Short-term Regimen Research Articles

Efficiency of Treatment of Tuberculosis Patients: Realities, Problems and Perspectives (Review)

An analysis of data from global experience and professional publications on modern treatment of tuberculosis patients and its effectiveness was carried out.The analysis of literary sources of recent years indicates an urgent problem regarding tuberculosis in Ukraine (especially in the conditions of martial law and the conduct of active hostilities). With early diagnosis and timely treatment, the number of patients decreases by 8 %.The effectiveness of the treatment of patients with pulmonary tuberculosis and the influence of various factors on it were evaluated. The effectiveness of treatment of newly diagnosed pulmonary tuberculosis in Ukraine does not exceed 70 %.An increase in the level of resistance of tuberculosis mycobacteria to anti-tuberculosis drugs was noted, and its treatment efficiency was not high. The effectiveness of treatment of such patients in Ukraine does not exceed 40—45 %. The inclusion of second-line drugs in the treatment regimen of patients with iso­niazid-­resistant tuberculosis increases the effectiveness of treatment by 11.8 %. The overall effectiveness of treatment of patients with multidrug-resistant tuberculosis (MDR-TB) in the world is 52 %, and only 10 % of patients are cured. The treatment of MRTB is three times longer (20 months) than that of the sensitive form and is significantly more expensive. Antimycobacterial drugs (AMBs) were used according to an individual regimen (18—20 months), then new AMBs were used (6 months), later versions of modified standardized short-term regimens (9 months). The BPaL regimen (bedaquiline, linezolid, pretomanide) was implemented for patients with multiple and extensively drug-resistant tuberculosis for 6 months (26 weeks or 182 doses), resulting in a cure rate of 90 % [35].The methods of optimizing the management of patients with pulmonary tuberculosis (including correction of treatment) in the conditions of martial law, which can be achieved by improving antimycobacterial and pathogenetic therapy, revealing new mechanisms and deepening the known regularities of the course of the disease, are evaluated.

Adherence to Short-Duration Treatment (3HP) for Latent Tuberculosis among International Migrants in Manaus, Amazonas: Evaluation of the Efficacy of Different Treatment Modalities.

Migration, a multifaceted phenomenon, has a significant impact on health. Migrants perform similar movement patterns within their country of origin, in transit, and in the country of destination, thus making it difficult to monitor TB treatment throughout the journey. The objective was to compare the effectiveness of different treatment modalities in adherence to the short-term regimen for LTBI (3HP) among international migrants and refugees. This is a quasi-experimental study conducted in Manaus-AM. The study population was made up of international migrants. The certification and monitoring of medication intake employed three strategies: self-administration (SA), directly observed conventional therapy (DOT), and Video Telemonitoring System for Tuberculosis Treatment (VDOT). The VDOT group and SA group exhibited the lowest rate of treatment dropout or interruption at 16.1%, followed by the DOT group at 23.1%. The results suggest that the most effective strategy for ensuring adherence among migrants and refugees was VDOT (OR_adj 0.26; CI 0.7-0.94), suggesting that migrants may be more likely to adhere to and complete their treatment. The results show that relying on different treatment strategies, adapted to the individuals' needs and risk factors, is a viable and effective way of providing person-centered TB care.

Short-term high fat diet impairs memory, exacerbates the neuroimmune response, and evokes synaptic degradation via a complement-dependent mechanism in a mouse model of Alzheimer’s disease

Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to a role of the diet itself in increasing risk. In AD, the complement system, an arm of the immune system which normally tags redundant or damaged synapses for pruning, becomes pathologically overactivated leading to tagging of healthy synapses. While the unhealthy diet to AD link is strong, the underlying mechanisms are not well understood in part due to confounding variables associated with long-term HFD which can independently influence the brain. Therefore, we experimented with a short-term diet regimen to isolate the diet’s impact on brain function without causing obesity. This project investigated the effect of short-term HFD on 1) memory, 2) neuroinflammation including complement, 3) AD pathology markers, 4) synaptic markers, and 5) in vitro microglial synaptic phagocytosis in the 3xTg-AD mouse model. Following the consumption of either standard chow or HFD, 3xTg-AD and non-Tg mice were tested for memory impairments. In a separate cohort of mice, levels of hippocampal inflammatory markers, complement proteins, AD pathology markers, and synaptic markers were measured. For the last set of experiments, BV2 microglial phagocytosis of synapses was evaluated. Synaptoneurosomes isolated from the hippocampus of 3xTg-AD mice fed chow or HFD were incubated with equal numbers of BV2 microglia. The number of BV2 microglia that phagocytosed synaptoneurosomes was tracked over time with a live-cell imaging assay. Finally, we incubated BV2 microglia with a complement receptor inhibitor (NIF) and repeated the assay. Behavioral analysis showed 3xTg-AD mice had significantly impaired long-term contextual and cued fear memory compared to non-Tg mice that was further impaired by HFD. HFD significantly increased inflammatory markers and complement expression while decreasing synaptic marker expression only in 3xTg-AD mice, without altering AD pathology markers. Synaptoneurosomes from HFD-fed 3xTg-AD mice were phagocytosed at a significantly higher rate than those from chow-fed mice, suggesting the synapses were altered by HFD. The complement receptor inhibitor blocked this effect in a dose-dependent manner, demonstrating the HFD-mediated increase in phagocytosis was complement dependent. This study indicates HFD consumption increases neuroinflammation and over-activates the complement cascade in 3xTg-AD mice, resulting in poorer memory. The in vitro data point to complement as a potential mechanistic culprit and therapeutic target underlying HFD’s influence in increasing cognitive vulnerability to AD.

Mitochondrial Fission Is Involved in Heat Resistance in Zebrafish.

Global warming and extreme weather events pose a significant threat to global biodiversity, with rising water temperatures exerting a profound influence on fish conservation and fishery development. In this study, we used zebrafish as a model organism to explore the impact of a heat acclimation period on their survival rates. The results demonstrated that a 2-month heat acclimation period almost completely mitigated heat stress-induced mortality in zebrafish. Subsequent analysis of the surviving zebrafish revealed a predominance of hepatic mitochondria in a fission state. Remarkably, a short-term fasting regimen, which induced hepatic mitochondrial fission, mirrored the outcomes of the protective effect of heat acclimation and augmented animal survival under heat stress. Conversely, treatment with a mitochondrial fission inhibitor within the fasting group attenuated the elevated survival rate. Furthermore, zebrafish embryos subjected to brief heat acclimation also exhibited increased heat resistance, a trait diminished by a chemical intervention inhibiting mitochondrial fission. This suggests a shared mechanism for heat resistance between embryos and adult zebrafish. These findings underscore the potential use of inducing mitochondrial fission to enhance heat resistance in zebrafish, offering promise for fish biodiversity conservation in the face of global warming.

Long-term pharmacodynamic and clinical effects of twice- versus once-daily low-dose aspirin in essential thrombocythemia: The ARES trial.

Patients with essential thrombocythemia (ET) are treated with once-daily low-dose aspirin to prevent thrombosis, but their accelerated platelet turnover shortens the antiplatelet effect. The short-term Aspirin Regimens in EsSential Thrombocythemia trial showed that twice-daily aspirin dosing restores persistent platelet thromboxane (TX) inhibition. However, the long-term pharmacodynamic efficacy, safety and tolerability of twice-daily aspirin remain untested. We performed a multicenter, randomized, open-label, blinded-endpoint, phase-2 trial in which 242 patients with ET were randomized to 100 mg aspirin twice- or once-daily and followed for 20 months. The primary endpoint was the persistence of low serum TXB2, a surrogate biomarker of antithrombotic efficacy. Secondary endpoints were major and clinically relevant non-major bleedings, serious vascular events, symptom burden assessed by validated questionnaires, and in vivo platelet activation. Serum TXB2 was consistently lower in the twice-daily versus once-daily regimen on 10 study visits over 20 months: median 3.9 ng/mL versus 19.2 ng/mL, respectively; p < .001; 80% median reduction; 95% CI, 74%-85%. No major bleeding occurred. Clinically relevant non-major bleedings were non-significantly higher (6.6% vs. 1.7%), and major thromboses lower (0.8% vs. 2.5%) in the twice-daily versus once-daily group. Patients on the twice-daily regimen had significantly lower frequencies of disease-specific symptoms and severe hand and foot microvascular pain. Upper gastrointestinal pain was comparable in the two arms. In vivo platelet activation was significantly reduced by the twice-daily regimen. In patients with ET, twice-daily was persistently superior to once-daily low-dose aspirin in suppressing thromboxane biosynthesis and reducing symptom burden, with no detectable excess of bleeding and gastrointestinal discomfort.

