming units/mL in a bronchoalveolar lavage or protected catheter lavage specimen) > or = 4 days after initiation of antibiotics for the primary episode. Recurrence with at least one of the initial causative pathogens was defined as a relapse. Initial causal pathogen, Acute Physiology and Chronic Health Evaluation II score, injury severity score, Glasgow Coma Score (GCS), age, white blood cell count (WBC), and duration of hospital stay before diagnosis were analyzed in univariate and multivariate regression models. RESULTS: A total of 55 patients met the criteria of recurrent VAP. Of these 55 recurrences, 19 (35%) were relapses. Acute Physiology and Chronic Health Evaluation II score, injury severity score, and GCS were not associated with VAP relapse by univariate analyses. Patients who relapsed had primary VAP involving nonfermenting gram-negative bacilli (NFGNB) (Acinetobacter, Pseudomonas, and Stenotrophomonas species) more frequently than other organisms (68% vs. 32%, p = 0.001). Primary VAP with NFGNB was found to be a significant predictor of VAP relapse by univariate and multivariate logistic regression analysis (OR = 5.1, p = 0.003; OR = 4.63, p = 0.005, respectively). CONCLUSIONS: There is a high rate of VAP relapse associated with primary infection by NFGNB, suggesting initial treatment failure. Trauma patients with primary VAP involving these organisms may benefit from increased surveillance for relapse.

Improving Decannulation and Swallowing Function: A Comprehensive, Multidisciplinary Approach to Post-Tracheostomy Care.

BACKGROUND: Multidisciplinary tracheostomy teams have been successful in improving operative outcomes; however, limited data exist on their effect on postoperative care. We aimed to determine the effectiveness of a multidisciplinary tracheostomy service alone and following implementation of a post-tracheostomy care bundle on rates of decannulation and tolerance of oral diet before discharge. METHODS: Prospective data on all subjects requiring tracheostomy by any trauma/critical care surgeon were collected from January 2011 to December 2013 following development of a tracheostomy service and continued following implementation of the post-tracheostomy care bundle. Rates of decannulation and tolerance of oral diet were compared between all groups: pre-tracheostomy service (baseline, historical control), tracheostomy service alone, and tracheostomy service with post-tracheostomy care bundle. RESULTS: Three hundred ninety-three subjects met the criteria for analysis with 61 in the baseline group, 124 following initiation of a tracheostomy service, and 208 after the addition of the post-tracheostomy care bundle. There were significant overall differences between all groups in the proportion of subjects decannulated, proportion of subjects tolerating oral diet, and number of subjects receiving speech evaluations. Pairwise comparisons showed no differences in decannulation or tolerance of oral diet following implementation of the tracheostomy service alone but significant improvement with the addition of the post-tracheostomy care bundle compared with baseline. (P = .002 and P = .005, respectively). Likewise, the number of speech language pathologist consults significantly increased compared with baseline only after the post-tracheostomy care bundle (P = .004). Time to speech evaluation significantly decreased with the post-tracheostomy care bundle compared with baseline and tracheostomy service (P < .013). CONCLUSIONS: The addition of a post-tracheostomy care bundle to a multidisciplinary tracheostomy service significantly improved rates of decannulation and tolerance of oral diet.

Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure.

Aortic banding in the rat has become a popular method to induce left ventricular (LV) hypertrophy and heart failure. However, because of often extensive intrathoracic adhesions and inflammatory cell infiltrates resulting from the traditional surgical approach, an uncomplicated second thoracic incision for genetic manipulation is impeded. In this study, we describe a novel surgical technique of aortic banding which avoids opening the sternum and thereby avoids adhesions and surgery-related inflammation. Placing a clip on the ascending aorta using a suprasternal approach in Sprague-Dawley rats created proximal aortic constriction. The present study was initiated to determine whether a replication-deficient adenovirus would enable efficient gene transfer to adult cardiac myocytes undergoing hypertrophy and transitioning to heart failure. Echocardiography performed at week 24 revealed significant concentric hypertrophy and increased fractional shortening followed by LV dilatation with decreased fractional shortening after 27 wk of banding. An adenoviral solution encoding for the reporter green fluorescent protein gene (GFP) was delivered to the heart. Fluorescent microscopy revealed global gene expression throughout hypertrophied and failing hearts. Our studies demonstrate that a novel suprasternal approach can be applied to create an LV hypertrophy model followed by heart failure which also allows investigators to perform genetic manipulations in vivo through gene transfer without the complication of adhesions and surgical trauma-induced inflammation. Furthermore, our approach to delivery of transgenes results in homogenous gene expression in both hypertrophied and failing hearts.

