Initial Course Of Treatment Research Articles

P-77. Ceftaroline versus Daptomycin as Definitive Treatment for Methicillin-Resistant Staphylococcus aureus Bone and Joint Infections

Abstract Background There are no comparative effectiveness studies of ceftaroline versus other antibiotics for MRSA bone and joint infections (BJI). We retrospectively compared the clinical outcomes of patients with MRSA BJI initially treated with vancomycin and then transitioned to either ceftaroline (VtoC) or daptomycin (VtoD). Methods This retrospective nested case-control study analyzed data from a large Midwest academic center collected from 2018-2022. Patients with MRSA BJI whose definitive treatment was ceftaroline were compared in a 1:2 ratio to patients whose definitive treatment was daptomycin. The primary outcome was clinical success after initial treatment course (i.e., at 6 weeks) defined by a composite endpoint which included resolution of signs and symptoms and no repeat surgery or re-admission for treatment of the index BJI. Results We identified 36 patients to be included in this case-control study, with 12 VtoC cases and 24 VtoD cases. The demographic make-up was similar, as was the frequency of comorbidities (including Charlson score). Of the VtoC patients, 42% had implant-related infection vs. 17% of the VtoD group (p=0.1). A larger proportion of VtoC patients had systemic MRSA infection as documented by positive blood cultures (58% vs 38%; p=0.2). More VtoC cases were direct ICU admits (50% vs 13%; p=0.04), required intubation (58% vs 17%; p=0.02), or were admitted to the ICU at any point during their stay (67% vs 29%; p=0.07). Transition away from vancomycin occurred at 14.3 vs 10.6 days (p=0.6). There was only a single clinical success in the 12 VtoC patients (8%) vs. 7/24 (29%) in the VtoD group (p=0.2), with the majority of cases being failures (30.5%), all-cause deaths (30.5%), or lost to follow-up (16.7%). Follow-up was 103 vs 123 days (p=0.8) in the two groups. Conclusion In this comparison of ceftaroline to daptomycin for MRSA BJI we found ceftaroline recipients to have more severe illness (as suggested by need for ICU care) and experience very little clinical success. We suspect that there is selection bias in that more severely ill cases anticipated to have poor outcomes were more likely to be transitioned to ceftaroline. Our next steps are to include more data and conduct a propensity score analysis to better understand what factors are associated with transition to ceftaroline. Disclosures All Authors: No reported disclosures

Zap-X Radiosurgery System: Initial Clinical Experience in a Recurrent Gamma Knife Case Series.

The ZAP-X® Gyroscopic Radiosurgery System (ZAP Surgical Systems, Inc., San Carlos, CA, USA) is expected to be a highly accurate next-generation treatment system that enables gyro-stereotactic irradiation of intracranial lesions. In this study, we report the initial treatment course using ZAP-X for intracranial lesions that recurred after Gamma Knife (GK) treatment. Patients with intracranial tumors treated with ZAP-X from April to August 2023 who relapsed after GK therapy were eligible for participating in this study. The primary endpoint was the progression control rate at six months; the secondary endpoints were the rate of target lesion reduction, treatment effect by tumor doubling time (TDT) before ZAP-X intervention, and adverse events. Six lesions were evaluated in six patients (two meningiomas, one solitary fibrous tumor, one auditory neuroma, one glomus tumor, and one metastatic tumor). The mean follow-up period was 10.6 months after treatment. The mean lesion volume was 5.3 cm3; the mean TDT was 241 days. The six-month progression control rate was 100%, with two partial responses and four stable diseases at the last evaluation. Adverse events were limited to only imaging changes in one patient (16.6%), indicating a significant correlation between ZAP-X pre-intervention TDT and post-intervention reduction rate. The initial results of ZAP-X treatment in patients with recurrent disease following GK are reported for the first time. ZAP-X demonstrated potent anti-tumor efficacy and adequate tolerability and should be considered a new treatment option for relapsed refractory patients. Future studies should increase the number of cases and follow-up periods to further evaluate treatment outcomes and adverse events.