Comparison of Anxiety Levels in MDR-TB Patients with Individual and Short-term Regimens at Dr. Soebandi Regional General Hospital, Jember, Indonesia

Comparison of Anxiety Levels in MDR-TB Patients with Individual and Short-term Regimens at Dr. Soebandi Regional General Hospital, Jember, Indonesia

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China

Background To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. Methods We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. Results Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were −3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. Conclusions For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don’t meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

Factors influencing pregnancy rate and loss after laparoscopic artificial insemination with frozen-thawed semen in Lohi sheep under sub-tropical conditions.

This study evaluates factors influencing pregnancy rates per artificial insemination (P/AI) and pregnancy loss in Lohi ewes undergoing laparoscopic AI with frozen-thawed semen under sub-tropical conditions. Data from three experiments comprising ewes (n = 358) of mixed parity (nulliparous; NP and parous; P), various body condition score (BCS) and assigned to long-term (LTP, 11 days) and short-term (STP, 5 days) oestrus synchronization regimen across high breeding season (HBS) and low breeding season (LBS) were analysed. Laparoscopic insemination was conducted 54 h post-sponge removal. Pregnancy diagnosis and loss were evaluated on days 35 and 90 post-insemination via ultrasonography. Results showed parity significantly influenced P/AI, with nulliparous ewes achieving higher pregnancy ratios than parous ewes (p = .001). BCS significantly influenced P/AI (p < .05), with a quadratic relationship observed between BCS and season (BCS*BCS*Season; p = .07). Progestin treatment did not significantly influence the ratio of pregnant ewes (p = .07). Pregnancy losses were significantly higher during LBS than HBS (p < .05), irrespective of progestin treatment. In conclusion, parity and BCS significantly influenced P/AI, with BCS demonstrating a quadratic association with season. Ewes bred during LBS experienced higher pregnancy losses than HBS, irrespective of progestin treatment.

Treatment of Nevus Sebaceous with Short-term Photodynamic therapy combined with simple Surgery

SignificanceNevus sebaceous is a benign cutaneous hamartoma involving the epidermis, pilosebaceous units, and other adnexal structures. To avoid or minimize the scar, photodynamic therapy (PDT) is recommended as a non-surgical treatment. ApproachIn this report, we present a successful case of recurrent nevus sebaceous treated with a combination therapy of PDT and surgical excision. The patient was followed-up for a period of 6 months to evaluate the effectiveness of the treatment. ResultsThe patient underwent three sessions of PDT at three-week intervals, followed by surgical resection. Following the procedure, there was no recurrence of the lesion after 6 months, and the achieved a favorable cosmetic outcome. ConclusionsIn cases where the nevus sebaceous affects larger areas, employing a short-term PDT regimen in conjunction with surgical intervention proves to be an effective strategy, reducing the extent of surgical excision and yielding superior cosmetic results for our patients.

Factors Associated with Non-Adherence to Tuberculosis Preventive Treatment among Adult Contacts of Pulmonary Tuberculosis Cases with Latent Tuberculosis Infection in Catalonia, Spain, in 2019-2021.

