Prolonged Treatment Course Research Articles

Linezolid Related Adverse Effects in Different Populations: A Practical Review.

Linezolid, an oxazolidinone antibiotic, is used to treat gram-positive infections. However, it may also lead to serious adverse effects, including bone marrow suppression, optic neuropathy, peripheral neuropathy, hyponatremia, and lactic acidosis. This review evaluates the existing evidence concerning the adverse effects of linezolid in patients undergoing treatment with this medication, both in the short and long term. The objective of this review is to summarize the most significant adverse effects associated with linezolid. A search of PubMed was conducted for articles related to linezolid and its potential adverse effects, which include thrombocytopenia, anemia, neutropenia, lactic acidosis, optic neuropathy, and peripheral neuropathy. Thrombocytopenia frequently develops within the first two weeks of therapy, whereas anemia is more likely to manifest during prolonged treatment courses. Risk factors for linezolid-induced thrombocytopenia include elevated trough concentrations (>8 mg/L), renal impairment, low body weight, and severe liver dysfunction. Patients with multidrug-resistant tuberculosis and bone infections are at an increased risk for anemia, peripheral neuropathy, and optic neuropathy. Additionally, lactic acidosis and hyponatremia can occur at any stage during treatment.

Equine Distal Limb Wounds: Economic Impact and Short-Term Prognosis of Non-Synovial Versus Synovial Lesions in Southern Germany

Injuries to the distal limb are common in horses. The clinical aspect of the lesions is variable based on the structures that are involved. Synovial structures as well as tendons and/or ligaments may be involved in such injuries, affecting treatment modalities and costs, and prognosis. This retrospective study compares wounds involving synovial structures to wounds without such involvement in terms of treatment duration and costs, and prognosis. Synovial wounds were much more expensive to treat and carried a lower prognosis. Involvement of tendons and/or ligaments in the wounds resulted in more expensive and prolonged treatment courses compared to cases without such involvement, even without synovial contamination. The prognosis for discharge was good overall for both groups.

Elderly Patients with Tuberculosis Combined with Diabetes Mellitus: A Comprehensive Analysis of Lymphocyte Subpopulation Dynamics, Clinical Features, Drug Resistance and Disease Regression.

The aim of this study was to evaluate lymphocyte subsets and clinical outcomes in patients with pulmonary tuberculosis (PTB) combined with type 2 diabetes mellitus (T2DM). Between January 2022 and March 2024, 320 patients aged > 60 years were included, 95 of whom had comorbid DM. Lymphocyte subsets (T-lymphocytes, B-lymphocytes, and natural killer cells, NK) were assessed in both groups of patients using fluorescence-associated cell sorting. Clinical characteristics, drug resistance, regression and lymphocyte subsets were compared in PTB patients with DM versus PTB patients alone. The correlation between lymphocyte subsets-related indices and the above characteristics in PTB patients with DM was analyzed. Compared with PTB patients alone, PTB patients with comorbid DM had a higher positive rate (81.05% vs 62.67%, P = 0.001), prolonged course of antituberculosis treatment (298 [244, 339] days vs 223 [179, 254], P < 0.001) and a lower cured rate (64.21% vs 75.56%, P = 0.039). Compared with PTB patients only, PTB patients with comorbid DM had higher T-lymphocytes and CD4+ T-lymphocytes (P < 0.001, P = 0.006) and lower NK cells (P < 0.001). In PTB patients with comorbid DM, both treatment-prolonged patients and drug-resistant patients showed reduced NK cells. NK cells were slightly elevated in cured patients, although there was no significant difference (P = 0.082). Lymphocyte homeostasis is altered in PTB patients with comorbid DM, making them more susceptible to severe clinical manifestations and therapeutic outcomes. Notably, NK cells have been identified as key regulatory cells with a significant impact on prolonged treatment course and drug resistance. This study provides new ideas and methods for individualized treatment of PTB combined with DM in the elderly, which can help to optimize the treatment plan and improve the outcome and quality of life of patients.

Comparative Analysis of Culture and Sputum Smear Conversion Timelines and Their Associated Factors in Smokers Versus Non-smokers With Drug-Resistant Tuberculosis.