Life After EBPs: Characterizing Subsequent Engagement in Evidence-Based Psychotherapy After Completion of an Initial Trauma-Focused EBP in a National Sample of VA Patients.

Many Veterans who complete prolonged exposure (PE) or cognitive processing therapy (CPT) report residual symptoms, but it is unclear how to best address the mental health needs of these individuals. Examining patterns of mental health service utilization following completion of these two treatments may provide insight into how to best serve this group of individuals. In a large cohort of Veterans (N = 12,514) who sought treatment in the Veterans Health Administration during Fiscal Years 2015-2019, logistic regression models were used to assess the odds of initiating an additional course of trauma-focused (i.e., PE or CPT) or depression-focused psychotherapy in the year following completion of PE or CPT based on demographic, psychiatric, and treatment effectiveness-related variables. Approximately 9% of Veterans engaged in either trauma-(6%) or depression-(3%) related psychotherapy in the year following discharge from PE or CPT. Factors associated with increased odds of trauma-focused treatment initiation included having a sleep disorder diagnosis (OR = 1.23), a substance use disorder diagnosis (OR = 1.27), or experiencing military sexual trauma (OR = 1.64). Factors associated with increased odds of depression-focused treatment initiation included having a depression diagnosis (OR = 2.02). This study suggests that certain subgroups of Veterans who engage in PE or CPT (e.g., Veterans with comorbid sleep or substance use problems) are more likely to seek additional evidence-based treatment and may require augmentations to maximize clinical benefits, either during the initial course of treatment or subsequent to PTSD treatment.

Efficacy of oral testosterone undecanoate in children with androgen insensitivity syndrome

Objective: To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS). Methods: A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children's Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results: The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses (t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions: Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

Experiences and meaningfulness of breast cancer survivorship care in improving the quality of life of immigrant women: A qualitative systematic review.

Holistic healthcare approaches tailored to people's needs can enhance quality of life. However, needs of immigrant women in breast cancer survivorship have received little attention. Language barriers can result in significant challenges to accessing healthcare and difficulty in translating information from healthcare providers into self-management. The purpose of this review was to examine the experiences and meaningfulness of breast cancer survivorship care in improving the quality of life for immigrant breast cancer survivors. A qualitative systematic review using a systematic search of peer-reviewed and non-peer-reviewed articles of empirical research was conducted. Articles about immigrant women who were diagnosed, treated, and completed their initial course of breast cancer treatment were included. Exclusion criteria were non-immigrant women, men, younger than 18 years, no breast cancer diagnosis, not currently undergoing active or advanced treatment, and not receiving palliative or end-of-life care. Thematic synthesis and qualitative systematic review included studies of survivorship care targeting breast cancer treatment and post-treatment. Articles were obtained from PubMed/MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, and Google Scholar searches, with findings configured according to the JBI methodology. Twenty studies, most of moderate-to high-quality were included. The thematic synthesis identified two overall themes regarding breast cancer survivorship care, as well as subthemes for both. The subthemes of the first theme, challenges and experiences accessing and using healthcare services, were inadequate insurance and benefits, less acculturation and decision-making, discrimination and differential treatment, and influencing sociocultural factors. The subthemes of the second theme, facilitators and barriers to accessing and using healthcare services, included ineffective knowledge and communication, lack of continuity and information, cultural and language barriers, limited access to services, and quality of care. Supporting and engaging immigrant women throughout their breast cancer journey is critical. To do so requires integrating advancements in survivorship care as a systematic approach to lead to a better quality of life and improving patient-reported outcomes.

A Comprehensive Study on Ruptured Liver Abscess in a Tertiary Care Center.

