Favorable Treatment Outcomes Research Articles

Multidrug-resistant tuberculosis treatment outcomes and associated factors at Yirgalem General Hospital, Sidama Region, South Ethiopia: a retrospective cohort study

BackgroundThe spread of multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to TB control efforts. This study evaluated the treatment outcomes and associated factors among patients receiving treatment for MDR-TB in southern Ethiopia.MethodsA retrospective follow-up study covering ten years, from 2014 to 2023, analyzed the records of confirmed cases of pulmonary TB admitted to Yirgalem General Hospital, an MDR-TB treatment initiation center in the Sidama Region. To compare the successful treatment outcomes across the years, a chi-square test of independence was conducted. Bivariate and multivariable logistic regression models were used to identify factors associated with treatment outcomes for MDR-TB.ResultsOut of 276 confirmed MDR-TB cases, 4(1.4%) were diagnosed with resistance to second-line drugs (SLDs). Overall, 138 patients achieved favourable treatment outcomes, resulting in a treatment success rate of 50.0% [95% CI 44.1–55.9%]. Among these 138 patients, 105(76.1%, 95 CI 68.7–83.5%) were cured, while 33(23.9%, 95 CI 16.5–31.3%) completed their treatment. The successful treatment outcomes varied significantly across the years, ranging from 3.6% in 2020 to 90% in 2021. The analysis indicated a statistically significant difference in treatment outcomes when considering data from 2014 to 2023 (χ2 = 44.539, p = 0.001). The proportion of patients with deaths, lost-to-follow-up (LTFU), treatment failures and not evaluated were 7.9% [95% CI 4.8–11.2%], 10.9% [95% CI 7.2–14.6%), 2.2% [95% CI 1.1–3.3%), and 28.9% [95% CI 23.7–34.2%] respectively. Individuals with a positive HIV status had significantly lower odds of a favorable treatment outcome [AOR = 0.628, 95% CI (0.479–0.824), p = 0.018]. Similarly, patients with a BMI of less than 18 are more likely to have unfavorable treatment outcomes compared to those with a BMI of 18 or higher [AOR = 2.353, 95% CI 1.404–3.942, p < 0.001].ConclusionThe study revealed a concerning 1.4% prevalence of additional resistance to SLDs. The 50% rate of unfavorable treatment among MDR-TB cases exceeds the target set by the WHO. A significant number of patients (10.9%) were LTFU, and the 28.9% categorized as ‘not evaluated’ is also concerning. Enhanced strategic interventions are needed to reduce such cases, and factors associated with poor treatment outcomes should receive greater attention. Future prospective studies can further explore the factors influencing improved treatment success.

Patient and provider costs of the new BPaL regimen for drug-resistant tuberculosis treatment in South Africa: A cost-effectiveness analysis.