Unusual complications of long-term percutaneous gastrostomy tubes.

Percutaneous endoscopic gastrostomy (PEG) has been popular since it was introduced in 1980. Gastrostomy tubes left in place for long periods often result in unusual complications. Complications may also result from simply replacing a long-term indwelling tube. Five patients who had gastrostomy tubes in place for as long as 4 years are presented and their complications reviewed. Various methods used in treating these complications are discussed, and suggestions for their prevention are given. Gastrointestinal erosion and jejunal perforation following migration of the gastrostomy tube, persistent abdominal wall sinus tracts, and separation of the flange head with small bowel obstruction were encountered. Reinsertion of a gastrostomy tube through a tract prior to adequate maturation was also noted to lead to complications. Complications may result from gastrostomy tubes left in place for extended periods of time and during replacement procedures. Awareness of such complications along with education of caregivers and timely intervention by the endoscopist may prevent such occurrences. In some cases one can only hope to minimize morbidity.

Resource-efficient mobilization programs in the intensive care unit: who stands to win?

BACKGROUND: Functional outcomes can improve with early intensive care unit (ICU) mobilization programs but require additional resources. Details regarding resource allotment and methods to deliver therapy are lacking. We describe an effective team-based, resource-efficient mobility program (REMP). METHODS: Consecutive admissions (November 2009 to March 2010) underwent an evaluation by a physical therapist and participation in the REMP. Sitting balance (SB), transfer from bed to chair, and ambulation were assessed on the initial evaluation and compared with ICU and hospital discharge using the Functional Independence Measure scale. RESULTS: Twenty-eight patients entered the REMP, and 31 patients served as controls. There were no differences in baseline characteristics or initial Functional Independence Measure scores for ambulation or SB. Bed-to-chair evaluation was higher in the controls (P < .024). Both groups improved across the 3 time periods on all measures; however, more REMP patients had a significantly improved SB at ICU and hospital discharge. CONCLUSIONS: A team-based, resource-efficient approach to early mobilization is feasible and effective in the ICU.

Simulation training in critical care: does practice make perfect?

BACKGROUND: Few data exist regarding the effectiveness of simulation in resident education in critical care. The purpose of this study was to determine whether multiple-simulation exposure (MSE) or single-simulation exposure (SSE) improved residents' recognition of shock and initial management of the critically ill simulated surgical patient. METHODS: Data were collected at a level 1 trauma center. Surgery, anesthesiology, and emergency medicine residents were given a multiple-choice question (MCQ) pretest before a tutorial on the recognition and management of shock followed by high-fidelity simulation/debriefing and MCQ post-test. MSE residents had 1.5 hours of simulation per resident over 3 days, and SSE residents had 1.5 hours of simulation as a group in 1 day. Pre- and posttest comparisons overall and subgroup analysis for MSE versus SSE were performed. RESULTS: Data was available for 45 MSE residents and 15 SSE residents. Overall posttest percent correct was greater than pretest percent correct (81% ± 9% vs 75% ± 13%, post- versus pre-, P = .01). Subgroup analysis demonstrated significantly improved post- versus pretest performance for MSE residents only. There were no differences in pre- or posttest performance for MSE residents during the first 4 months of the academic year versus the last 4 months. Pretest performance over 12 months of observation for MSE residents showed no significant differences. CONCLUSION: Repeated simulation exposure was more effective than single simulation exposure at improving MCQ performance designed to measure the recognition and management of shock in the critically ill simulated surgical patient. Duration of training did not impact MCQ performance.