Background Drug-resistant tuberculosis (DR-TB) is a global health challenge, with smoking potentially affecting treatment outcomes. Smoking compromises immune function and may interfere with the pharmacokinetics of anti-TB drugs. Delayed sputum smear and culture conversion are key indicators of prolonged treatment and infectiousness. This study explores the impact of smoking on these conversion timelines in DR-TB patients. Objective To identify and assess the overall treatment outcomes and the factors associated with delayed culture and sputum smear conversion in smokers compared to non-smokers among patients with drug-resistant tuberculosis. Methods This prospective cohort study was conducted at the Programmatic Management of Drug-Resistant TB (PMDT) unit at Mardan Medical Complex in Khyber-Pakhtunkhwa, Pakistan, from June 2020 to December 2024. All patients diagnosed with drug-resistant tuberculosis (DR-TB) were categorized into two groups based on their smoking status: smokers and non-smokers. Patient demographic and clinical information was collected through structured interviews and standardized questionnaires. The time to sputum smear and culture conversion (SCC) was longitudinally measured from the start of treatment until the patient achieved two consecutive negative smears and three consecutive negative cultures, respectively. Cox proportional hazards analysis was employed to evaluate the relationship between smoking status and time to SCC, adjusting for potential confounding factors. Kaplan-Meier survival curves were used to compare the time to SCC between the two groups, with statistical significance set at p < 0.05. Analyses were performed using SPSS software (version 29.0). Results Out of 281 DR-TB patients, 138 were smokers (49.12%) and 143 were non-smokers (50.88%). Non-smokers achieved faster sputum and culture conversion, with survival proportions dropping to 0.000 by 90 and 70 days, respectively. In contrast, smokers showed slower declines, with sputum conversion at 0.137 and culture conversion at 0.035 by 120 days. The mean sputum conversion time was 59 days for non-smokers and 104 days for smokers, while culture conversion took 43 days for non-smokers and 98 days for smokers. Multivariate analysis identified significant determinants for both groups: older age (≥36 years), lower BMI (<16 kg/m²), and higher sputum smear grades. Non-smokers were adversely affected by gastrointestinal upset and nephrotoxicity, while smokers were more negatively impacted by higher cigarette consumption, diabetes, and lung lesions. Long-term treatment regimens and resistance to antibiotics like levofloxacin and moxifloxacin reduced conversion rates in both groups. Conclusion Smoking not only impairs immune function but also influences the pharmacokinetics of anti-TB drugs, potentially leading to more prolonged and complicated treatment courses.

P-1888. Quantifying the Potential Impact of Dalbavancin on Health Care Metrics Associated with Outpatient Parenteral Antibiotic Therapy Management of Streptococcus and Staphylococcus Infections

Abstract Background Socially vulnerable patients often complete parenteral antibiotic courses in healthcare facilities due to injection drug use (IDU) history or unstable housing situations, which leads to significant personal and health system costs and prolonged hospitalization risks. Our aim was to assess the potential impact of dalbavancin (DBV) utilization on length of stay (LOS) and adverse outcomes in this patient population. Methods Retrospective study of patients ≥ 18 years old who were followed in the Johns Hopkins Health System Outpatient Parenteral Antibiotic Therapy (OPAT) program from 1/1/2021 to 6/30/2023 for Streptococcus and Staphylococcus bone/joint and endovascular infections (n = 900). Descriptive statistics were used to evaluate demographic, microbiologic, and clinical characteristics. Potential demand for DBV was quantified by estimating the impact of transitioning patients to DBV in terms of possible hospital days saved and OPAT-related complications avoided. Subanalyses were completed for patients with IDU history. Results Median patient age was 58 years (IQR 44-68 years) and 501/900 (56%) were male. Most patients received vancomycin (30%) followed by cefazolin (24.4%) or anti-staphylococcal penicillin (24.0%), which required central venous catheter placement in 86.6% of patients. The most common indication for OPAT was osteomyelitis (54.8%) followed by endovascular infection. The median LOS after finalization of antibiotic recommendations was 5 days (IQR 3-10 days) with 44.3% requiring skilled nursing facility (SNF) placement. 43.7% of patients experienced an OPAT-related adverse event, almost half of which involved a return to the hospital. Among OPAT patients, 16.4% had an IDU history and 75.8% of them injected within the last 6 months. These patients had longer LOS (8 vs 5 days) after finalization of antibiotic recommendations and more OPAT-related adverse events compared to patients without IDU history (48.0% vs 43.7%). Conclusion Patients, especially those with recent IDU, could benefit from DBV in lieu of parenteral antibiotics to complete prolonged treatment courses. Completion of deep-seeded gram-positive infection therapy with DBV vs OPAT has the potential to shorten hospital LOS and reduce the incidence of OPAT-associated adverse events. Disclosures All Authors: No reported disclosures

P-132. Retrospective Comparison of Short and Prolonged Treatment Strategies for Patients with Neutropenic Enterocolitis