Drug-resistant (DR) tuberculosis (TB) is typically characterized by resistance to a single or combination of first- and/or second-line anti-TB agents and commonly includes rifampicin-resistant (RR)-TB, multidrug-resistant (MDR)-TB, pre-extensively drug-resistant (pre-XDR)-TB and XDR-TB. Historically, all variations of DR-TB required treatment with second-line drugs which are less effective and more toxic than first-line options, have a longer treatment duration and are more expensive to both patients and providers. The World Health Organization (WHO) now recommends a new second-line 3-drug 6-month all-oral regimen consisting of bedaquiline, pretomanid, and linezolid referred to as BPaL. We estimate patient and provider costs of DR-TB treatment with BPaL compared to the current standard of care in South Africa. In coordination with South Africa's BPaL clinical access programme (CAP) we conducted an economic evaluation of A) patient costs through a cross-sectional patient cost survey and B) provider costs through a bottom-up costing analysis consisting of a retrospective medical record review (patient resource-use) and top-down financial record review (fixed/shared costs such as overhead). Across both costing perspectives, we compare costs of 1) BPaL, to current standard of care options including the 2) 9-11-month standard short oral regimen (SSOR) and 3) 18-21-month standard long oral regimen (SLOR). Eligible patients included those ≥14 years old with confirmed sputum pulmonary RR/MDR-TB, pre-XDR or XDR-TB. All costs are reported in 2022 United States Dollar (US$). A total of 72 patients were enrolled and completed the patient cost survey (41.7% on BPaL, 16.7% on the SSOR and 41.7% on the SLOR). Mean on-treatment patient costs were lowest among those on BPaL ($56.6) and increased four-fold among those on the SSOR ($228.1) and SLOR ($224.7). Direct medical patient costs were negligible across all treatment regimens, while direct non-medical patient and guardian costs for travel, food and nutritional supplementation accounted for the largest proportion of total costs ($54.6, $227.8 and $224.3 for BPaL, the SSOR and SLOR respectively). In assessing provider costs, a total of 112 medical records were reviewed (37.5%, 41.1% and 21.4% on BPaL, the SSOR and SLOR respectively). Total provider costs for producing a favorable treatment outcome (cured/completed treatment) were similar among those on BPaL ($4,948.7 per patient) and the SSOR ($4,905.6 per patient) with costs increasing substantially among those on the SLOR ($8,919.9 per patient). Based on incremental cost-effectiveness ratios (ICERs), at even the lowest willingness to pay (WTP) threshold, treatment with the new BPaL regimen was more cost-effective than current standard of care treatment options (ICER: $311.4 < WTP: $3,341). When using the newly recommended BPaL regimen, cost to patients decreased by 75% compared to current standard of care treatment options in South Africa. Due in part to higher resource-use within the BPaL CAP offsetting the shorter treatment duration, cost of treatment provision through BPaL and the 9-11-month SSOR were similar. However, when considering cost and treatment outcomes, BPaL was more cost-effective than other standard of care regimens currently available for DR-TB in South Africa.

Tamponing in severe liver injuries (two clinical cases)

Favorable outcomes of surgical treatment of two patients with blunt liver damage of IV degree according to E. Moore as part of polytrauma are presented. In conditions of unstable hemodynamics and extremely severe state of the patient, the authors used a method of liver damage tamponing with a single tampon material (cotton surgical sheet) as an initial hemostasis. The applied method of liver damage tamponing helps to achieve a stable initial hemostasis, it does not require a highly-qualified surgical team and can be used in second- and third-level trauma centers.

Targeting Cervical Cancer Stem Cells by Phytochemicals.

Cervical cancer (CaCx) poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide. Despite the emergence of advanced treatment strategies, recurrence remains a bottleneck in favorable treatment outcomes and contributes to poor prognosis. The chemo- or radio-therapy resistance coupled with frequent relapse of more aggressive tumors are some key components that contribute to CaCx-related mortality. The onset of therapy resistance and relapse are attributed to a small subset of, slow-proliferating Cancer Stem Cells (CSC). These CSCs possess the properties of tumorigenesis, self-renewal, and multi-lineage differentiation potential. Because of slow cycling, these cells maintain themselves in a semi-quiescent stage and protect themselves from different anti-proliferative anti-cancer drugs. Keeping in view recent advances in their phenotypic and functional characterization, the feasibility of targeting CSC and associated stem cell signaling bears a strong translational value. The presence of CSC has been reported in CaCx (CCSC) which remains a forefront area of research. However, we have yet to identify clinically useful leads that can target CCSC. There is compelling evidence that phytochemicals, because of their advantages over synthetic anticancer drugs, could emerge as potential therapeutic leads to target these CCSCs. The present article examined the potential of phytochemicals with reported anti-CSC properties and evaluated their future in preclinical and clinical applications against CaCx.

Treatment outcomes among patients with isoniazid mono-resistant tuberculosis in Mumbai, India: A retrospective cohort study