The aim of this study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection for new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables; a p < 0.05 was considered statistically significant. Multiple logistic regression analysis was used to detect the independent factors associated with TB preventive treatment non-adherence; a p < 0.05 was considered statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: "exposure at school or workplace" (aOR = 3.34), "exposure to an index case without laboratory confirmation of TB" (aOR = 2.07), "immigrant contact" (aOR = 1.81), "male gender" (aOR = 1.75) and "exposure duration < 6 h per week or sporadic" (aOR = 1.60. By contrast, the factor "short-term TB preventive treatment regimen" (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Comparison of short term and long term multidrug resistant tuberculosis treatment outcomes in tertiary care settings

IntroductionTuberculosis is a contagious and communicable disease while drug resistant tuberculosis is difficult to treat and requires long duration. Various strategies are focused to treat the drug resistant tuberculosis focusing lesser side effects and shorter duration of treatment. ObjectiveTo compare treatment outcomes between short-term and long-term regimens among patients registered at a tertiary care hospital's Programmatic Management of Drug-Resistant TB (PMDT) site in Pakistan. MethodsA comparative prospective cohort study was conducted at IMBB, The University of Lahore, in collaboration with the Health Research Institute (HRI) TB Research Centre at King Edward Medical University/Mayo Hospital, Lahore. The study included a sample size of 136 patients, with 68 patients in each treatment regimen (long-term and short-term). Adult pulmonary MDR TB patients seeking treatment from the facility were included based on predefined criteria. Data was collected using a pre-designed questionnaire after obtaining ethical approval and informed consent. The rates of patients' cure, treatment completed, treatment failure and death were calculated. ResultsA total of 131 patients were successfully followed up and included in the final analysis. Of these, 66 patients were in the long-term treatment group and 65 patients were in the short-term treatment group. The cure rate was 74.8 %, with 98 patients successfully cured, and 13.8 % of patients completed their treatment successfully. In the long-term treatment group, the cure rate was 75.6 %, with a treatment failure rate of 6.2 %. In the short-term treatment group, the cure rate was 73.8 %, with a treatment failure rate of 6.1 %. The death rate was 4.5 % in the short-term treatment group and 6.2 % in the long-term treatment group. However, these differences in treatment outcomes were statistically insignificant (p-values > 0.05). The newer drugs, bedaquiline and delamanid, did not show significant improvements in the treatment of multidrug-resistant TB patients. Side effects at completion of treatment remained to be significantly lesser (p < 0.05) among short term treatment group as compared to long term treatment group. ConclusionThe findings suggest that short-term treatment regimens are equally effective as long-term treatment regimens, with the added benefit of presenting fewer side effects.

Antibiotic prophylaxis in urologic interventions: Who, when, where?

Periprocedural prophylaxis in medicine encompasses the set of measures (physical, chemical, and pharmacological) used to reduce the risk of infection. Antibiotic prophylaxis (AP) refers to the administration of a short-term regimen of antibiotics shortly before a medical procedure to reduce the risk of infectious complications that can result from diagnostic and therapeutic interventions. The outspreading growth of multidrug-resistant bacterial species and changes in the bacterial local ecosystem have impeded the development of a unique scheme of AP in urology. To review the literature and current guidelines regarding AP for urological diagnostic and therapeutic procedures, and to define agents, timing, and occasions when administering pharmacological prophylaxis. Secondly, according to current literature, to open new scenarios where AP can be useful or useless. Major gaps in evidence still exist in this field. AP appears useful in many invasive procedures and some sub-populations at risk of infectious complications. AP is not routinely recommended for urodynamic exams, diagnostic cystoscopy, and extracorporeal shock-wave lithotripsy. The available data regarding the use of AP during the transperineal prostate biopsy are still unclear; conversely, in the case of the transrectal approach AP is mandatory. AP is still considered the gold standard for the prevention of postoperative infective complications in the case of ureteroscopy, percutaneous nephrolithotomy, endoscopic resection of bladder tumor, endoscopic resection of the prostate, and prosthetic or major surgery. The review highlights the complexity of determining the appropriate candidates for AP, emphasizing the importance of considering patient-specific factors such as comorbidities, immunocompetence, and the nature of the urologic intervention. The evidence suggests that a one-size-fits-all approach may not be suitable, and a tailored strategy based on the specific procedure and patient characteristics is essential.

