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Veterinary World May 2024Lincomycin is an antibiotic used in broiler farming and is commonly combined with other substances to achieve synergistic and complementary effects on the antibacterial...
BACKGROUND AND AIM
Lincomycin is an antibiotic used in broiler farming and is commonly combined with other substances to achieve synergistic and complementary effects on the antibacterial spectrum and mechanism. We developed a specific high-performance liquid chromatography (HPLC) method to measure lincomycin levels in broiler tissues. This study aimed to determine the lincomycin level in tissues and compare it with the minimum inhibitory concentration (MIC) and maximum residue limit (MRL) of certain pathogenic bacteria.
MATERIALS AND METHODS
Three groups of broiler chickens were involved in the study (n = 20 in each group): A control group without lincomycin treatment and two groups (each further divided into two sub-groups) that received oral lincomycin at a dose of 1 g/10 kg of body weight daily for 7 and 14 consecutive days. Tissue samples were collected from each group 1 day and 1 week after lincomycin administration (ALA). This study validated the development of a technique for analyzing drug level degradation in tissues using HPLC. Descriptive and statistical analyses were performed for drug levels to assess their therapeutic value and safety based on lincomycin MIC of certain pathogenic bacteria and MRL.
RESULTS
The method validation resulted in linear regression and coefficient of determination for tissues with r > 0.99, with a recovery rate of 90%-110%, precision as the coefficient of variation 15%, and specificity with no peak overlap for lincomycin. The limits of detection for the liver and kidney were 0.01 μg/g, 0.05 μg/g, and 0.1 μg/g for the breast muscle and all tissues. Administration of lincomycin for 7 and 14 days resulted in therapeutic value concentrations. Lincomycin levels in the liver and kidney of ALA exceeded the MRL, whereas breast muscles were below the MRL for a week of ALA treatment.
CONCLUSION
Administration of lincomycin for 7 and 14 consecutive days resulted in therapeutic value; however, after a week, most tissues showed high drug concentrations that exceeded the MRL. It is necessary to carefully consider the prolonged therapeutic dose of lincomycin in broilers. Antibiotic therapy must be guided in such a way as to protect the product from harmful residues.
PubMed: 38911093
DOI: 10.14202/vetworld.2024.1026-1034 -
Pediatric Investigation Jun 2024It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A...
IMPORTANCE
It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS regimen).
OBJECTIVE
To compare the efficacy of the LD-ITI-IS regimen with that of the LD-ITI-IS regimen for SHA patients with high-titer inhibitors.
METHODS
A prospective cohort study on patients receiving LD-ITI-IS compared to those receiving LD-ITI-IS from January 2021 to December 2023. Both received LD-ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD-ITI-IS regimen and ≥40 BU/mL in the LD-ITI-IS regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected.
RESULTS
We enrolled 30 patients on LD-ITI-IS and 64 patients on LD-ITI-IS, with similar baseline clinical characteristics. A lower IS-use rate was discovered in the LD-ITI-IS regimen compared to the LD-ITI-IS regimen (30.0% vs. 62.5%). The two regimens (LD-ITI-IS vs. LD-ITI-IS) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD-ITI-IS than for LD-ITI-IS (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor-titer 40-199 BU/mL, 10 non-IS-using (on LD-ITI-IS regimen) and 28 IS-using (on LD-ITI-IS regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months).
INTERPRETATION
In LD-ITI, IS are not necessary for inhibitor titer <200 BU/mL.
PubMed: 38910855
DOI: 10.1002/ped4.12429 -
Cureus May 2024Background Hepatitis C virus (HCV) infection is still common in patients with chronic renal failure, even those on maintenance dialysis. A bidirectional association...
Background Hepatitis C virus (HCV) infection is still common in patients with chronic renal failure, even those on maintenance dialysis. A bidirectional association exists between HCV infection and chronic renal disease. Objective To assess the efficacy of sofosbuvir and velpatasvir combination in the treatment of chronic HCV in chronic kidney disease (CKD) patients. Methodology This descriptive, cross-sectional study was undertaken at the departments of Gastroenterology and Nephrology Lady Reading Hospital, Peshawar, from April 7, 2021, to October 7, 2021. Patients with chronic HCV and chronic renal disease at stage 4 or 5 were included while patients with decompensated cirrhosis liver, hepatoma, hepatitis B virus/HCV (HBV/HCV) coinfection, and post liver transplant patients were excluded. HCV infection was diagnosed based on detectable HCV ribonucleic acid (HCV RNA) by PCR (polymerase chain reaction). In contrast, CKD was diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria for CKD. Sofosbuvir 400 mg orally daily and velpatasvir 100 mg orally with meals were given daily for 12 weeks. Effectiveness was defined as negative HCV RNA by PCR 12 weeks after treatment completion called sustained virological response rate 12 weeks after treatment completion (SVR12). Results A total of 73 patients including 67 (91.78%) males and six (8.22%) females between the ages of 20 years and 70 years were included in this study. The mean age of the participants was 48.77±8.0 years. Twelve weeks after the treatment completion, 69 (94.52%) had negative HCV RNA, whereas four (5.48%) patients had detectable HCV RNA. Conclusion It can be concluded from our study that a fixed-dose combination of sofosbuvir 400 mg and velpatasvir 100 mg is quite effective and recommended for treating chronic hepatitis C infection in patients with chronic renal disease in our local setup.