BackgroundTuberculosis (TB) remains a significant cause of mortality globally, with India accounting for 27% of the estimated number of people with TB. Multidrug-resistant TB (MDR-TB) and isoniazid (INH) resistance pose additional challenges to effective treatment. We aimed to describe treatment outcomes of INH mono-resistant TB patients under programmatic conditions in Mumbai, India. MethodsThis retrospective cohort study was conducted at Shatabdi Hospital in Mumbai between 2019–2021.We described the clinical and demographic characteristics, treatment outcomes, and risk factors for unfavourable outcomes among patients with INH mono-resistant TB treated with rifampicin, ethambutol, pyrazinamide, and levofloxacin (LfxREZ) for a duration of 6 months. ResultsAmong 3105 patients with drug-resistant TB initiated on treatment, 217 (7 %) had INH mono-resistant TB. Of these, 54 % (117/217) were female, with a median age of 26 years (interquartile range: 20–40). The majority (88 %; 191/217) presented with pulmonary TB, and most (87 %; 188/217) had favourable treatment outcomes, including treatment completion (52 %; 112/217) and cure (35 %; 76/217). Unfavourable outcomes, including treatment failure (2.3 %; 5/217), loss to follow-up (9.2 %; 20/217), or death (1.8 %; 4/217), were observed in 13 % (29/217) of patients. A total of ten (5 %) patients experienced at least one non-severe adverse drug reaction. Factors associated with unfavourable outcomes included severe thinness (p = 0.019) and male gender (p = 0.012). ConclusionTreating INH mono-resistant patients with LfxREZ resulted in satisfactory outcomes and low toxicity. It is important to rule out drug resistance to INH while determining the treatment regimen.

A case of salvage surgery following chemoradiotherapy and durvalumab for initially unresectable superior sulcus tumor with N3 involvement

BackgroundDurvalumab after chemoradiation (PACIFIC regimen) provides favorable treatment outcomes for unresectable stage III non-small cell lung cancer (NSCLC). The feasibility of salvage surgery after the PACIFIC regimen has been reported in some studies; however, its efficacy remains unclear. We herein present the first case of salvage surgery after the PACIFIC regimen for a superior sulcus tumor with N3 involvement, in which a pathological complete response was achieved.Case presentationA 53-year-old man with a left superior sulcus tumor with N3 (# 1L, #4R) involvement (adenocarcinoma, clinical T3N3M0/IIIC) underwent concurrent chemoradiotherapy (2 cycles of cisplatin plus vinorelbine with 60 Gy radiotherapy) followed by durvalumab treatment for 1 year at a previous hospital. The PACIFIC regimen provided a significant primary tumor shrinkage (diameter 3.1 cm to 0.5 cm) with the disappearance of 18F-fluorodeoxyglucose uptake in all nodes. Six months after the end of the PACIFIC regimen, only the primary tumor showed enlargement (diameter 0.5 cm to 2.0 cm). Accordingly, local tumor recurrence was suspected. Salvage surgery (left upper lobectomy with combined chest wall resection [1st to 4th rib]) was performed. The histological examination revealed no viable tumor cells (ypT0N0M0). At 7 months after salvage surgery, the patient remains alive with no signs of tumor recurrence.ConclusionsThe present case suggests that salvage surgery may be feasible after the PACIFIC regimen for superior sulcus tumors. A long-term follow-up is essential to determine the efficacy of salvage surgery.

Long-Term Evaluation of Allopurinol Effectiveness in the Thai Population: Insights from 10 Years of Real-World Big Data Analysis

Objective: This study aimed to evaluate the effectiveness and safety profile of allopurinol in Songklanagarind hospital, Thailand. Material and Methods: Electronic medical records (EMRs) of patients having undergone allopurinol treatment for gouty arthritis, or other pertinent indications, were retrospectively reviewed. The primary outcome of this study was the longitudinal measurement of uric acid levels. A linear mixed model (LMM) analysis assessed the statistical significance of uric acid reduction across hospital visits. The safety profile regarding allopurinol-related adverse drug reactions was assessed.Results: A total of 11,277 EMRs were extracted, of which 8,801 EMRs were eligible for further analyses. These records pertain to a cohort of 3,219 unique patients whose visits were arranged chronologically from the earliest to the fifth recorded visit. Overall, uric acid level decreased after allopurinol treatment in all patients. Across subsequent visits, the analysis, using LMM, found a significant reduction in uric acid levels (χ²=1465.4, df=4, p-value&lt;0.001), with the early reduction observed as early as the second visit. The incidence of allopurinol-related adverse reactions was 4.37% (385/8801 cases). Conclusion: The current dosing regimen of allopurinol at Songklanagarind Hospital has demonstrated favorable treatment outcomes and continues to be effective. This data provides insights into pharmacological management and its real-world outcomes.