The Overview Side Effects of MDR TB Short Term Regimen for Heart and Kidney Function in MDR TB Patients at H. Adam Malik General Hospital Medan, North Sumatra

The Overview Side Effects of MDR TB Short Term Regimen for Heart and Kidney Function in MDR TB Patients at H. Adam Malik General Hospital Medan, North Sumatra

Comparison of different regimens of short-term antibiotic prophylaxis in transrectal prostate biopsy

Prostate cancer is the most common malignant solid tumour in men aged >70 years and is the second most common cause of death from oncological circumstances. To evaluate the effect of different short-term prophylactic antibiotic regimens in transrectal prostate biopsy (PB) on the incidence of infectious complications. Patients who underwent transrectal ultrasound-guided PB between January 2021 and December 2022 were included in the prospective randomized study. According to the regimen of prophylaxis, patients were randomized into three groups: (1) fosfomycin trometamol 3g, 3h before the procedure+ ciprofloxacin 500mg, 2h before the procedure; (2) fosfomycin trometamol 3g, 3h before and 24h after the procedure; (3) ciprofloxacin 500mg 12, 2h before the procedure, and 12h after the procedure. A rectal swab was performed 1-2 weeks before PB to evaluate the culture findings. Complications were evaluated during follow-up visits within one month after PB. In the monitored period, 605PBs were performed, and 544 patients met the inclusion criteria (184, 161, and 199 in groups 1, 2, and 3). Infectious complications occurred in 10 cases (1.83%), namely 3, 4, and 3 according to patient groups. There was no statistically significant difference between the individual groups. None of the patients required hospitalization and all were free of symptoms of sepsis. Short-term antibiotic prophylaxis in PB using fosfomycin trometamol, ciprofloxacin, or their combination appears to be effective. Fosfomycin trometamol is a suitable alternative to fluoroquinolone antibiotics.

Enhancing ventricular remodeling and cardiac function in post-acute myocardial infarction with sacubitril/valsartan.

To evaluate the therapeutic effect of sacubitril/valsartan compared to enalapril in managing heart failure (HF) after percutaneous coronary intervention (PCI). From January 2018 to December 2021, 63 hospitalized patients diagnosed with HF following acute myocardial infarction (AMI) were enrolled in this prospective clinical trial. The observation group was comprised of 31 patients treated with sacubitril/valsartan (LCZ696) sodium tablets, while the control group, including 32 patients, received enalapril maleate tablets. All patients received standard HF therapy, including water-soluble aspirin, hydroclopidogrel sulfate, once-daily bivalirudin calcium, twice-daily metoprolol tartrate (dose titrated based on heart rate), once-daily spironolactone (dose adjusted for electrolytes), and once-daily dehydroimidazole (dose adjusted for electrolytes). HF symptom control, N-terminal B-type natriuretic peptide precursor (NT-proBNP) levels, cardiac anatomical parameters, heart rate, blood pressure, and 6-minute walking distance over a 90-day follow-up were assessed. The study is registered under ClinicalTrials.gov [ChiCTR2100042944]. On the 30th day post-discharge, the observation group exhibited a marked decrease in NT-proBNP levels and an improvement in left ventricular end-diastolic diameter, in contrast to the control group (both P<0.05). By the 90th day, the observation group showed significant improvements in left ventricular ejection fraction and left ventricular end-systolic diameter index, along with reduced blood pressure and serum creatinine levels (all P<0.05). Furthermore, the observation group displayed a more favorable New York Heart Association class distribution and enhanced performance in the 6-minute walk test (both P<0.05). No significant difference in the incidence of major adverse cardiovascular events was observed between the two groups during the 90-day follow-up period (P>0.05). Our findings indicate that sacubitril/valsartan (LCZ696) Sodium Tablets effectively enhance ventricular remodeling and cardiac function in patients with HF post-AMI, following a short-term treatment regimen. This therapeutic approach holds promise for improving clinical outcomes in this patient population.