Abstract Background Neutropenic enterocolitis (NE) is a severe necrotizing condition affecting the small and/or large intestines in neutropenic patients. With a lack of high-quality studies looking at antimicrobial duration and outcomes for patients with NE, this study aims to evaluate the impact of short versus prolonged antimicrobial treatment durations on clinical outcomes in patients with NE. Methods This was a single-center, retrospective, cohort study conducted at a tertiary care academic medical center in New Jersey. Medical records of adult patients with hematologic malignancies admitted between January 2015 to September 2023, with diagnosis of NE and receipt of treatment with broad-spectrum antimicrobials, were reviewed. This study compared patients who received short versus prolonged antimicrobial treatment courses for NE. Patients in the short treatment group included those who received broad antimicrobials for NE treatment, that were stopped or switched to prophylaxis while the patient’s absolute neutrophil count (ANC) was less than 0.5 x 103/uL. The prolonged treatment group included patients who received broad antimicrobials at least until ANC was over 0.5 x 103/uL. The primary endpoint was the time to clinical improvement of symptoms between the two groups. Secondary endpoints included hospital length of stay (LOS), intensive care unit (ICU) admission, incidence of NE complications, and 30-day mortality. Results A total of 17 patients were included, with 5 (21.7%) patients who underwent hematopoietic stem cell transplantation. Time to clinical improvement, defined as improvement in symptoms (including resolution of abdominal pain, abdominal distension and/or cramps, diarrhea, nausea, vomiting, lower GI bleed), and 30-day mortality were similar in both treatment groups. However, hospital LOS, ICU admission, and incidence of NE complications were higher in the prolonged treatment group. Conclusion Between short and prolonged treatment groups in patients with NE, time to clinical improvement was similar. Larger, randomized controlled trials are needed in this patient population to assess the appropriate duration of therapy for patients with NE. Disclosures Navaneeth Narayanan, PharmD, MPH, BCIDP, Astellas: Honoraria|Beckman Coulter: Honoraria|Merck: Grant/Research Support|Shionogi: Grant/Research Support Pinki Bhatt, MD, Sanofi: Grant/Research Support

P-752. Do Antibiotics Improve Wound Necrosis Following Biodegradable Temporizing Matrix (BTM) Placement in Patients with Xylazine-associated Wounds?

Abstract Background Xylazine-associated wounds are a unique wound typology among patients with injection behavior in geographic areas where xylazine has infiltrated the fentanyl drug supply. The use of the dermal substitute biodegradable temporizing matrix (BTM) is being evaluated to promote wound stabilization in the presence of severe soft tissue necrosis, a well-known characteristic of xylazine wounds. The role of antibiotics in the treatment of BTM placement for xylazine wounds is unclear. Methods All patients with xylazine-associated wounds who underwent BTM placement at Temple University Hospital since August 2023 were identified. The electronic medical record was used to collect data including demographics, antibiotic course, microbiologic data, discharge disposition, and appearance of the wound. The primary outcome was evidence of less necrotic tissue on a stable wound within 60 days. Results A total of 37 patients were identified. 60% of patients had an infectious disease consult. 89% of patients had clinical or radiographic evidence of osteomyelitis underlying their xylazine wound. 25 patients (68%) received antibiotics during their admission for BTM. 15 (41%) of patients received at least 4 weeks of antibiotics. 12 patients (33%) did not receive any antibiotics during their admission. 25% of patients received antibiotics for an indication unrelated to their xylazine wound. Treatment regimens varied and included both oral and intravenous antibiotics. 49% of patients lacked stable housing at the time of discharge. 13 (35%) patients had evidence of less necrotic tissue on a stable wound at 60 days. Of those 13 patients, 9 received antibiotics and 4 received none. Of the patients who received at least 4 weeks of antibiotics, only 11% had evidence of less necrotic tissue at 60 days. Of the patients who received no antibiotics, 8% had evidence of less necrotic tissue at 60 days. Conclusion Severe tissue necrosis related to injection of xylaxine requires new treatment paradigms. Our small study questions the utility of prolonged antibiotic treatment courses for patients with xylazine wounds and BTM placement, including in the setting of osteomyelitis, as we did not see high treatment success in these patients. Disclosures Sara K. Schultz, MD FACP FIDSA, AbbVie: Advisor/Consultant

BCMA/CS1 bispecific CAR-T cell therapy for multiple myeloma complicated with thrombocytopenia: a case report and literature review