PubMed: 38910758
DOI: 10.7759/cureus.60861 -
Cureus May 2024Background Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that clinically presents as tender erythematous evanescent nodules, mostly associated...
Background Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that clinically presents as tender erythematous evanescent nodules, mostly associated with systemic symptoms. Oral prednisolone is the drug of choice, with doses ranging from 0.5 to 1 mg/kg. Some cases may develop new lesions and systemic symptoms despite 1 mg/kg prednisolone, and in ideal practice, physicians escalate the prednisolone dose for immediate arrest of inflammation to prevent complications. However, a high dose of prednisolone has more side effects in the long term and causes more immunosuppression. Methods In cases of ENL, those not responding to a conventional once-daily regimen were given a split dose of oral prednisolone instead of increasing the dose. They were followed up for response, and serum cortisol was measured to see for hypothalamic-pituitary-adrenal (HPA) axis suppression. Results Eight cases of ENL (three nodular, three necrotic, one pustular, and one nodulcerative) had a dramatic response to split-dose therapy without any relapse and HPA axis suppression. Conclusion A split-dosing regimen can be a good treatment option in ENL with better control, less steroid dependency, and a lower relapse rate.
PubMed: 38910715
DOI: 10.7759/cureus.60888 -
Cureus May 2024Introduction The acute gastrointestinal injury (AGI) score was proposed by the Working Group on Abdominal Problems of the European Society of Intensive Care Medicine...
Introduction The acute gastrointestinal injury (AGI) score was proposed by the Working Group on Abdominal Problems of the European Society of Intensive Care Medicine (ESICM) as a tool to define and grade gut dysfunction. There have not been any studies in India to validate this tool. The objective of this preliminary study was primarily to study the frequency of AGI in the first week of ICU stay in critically ill patients in our intensive care unit (ICU). We also sought to determine the risk factors predisposing to the development of AGI and to determine the prognostic implication of gastrointestinal (GI) injury in critically ill patients. Materials and methods A prospective, observational, preliminary, single-center study was conducted on critically ill patients (APACHE II > 8) who were on enteral tube feeds and admitted to a mixed ICU of a tertiary care hospital. Anthropometric data, admission diagnosis, APACHE II score, and comorbidities were recorded. Data of daily heart rate, mean arterial pressure, dose of vasopressors, intra-abdominal pressure, fluid balance, feeding intolerance, mechanical ventilation, and laboratory tests were noted for the first seven days of ICU stay or till ICU discharge, whichever was earlier. The occurrence of AGI score (1-4) during the first seven days of critical illness was the primary outcome of interest. Patient outcome at 28 days was recorded and the impact of the occurrence of AGI on patient outcome was analyzed using the Chi-square test. The patient characteristics associated with AGI were characterized as risk factors and analyzed using a multivariate model. Results Data were collected from 33 patients over 201 patient days. The frequency of acute GI dysfunction in the first seven days of ICU stay in our group of patients was 45.45% (15/33). APACHE II, fluid balance, creatinine, and lactate were identified as possible predictors of GI injury based on existing literature. These four variables were entered into an ordinal logistic regression model to assess their ability to predict the occurrence of GI Injury. When fitted into a predictive model, only fluid balance and creatinine were predictive of the final model (p-value < 0.05). A greater fluid balance was predictive in the final model of the development of GI injury; however, it showed negligible clinical significance (OR: 1.00033, 95% CI: 1.000051-1.00061). Lower creatinine levels were predictive in the final model of the development of AGI Injury, as demonstrated by the negative coefficient. Creatinine also had a greater clinical significance (OR: 0.63, 95% CI: 0.44-0.90) in the development of AGI. The impact of the AGI scores on mortality was analyzed. The number of patient days with higher AGI scores was significantly associated with increased mortality at 28 days (p-value < 0.001). Conclusion The study showed that nearly half of the critically ill patients included in the study developed acute GI dysfunction. We could not identify any predictors of GI injury based on our results. The result suggested an association between the severity of GI dysfunction and mortality at 28 days.
PubMed: 38910699
DOI: 10.7759/cureus.60903 -
The Korean Journal of Internal Medicine Jun 2024Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with...
BACKGROUND/AIMS
Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI.
METHODS
A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups.
RESULTS
The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001).
CONCLUSIONS
Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.
PubMed: 38910509
DOI: 10.3904/kjim.2024.080 -
Journal of Zhejiang University.... Jun 2024: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19...