Diagnosing blunt hollow viscus injury: is computed tomography the answer?

BACKGROUND: Blunt hollow viscus injury (BHVI) is challenging to diagnose. The purpose of this study was to determine the reliability of physical exam and the role of computed tomography (CT) in the diagnosis of BHVI. METHODS: All blunt abdominal trauma (BAT) admissions to a level 1 trauma center from January 2009 through December 2011 were identified through the trauma registry. Data collected included demographics and findings on CT and physical exam. RESULTS: Of 2,912 patients with blunt trauma, 340 had BAT, and 30 (9%) had BHVIs. The sensitivity and specificity of CT were 86% and 88%, respectively, whereas the sensitivity and specificity of clinical exam were 53% and 69%. Twenty-seven percent of patients with BAT and bladder injuries had concomitant BHVIs. CONCLUSIONS: This is the largest single series of BHVI after BAT. CT is superior to clinical exam in establishing the diagnosis of BHVI. Although associated injuries are common, bladder injury may be an important marker for BHVI.

Optimizing advanced practitioner charge capture in high-acuity surgical intensive care units.

OBJECTIVE: To determine the impact of standardized critical care documentation tools on charge capture by intensive care unit (ICU) advanced practitioners (APs). DESIGN: Prospective charge capture analysis of AP critical care charges (Current Procedural Terminology codes 99291 or 99292). SETTING: Neurosurgical, general surgical, and cardiothoracic ICUs in a level I, 800-bed hospital. The AP provider to patient ratio was 1:6, with 24-hour surgical intensivist oversight. PARTICIPANTS: Advanced practice registered nurses and physician assistants in the ICU. INTERVENTIONS: Standardized templates were developed to simplify documentation and optimize billing of critical care. All APs participated in comprehensive educational sessions on billing compliance and documentation. MAIN OUTCOME MEASURES: Charge capture was collected for 3 years, and comparisons were made between the first quarter before (fiscal year [FY] 2008), during (FY 2009) and after (FY 2010) implementation. The number of ICU patient-days, length of stay, and of beds was collected. RESULTS: During the implementation/education phase (FY 2009), there were no differences in charge capture compared with FY 2008. Each unit demonstrated an increase in charge capture after implementation, and an overall increase of 48% for all 3 ICUs was seen. The number of admissions and length of stay were not statistically different. The total number of ICU beds increased from 42 to 45 during the evaluation period. The salary offset for APs increased from 62% to 80%. CONCLUSIONS: Advanced practitioners represent an important component of the critical care services provided to patients in high-acuity surgical ICUs. Standardized critical care documentation and comprehensive education on evaluation and management guidelines significantly increased charge capture.

Coronary effluent from a preconditioned heart activates the JAK-STAT pathway and induces cardioprotection in a donor heart.

Preconditioning (PC) protects against ischemia-reperfusion (I/R) injury via the activation of the JAK-STAT pathway. We hypothesized that the mediators responsible for PC can be transferred to naive myocardium through the coronary effluent. Langendorff-perfused hearts from male Sprague-Dawley rats were randomized to paired donor/acceptor protocols with or without PC in the presence or absence of the JAK-2 inhibitor AG-490 (n = 6 for each group). Warmed, oxygenated coronary effluent collected during the reperfusion phases of PC (3 cycles of 5 min ischemia and 5 min reperfusion) was administered to acceptor hearts. The hearts were then subjected to 30 min ischemia and 40 min reperfusion. The left ventricles were analyzed for phosphorylated (p)STAT-1, pSTAT-3, Bax, Bcl, Bcl-X(L)/Bcl-2-associated protein (BAD), and caspase-3 expression by Western blot. A separate group of hearts (n = 6) was analyzed for STAT activation immediately after the transfer of the PC effluent (no I-R). Baseline cardiodynamics were not different among the groups. End-reperfusion maximal change in pressure over time (+dP/dt(max)) was significantly (P < 0.05) improved in acceptor PC (3,637 +/- 199 mmHg/s) and donor PC (4,304 +/- 347 mmHg/s) hearts over non-PC donor (2,020 +/- 363 mmHg/s) and acceptor (2,624 +/- 345 mmHg/s) hearts. Similar differences were seen for minimal change in pressure over time (-dP/dt(min)). STAT-3 activation was significantly increased in donor and acceptor PC hearts compared with non-PC hearts. Conversely, pSTAT-1 and Bax expression was decreased in donor and acceptor PC hearts compared with non-PC hearts. No differences in Bcl, BAD, or caspase-3 expression were observed. Treatment with AG-490 attenuated the recovery of +/-dP/dt in acceptor PC hearts and significantly reduced pSTAT-3 expression. The PC coronary effluent activates JAK-STAT signaling, limits apoptosis, and protects myocardial performance from I/R injury.