The interplay of knowledge, motivation, and treatment response in medication adherence among patients with chronic myeloid leukemia treated with Imatinib

Chronic Myeloid Leukemia (CML) requires consistent medication adherence to Imatinib (IM) for optimal outcomes, however, adherence to oral chemotherapy is challenging. This observational study explores the relationship between patient knowledge, motivation, and adherence to IM therapy, and their collective impact on clinical outcomes. A prospective, observational study was conducted with 101 CML patients. The 6-Item Morisky Medication Adherence Scale (MMAS-6) was used to assess adherence, motivation, and knowledge levels. The study found that high motivation was significantly associated with lower BCR-ABL expression (p = 0.025). Patients with high knowledge and motivation had a 71% favorable response rate, compared to 0% in those with low knowledge and motivation (p = 0.01). As conclusion both patient motivation and knowledge are crucial for favorable treatment outcomes in CML. High levels of both significantly correlate with better clinical responses. Tailored interventions to enhance patient knowledge and motivation are essential.

Novel Clinical Manifestation and Favorable Treatment Outcome of Cochlear Implant in a Chinese Family With Likely Pathogenic Variant of the P2RX2 Gene.

The rapid development and clinical application of sequencing technologies enable the genetic diagnosis of inherited deafness. P2RX2, as the gene responsible for autosomal dominant non-syndromic deafness-41 (DFNA41), has been proven to be essential for life-long normal hearing and for the protection of noise-induced hearing loss (NIHL). Our present study reports a missense variant in the P2RX2 gene (c.178G > T (p.V60L)), for the second time worldwide, in a five-generation kindred living in Henan, China. Despite carrying the same variant, the affected members in this family appear to present with earlier-onset hearing loss and poorer hearing compared to the original DFNA41 families. In addition, this study supplements some content that was not covered in previous reports. We quantitatively evaluated the pain perception ability of some members using the Pain Vision PS-2100 system, and further found an interesting clinical manifestation, that is, hyperalgesia, in heterozygotes for P2RX2 p.V60L. The cochlear implant (CI) was also provided for the proband of profound deafness, resulting in satisfactory clinical outcomes. Finally, we carried out a systematic review of recently published articles on the P2RX2 gene, which is beneficial for better understanding the role of the P2RX2 gene in the auditory system and the pathogenic mechanisms in sensorineural hearing loss (SNHL).

Ultrasound-Guided Percutaneous Ultrasonic Tenotomy for Refractory Patellar Tendinopathy in High-Level Athletes: A Case Series.

To elucidate the clinical outcomes and return-to-sport status of high-level athletes with refractory patellar tendinopathy treated with ultrasound-guided percutaneous ultrasonic tenotomy (PUT). Case series study. Single orthopaedic clinic. Five cases involving 8 knees from athletes (average age: 22 years, range: 17-30 years) who presented with refractory patellar tendinopathy and underwent PUT between 2022 and 2024. Conservative treatments had previously been attempted without sufficient pain relief or return to sports. All patients underwent ultrasound-guided PUT using the TX-2 device from Tenex Health. Jogging was resumed 1 month after surgery, and a return to competitive sports was permitted as early as 3 months postsurgery. Preoperative and postoperative Victorian Institute of Sport Assessment (VISA) scores and Numerical Rating Scale (NRS) scores for pain. Time to return to full training and competitive sports, and presence of postoperative infection signs. The VISA score significantly improved from a preoperative average of 43.1 to a postoperative average of 77.1 (P = 0.0004). The NRS significantly decreased from a preoperative average of 6.4 to a postoperative average of 2.8 (P = 0.0005). Four cases involving 6 knees fully returned to sports, with an average return time of 3 months and 19 days (range: 3 months to 4 months and 13 days). One case involving 2 knees did not show sufficient pain improvement and the patient could not return to sports. No signs of infection were observed in any case. PUT for refractory patellar tendinopathy in high-level athletes generally results in favorable treatment outcomes and successful return to sports. This study provides novel insights into the effectiveness of PUT for patellar tendinopathy in athletes, highlighting the need for future studies with larger sample sizes to validate these findings and explore factors associated with poor outcomes.