Treatment Duration and Drug Regimen Correlation with Side Effects Incidence in Drug-Resistant Tuberculosis (DR-TB) Patients at Pulmonary Hospital

The bacteria Mycobacterium tuberculosis causes Drug-Resistant Tuberculosis (DR-TB). Excessive use of drugs can result in drug resistance with various side effects. This study aimed to analyze the correlation between the treatment duration and drug regimen with the side effects incidence in DR-TB Patients at Pulmonary Hospital Dr. M. Goenawan Partoidigdo (RSPG) Bogor. This is an observational study with a cross-sectional design. Subjects were selected with purposive sampling methods based on inclusion and exclusion criteria. The research showed that DR-TB patients were mostly male (50.2%) with productive age (46.1%). The most common DR-TB treatment experienced by patients in the advanced phase, generally for 9-24 months (75.3%), and the type of drug side effect most experienced was gastrointestinal disorders, that is nausea (55.1%). The use of standard conventional drug regimens mostly in Z, E, Eto, Km, Lfx, Cs (Pyrazinamide, Ethambutol, Ethionamide, Kanamycin, Levofloxacin, Cycloserine) of 51.4%. The chi-square analysis showed no significant correlation between the treatment duration and the incidence of side effects. At the same time, there was a meaningful correlation between the drug regimen (short-term, long-term, and conventional standard regimen) and the side effects incidence. The suspected drugs causing gastrointestinal side effects were pyrazinamide, ethambutol, ethionamide, and levofloxacin. The side effects of arthritic arthralgia were suspected to be caused by pyrazinamide, ethionamide, and levofloxacin.

Drug-resistant Tuberculosis in Pediatric

Introduction: Drug-resistant tuberculosis (DR TB) is a condition where Mycobacterium tuberculosis is resistant to isoniazid, rifampicin or resistant to isoniazid and rifampin as well as other first-line anti-tuberculosis drugs (OAT). Tuberculosis (TB) is a contagious infectious disease, caused by Mycobacterium tuberculosis germs where the source of transmission is through droplets containing TB germs. Case Report: A 10 years 7 months girl, came to the MDR Polyclinic at the Haji Adam Malik Medan Central General Hospital (RSUP HAM Medan) on March 21 2023 bringing the results of the TB Molecular Rapid Test (TCM-TB) examination from the Teladan Barat Health Center with Rifampicin results were resistant and on March 24 2023 the patient was hospitalized. Currently, the patient is complaining of a cough that has been experiencing for ± 3 weeks. Cough with the impression of a dry cough and is continuous so that it interferes with daily activities. The cough does not improve even though the patient has taken cough medicine. There is no fever, there is also no history of previous fever. According to the anamnesis from the patient's parents, there has been a weight loss in the last 2 months, around ± 4 kg. There is no family history of long-term cough, but according to parents, there is a neighbor of the patient who suffers from pulmonary TB and is undergoing treatment. Discussion: After the diagnosis of drug-resistant tuberculosis is confirmed, an evaluation is carried out whether the patient meets the criteria for drug-resistant TB treatment guided by short-term or long-term oral drug-resistant tuberculosis. Patients who meet the evaluation criteria for treatment can immediately be given short-term oral drug-resistant tuberculosis therapy. If the patient does not meet the criteria for short-term treatment, long-term drug-resistant tuberculosis treatment is given. Routine evaluations are carried out during treatment and when the results of drug sensitivity tests are available, treatment is adjusted according to the examination results. Conclusion: A case of drug-resistant tuberculosis in a girl aged 10 years 7 months has been reported which was diagnosed based on anamnesis, physical examination, and supporting examinations, there was also a history of close contact with TB sufferers, and the results of TCM examination of sputum fluid showed rifampicin resistant MTB growth. Patients are treated as drug-resistant TB cases with a short-term regimen with regular monitoring of treatment response and side effects.

