Physiological impact of Tabata exercise on cardiometabolic and cardiorespiratory parameters in transgender people of Multan.

Objective: To investigate factors directly related to cardiometabolic and cardiorespiratory fitness in transgender people. METHODS: The cross-sectional, experimental study was conducted at the Government Girls Comprehensive Higher Secondary School, Multan, Pakistan, from January to February 2023, after approval from the ethics review committee of the Muhammad Institute of Medical and Allied Sciences, Multan, and comprised transgender people aged 17-28 years. Data was collected using the physical activity readiness questionnaire. All the participants were subjected to Tabata sessions for 4 weeks. Standard cardiometabolic and cardiorespiratory fitness values were noted at baseline and post-intervention. Data was analysed using SPSS 23. RESULTS: Of the 44 participants, 26(59%) were trans-men, 18(40.9%) were trans-women, 16(36.3%) were aged 17-19 years, and 10(22.7%) had other transgender individuals in their families. Cardiorespiratory and cardiometabolic parameters showed significant improvement post-intervention compared to baseline values (p<0.05). Conclusion: Tabata exercises were found to be useful in maintaining cardiorespiratory and cardiometabolic parameters as well in increasing the participants' motor performance.

Association of body mass index, cardiorespiratory fitness, and their correlates among female physical therapy students in Multan.

OBJECTIVE: To explore the correlates directly associated with body mass index and cardiorespiratory fitness among undergraduate female physiotherapists. METHODS: The cross-sectional study was conducted from October to December 2020 at Ali-Ul-Murtaza Department of Rehabilitation Sciences, Muhammad Institute of Medical and Allied Sciences, Multan, Pakistan, and comprised undergraduate female physiotherapists aged17-25 years. The subjects were assessed on the basis of Physical Activity Readiness Questioner, body mass index and standard criteria of cardiorespiratory fitness. Data was analysed using SPSS 20. RESULTS: Of the 334 subjects with a mean age of 20.89±1.66 years, 200(59.88) were overweight and 34(10.17) were underweight. Overall 83(24.9) reported good quality of life, 194(58.1) were satisfied with their general health, and 228(68.3) presented with a history of cardiometabolic disorder. There was a highly significant positive correlation in overweight and negative correlation in underweight subjects (p≤0.05). CONCLUSIONS: The frequency of overweight female physical therapy students was high.

Engaging fathers to improve complementary feeding is acceptable and feasible in the Lake Zone, Tanzania.

In Tanzania, suboptimal complementary feeding practices contribute to high stunting rates. Fathers influence complementary feeding practices, and effective strategies are needed to engage them. The objectives of this research were to examine the acceptability and feasibility of (1) tailored complementary feeding recommendations and (2) engaging fathers in complementary feeding. We conducted trials of improved practices with 50 mothers and 40 fathers with children 6-18 months. At visit 1, mothers reported current feeding practices and fathers participated in focus group discussions. At visit 2, mothers and fathers received individual, tailored counselling and chose new practices to try. After 2 weeks, at visit 3, parents were interviewed individually about their experiences. Interview transcripts were analysed thematically. The most frequent feeding issues at visit 1 were the need to thicken porridge, increase dietary diversity, replace sugary snacks and drinks and feed responsively. After counselling, most mothers agreed to try practices to improve diets and fathers agreed to provide informational and instrumental support for complementary feeding, but few agreed to try feeding the child. At follow-up, mothers reported improved child feeding and confirmed fathers' reports of increased involvement. Most fathers purchased or provided funds for recommended foods; some helped with domestic tasks or fed children. Many participants reported improved spousal communication and cooperation. Families were able to practice recommendations to feed family foods, but high food costs and seasonal unavailability were challenges. It was feasible and acceptable to engage fathers in complementary feeding, but additional strategies are needed to address economic and environmental barriers.

Top 100 Most Influential Articles in the Field of Myeloid Neoplasms: A Bibliometric Study.

BACKGROUND: Bibliometric analyses are a tool employed by researchers and funding agencies to establish the most important areas of research in a particular field, and to determine which foci need increased research attention. Such analyses have been published in a variety of clinical specialties; however, a detailed literature search showed that no such study has been done for "myeloid neoplasms." In order to bridge this gap, we conducted a citation analysis of the 100 most influential articles on myeloid neoplasms. METHODS: Two independent researchers extracted relevant articles from the Scopus database. These articles were then ranked in descending order of citations and a list of the top 100 original articles was made. A further, more detailed list was created containing significant discriminating characteristics. RESULTS: The top cited articles were published over a period of 47 years, with most of them being published in the 5-year interval of 2001-2005. The citations ranged from 636 to 4,039. The articles originated from 28 different countries. Most of the articles were published in high-impact journals. CONCLUSION: Our analysis sheds light on the quality of work and driving trends, listing the most cited and impactful guideline articles within this field and aiding clinicians.