The Performance of Peroral Endoscopic Myotomy in Sigmoid-Type Achalasia

Objective: Sigmoid-type achalasia represents an advanced stage of achalasia characterized by significant dilation and tortuosity of the esophageal lumen. Considering the demonstrated efficacy of peroral endoscopic myotomy (POEM) in treating early-stage achalasia, this procedure may offer an alternative therapeutic approach for sigmoid-type achalasia. This study aimed to assess POEM’s feasibility and short-term efficacy in patients with sigmoid-type achalasia. Materials and Methods: We enrolled 16 consecutive patients with sigmoid-type achalasia (eight with type 1 and eight with type 2). The anticipated outcomes were symptom relief during the 12-month follow-up period (evaluated through a reduction in Eckardt symptom scores), an acceptable incidence of procedure-related adverse events, and a decrease in esophageal diameter and barium height. Results: POEM was successfully performed in all cases, with a median operative time of 118.50 minutes (range: 52–206 minutes). No serious complications associated with POEM were observed. During the 12-month follow-up period, the median Eckardt symptom score decreased from 6 (2-10) preoperatively to 1 (0-3) (P = 0.008). Complications were mucosal injuries (31.25% of cases), pneumoperitoneum (12.5%), and minor bleeding (6.25%), although no interventions were needed. Conclusion: POEM procedure has exhibited favorable treatment outcomes, showcasing a high clinical success rate in addressing sigmoid-type achalasia. Despite the occurrence of acceptable adverse events, the procedure remains a viable alternative treatment or bridging therapy for sigmoid-type achalasia. Nonetheless, it is crucial to acknowledge that this procedure presents greater challenges in comparison to the treatment of typical achalasia.

The expression of programmed cell death ligand 1 (PD-L1) involves in the clinicopathologic characteristics and prognostic implications of testicular germ cell tumor (TGCT): a systematic review and meta-analysis.

Testicular germ cell tumor (TGCT) is a type of tumor with relatively lower incidence but being more prevalent in young men. The expression of programmed cell death ligand 1 (PD-L1) serves as a potential biomarker for predicting the survival outcomes of other tumors. Some studies discovered higher prevalence of PD-L1 in TGCT patients who achieved favorable treatment outcomes, while other studies showed lower or absent expression of PD-L1 in TGCT with the better prognosis as well. Therefore, in order to address this controversy and clarify the association between the expression of PD-L1 and pathological features and prognosis of TGCT, this meta-analysis was conducted. A comprehensive literature search was performed using following search terms: "testis", "testicle", "testicular", "cancer", "carcinoma", "tumor", "neoplasm", "programmed cell death ligand 1", "programmed death ligand 1", "PD-L1", "PDL1", "B7 homolog 1", "B7-H1", "B7H1" and "CD274". Relevant studies were retrieved according to the inclusion criteria from reputable databases including PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI). These studies investigated the expression of PD-L1 in both tumor cells and tumor infiltrating immune cells (TIICs) in TGCT. The overall proportion of PD-L1 positivity was assessed using R programming. Pooled hazard ratio (HR) and odds ratio (OR) with corresponding 95% confidence interval (CI) were calculated using Revman software to evaluate the involvement of PD-L1 expression in TGCT. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality assessment of included studies. Sensitivity analysis and publication bias evaluation were subsequently performed. A total of eight eligible studies compromising 1,589 patients diagnosed with TGCT were finally included in this study. PD-L1 positivity was detected in 31% and 41% of TGCT patients' tumor cells and TIICs, respectively. The pooled data demonstrated a significant association between elevated PD-L1 expression levels in TIICs and a favorable prognosis characterized by the reduced disease progression and relapse events (HR =0.21, 95% CI: 0.13-0.33). Furthermore, PD-L1+ TIICs exhibited higher prevalence rates in seminoma (OR =2.11, 95% CI: 1.57-2.84) and embryonal carcinoma (OR =6.23, 95% CI: 2.42-16.02) patients. Notably, PD-L1 expression in TIICs displayed a tendency to increase in TGCT patients with lower stages or without lymph node metastasis. PD-L1 expression was observed in choriocarcinoma tumor cells, while yolk sac tumor and teratoma tumor cells exhibited lower or absent expression of PD-L1. Conversely, PD-L1 expression in TIICs was associated with seminoma and embryonal carcinoma, which was more commonly observed in TGCT patients with lower stages and better prognosis, thereby providing a theoretical foundation for the application of immunotherapy in relapsed/refractory TGCT patients.