Background Bacteria and parasites cause liver abscesses (LAs), with the unusual but fatal consequence of ruptured LA. Along with the clinical signs of icterus, right upper quadrant pain, and a history of loose stools, patients present with non-specific symptoms such as fever, nausea, and generalized weakness. Consistent findings include male sex prevalence and frequent alcohol consumption. Leukocytosis, abnormal liver function, and an increased international normalized ratio have been identified by biochemical analysis; however, these findings are not specific to a ruptured LA diagnosis, and imaging is necessary to reach a definitive diagnosis. Ultrasonography usually confirms the diagnosis, and computed tomography is required in certain situations. In confined ruptures, percutaneous drainage combined with antibiotic therapy is typically the initial treatment course. Generally reserved for non-responders or moribund patients with delayed presentation, an open surgical approach may involve simple draining of a ruptured abscess or ileocecal resection, or right hemicolectomy in cases of large bowel perforations, both of which increase patient morbidity. A definite guide to management is still missing in the literature. In this article, we have discussed and correlated with data the predictors of surgery and preoperative predictors of perforation. Materials and methods This retrospective study was performed at Safdarjung Hospital, New Delhi, between January 2022 and December 2023. The study included 115 patients diagnosed with ruptured LA by ultrasound. Medical records were analyzed, and various parameters of the illness, clinical features, hematological and biochemical profiles, ultrasound features, and therapeutic measures were noted and assessed. Results Of the 115 patients, 88% (n = 101) were male. The most common symptoms were abdominal pain (114 patients) and right upper abdominal tenderness (107 patients).Fifty-two patients were treated with percutaneous drainage, and 42 underwent laparotomy. Intercostal drainage (ICD) tubes were placed in 19 patients. Sixteen patients had large bowel perforations. Twenty-three patients died (20%), including 17 patients who underwent laparotomy and nine patients who had large bowel perforation (39.1% associated with overall mortality, 52.9% associated with mortality in laparotomy). One patient with percutaneous drainage and a right ICD tube died in the intensive care unit. Four patients died before intervention. Significant associations were noted between perforation and mortality in patients who underwent surgical drainage. Loose motions, alcohol and smoking consumption, and deranged creatinine and albumin levels were found to have a significant association with surgical drainage. Conclusion The study found that a ruptured liver abscess (LA)may require surgery to drain the collection or repair the pathological bowel, which increases the morbidity, but it is a lifesaving procedure over percutaneous catheter drainage. The study also identified factors associated with a higher risk of death, such as a history of loose stools and low blood albumin levels.

What is the Optimal Treatment Protocol for Traumatic Popliteal Artery Injury? A Comparative Study between Two Institutions.

While rare, popliteal artery injury is a potentially devastating complication of knee trauma. Delayed diagnosis or inadequate management of popliteal artery injury can result in limb ischemia, amputation, and long-term disability. This study aimed to compare the treatment outcomes of popliteal artery injury between different medical centers and to reconsider the optimal protocol at our institution. Medical records of patients sustaining traumatic popliteal artery injury from 2011 to 2022 at two institutions (one hospital: Group A; the other hospital: Group B) were retrospectively reviewed. Demographic data, radiological assessment, time course and content of initial treatment, clinical outcomes, and follow-up period were recorded. Group A included seven patients (dislocations, n = 3; fractures, n = 2; and glass penetration injuries, n = 2), with a mean follow-up period of 39 months. Group B included five patients (dislocations, n = 3 and fractures, n = 2), with a mean follow-up period of 36 months. Two patients in Group A and four patients in Group B exhibited contrast-medium resumption (average deficit: 57 mm and 60 mm, respectively). The time from injury to reperfusion was significantly shorter in Group A than in Group B (300 min vs. 749 min, P < 0.05). Group A underwent four temporary vascular shunting procedures, four external fixations, six fasciotomies, and five bypass grafting procedures. In Group B, temporary vascular shunt (TVS) was not used in any patient; however, three, two, and three patients underwent external fixation, fasciotomy, and bypass grafting, respectively. One patient in each group required above-the-knee amputation. The mean Lysholm score was 80.4 points in Group A and 72.0 points in Group B. TVS considerably reduces the reperfusion time. Various options for the content and sequence of treatment must be carefully considered in advance. Early diagnosis, prompt intervention, and comprehensive management can improve the quality of care and patient outcomes.