An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL).

Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression. MPAL typically carries a worse prognosis than either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). Given the rarity of MPAL, there is a lack of prospective trial data to guide therapy; treatment generally relies on ALL-like regimens followed by consolidation chemotherapy or hematopoietic stem cell transplant (HSCT). Here, we review the updated classification, biology, clinical features, and treatment approach to MPAL.

Approach to Richter transformation of chronic lymphocytic leukemia in the era of novel therapies.

Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. About 2-10% of CLL patients develop aggressive histological transformation, most commonly to diffuse large B cell lymphoma (DLBCL), historically called Richter transformation (RT). Clinical features suggestive of RT include elevated LDH and non-specific symptoms such as fever, weight loss, and lymphadenopathy. 18-fluorodeoxyglucose (18-FDG) uptake is increased on PET scan (standardized uptake value max most commonly ≥ 10). PET/CT study can identify optimal site for excisional biopsy, which is the gold standard for RT diagnosis, as well as aid in disease staging and prognostication. In addition to clinical prognostic features such lactate dehydrogenase level, platelet count, and performance status, important predictors of poor outcome in RT are TP53 disruption and clonal relationship of DLBCL to underlying CLL. Chemoimmunotherapy constitutes the standard treatment for RT, followed by stem cell transplant (SCT) in eligible patients. However, the majority of patients do not proceed to allogeneic SCT, either due to inadequate disease control with initial therapy, poor performance status, or lack of donor availability. Overall outcome is dismal. Some novel agents under investigation, particularly PD-1 inhibitors, are showing clinical activity in Phase I and II trials. An ongoing incidence of RT has been noted in studies of previously treated patients receiving targeted therapies such as ibrutinib and venetoclax; the frequency of RT in patients initially treated with novel agents rather than chemoimmunotherapy will be important to determine with longer follow-up. This review focuses on the development, clinicopathologic features, and treatment of RT in the context of novel therapies.

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia.

The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p = 0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p = 0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32-6.35; HR 2.90; p = 0.008), but not event-free survival (EFS; 95% CI 0.62-2.67; HR 1.28; p = 0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01-1.09; HR 1.05; p = 0.009), while both ANC (95% CI 1.00-1.07; HR 1.04; p = 0.04) and peripheral blood blast percentage (95% CI 1.02-1.32; HR 1.16; p = 0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.

Prognosis of patients with intermediate risk IPSS-R myelodysplastic syndrome indicates variable outcomes and need for models beyond IPSS-R.

The International Prognostic Scoring System-Revised (IPSS-R) is one standard for myelodysplastic syndrome (MDS) risk stratification. It divides patients into five categories including an intermediate subset (IPSS-R int-risk). Outcomes and clinical interventions for patients with IPSS-R int-risk are not well defined. We performed an analysis of outcomes of this group of patients. Out of 3167 patients, a total of 298 were identified with IPSS-R int-risk MDS and retrospectively analyzed to assess characteristics affecting outcomes. Cox proportional hazard models for overall survival (OS) were performed to identify statistically significant clinical factors that influence survival. Age of 66 years or greater, peripheral blood blasts of 2% or more, and history of red blood cell (RBC) transfusion were significantly associated with inferior survival. Based on these features, MDS patients with IPSS-R int-risk were classified into two prognostic risk groups for analysis, an int-favorable group and an int-adverse group, and had significantly divergent outcomes. Sequential prognostication was validated using two independent datasets comprising over 700 IPSS-R int-risk patients. The difference in median survival between int-favorable and int-adverse patients was 3.7 years in the test cohort, and 1.8 and 2.0 years in the two validation cohorts. These results confirm significantly variable outcomes of patients with IPSS-R int-risk and need for different prognostic systems.

Comparative outcomes of thrombocytopenic acute leukemic patients with venous thromboembolism at a Comprehensive Cancer Center.