Clinicopathological features and treatment outcome of juvenile idiopathic inflammatory myopathies with anti-melanoma differentiation associated gene 5 antibodies: A case series study.

To characterize the clinicopathological features and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIM) with anti-melanoma differentiation associated gene 5 (MDA5) antibodies in a Chinese cohort. Anti-MDA5 antibody was detected by immunodot assay and indirect immunofluorescence assay on HEK293 cells in a series of Chinese JIIM cohort between 2005 and 2022. The clinical features, histological findings, and treatment outcomes of these anti-MDA5-antibody-positive patients were summarized. Of 59 JIIM patients, 3 (5.08%) were found to be anti-MDA5-antibody-positive. The frequency of anti-MDA5 antibody did not show significant difference between adult idiopathic inflammatory myopathies and JIIM cohorts (P = .720). The disease duration in patients with anti-MDA5 antibody was 2.83 ± 1.04 months. All 3 patients had typical skin lesions including Gottron sign and heliotrope rash, while interstitial lung disease and arthritis was only found in 1 patient. All 3 patients showed normal creatine kinase levels. On muscle biopsy, diffuse major histocompatibility complex class-I expression was seen in 3 patients and myxovirus-resistance protein A expression was found in 2 patients. All patients received long-term follow-up (6.42 ± 4.01 years). They were all drug-free and showed favorable treatment outcome with prednisone and additional immunosuppressant. Our study indicates that anti-MDA5 antibodies may not be common in Chinese JIIM. Anti-MDA5-positive JIIMs are characterized by typical skin lesions of dermatomyositis, normal CK levels, and increased major histocompatibility complex class-I expression. JIIMs with anti-MDA5 generally have good response to immunotherapies.

Mechanism of action and selection of endoscopic bariatric therapies for treatment of obesity.

Endoscopic bariatric therapies (EBTs) are minimally invasive and safe procedures with favorable weight loss outcomes in obesity treatment. We aimed to present the weight loss mechanism of action of EBTs and an individualized selection method for patients with obesity. We searched PubMed, Medline, Scopus, Embase, and Google Scholar databases for studies on the topic from databases inception to July 1, 2023, written in English. We focused on EBTs potential mechanism of action to induce weight loss. We also present an expert opinion on a novel selection of EBTs based on their mechanism of action. EBTs can result in weight loss through variable mechanisms of action. They can induce earlier satiation, delay gastric emptying, restrict the accommodative response of the stomach, decrease caloric absorption, and alter the secretion of gastrointestinal hormones. Selecting EBTs may be guided through their mechanism of action by which patients with abnormal satiation may benefit more from tissue apposition devices and aspiration therapy while patients with fast gastric emptying may be better candidates for intragastric devices, endoscopic anastomosis devices, and duodenal mucosal resurfacing. Consequently, the selection of EBTs should be guided by the mechanism of action which is specific to each type of therapy.

Genomic landscape of early-stage prostate adenocarcinoma in Mexican patients: an exploratory study

BackgroundHealth disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients.MethodsParaffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants.ResultsPatients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA’s. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified.ConclusionsThis pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.

PARK2 as a susceptibility factor for nontuberculous mycobacterial pulmonary disease