Abstract PO2-14-07: Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women

Abstract Background: Breast cancer prognosis is influenced by tumor biomarker expression. For example, tumors that express the estrogen receptor (ER+) have a lower hazard of recurrence in the first five years following treatment than tumors that do not express the estrogen receptor. Identifying additional biomarkers that are prognostic of breast cancer recurrence may aid in risk stratification and the development of targeted therapies. The androgen receptor (AR) is one such candidate biomarker. While some previous studies have found lower breast cancer mortality associated with AR expression, others have shown no association. However, these studies were conducted in populations exclusively or primarily comprised of postmenopausal women. Since menopause is associated with an increased concentration of androgens relative to estrogens, the role of AR may differ in premenopausal women. Methods: Using the Predictors of Breast Cancer Recurrence cohort (N=5,959)—a prospective cohort study of premenopausal women diagnosed with stage I–III primary breast cancer between 2002 and 2011 and registered in the Danish Breast Cancer Cooperative Group (DBCG) clinical database—we measured the association between tumor AR expression and breast cancer recurrence. The majority of the cohort (77%) had ER+ tumors and were intended to be treated with tamoxifen. Primary paraffin-embedded tumors were collected from treating hospitals, and 2–3 cores were included in a tissue microarray for immunohistochemistry. AR staining of each core was automatically scored using a trained software application and quantified as the percent of tumor nuclei with positive staining. Patients were considered to have AR positive (AR+) tumors if the maximum score across replicate cores was &amp;gt;1% positive. Otherwise patients were classified as having AR negative (AR−) tumors. Patients were followed from breast cancer diagnosis until the first of recurrence, death, emigration, another malignancy, or 10 years. The DBCG defines breast cancer recurrence as any breast cancer diagnosed after the initial course of treatment, including contralateral breast cancers. The association between AR expression and breast cancer recurrence was computed as an unadjusted risk ratio and corresponding 95% confidence interval. Results: Among the 4,658 cohort members with available tumor tissue, 72% had AR+ tumors; 720 recurrences occurred over the 10-year follow-up. Patients with AR+ tumors were less likely to experience a recurrence than patients with AR− tumors [14% vs. 18% respectively; unadjusted risk ratio=0.80, 95% CI: (0.70, 0.92)]. Conclusion: AR expression in primary tumor tissue was associated with a lower risk of breast cancer recurrence in a large population-based cohort of premenopausal women. Additional analyses adjusting for clinical factors, examining the association by breast cancer subtype, and accounting for time to recurrence are forthcoming. Citation Format: Rebecca Nash, Anders Kjærsgaard, Kristina Christensen, Thomas Ahern, Lindsay Collin, Stephen Hamilton-Dutoit, Lauren McCullough, Joellen Schildkraut, Henrik Sørensen, Kevin Ward, Kirsten Woolpert, Timothy Lash, Deirdre Cronin-Fenton. Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-07.

Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France.

Cladribine tablets (CladT) has been available for therapeutic use in France since March 2021 for the management of highly active relapsing multiple sclerosis (RMS). This high-efficacy disease-modifying therapy (DMT) acts as an immune reconstitution therapy. In contrast to most high-efficacy DMTs, which act via continuous immunosuppression, two short courses of oral treatment with CladT at the beginning of years 1 and 2 of treatment provide long-term control of MS disease activity in responders to treatment, without the need for any further pharmacological treatment for several years. Although the labelling for CladT does not provide guidance beyond the initial treatment courses, real-world data on the therapeutic use of CladT from registries of previous clinical trial participants and patients treated in routine practice indicate that MS disease activity is controlled for a period of years beyond this time for a substantial proportion of patients. Moreover, this clinical experience has provided useful information on how to initiate and manage treatment with CladT. In this article we, a group of expert neurologists from France, provide recommendations on the initiation of CladT in DMT-naïve patients, how to switch from existing DMTs to CladT for patients with continuing MS disease activity, how to manage patients during the first 2years of treatment and finally, how to manage patients with or without MS disease activity in years 3, 4 and beyond after initiating treatment with CladT. We believe that optimisation of the use of CladT beyond its initial courses of treatment will maximise the benefits of this treatment, especially early in the course of MS when suppression of focal inflammation in the CNS is a clinical priority to limit MS disease progression.