: Following the short-term outbreak of coronavirus disease 2019 (COVID-19) in December 2022 in China, clinical data on kidney transplant recipients (KTRs) with COVID-19 are lacking. : We conducted a single-center retrospective study to describe the clinical features, complications, and mortality rates of hospitalized KTRs infected with COVID-19 between Dec. 16, 2022 and Jan. 31, 2023. The patients were followed up until Mar. 31, 2023. : A total of 324 KTRs with COVID-19 were included. The median age was 49 years. The median time between the onset of symptoms and admission was 13 d. Molnupiravir, azvudine, and nirmatrelvir/ritonavir were administered to 67 (20.7%), 11 (3.4%), and 148 (45.7%) patients, respectively. Twenty-nine (9.0%) patients were treated with more than one antiviral agent. Forty-eight (14.8%) patients were treated with tocilizumab and 53 (16.4%) patients received baricitinib therapy. The acute kidney injury (AKI) occurred in 81 (25.0%) patients and 39 (12.0%) patients were admitted to intensive care units. Fungal infections were observed in 55 (17.0%) patients. Fifty (15.4%) patients lost their graft. The 28-d mortality rate of patients was 9.0% and 42 (13.0%) patients died by the end of follow-up. Multivariate Cox regression analysis identified that cerebrovascular disease, AKI incidence, interleukin (IL)-6 level of >6.8 pg/mL, daily dose of corticosteroids of >50 mg, and fungal infection were all associated with an increased risk of death for hospitalized patients. : Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality. The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival, while higher doses of corticosteroids may increase the death risk.
Topics: Humans; Kidney Transplantation; Middle Aged; Male; Female; COVID-19; Retrospective Studies; China; Antiviral Agents; Adult; SARS-CoV-2; Hospitalization; Transplant Recipients; Aged; COVID-19 Drug Treatment; Antibodies, Monoclonal, Humanized; Azetidines; Purines; Pyrazoles; Sulfonamides
PubMed: 38910497
DOI: 10.1631/jzus.B2300538 -
International Journal of Infectious... Jun 2024To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety.
OBJECTIVES
To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety.
METHODS
This target trial emulation study included individuals aged ≥ 12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups.
RESULTS
639,818 and 1,804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (HRs) (95% confidence intervals [CI]) were 0.844 [0.833-0.856] and 0.749 [0.743-0.755] for COVID-19 infection, 0.692 [0.656-0.731] and 0.582 [0.559-0.605] for hospitalization, 0.566 [0.417-0.769] and 0.590 [0.458-0.76] for severe COVID-19, and 0.563 [0.456-0.697] and 0.457 [0.372-0.561] for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (Incidence rate ratio[IRR][95% CI]: 8.999 [1.14-71.017]) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR [95% CI]: 2.000 [0.500-7.996]).
CONCLUSIONS
BNT162b2 has higher effectiveness among individuals aged ≥ 12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk. (200 words).
PubMed: 38909928
DOI: 10.1016/j.ijid.2024.107149 -
Ophthalmology Jun 2024To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry...
OBJECTIVE
To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD).
DESIGN
Phase 1, open-label, single-center, first-in-human clinical study.
SUBJECTS
Adult patients (aged ≥50 years) with GA secondary to AMD in the study-treated eye (treated eye) with a best corrected visual acuity (BCVA) Snellen equivalent of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm (2-8 disc area), and BCVA of 20/800 or better in fellow, non-treated eye were included.
METHODS
Patients (N=17) were sequentially enrolled into low (3.56×10 viral genome [vg]/eye; n=3), intermediate (1.07×10 vg/eye; n=3), and high (3.56×10 vg/eye; n=11) dose cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months.
MAIN OUTCOME MEASURES
Safety and tolerability outcomes included assessment of ocular and non-ocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate.
RESULTS
Baseline patient characteristics were consistent with the disease under study, and all enrolled patients had foveal center-involved GA. JNJ-1887 was well tolerated across all cohorts, with no dose-limiting AEs. There were no serious or systemic AEs related to study intervention. Overall, 5/17 (29%) patients experienced 6 events of mild ocular inflammation related to study treatment; exam findings in all resolved, and AEs resolved in 4 of 5 patients following topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. GA lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0-6 to 0.056 mm at months 18-24.
CONCLUSIONS
All 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.
PubMed: 38909914
DOI: 10.1016/j.ophtha.2024.06.013 -
Radiation Oncology (London, England) Jun 2024Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided...
The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience.
BACKGROUND
Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer.
METHODS AND MATERIALS
This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS.
RESULTS
Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities.
CONCLUSION
VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.
Topics: Humans; Female; Uterine Cervical Neoplasms; Radiotherapy, Intensity-Modulated; Brachytherapy; Retrospective Studies; Middle Aged; Adult; Aged; Radiotherapy, Image-Guided; Tomography, X-Ray Computed; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Aged, 80 and over; Survival Rate
PubMed: 38909242
DOI: 10.1186/s13014-024-02476-9