BackgroundThe genetic signatures associated with the susceptibility to nontuberculous mycobacterial pulmonary disease (NTM-PD) are still unknown. In this study, we performed RNA sequencing to explore gene expression profiles and represent characteristic factor in NTM-PD.MethodsPeripheral blood samples were collected from patients with NTM-PD and healthy individuals (controls). Differentially expressed genes (DEGs) were identified by RNA sequencing and subjected to functional enrichment and immune cell deconvolution analyses.ResultsWe enrolled 48 participants, including 26 patients with NTM-PD (median age, 58.0 years; 84.6% female), and 22 healthy controls (median age, 58.5 years; 90.9% female). We identified 21 upregulated and 44 downregulated DEGs in the NTM-PD group compared to those in the control group. NTM infection did not have a significant impact on gene expression in the NTM-PD group compared to the control group, and there were no differences in the proportion of immune cells. However, through gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analysis, we discovered that PARK2 is a key factor associated with NTM-PD. The PARK2 gene, which is linked to the ubiquitination pathway, was downregulated in the NTM-PD group (fold change, − 1.314, P = 0.047). The expression levels of PARK2 remained unaltered after favorable treatment outcomes, suggesting that the gene is associated with host susceptibility rather than with the outcomes of infection or inflammation. The area under the receiver operating characteristic curve for the PARK2 gene diagnosing NTM-PD was 0.813 (95% confidence interval, 0.694–0.932).ConclusionWe identified the genetic signatures associated with NTM-PD in a cohort of Korean patients. The PARK2 gene presents as a potential susceptibility factor in NTM-PD .

The implications of incorporating nutritional supplements into the treatment regimen for children aged 5-12 years with Visceral Leishmaniasis in Baringo and West Pokot counties in Kenya.

Purpose: The purpose of this article is to inform the Ministry of Health Management and all stakeholders in Kenya, the importance of the intervention, fills gaps, and provides guidance on future research direction to accelerate control and eventually eliminate Leishmaniasis. This will also shed new light on the importance of micronutrients and trace elements and their role in immunology, patient outcomes, and the physiology of Visceral Leishmaniasis (VL). The results of this study will also pave way to explore possibilities to fill the research gaps and address challenges like the resistance and relapse of the infection, in patients with VL. Furthermore, this study may help in developing evidence-based strategies related to malnutrition and trace elements, which may be implemented in the eradication program of VL. Materials and Methods: A quasi-experimental study design was conducted in Kenya from January 2022 to March 2022 in 204 VL-infected children aged 5-12 years. Demographic and clinical data were abstracted from questionnaires and lab forms. Descriptive and inferential analyses were conducted to determine the effect of the intervention on VL outcomes among the study children. Variables with a P-value &lt; 0.05 were considered statistically significant. A total of 204 VL study participants, 102 in each intervention and comparison group were included in this study. Baseline characteristics of the study participants were taken and recorded. The treatment and intervention were started and the trend of BMI, body temperature, vitamins A, B12, C, and D together with minerals Zinc, iron, and iodine levels were monitored weekly for four weeks to determine their effect on the treatment outcomes. Findings: The results showed that the outcome of administering the micronutrients is significant at 5% level, indicating that the intervention has a favorable effect. The micronutrients increased their levels in the body by increasing BMI, reducing spleen size, and controlling the body temperature of the study participants. In conclusion, the intervention accelerated the recovery from VL. Implications to Theory, Practice and Policy: This study was informed by the previous researchers' outputs (Mashayekhi Goyonlo V, 2020) indicating that administering the anti-leishmaniasis treatment alone will not yield a favorable treatment outcome in Visceral Leishmaniasis patients and also a study by Nweze JA, Nweze EI (2019) which indicated that malnourished patients with VL had an unfavorable outcome, which was recurrence in 21.4% and also that serum micronutrients levels favor good treatment outcome in Visceral Leishmaniasis. It is therefore important to note that Baringo and West-Pokot Counties, where the present study was conducted, are the Counties in Kenya with the highest percentage of VL patients. The study’s outcomes highlight the potential benefits of micronutrients to improve treatment outcomes in this regard, we recommend that the MOH should encourage the integration of micronutrients with the VL treatment in Baringo and West Pokot Counties. This research provides this new insight indicating that micronutrients affect the nutritional status and the treatment outcomes of VL by controlling body temperature, improving BMI, decreasing spleen size, negative VL tests, and therefore there is need to incorporate micronutrients to the treatment of children with VL. This study also raises several questions that warrant further investigation, such as the research on all the other micronutrients that were not analyzed in this study.

Effect of short-term 10 Hz repeated transcranial magnetic stimulation on postural control ability in patients with mild hemiparesis in acute ischemic stroke: a single-blinded randomized controlled trial.