Acquired rifamycin resistance among patients with tuberculosis and HIV in new York City, 2001–2023

IntroductionAcquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients. MethodsPLWH who developed ARR 2001–2023 were identified from the NYC TB registry. ResultsSixteen PLWH developed ARR; 15 were diagnosed 2001–2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm3. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up. ConclusionsPLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).

POTENTIAL OF NATURAL BIOACTIVE COMPOUNDS IN MANAGEMENT OF MELASMA

Melasma is a form of inherited hyper-melanosis that appears as asymmetrical, brown-colored, uneven, reticulated macules on UVR-exposed skin, particularly on the facial area. The etiopathogenesis of melasma has been linked to several causes, including UV exposure, endocrine factors, genetic predisposition, anti-epileptic medications, and various cosmetics. The initial course of treatment for hyperpigmentation involves applying topical formulations of widely used substances like kojic acid, glycolic acid, and hydroquinone. Pharmaceuticals such as melatonin, tranexamic acid, and cysteamine hydrochloride are administered orally in this process. Chemical peels and laser therapy are examples of second-line therapies that are applied under the direction of trained experts. Unfortunately, these treatments have certain drawbacks and complications, including erythema, dryness, and skin peeling, and they take time to work, necessitating the use of herbal formulations for the management of hyperpigmentation. Bioactive compounds isolated from plants, such as arbutin, aloesin, flavonoids, hesperidin, licorice, ellagic acids, genistein, and quercetin, inhibit melanogenesis without melanocytotoxicity by different mechanisms. This review provides information on natural bioactive compounds used for the management of melasma.

A Study to Compare the Efectiveness of Tibio Femoral Joint Mobilization Versus Maitland Mobilization in Patellofemoral Pain Syndrome

Background and need of research: Abnormal patellar biomechanics and patellar arrangement result in patellofemoralpain syndrome. The initial course of treatment for non-operative management is physical therapy.Therefore, it is necessary to compare the effectiveness of Tibio femoral joint mobilisation with Maitland mobilisationin treating patellofemoral pain syndrome.Methods: Sample where collected from YMT college of Physiotherapy. Group A consists of 20 female and 10 Malesubjects of age group 30 to 40 years Tibiofemoral mobilization was given while Group B Maitland Mobilizationhaving 17 female and 13 male subjects. The study was conducted during the month of March 2023 to June 2023.Each group attended five therapy sessions a week for a total of 6six weeks. As pre and Post outcome assessments,the NPRS scale, Knee range of motion and KUJALA Score Questionnaire were utilised,both before and after thetreatment. patients with patellofemoral pain syndrome, ranging in age from 25 to 40, were both male and female.Tibiofemoral mobilisation was used in Group A’s conventional therapy while Maitland mobilisation was used inGroup B’s conventional therapy. Each group attended five therapy sessions a week for a total of six weeks. As preandpost-outcome assessments, the visual analogue scale, knee range of motion, and KUJALA score Questionnairewere utilised. both before and after the treatment, in the sixth week.Result: The intragroup comparison of the NPRS, knee range of motion, and KUJALA patellofemoral scale among the30 patients in each group was statistically highly significant with p=0.001 for both groups. In contrast to the Maitlandmobilisation in Group B, the Tibiofemoral mobilisation in Group A demonstrated a Highly Significant improvement.Conclusion: Tibiofemoral mobilisation combined with traditional therapy is more effective at reducing pain,enhancing range of motion, and improving functional ability in PFPS after six weeks.