Objective: To investigate the clinical manifestations, diagnostic and therapeutic strategies, for thrombocytopenia after BCMA/CS1 bispecific chimeric antigen receptor T-cell (CAR-T cell) therapy in patients with multiple myeloma. Methods: Retrospective collection and analysis were conducted on the clinical data of a patient with multiple myeloma who received BCMA/CS1 bispecific CAR-T cell therapy in the Hematology Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, in June 2021. To review the literature, Chinese databases (CNKI, Wanfang Database) and PubMed were searched from their inception up to November 2024 using the keywords "chimeric antigen receptor T-cell therapy", "thrombocytopenia", "CAR-T", "BCMA", and "CS1" . Results: A 72-year-old male patient was diagnosed with light chain κ-type multiple myeloma (R-ISS stage Ⅱ) in a local hospital and had a prolonged treatment course with poor disease control despite multiple adjustments of chemotherapy regimens. The patient met the inclusion criteria for the BCMA/CS1 dual-target CAR-T cell clinical trial (NCT04662099) and achieved complete remission two months after receiving a low dose of CAR-T cells. On the 8th day after CAR-T cell infusion, the patient developed grade 3 cytokine release syndrome, followed by severe gastrointestinal bleeding and persistent grade ≥3 thrombocytopenia, accompanied by a significant increase in thrombopoietin levels, with no megakaryocytes observed in bone marrow cytology. After treatment with rituximab, significant improvement was observed with platelet count gradually increased. However, the patient experienced persistent malnutrition and cachexia, and transferred to the gastroenterology department, after which follow-up was lost. A total of 24 relevant English articles and 8 Chinese articles were retrieved from the literature search. Conclusion: CAR-T cell therapy associated thrombocytopenia is characterized by thrombocytopenia and megakaryocyte production disorders. Persistent thrombocytopenia increases the risk of bleeding, and the use of CD20 monoclonal antibodies and supportive therapy can effectively improve thrombocytopenia.

Corneal protein repair after amniotic membrane photo-tissue bonding versus amniotic membrane graft in the treatment of corneal ulcer (an experimental study)

Corneal alkali burns persist as a significant challenge in our field, often leading to a prolonged treatment course with various sight-threatening problems. This work, of utmost importance, aimed to apply the photo-tissue bonding technique (PTB) to weld the amniotic membrane (AM) to the corneal surface versus an amniotic membrane graft (AMG) and explore its safety in saving corneal protein against alkali burn.Methods Twenty-seven rabbits with an induced corneal ulcer using 1 mol/L NaOH solution. Nine rabbits were used as an ulcer group without treatment, and the rest (n = 18) were subjected to two treatment protocols with AM. The first was attaching the AM to the corneal ulcer through photo-tissue bonding using 532 nm and rose Bengal stain as a photosynthesizing agent. The second was using cyanoacrylate glue as a tissue adhesive. The corneal total protein (TP), refractive index (RI), DNA fragmentation, and oxidative stress index (OSI) were evaluated. Results: The cornea’s TP showed a significant decrease (p˂0.001) immediately, 1 week, and 2 weeks after ulcer induction (-58.9%, -64.4%, and − 72.6%, respectively). The treatment with AM PTB showed improvement immediately (-45.2%, p˂0.001), after one week (-27.4%, p˂0.01), and after two weeks (-14.38%, p˂0.05). Moreover, the treatment with AMG showed improvement after the same periods with percentage changes of -52.05%, (p˂0.001), -41.8% (p˂0.001), and − 32.2%, (p˂0.01) with respect to the control. Moreover, RI of corneal protein showed improvement after two weeks of treatment with AM PTB (3%, p˃0.05) and AMG (7%, p˃0.05), respectively. The corneal protein DNA base pairs improved 88.49% for AM PTB and 82.35% for the AMG group. The oxidative stress was shifted towards an antioxidative state in AM PTB (-3.9%, P > 0.05) and the AMG group (15.9%, P < 0.05). Conclusion: The AM PTB technique used in corneal ulcers showed promising improvement in total corneal proteins, refractive index, DNA fragmentation, and OSI than AMG using cyanoacrylate glue. These results strongly support the use of AM PTB for ophthalmic purposes, suggesting its potential to enhance clinical research and practice for patients with corneal ulcers and ocular surface diseases.

Combined tofacitinib citrate and 308-nm excimer laser treatment for vitiligo: a pilot study.

Vitiligo is a clinically prevalent acquired skin disorder characterized by depigmentation. Currently, the therapeutic options for vitiligo are restricted, and numerous issues exist, such as a prolonged treatment course, unsatisfactory therapeutic efficacy, adverse reactions and a high propensity for recurrence after treatment cessation. To assess the safety and efficacy of combined treatment involving oral tofacitinib citrate (TC) and a 308-nm excimer laser (EL), with the aim of discovering a rapid and effective treatment approach to minimize the side-effects of various drugs. In total, 63 patients with progressive vitiligo and a Vitiligo Disease Activity Score of 4 from January 2022 to January 2024 were enrolled and divided into three groups. The three groups were: the TC combined with 308-nm EL and methylprednisolone treatment group (group 1); the TC and 308-nm EL treatment group (group 2); and the methylprednisolone alone treatment group (group 3). The treatment was continued for 24 weeks, and an assessment of therapy outcomes was performed. When TC was combined with 308-nm EL and methylprednisolone treatment (group 1), the effect was more rapid than in the other two groups. When TC was combined with 308-nm EL (group 2), it had a more favourable treatment effect than that of methylprednisolone alone (group 3), despite having a slower onset of effect. After 24 weeks of treatment, there was no significant difference between group 1 and group 2 in terms of the total response rate or significant response. However, when only methylprednisolone treatment was applied, the effect was relatively slow and ineffective. This study confirmed a rapid and effective treatment of vitiligo was achieved through a combination of TC and 308-nm EL. No serious adverse reactions were reported, and therefore this could potentially offer an optimal treatment plan for patients with vitiligo.

