Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study.

BACKGROUND: Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score. This real-world study compared the effectiveness of switching patients with COPD in England from MITT to once-daily SITT with FF/UMEC/VI by evaluating rates of COPD exacerbation, healthcare resource use (HCRU) and associated direct medical costs. METHODS: Retrospective cohort pre-post study using linked primary care electronic health record and secondary care administrative datasets. Patients diagnosed with COPD at age ≥35 years, with smoking history, linkage to secondary care data and continuous GP registration for 12 months pre-switch and 6 months post-switch to FF/UMEC/VI were included. Index date was the first initiation of an FF/UMEC/VI prescription immediately following MITT use from 15 November 2017 to 30 September 2019. Baseline was 12 months prior to index, with outcomes assessed 6/12 months pre-switch and post-switch, and stratified by prior COPD exacerbation status. RESULTS: We included 2533 patients (mean [SD] age: 71.1 [9.9] years; 52.1% male). In the 6 months post-switch, there were significant decreases in the proportion of patients experiencing ≥1 moderate-to-severe (36.2%-28.9%), moderate only (24.4%-19.8%) and severe only (15.4%-11.8%) COPD exacerbation (each, p<0.0001) compared with the 6 months pre-switch. As demonstrated by rate ratios, there were significant reductions in exacerbation rates of each severity overall (p<0.01) and among patients with prior exacerbations (p<0.0001). In the same period, there were significant decreases in the rate of each COPD-related HCRU and total COPD-related costs (-24.9%; p<0.0001). CONCLUSION: Patients with COPD switching from MITT to once-daily SITT with FF/UMEC/VI in a primary care setting had significantly fewer moderate and severe exacerbations, and lower COPD-related HCRU and costs, in the 6 months post-switch compared with the 6 months pre-switch.

Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Prostate fibroblasts and prostate cancer associated fibroblasts exhibit different metabolic, matrix degradation and PD-L1 expression responses to hypoxia.

Fibroblasts are versatile cells that play a major role in wound healing by synthesizing and remodeling the extracellular matrix (ECM). In cancers, fibroblasts play an expanded role in tumor progression and dissemination, immunosuppression, and metabolic support of cancer cells. In prostate cancer (PCa), fibroblasts have been shown to induce growth and increase metastatic potential. To further understand differences in the functions of human PCa associated fibroblasts (PCAFs) compared to normal prostate fibroblasts (PFs), we investigated the metabolic profile and ECM degradation characteristics of PFs and PCAFs using a magnetic resonance imaging and spectroscopy compatible intact cell perfusion assay. To further understand how PFs and PCAFs respond to hypoxic tumor microenvironments that are often observed in PCa, we characterized the effects of hypoxia on PF and PCAF metabolism, invasion and PD-L1 expression. We found that under normoxia, PCAFs displayed decreased ECM degradation compared to PFs. Under hypoxia, ECM degradation by PFs increased, whereas PCAFs exhibited decreased ECM degradation. Under both normoxia and hypoxia, PCAFs and PFs showed significantly different metabolic profiles. PD-L1 expression was intrinsically higher in PCAFs compared to PFs. Under hypoxia, PD-L1 expression increased in PCAFs but not in PFs. Our data suggest that PCAFs may not directly induce ECM degradation to assist in tumor dissemination, but may instead create an immune suppressive tumor microenvironment that further increases under hypoxic conditions. Our data identify the intrinsic metabolic, ECM degradation and PD-L1 expression differences between PCAFs and PFs under normoxia and hypoxia that may provide novel targets in PCa treatment.

Submental Artery Island Flaps (SAIF) for Oral Cavity Cancer: Surgical Technique and Tertiary Care Experience.