Now You See It, Now You Don't: Point-of-Care Ultrasound Identification of Left Ventricular Thrombus-in-Transit

Background: Left-sided intracardiac thrombi are most commonly seen in conditions with decreased cardiac flow, such as myocardial infarction or atrial fibrillation. They can be propagated into the systemic circulation, leading to a cerebrovascular accident. Identification of thrombus-in-transit via point-of-care ultrasound (POCUS) has the potential to change patient management given its association with high patient morbidity and mortality.Case Report: An intubated 60-year-old man was transferred to our emergency department for management of altered mental status and seizure-like activity. The patient was markedly hypotensive on arrival, and cardiac POCUS was performed to identify potential causes of hypotension. A left ventricular thrombus-in-transit was identified. The thrombus was notably absent on a repeat POCUS examination < 10 min later, which led to concern for thrombus propagation. Furthermore, the patient's vasopressor requirements had significantly increased in that time period. Subsequent emergent neuroimaging revealed a large ischemic stroke in the left internal carotid and middle cerebral artery distribution. The patient was, unfortunately, deemed to not be a candidate for either thrombectomy or thrombolysis and ultimately expired in the hospital.Why Should an Emergency Physician Be Aware of This? Serial POCUS examinations identified the propagation of this patient's thrombus-in-transit, leading the physician to change the initial presumptive diagnosis and treatment course, and pursue further imaging and workup for ischemic stroke. Identification of a thrombus-in-transit is a clue to potentially underlying critical pathology and should be followed with serial POCUS examinations to assess for treatment efficacy and thrombus propagation.

Improved range of motion after manipulation under anesthesia versus physiotherapy for stage two frozen shoulder: a randomized controlled trial

BackgroundFrozen shoulder (FS) is a common cause of shoulder pain and stiffness. Conservative treatment is sufficient for the majority of patients with recovery of shoulder function at long term. Manipulation under anesthesia (MUA) is known as a well-established treatment option if conservative treatment fails. It is unknown whether MUA does indeed shorten the duration of symptoms or leads to a superior outcome compared to conservative treatment. The objective of the current trial is to evaluate the effectiveness of MUA followed by a physiotherapy program (PT) compared to a PT program alone in patients with stage two FS. MethodsA prospective, single center randomized controlled trial was performed. Patients between 18 and 70 years old with a stage two FS were deemed eligible if an initial course of conservative treatment, consisting of physiotherapy and an intra-articular corticosteroid infiltration was considered unsatisfactory. Patients were randomized and data was collected with an online data management platform (CASTOR). MUA was performed by a single surgeon under interscalene block and an intensive physiotherapy treatment protocol was started within 4 hours after MUA. In the PT group patients were referred to instructed physiotherapist, and treatment was guided by tissue irritability. The primary outcome was the SPADI score. Secondary outcomes were pain, range of motion, OSS, quality of life and ability to work. ResultsIn total, 82 patients were included, 42 in the PT group and 40 in the MUA group. There was a significant improvement in SPADI, OSS, pain, range of motion and quality of life in both groups at 1 year follow-up. SPADI scores at three months were significantly improved in favor of MUA. MUA showed a significant bigger increase in anteflexion and abduction compared to PT at all points of follow-up. No significant differences between both groups were found for all other parameters. No fractures, dislocations or brachial plexus injuries occurred in this trial. ConclusionMUA in stage 2 FS can be considered safe and results in a faster recovery of range of motion and improved functional outcome, measured with SPADI scores, compared to PT alone at short term. After 1 year, except for slightly better range of motion scores for MUA, the result of MUA is equal to PT.