CCR8/CCL1 and CXCR3/CXCL10 axis-mediated memory T-cell activation in patients with recalcitrant drug-induced hypersensitivity.

As a drug-induced hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) is potentially fatal. Most patients with DRESS recover within a few weeks; however, some patients may suffer from a prolonged disease course and develop autoimmune sequelae. To investigate the immune mechanism and therapeutic targets of patients with recalcitrant DRESS with a prolonged disease course. Thirty-two patients with recalcitrant DRESS with a prolonged treatment course (≥ 8 weeks; 'prolonged DRESS'), 28 patients with DRESS with a short treatment course (< 2 weeks; 'short-duration DRESS') and 26 healthy donors (HDs) were enrolled. Bulk transcriptome results showed that the mRNA expression levels of CCR8 and CXCR3 were significantly increased in blood samples from patients in the acute stage of prolonged DRESS [Padj = 1.50 × 10-9 (CCR8) and Padj = 2.60 × 10-4 (CXCR3), patients with prolonged DRESS compared with the HD group]. Serum and skin lesion concentrations of CCL1 and CXCL10 (ligands of CCR8 and CXCR3, respectively) were significantly increased in patients with prolonged DRESS compared with patients with short-duration DRESS. The results from high-parameter flow cytometry and autoantibody screening also identified significant increases in CD8+ GNLY+ CXCR3+ effector memory T cells, CD8+ central memory T cells, CD4+ CCR8+ T helper 2 cells and IgG anti-HES-6 autoantibodies in patients with prolonged DRESS. Furthermore, in vitro blocking assays revealed that Janus kinase inhibitors (JAKi; mainly tofacitinib and upadacitinib) significantly decreased the release of CCL1 and CXCL10. Some patients with prolonged DRESS were successfully treated with JAKi. JAKi (tofacitinib and upadacitinib) were associated with decreased concentrations of CCL1 and CXCL10, suggesting that they may attenuate CCR8/CCL1 and CXCR3/CXCL10 axis-mediated memory T-cell activation, which contributes to disease pathogenesis in patients with recalcitrant DRESS and a long-term treatment course.

Antibiotic Appropriateness for Urinary Tract Infections in Children.

We examined local prescribing patterns across the entire treatment course for children treated for uncomplicated urinary tract infection (UTI) to determine opportunities for antibiotic stewardship initiatives. We conducted a retrospective review of emergency department and inpatient encounters for febrile and afebrile UTI in a children's hospital from 2021 to 2022. An antibiotic spectrum ranking was established, and providers' choices were assessed for appropriateness on the basis of the individuals' urine culture (UCx). Groups were stratified by fever presence and compared using χ2, Fisher's exact, and Mann-Whitney U tests. Of 172 encounters (83% emergency department), 99 (58%) had a positive UCx. Eighty (80%) grew Escherichia coli, with 67 (84%) being susceptible to cefazolin (minimum inhibitory concentration ≤16 mg/L). There were 229 antibiotic regimens and 39 (17%) were appropriate. Inappropriate antibiotic choices included unnecessary use of broad-spectrum antibiotics and misdiagnosed UTI. Grouping by encounter, at least 1 dose of a third cephalosporin was given in 51% of encounters, and 80% of these received it unnecessarily because of UTI misdiagnosis or suitability of a narrower-spectrum antibiotic. The median prescribed antibiotic duration was 7 days (interquartile range 7-10). Of 73 encounters with UCx growing mixed flora or a nonuropathogen, only 29 (40%) had antibiotics discontinued. Confirmed UTI was associated with fever and nitrite positivity. Our study revealed high prevalence of inappropriate antibiotics, particularly unnecessary prescribing of third cephalosporin, prescriptions not supported by laboratory data, and prolonged treatment courses. Our results identify factors that can be used to support UTI treatment pathways and ensure antibiotic stewardship.