Patients with hematological malignancies often have severe thrombocytopenia, which poses problems when making thrombosis management decisions. A retrospective study was conducted to analyze the clinical outcomes associated with different management options in acute leukemic patients with thrombocytopenia (≤ 50 × 109/L) following an acute venous thromboembolic event. A total of 74 patients were divided into three treatment groups: observation only (n = 30); anticoagulation (n = 23); or inferior vena cava placement (n = 21). Multivariate analysis showed that anticoagulant administration was significantly associated with improved overall survival without an increased rate of clinical relevant bleeding events when compared to other thrombosis management modalities. This study notes that dose adjusted-anticoagulant therapy may offer a safe and clinical advantageous strategy for the treatment and secondary prevention of recurrent venous thrombosis in thrombocytopenic patients with hematologic malignancies.

The role of mesenchymal stem cells in oncology and regenerative medicine.

Mesenchymal stem cells (MSCs) have long been used as therapeutic agents in disease affecting various organ systems. However, MSCs are fast emerging as promising anticancer agents which have the potential to treat a number of different cancer types, including glioblastoma and metastatic breast, ovarian and hepatic carcinoma. The ability of MSC to migrate directly into the tumor microenvironment and to produce IFN-α and -ß makes this possible. However, the possibility of MSC undergoing either malignant transformation or transformation into protumorigenic fibroblasts currently limits their role in clinical use. It is hoped that future research can overcome these limitations and facilitate the use of MSC clinically.

Future prospects of therapeutic clinical trials in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy that is most commonly seen in elderly adults. The response to current therapies to AML is quite variable, and very few new drugs have been recently approved for use in AML. This review aims to discuss the issues with current trial design for AML therapies, including trial end points, patient enrollment, cost of drug discovery and patient heterogeneity. We also discuss the future directions in AML therapeutics, including intensification of conventional therapy and new drug delivery mechanisms; targeted agents, including epigenetic therapies, cell cycle regulators, hypomethylating agents and chimeric antigen receptor T-cell therapy; and detail of the possible agents that may be incorporated into the treatment of AML in the future.

A Rare Case of Primary Myelofibrosis in a 14-Year-Old Patient With Congenital Asplenia.

Primary myelofibrosis (PMF) is rarely diagnosed in children, and in most cases in children younger than 3 years old. Pediatric PMF generally follows a benign course and is usually managed supportively with blood transfusions and prophylactic antibiotics for infections. We present a case of a 17-year-old girl diagnosed with PMF at the age of 14 years. A computed tomography scan performed at the time of an appendectomy showed congenital asplenism. To our knowledge, this is only the third case of myelofibrosis and congenital asplenism to be reported in the literature. Whether asplenism contributed to the development of myelofibrosis is not known.

Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia.

(1) Runt-related transcription factor 1 (RUNX1) mutations in acute myeloid leukemia (AML) are often associated with worse prognosis. We assessed co-occurring mutations, response to therapy, and clinical outcomes in patients with and without mutant RUNX1 (mRUNX1); (2) We analyzed 328 AML patients, including 177 patients younger than 65 years who received intensive chemotherapy and 151 patients >65 years who received hypomethylating agents. RUNX1 and co-existing mutations were identified using next-generation sequencing; (3) RUNX1 mutations were identified in 5.1% of younger patients and 15.9% of older patients, and were significantly associated with increasing age (p = 0.01) as well as intermediate-risk cytogenetics including normal karyotype (p = 0.02) in the elderly cohort, and with lower lactate dehydrogenase (LDH; p = 0.02) and higher platelet count (p = 0.012) overall. Identified co-occurring mutations were primarily ASXL1 mutations in older patients and RAS mutations in younger patients; FLT3-ITD and IDH1/2 co-mutations were also frequent. Younger mRUNX1 AML patients treated with intensive chemotherapy experienced inferior treatment outcomes. In older patients with AML treated with hypomethylating agent (HMA) therapy, response and survival was independent of RUNX1 status. Older mRUNX1 patients with prior myelodysplastic syndrome or myeloproliferative neoplasms (MDS/MPN) had particularly dismal outcome. Future studies should focus on the prognostic implications of RUNX1 mutations relative to other co-occurring mutations, and the potential role of hypomethylating agents for this molecularly-defined group.

Central nervous system relapse in patients with untreated HER2-positive esophageal or gastroesophageal junction adenocarcinoma.

Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs. 1.2%; p = 0.0058) and at any time (8.3% vs. 2.4%; p = 0.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (p = 0.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; p = 0.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases.