Effect of Lycopene Compared to Vitamin C Added to Diets of Broilers Exposed to Stress and Its Impact on Physiological Performance

From July 20, 2022, to August 24, 2022, this study was done in the chicken grounds of Kosar chicken Company - Erbil. The experiment lasted for 65 days (35 field days and 30 lab days) and examined the effectiveness of lycopene and vitamin C at mitigating the negative effects of heat stress on productivity and health. for roasting. The Ross 308 broiler chicks utilized were one day old, sexless, and weighed 42 g each. The Kosar Poultry Company provided the chicks. These chicks were raised in a room with a mattress on the floor in 15-by-1-meter enclosures. Chicks were randomly assigned to one of five treatments, each with three replications and eight birds per replication, using sawdust with a thickness of 5 centimeters. The following experimental treatments were used, with repetitions spread randomly beginning on day one: Diet alone (T1) is the initial course of treatment. T2: 1 g of lycopene per kilogram of body weight. T3: 2 g of lycopene per kilogram of body weight. Fourth treatment (T4): 1 g of lycopene per kilogram of feed with 25 milligrams of vitamin C per kilogram of feed, in accordance with current recommendations. The results showed that the concentration of globulin and albumin in the addition treatments were significantly superior to the control treatment (P≤0.05), and this was especially true for the fifth treatment (T5), which was a mixture of lycopene at a rate of 2 g / kg with vitamin C according to the standard recommendations of 25 mg / kg of feed. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and total protein levels all showed no statistically significant differences. When comparing the addition treatments to the control treatment, liver enzyme activity was found to be significantly lower in the addition treatments (P≤ 0.05).

Primary Site Surgery in Distantly Metastatic Oropharyngeal Squamous Cell Carcinoma.

Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC). Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors. Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone. Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status. 3 Laryngoscope, 134:2243-2251, 2024.

Mesoglycan for the secondary prevention of superficial vein thrombosis: a randomized, controlled, double-blind study (METRO Study)—rationale and protocol

No data is available about pharmacological secondary prevention of superficial vein thrombosis (SVT) despite 10–15% of patients develop venous thromboembolic complications at 3–6 months after an adequate treatment of the acute phase. To verify efficacy and safety of mesoglycan in secondary prevention of SVT recurrence and venous thromboembolic complications. Phase III multicenter, double-blind, randomized, superiority trial comparing mesoglycan 50 mg bid vs placebo in consecutive patients with a SVT extended at least 5 cm, after the initial 45-day treatment course with fondaparinux 2.5 mg once-daily. Primary efficacy outcome: SVT recurrence/extension, symptomatic venous thromboembolism (VTE), asymptomatic proximal deep-vein thrombosis, death. Primary safety outcome: major bleeding. We hypothesized a 12-month 15% incidence of the primary efficacy outcome in placebo group and a 50% risk reduction in mesoglycan group. A bilateral log-rank test with a sample of 650 patients (randomization 1:1) reach a 90% power, with an α-error of 0.025, of detecting a 7.0% difference (HR = 0.51) after 12 months of treatment, considering a 10% patients drop-out. At deadline (December 31, 2022) 570 patients have been randomized (10% drop rate). Mean age was 63.9 years, 58.8% were women. SVT involved great saphenous vein in 69.3%, small saphenous vein in 13.1%, and collaterals in 17.6% of patients. SVT was the first event in 61.7%, a recurrence in 38.3%, provoked in 50.2% and unprovoked in 49.8%. Patients not experiencing a primary outcome, or not retiring their consent will be followed up to December 31, 2024 when the final data analysis will be performedClinicalTrials.gov: NCT03428711.