6634 Dual-Mediated PTH And Osteolytic Hypercalcemia In Metastatic Endometrial Carcinoma

Abstract Disclosure: C.K. Persaud: None. D.J. Beckman: None. Background: Hypercalcemia of malignancy occurs in 20-30% of advanced stage cancer patients. Etiologies include parathyroid hormone-related peptides (PTHrP)-mediated, osteolytic metastases-mediated, overproduction of 1,25-dihydroxycholecalciferol, and rarely parathyroid hormone (PTH)-mediated. PTH-mediated hypercalcemia of malignancy is rare and occurs through ectopic PTH production or primary hyperparathyroidism. We report a rare case of both PTH-mediated and osteolytic-mediated hypercalcemia in the setting of malignancy. Clinical Case: A 57-year-old female with history of endometrial cancer and multiple solid organ metastasis, presented with two weeks of progressive poor oral intake, nausea, emesis, and right flank pain. On hospital admission, she had a serum calcium of &amp;gt;20.1 mg/dL (8.6-10.2), PTH of 203 pg/mL (15.0-65.0), and creatinine of 1.7 mg/dL (0.7-1.2, baseline 1.3). Non-contrasted CT chest/abdomen/pelvis noted increased size of known right adrenal metastasis, new left adrenal metastasis, periaortic lymphadenopathy, and scattered nodules in the subcutaneous tissues of the abdomen and chest, however bone metastasis were not noted. Patient’s hypercalcemia was treated with zoledronic acid, calcitonin, cinacalcet, and eventually denosumab due to difficulty controlling hypercalcemia. Additional labs obtained during evaluation included ionized calcium &amp;gt;2.5 nmol/L (1.12-1.32), PTHrP &amp;lt;2.0 pmol/L (&amp;lt;2.0), 1,25-dihydroxycholecalciferol &amp;lt;10 pg/mL (21-65). Patient’s right adrenal metastasis biopsy one month prior to admission was subsequently stained for PTH and was negative. Technetium-99m sestamibi scan was obtained for localization of parathyroid adenoma or carcinoma. The scan did not localize, however did show numerous new lytic lesions in the skull, spine, sternum, rib cage, and right humerus. Patient’s hospital course was complicated by progressively worsening renal function, anemia, and thrombocytopenia. Patient was discharged to a long-term acute rehab facility off hypercalcemia treatment with a corrected calcium of 10.0 mg/dL. Conclusion: PTH-mediated hypercalcemia is a rare cause of hypercalcemia of malignancy. PTH levels are typically low or low-normal in osteolytic mediated hypercalcemia. Generally, if PTH is elevated in hypercalcemia, an alternate etiology is not evaluated. This case highlights a rare dual-mediated hypercalcemia of malignancy. The patient’s PTH level elevation was discordant with her high degree of hypercalcemia and prolonged treatment course. She was subsequently found to have widespread bone metastases contributing to hypercalcemia. While multiple etiologies of hypercalcemia can be rare, it is important to evaluate for all contributing causes, especially with additional clinical conditions, such as malignancy. Presentation: 6/3/2024

Descriptive Epidemiology of Haglund’s Syndrome: A Large Retrospective Cohort Study

Category: Hindfoot; Ankle Introduction/Purpose: Approximately 6% of individuals will experience Achilles tendon pain during their lifetime, with one-third of these patients having Haglund’s syndrome. The condition represents a triad of posterosuperior calcaneal bony enlargement (Haglund’s deformity), retrocalcaneal bursitis, and Achilles tendinopathy and may be bilateral or unilateral. If a prolonged course of conservative treatment fails, surgical options include utilizing a suture bridge (SB), corkscrew anchors (CS), or suture anchors (SA). The goal of this study is to investigate outcomes comparing various surgical techniques and postoperative weightbearing status. Methods: After institutional approval, retrospective data were collected from 476 patients who received surgical treatment for Haglund’s syndrome across 8 surgeons at an academic institution from January 2015 to July 2022. Demographic data and surgical repair technique data (suture bridge – SB, corkscrew – CS, suture anchors – SA) were collected. Additional data included weightbearing status (weightbearing as tolerated -WBAT, non-weightbearing – NWB, partial weightbearing – PWB, touch down weightbearing – TDWB), complications, revisions, and date of patients’ last follow-up. Post-operative complications included Achilles rupture, wound breakdown/infection, deep venous thrombosis, plantarflexion weakness, or other complications. Descriptive statistics were completed. Results: Across 390 patients, the cohort averaged 55.14 years old and was 66.4% female. The most common racial groups were Caucasian (72.8%), African American (20.8%), and Asian (1.3%). Average BMI was 34.83 (σ =7.00) and 17.4% had diabetes. Smoking status was reported as 267 (68.5%) never, 120 (30%) current or former. ASA III was the most common scoring with n=186 (47.7%). Repair type was divided among SB (58%), SA (20.8%), and CS (21.3%). Time to last follow-up had a median of 5.8 months, range [0 days-7 years]. Postoperative recommendations also varied from NWB (68.7%), TDWB (14.4%), WBAT (13.8%), and PWB (2.3%). Overall, 75 (19.2%) patients experienced a complication, including 40 (10.3%) persistent pain, 32 (8.2%) wound breakdowns, and 1 (10.3%) rupture, with 7 (1.8%) requiring revision. Conclusion: This study offers the largest single-institution series for the operative management of Haglund’s syndrome with long-term follow-up. Certain patient characteristics (increased age, Black or African American race, female sex, and diabetes) were greater in this cohort compared to national averages. The postoperative complication rate was 20% (n=78), with WBAT reporting the highest rate of pain (14.8%) and PWB reporting the lowest (0.0%). Wound breakdown was highest for NWB (9.7%), and one rupture occurred in the WBAT group. Future research should utilize multicenter institutional data with large sample sizes to analyze associations between patient characteristics, surgical technique, and complication rates.