A Parallel Comparison of the Safety and Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation for Refractory and Relapsed T-ALL/Lbl Patients Who Achieved Complete Remission with CD7 CAR-T Versus Patients Who Achieved First Complete Remission with Chemotherapy before Transplantation

Introduction We have developed a fratricide-resistant CD7 CAR-T cells from bulk T cells transduced with CD7 CAR without gene editing or additional gene transfer, named naturally selected CD7 CAR-T (NS7CAR-T). NS7 CAR-T therapy has shown a robust complete remission (CR) rate in patients with refractory or relapsed (R/R) T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma (T-ALL/LBL). Nonetheless, the risk of relapse remains a challenge post-CD7 CAR-T therapy alone, suggesting the potential benefits of consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question remains whether CD7 CAR-T therapy could increase the incidence of post-transplant complications. Here we conduct a parallel study to compare the safety and efficacy of allo-HSCT in R/R T-ALL/LBL patients who achieved CR with NS7 CAR-T therapy vs those who reached first CR (CR1) using chemotherapy prior to transplantation. Methods Between November 2020 and January 2023, a total of 223 consecutive patients with T-ALL/LBL who underwent allo-HSCT at our center were retrospectively analyzed. Patients who met the following criteria were included in this parallel study: 1) underwent the first allo-HSCT in our hospital, 2) achieved CR before transplantation either from NS7CAR-T therapy or CR1 from chemotherapy (Fig. 1). A total of 139 patients met the criteria for analysis and underwent allo-HSCT after achieving CR either from NS7CAR-T therapy (n=43) or chemotherapy (CR1=96). The median patient age at the time of transplantation was 15 years (range: 1-51 years). The median follow-up time was 370 days (2-941 days). CD7 CAR-T patients were from two clinical trials registered at www.clinicaltrials.gov NCT04572308, NCT04916860. Transplant donor types included sibling identical (n=12), haploidentical (n=110), and unrelated donors (n=17). We used total body irradiation (TBI)-based conditioning regimens (n=128) or Busulfan/Melphalan-based regimens (n=11). To prevent graft-versus-host disease (GVHD), we used ATG along with a short-term regimen combining methotrexate, cyclosporine/tacrolimus, and mycophenolate mofetil. Results The characteristics of patients from both groups are detailed in Table 1. The median interval between CD7 CAR-T treatment and transplantation was 59 (39-131) days. Within the CAR-T group, 16 patients had primary refractory disease, 18 had relapsed disease and 9 in minimal residual disease (MRD)-positive status in bone marrow before CD7 CAR-T therapy. Prior to CAR-T therapy, 55.8% (24 patients) had extramedullary lesions. In comparing the CAR-T and chemotherapy CR1 groups, we observed no significant differences in long-term efficacy post-allo-HSCT. The 2-year leukemia-free survival (LFS) rates were 64.9 (95% CI, 49.1-79.2)% and 69.8 (95% CI, 59.0-79.6)% (p=0.340); the 2-year overall survival (OS) rates were 64.1 (95%CI, 48.0-78.6)% and 71.8 (95%CI, 60.5-81.9)% (p=0.107); the 2-year relapse incidence (RI) rates were 9.3 (95%CI, 3.7-23.7)% and 11.5 (95%CI, 6.4-20.7)% (p=0.873); and the 2-year non-relapsed mortality (NRM) rates were 28.3 (95% CI, 16.9-47.4)% and 21.6 (95% CI, 13.9-33.4)% (p=0.244), for the CD7 CAR-T and non-CAR-T groups, respectively. The incidence of all grades of acute GVHD (aGVHD) 37.2 (95%CI, 25.2-54.9)% vs. 42.1 (95%CI, 33.3-53.3)% did not significantly differ between the CAR-T and non-CAR-T groups. A trend toward an increased rate but no P significance was observed in Grade 3-4 aGVHD incidence of 20.93 (95%CI, 11.7-37.4)% vs. 9.5 (95%CI, 5.1-17.6)% (p=0.139). One-year incidences of moderate to severe chronic GVHD (cGVHD) were 12.2 (95%CI, 5.4-28.0)% and 18.0 (95%CI, 11.5-28.0)% (p=0.357) in the CD7CAR-T and non-CAR-T groups, respectively (Table 2). No statistically significant differences were detected in the occurrences of transplant-associated thrombotic microangiopathy (TA-TMA), CMV, EBV, and HHV-6 infections between the two groups. Upon analyzing, we found that r/r patients who received allo-HSCT after achieving remission with NS7 CAR-T had a similar OS to CR1 patients (Fig. 2). Conclusions Our parallel study showed that T-ALL/LBL patients, who achieved CR via CD7 CAR-T therapy followed by a consolidation allo-HSCT, had similar favorable OS and LFS compared to patients who underwent allo-HSCT in the CR1 state induced by chemotherapy. This was achieved without increasing the incidence of GVHD, infections, or TA-TMA.