LACK OF AN ASSOCIATION BETWEEN BMI AND TSH IN TREATED HYPOTHYROID PATIENTS AND EUTHYROID CONTROLS.

OBJECTIVE: The standard treatment for primary hypothyroidism is replacement with levothyroxine to achieve a thyroid-stimulating hormone (TSH) level within the normal range, (0.45-4.5 mIU/L), which is known to prevent complications including weight gain. While the normal TSH range includes the 95% confidence intervals, it is not known if there is an association between weight and TSH within this interval in treated hypothyroid patients. METHODS: We conducted a retrospective analysis of patients treated within the Cooper Health System from January 1 to August 31, 2014. A sample of 245 treated hypothyroid patients and 162 euthyroid controls were studied. Data collected included age, sex, race/ethnicity, height, weight, levothyroxine dose, and diabetes and smoking history. RESULTS: Hypothyroid and control groups were similar in height, weight, body mass index (BMI), and the number of patients with diabetes. There were more females, Caucasians, and nonsmokers in the hypothyroid group. The average TSH was slightly higher in the treated hypothyroid patients versus nonhypothyroid controls (median 1.87 vs. 1.55, P<.01). There was no significant relationship between TSH and BMI in the treated hypothyroid patients or the euthyroid controls. CONCLUSION: Since no significant relationship was found between BMI and TSH in treated hypothyroidism, there may be no weight reduction benefit gained by adjusting TSH to the lower end of normal range. Patients should be counseled that properly treated hypothyroidism is unlikely to contribute to weight gain. Other treatments such as nutrition and exercise counseling should be offered instead.

Evaluation of polyherbal gel for musculoskeletal injuries in industrial workers.

BACKGROUND: Industrial workers often have musculoskeletal disorders due to the nature of their work. OBJECTIVE: The goal was to investigate the scientific use of polyherbal gel in relieving pain and stiffness due to musculoskeletal injuries and improving activities of daily living (ADLs) in industrial workers. METHODS: A pragmatic, single-blinded, randomized control study divided 200 musculoskeletal injury patients into four parallel groups (n = 50). Groups 1 and 2 were applied polyherbal gel via phonophoresis with therapeutic ultrasound and superficial massage. Groups 3 and 4 received diclofenac diethyl-ammonium 1% gel by phonophoresis and superficial massage. The Global Pain Relief Scale, Numeric Pain Rating Scale (NPRS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to measure pain, stiffness, and ADLs. Data was analyzed using one-way analysis of variance (ANOVA) and paired t-test to compare mean±SD of four independent groups before and after gel application. The confidence interval was 95%, with p < 0.05 considered significant. RESULTS: The results revealed that polyherbal gel reduced pain (NPRS, WOMAC and Global pain relief scales) more efficiently (p≤0.000) when applied with phonophoresis as compared to applied with massage and standard diclofenac (p≤0.005), furthermore, polyherbal gel when applied with phonophoresis showed more efficient results. CONCLUSION: Industrial workers with musculoskeletal injuries benefited from the use of polyherbal gel for pain and inflammation relief. The polyherbal gel is natural, cost-effective, and easy to formulate.

DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.

The autosomal-recessive diphthamide deficiency syndrome presents as intellectual disability with developmental abnormalities, seizures, craniofacial and additional morphological phenotypes. It is caused by reduced activity of proteins that synthesize diphthamide on human translation elongation factor 2. Diphthamide synthesis requires seven proteins (DPH1-DPH7), with clinical deficiency described for DPH1, DPH2 and DPH5. A limited set of variant alleles from syndromic patients has been functionally analyzed, but databases (gnomAD) list additional so far uncharacterized variants in human DPH1 and DPH2. Because DPH enzymes are conserved among eukaryotes, their functionality can be assessed in yeast and mammalian cells. Our experimental assessment of known and uncharacterized DPH1 and DPH2 missense alleles showed that six variants are tolerated despite inter-species conservation. Ten additional human DPH1 (G113R, A114T, H132P, H132R, S136R, C137F, L138P, Y152C, S221P, H240R) and two DPH2 (H105P, C341Y) variants showed reduced functionality and hence are deficiency-susceptibility alleles. Some variants locate close to the active enzyme center and may affect catalysis, while others may impact on enzyme activation. In sum, our study has identified functionally compromised alleles of DPH1 and DPH2 genes that likely cause diphthamide deficiency syndrome.