Clinical characteristics and prognosis of liver injury induced by immune checkpoint inhibitors in patients with malignancies: A real-world retrospective study.

Programmed cell death receptor (ligand)-1 inhibitors (PD-(L)1), as the preferred immunotherapy, have been widely used in the Chinese mainland and drug-induced liver injury (DILI) has been reported. The study aimed to investigate the clinical features or risk factors for immunotherapy-related DILI. Patients who received PD-(L)1 inhibitors from January 2020 to July 2021 were retrospectively reviewed. The likelihood of DILI was adjudicated by the Roussel-Uclaf causality assessment. A total of 1175 patients were included in the study and 89 patients (7.6%) developed DILI, of which 12 (13.5%) progressed to acute liver failure (ALF) and three (3.4%) died. Among the DILI population, 56 (62.9%) had a cholestatic pattern and exhibited a prolonged treatment course and duration for resolution compared to the hepatocellular and mixed patterns. Hepatocellular carcinoma (HCC), hepatitis B virus (HBV) and abnormal baseline of alkaline phosphatase (ALP) had increased risks of DILI by 2.1-fold (95% confidence interval [CI], 1.231-3.621), 1.9-fold [95% CI, 1.123-3.325] and 2.1-fold [95% CI, 1.317-3.508], respectively. The model for end-stage liver disease (MELD) score had a c-statistic of 0.894 (95% CI, 0.778-1.000) with a sensitivity of 67% and a specificity of 95% for poor outcomes. COX analysis showed that the MELD ≥ 18 was predictive of immunotherapy-related ALF or death. PD-(L)1 inhibitor-related liver injury manifests primarily as a cholestatic pattern, on which corticosteroid treatment has minimal effect compared to hepatocellular and mixed patterns. MELD score ≥ 18 at the time of liver injury performed best in the prediction of ALF or death in immune checkpoint inhibitor (ICI)-related DILI.

An International, Multicenter Feasibility Study on Active and Continuous Irrigation With Cerebrospinal Fluid Exchange for Improving Outcomes in Cerebral Ventriculitis.

Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRA flow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis. We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRA flow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths. Four centers contributed data for a total of 21 patients who had IRRA flow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRA flow placement. Antibiotics were administered through the IRRA flow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths. The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis.

Innovating Leishmaniasis Treatment: A Critical Chemist's Review of Inorganic Nanomaterials.

Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts. By leveraging the adjustable properties of these nanomaterials─including size, shape, and surface charge, tailored treatments for various diseases can be developed that are less harmful to the environment and nontarget species. We review recent advances in metal-, oxide-, and carbon-based nanomaterials for combating Leishmaniasis, examining their mechanisms of action and their dual use as standalone treatments or drug delivery systems. Our analysis highlights a promising yet underexplored frontier in employing these materials for more holistic and effective disease management.

Financial Toxicity Among Patients With Metastatic Prostate Cancer: A Mixed Methods Approach to Identify Effective Interventions.

Financial toxicity associated with treatments for metastatic prostate cancer remains poorly defined. We sought to understand aspects of financial toxicity not captured in a commonly employed financial toxicity questionnaire and identify potential interventions to help alleviate financial toxicity through a convergent mixed methods approach. Patients seen at our institution's advanced prostate cancer clinic were approached for completion of the Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire (quantitative analysis). A maximal variation purposive sample was chosen to participate in focus group discussions (qualitative analysis). Conventional content analysis was performed using an inductive approach. COST-FACIT scores were compared between patients experiencing high and low financial toxicity using Wilcoxon rank sum test. Three themes were identified through qualitative analysis: (1) workload, (2) coping strategies, and (3) communication. We found alignment with the existing theory of financial capacity across our findings. Two unique aspects of financial toxicity emerged that were not assessed quantitatively and deemed to be significant. Specifically, cost transparency (including health care teams knowledgeable about and willing to discuss costs) and inclusion of informal caregivers in financial toxicity screening and decision-making may guide future interventions aimed at limiting financial toxicity in this population. Prolonged treatment courses involving multiple lines of treatment with varying costs result in distinct financial toxicity components for patients with metastatic prostate cancer that are not assessed with COST-FACIT. Improving cost transparency, health care team knowledge and engagement, and providing resources to support informal caregivers may have a significant impact on the financial toxicity experienced by these patients.