Pregnant Women with Severe Factor VII Deficiency Undergoing Cesarean Section Managed with a Short-Term Regimen of Recombinant Factor VIIa

Pregnant Women with Severe Factor VII Deficiency Undergoing Cesarean Section Managed with a Short-Term Regimen of Recombinant Factor VIIa

Single-Institution Prospective Evaluation of Moderately Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Integrated Boost With or Without Lymphatic Drainage Irradiation After Breast-Conserving Surgery

We report treatment outcomes for patients who received adjuvant moderate hypofractionated whole-breast radiation therapy with simultaneous integrated boost (SIB-mhWBRT) after breast-conserving surgery. SIB-mhWBRT for patients with breast cancer was introduced in our department in July 2017. This prospective evaluation includes 424 consecutive patients treated with SIB-mhWBRT for stage I-III invasive breast cancer (n=391) and/or ductal carcinoma in situ (n=33) until December 2021. SIB-mhWBRT was applied with 40 Gy in 15 daily fractions over 3 weeks according to the START B trial, with an SIB dose to the tumor bed of 48 Gy according to Radiation Therapy Oncology Group 1005/UK-IMPORT-HIGH, delivered as 3-dinemsional conformal radiation therapy (RT; n=402), intensity modulated RT (n=4), or volumetric modulated arc therapy (n=18). The mean patient age was 60 years (range, 27-88). Since May 2018, patients with indications for lymphatic pathway RT were included (n=62). Baseline parameters and follow-up data were recorded and reported, including objective assessment of treatment-related outcomes and subjective patient-reported outcome measures (PROMs). Mean/median follow-up was 29/33 months (range, 2-60). Acute toxicity grade 0, 1, 2, and 3 was observed in 25.0%, 61.4%, 13.3%, and 0%, respectively, at the completion of RT. Data of 281, 266, 243, 172, and 58 patients were available for 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Grade 2 late effects were identified in 8.5%, 6.0%, 4.9%, 2.2%, and 10.2% and grade 3 in 2.8%, 1.1%, 1.2%, 0%, and 0% of patients at 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Medical treatment of breast edema was the only grade 3 late effect observed. PROM cosmesis results were evaluated as excellent-good, fair, and poor in 97.2%, 2.5%, and 0.4%; 96.5%, 3.1%, and 0.4%; 97.4%, 2.2%, and 0.4%; 97.5%, 2.5%, and 0%; and 96.5%, 3.5%, and 0.0% at 6 months and 1, 2, 3, and 4 years post-RT, respectively. For all patients, the 3-year overall, cancer-specific, and disease-free survival rates were 98.2%, 99.1%, and 95.9%, respectively. Three-year risk of any locoregional recurrence was 0.6%. No mortality or relapse was observed in patients with ductal carcinoma in situ. SIB-mhWBRT demonstrated very favorable side effect profiles and cosmesis/PROMs. Three-year results demonstrate excellent locoregional control. This short-term regimen offers substantial patient comfort and improves institutional efficacy.