Equine-related injury: a retrospective analysis of outcomes over a 10-year period.

BACKGROUND: Morbidity and financial loss caused by equine-related injuries may be significant. The purposes of this study were to determine the patterns of equine-related injury and the impact on outcomes. METHODS: A 10-year retrospective review of equine-related injuries was performed. Age, gender, mechanism, injury severity score, Glasgow Coma Score, length of stay, surgical interventions, and mortality were assessed. RESULTS: Of 80 emergency department evaluations, 76 patients were admitted and form the basis of this study. The most frequent mechanism of injury was fall (68%), followed by crush injuries (15%), kicks (8%), and trampling (5%). Musculoskeletal injuries were most common (64%). Thirty-eight (50%) patients required surgical intervention. Thirty-seven (52%) patients were discharged home; 34% required outpatient physical therapy, and 14% required inpatient rehabilitation. The mortality rate was 7%. CONCLUSIONS: Equine-related injuries resulted in significant morbidity; most victims required outpatient or inpatient rehabilitation. The use of preventive strategies may minimize mortality and reduce the financial impact of postinjury morbidity.

Regulating RISK: a role for JAK-STAT signaling in postconditioning?

Postconditioning (POC), a novel strategy of cardioprotection against ischemia-reperfusion injury, is clinically attractive because of its therapeutic application at the predictable onset of reperfusion. POC activates several intracellular kinase signaling pathways, including phosphatidylinositol 3-kinase (PI3K)-Akt (RISK). The regulation of POC-induced survival kinase signaling, however, has not been fully characterized. JAK-STAT activation is integral to cardiac ischemic tolerance and may provide upstream regulation of RISK. We hypothesized that POC requires the activation of both JAK-STAT and RISK signaling. Langendorff-perfused mouse hearts were subjected to 30 min of global ischemia and 40 min of reperfusion, with or without POC immediately after ischemia. A separate group of POC hearts was treated with AG 490, a JAK2 inhibitor, Stattic, a specific STAT3 inhibitor, or LY-294002, a PI3K inhibitor, at the onset of reperfusion. Cardiomyocyte-specific STAT3 knockout (KO) hearts were also subjected to non-POC or POC protocols. Myocardial performance (+dP/dt(max), mmHg/s) was assessed throughout each perfusion protocol. Phosphorylated (p-) STAT3 and Akt expression was analyzed by Western immunoblotting. POC enhanced myocardial functional recovery and increased expression of p-STAT3 and p-Akt. JAK-STAT inhibition abrogated POC-induced functional protection. STAT3 inhibition decreased expression of both p-STAT3 and p-Akt. PI3K inhibition also attenuated POC-induced cardioprotection and reduced p-Akt expression but had no effect on STAT3 phosphorylation. Interestingly, STAT3 KO hearts undergoing POC exhibited improved ischemic tolerance compared with KO non-POC hearts. POC induces myocardial functional protection by activating the RISK pathway. JAK-STAT signaling, however, is insufficient for effective POC without PI3K-Akt activation.