Depressive symptom trajectories with prolonged rTMS treatment

BackgroundA prolonged repetitive transcranial magnetic stimulation (rTMS) treatment course could be beneficial for some patients experiencing major depressive episodes (MDE). We identified trajectories of rTMS response in depressive patients who received an extended rTMS treatment course and sought to determine which trajectories achieved the greatest benefit with a prolonged treatment course. MethodWe applied group-based trajectory modeling to a naturalistic dataset of depressive patients receiving a prolonged course of sequential bilateral rTMS (up to 51 treatment sessions) to the dorsolateral prefrontal cortex. Trajectories of the PHQ-9 with extended treatment courses were characterized, and we explored the association between baseline clinical characteristics and group membership using multinomial logistic regression. ResultsAmong the 324 study participants, four trajectories were identified: “linear response, extended course” (N = 73; 22.5 %); “nonresponse” (N = 23; 7.1 %); “slowed response” (N = 159; 49.1 %); “rapid response, standard treatment length” (N = 69; 21.3 %). Only the “linear response, extended course” group showed considerable clinical improvement after receiving additional rTMS treatments. Greater baseline depressive symptoms were associated with linear response and non-response. ConclusionOur results confirmed the distinctive response trajectories in depressive patients receiving rTMS and further highlighted that prolonged rTMS treatment courses may be beneficial for a subset of patients with higher initial symptom levels and linear early treatment response.

Evaluation of the effect of therapeutic durations on small ruminant bacterial pneumonia

BackgroundSheep and goat production in Ethiopia is hindered by numerous substandard production systems and various diseases. Respiratory disease complexes (RDC) pose a significant threat to the productivity of these animals. Pneumonia is a common manifestation of respiratory disease complexes and often necessitates a prolonged course of antibiotic treatment. This study aimed to optimize and propose the ideal duration of therapy for pneumonia in sheep and goats.MethodsThe study was conducted from February to June 2021 at the Veterinary Teaching Hospital of the College of Veterinary Medicine and Agriculture, Addis Ababa University. The study recruited 54 sheep and goats presented to the hospital for treatment with a confirmed RDC as determined based on clinical signs and bacteriological methods. The animals were randomly allocated to 5 groups each group receiving 10% oxytetracycline (Phenxyl, Phenix, Belgum) intramuscularly for a duration of 3, 4, 5, 6 and 7 consecutive days. The treatment outcomes were assessed by recording vital signs (body temperature, respiratory rate, heart rate, coughing, and nasal discharges), performing lung ultrasonography (L-USG) as well as collection of nasal swabs for bacterial isolation and molecular identification before and after completion of the treatment. An ordered logistic regression model with random effects was employed to determine the optimal therapeutic duration, taking into account the cumulative scores of the outcome variables across the different groups.ResultsAmong the 54 sheep and goats treated with 10% oxytetracycline, a total of 74.07% (95% CI, 60.35–85.04) achieved complete recovery, as confirmed through clinical, ultrasound, and bacteriological methods. In Group 1 (G1), out of 12 sheep and goats, 8 (83.0%) recovered completely; in Group 2 (G2), out of 11 animals, 9 (82.0%) recovered completely; in Group 3 (G3), out of 11 animals, 10 (93.0%) recovered completely; in Group 4 (G4), out of 9 animals, 9 (100.0%) recovered completely; and in Group 5 (G5), out of 11 animals, 10 (91.0%) recovered completely. Bacteriological examination of nasal swabs indicated involvement of M. hemolytica in 27 (50.00%) and P. multocida in 13 (24.07%) of pneumonic animals. Detection of specific marker genes confirmed only five of the presumptive M. hemolytica isolates, whilst no isolates tested positive for P. multocida. Post-treatment samples collected from recovered animals did not yield any M. hemolytica nor P. multocida. Based on results from clinical signs, L-USG, and bacterial infection variables, the group of sheep and goats treated for seven consecutive days (G5) showed the highest recovery score compared to the other groups, and there was a statistically significant difference (coefficient (β) = − 2.296, p = 0.021) in variable score between G5 and G1. These findings suggest that the administration of 10% oxytetracycline for a full course of seven consecutive days resulted in symptomatic and clinical recovery rates from respiratory disease in sheep and goats.