23 Tamoxifen Effects on Cognition and Language in Women with Breast Cancer

Objective:Cognitive changes following adjuvant treatment for breast cancer (BC) are well documented particularly following chemotherapy. However, limited studies have examined cognitive and/or language functions in chemotherapy-naive women with BC taking tamoxifen (TAM). While there is some compelling evidence TAM affects cognitive and language domains, language has not been studied beyond semantics (i.e., content of language), which is just one aspect of language. Using ambulatory cognitive assessment, we investigated the trajectory of cognitive and language changes during early period of adjuvant endocrine treatment (tamoxifen) in women with BC at two time periods (pre-treatment and two months after treatment begins).Participants and Methods:Four women with BC (mean age = 62.25 years, SD = 8.38) and 18 cognitively healthy age-matched controls (mean age = 59.77, SD = 7.45) completed 3 cognitive tasks using smartphones, during a short time period (5 days) and repeated at two time periods. Symbol search, dot memory and color dots tasks were used to measure the cognitive constructs - processing speed and working memory. Response times were recorded in milliseconds. To determine language ability, language samples were collected at two time periods, where the participants described two stories from two wordless picture books and samples were assessed using core lexicon analyses.Results:Wilcoxon-signed rank test was computed to identify cognitive and linguistic changes during early period of TAM administration in women with BC at two time periods. No significant within group or between group differences were seen on the cognitive and language tasks at the two time periods, however, a trend for decline in performance was seen in some BC participants across different tasks.Conclusions:This is the first study to our knowledge to use ambulatory cognitive assessment method and study discourse-level language function during this early period (pre-treatment and 2 months post-TAM). Findings from the current study advance our understanding of trajectories of cognition and language changes during the initial course of adjuvant endocrine treatment for women with BC with ER+ tumors. Using a measurement-burst design and ambulatory cognitive assessment, we were able to apply better precision measurement to identify distinct cognitive constructs affected by adjuvant endocrine treatment. In addition, insight into changes in discourse ability are impactful for numerous reasons: (1) better understanding of how adjuvant endocrine therapy impacts communication and (2) discernment into language domains that may require early behavioral intervention.

MGMT Promoter Methylation Predicts Survival in 1p19q-Codeleted Gliomas after Chemotherapy

MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy in glioblastomas and used to guide treatment decisions. However, the role of MGMT promoter status in low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large datasets. We recently found that MGMT promoter methylation predicts progression-free survival in 1p19q-codeleted gliomas after alkylating chemotherapy in a meta-analysis of three prospective cohorts. There were not enough deaths to determine the effect on overall survival. Here, we query a large national database to determine the association between MGMT promoter methylation and overall survival in patients with 1p19q-codeleted gliomas. We identified all patients with newly diagnosed gliomas in the National Cancer Database (NCDB) from 2010-2016 with 1p19q-codeletion and information on MGMT promoter methylation status. The cohort was stratified based on receipt of chemotherapy. Multivariable Cox proportional hazards regression modeling was used to assess the effect of MGMT promoter methylation status on overall survival after adjusting for age, sex, race, co-morbidity, grade, extent of resection, chemotherapy, and radiotherapy. We identified 530 eligible patients, 373 (70.4%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 400 (75.5%) patients. For all patients, unmethylated MGMT (uMGMT) was associated with poorer survival compared to mMGMT (75% survival time [75%ST] 45 months vs. not reached, P = .003, adjusted hazard ratio [aHR] 2.36 [95% confidence interval (95% CI) 1.53-3.62]). uMGMT was associated with poorer survival in patients who received chemotherapy (75%ST 22 vs. 66 months, P<.001, aHR 2.55 [95% CI 1.60-4.06]) but not in patients who did not receive chemotherapy (75%ST 110 months vs. not reached, P = 0.7, HR 1.24 [95% CI 0.40-3.81]). To our knowledge, this is the first study to demonstrate an association between overall survival and MGMT promoter status in 1p19q-codeleted gliomas. MGMT promoter status should be used as a stratification factor in future clinical trials of 1p19q-codeleted gliomas that use overall survival as an endpoint.

MGMT Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas.

While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated. We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy. We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT [70% {95% confidence interval (CI), 64%-77%} vs. 81% (95% CI, 78%-85%); P < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77-3.14)]. uMGMT was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55-73%) vs. 80% (95% CI, 76%-84%); P < 0.001; aHR, 2.61 (95% CI, 1.89-3.60)] but not in patients who did not receive chemotherapy [P = 0.38; HR, 1.31 (95% CI, 0.71-2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy. Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.