Previous studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can improve postural control in subacute and chronic ischemic stroke, but further research is needed to investigate the effect of rTMS on acute ischemic stroke. We compared the therapeutic effects of rTMS plus conventional rehabilitation and conventional rehabilitation on postural control in patients with mild hemiparesis in acute ischemic stroke. Eighty-six patients with acute ischemic stroke were randomly assigned to either the experimental group or the control group within 1-7 days of onset. Patients in both groups received conventional rehabilitation for 2 weeks. Patients in the experimental group received rTMS treatments lasting for 2 weeks. Before and after the 2-week treatment, patients were assessed based on the Timed up and Go (TUG) test, Dual-Task Walking (DTW) test, Functional Ambulation Category (FAC), Tinetti Performance Oriented Mobility Assessment (POMA), gait kinematic parameters, Barthel Index (BI), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and National Institutes of Health Stroke Scale (NIHSS). Additionally, TUG and single-task gait velocity were assessed at 2 months after the start of treatment, and independent walking recovery was also followed up. After 2 weeks of treatment, compared to conventional rehabilitation, participants who underwent rTMS treatment plus conventional rehabilitation exhibited notable enhancements in TUG, FAC, POMA, and some gait parameters [single-task gait velocity, gait stride length, gait cadence, gait cycle]. Changes in cognitive function partially mediated the improvement in single-task gait velocity and gait stride length by rTMS plus conventional rehabilitation. Generalized Estimating Equation (GEE) analysis showed that the trend of improvement in single-task gait velocity over time was more pronounced in the experimental group than in the control group. The results of the Kaplan-Meier curve indicated a median gait recovery time of 90 days for patients in the experimental group and 100 days for the control group. Multifactorial Cox regression analyses showed that rTMS plus conventional rehabilitation promoted faster recovery of independent walking compared with conventional rehabilitation. rTMS plus conventional rehabilitation outperformed conventional rehabilitation in improving postural control in patients with acute ischemic stroke. Improvements in cognitive function may serve as a mediating factor in the favorable treatment outcome of rTMS plus conventional rehabilitation for improving postural control. https://www.chictr.org.cn, identifier ChiCTR1900026225.

Effectiveness of acupuncture in treating patients with pain and mental health concerns: the results of the Alberta Complementary Health Integration Project.

This study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above). Over 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients' specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively. Analysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life. Integrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

Effectiveness of food supplement on treatment outcomes and quality of life in pulmonary tuberculosis: Phased implementation approach.

By encouraging treatment adherence and lowering mortality, dietary supplements can serve as adjuvant therapy for the success of medical interventions. We determined the effect of locally accessible food supplements on treatment outcomes, and health-related quality of life in patients with pulmonary tuberculosis initiating anti-tuberculosis treatment (ATT) in Odisha, India. Between September 2017 and December 2018, implementation research in patients with newly diagnosed sputum smear-positive pulmonary tuberculosis initiating ATT in five districts of the tribal belt of Odisha, offered food supplements along with ATT in a phased manner. Clinical symptoms, anthropometry, sputum for M. tuberculosis (M. tb), health-related quality of life and return to normal function were assessed periodically, and favourable treatment outcome (cure or treatment completed) was measured at the end of treatment. The effect of the food supplement on unfavorable outcomes (treatment failure, death, or lost-to-follow-up) was modelled using mixed-effects Poisson regression to determine the risk factors. Among the 761 participants enrolled, 614 participants received the food supplement and 147 did not receive the food supplement. Among the 614 participants in the supplement group, 537 (87%) had a favorable outcome and among the 147 participants in the no-supplement group, 113 (77%) had a favorable outcome (p = 0.0017). Higher age (>55 years) [aRR = 2.1(95% CI: 1.1-3.8)], male gender [aRR = 1.7(95% CI: 1.2-2.9)], and smear grading ≥2+ [aRR = 1.5 (95% CI: 1.1-2.2)] were associated with unfavorable treatment outcomes. Nutritional status, quality of life and lung health showed significant improvement from baseline in the supplement group. Improvement in the nutritional status of the patient can be considered a predictor of treatment success rates. Early food supplementation has a positive impact on the nutritional status.