In oral cancer surgeries, oncological outcomes take precious driverseat. But the copassengers like reconstruction, cosmesis, swallowing and speech outcomes deserve equivalent importance. Submental Artery Island Flaps (SAIF) provide an underutilized and extremely versatile option for reconstruction of defects following early stage oral cavity tumour resections. In this prospective observational analysis, we describe the technique, challenges and outcomes of SAIF at our tertiary care institute. Sixteen patients with Stage I and II oral cavity cancers were enrolled between June 2020 to May 2021. Verrucous carcinomas were five and well differentiated carcinomas were 11 patients. After tumour excision and neck dissections, defects were reconstructed with Pedicled submental flaps. Complications and functional outcomes were analyzed over two years. Nineteen percent were ladies and 81% were gentlemen. Median age was 52 years. Tongue tumours formed majority with 56% cases. Largest skin paddle taken was 36 cm2. Flap survival was 88%. There were variations in venous drainage of flaps which have been depicted in case figures. There was no report of orocutaneous fistula. Grade 3-4 speech satisfaction was achieved by 81.2% patients at 6 months. Swallowing was excellent, grade 4-5 for 100% of patients at 6 months. One patient had distant metastasis at 7 months and died. SRLR (Submental flap Recurrences) and trismus were zero percent at two years. The unexplored field of submental flaps can be used for oral cancer reconstructions in a versatile way. Donor site easy closures, no scars on face, early resumption of daily activities and short hospital stay makes it one of the ideal options in early stage oral cavity defects.

Epidemiological and Histopathological Analysis of Head and Neck Cancers in Northern India- A Retrospective Review.

INTRODUCTION: Head and neck malignancies are responsible for 30% of all cancers in India with a dramatic increase in numbers due to widespread tobacco consumption. This study aims to assess the epidemiological and histopathological spectrum of these tumors. MATERIALS AND METHODS: A large retrospective review of 5469 biopsy-proven patients presenting between 2018 and 2022 with head and neck cancers was done. Tumors were analysed for distribution according to sites of presentations, gender, age and histopathological profiles. RESULTS: With a male-to-female ratio of 4.2:1, men constituted 80.80% of the study population. Mean age of presentation in women was 53.5 years, whereas men presented at an earlier age of 47.2 years. Oral cavity was the commonest site involved (59.7% cases) followed by the oropharynx (23.8% cases). Buccal mucosa was the commonest subsite involved with 1112 cases followed by tongue lesions with 1088 cases. Larynx was responsible for 17.04% of cases. All subsites were more commonly affected in men with the highest Male: Female ratio of 8.29:1 seen in larynx. The lowest ratio of 1.02:1 was seen in lesions of the face and scalp. Squamous cell carcinoma (SCC) was the most common histopathological diagnosis encountered in 88.97% of cases followed by basal cell carcinoma which was seen in 2.10% lesions. CONCLUSION: Oral cavity lesions constitute the bulk of head and neck cancer presentations in India. The disease is more prevalent in men overall and men present at a younger age in comparison to women. SCC is the most prominent histopathology encountered in our study.

Risk Factors Associated with a First Exacerbation Among Patients with COPD Classified as GOLD A and B in Routine Clinical Practice in the UK.

Purpose: Risk factors for exacerbations of chronic obstructive pulmonary disease (COPD) have been previously characterized for patients with more severe cases of COPD. It is unclear how the risk of first exacerbation may best be identified in patients with less severe disease. This study investigated risk factors for first exacerbation among English patients with COPD classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A or B. Patients and Methods: A retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) AURUM linked to Hospital Episode Statistics. Patients with COPD aged ≥35 years and classified as GOLD group A or B (2020 criteria) from January 2013-December 2019 were eligible. Patients were required to have 24 months history in CPRD (baseline). Two cohorts were defined: cohort 1 included patients with no severe exacerbations during baseline; cohort 2 included patients with no moderate or severe exacerbations during baseline. Risk factors associated with severe, or combined moderate and severe exacerbation were examined for up to 5 years of follow-up. Results: Overall, 194,948 patients were included in cohort 1 (mean age 66.2 years; 55.2% male), and 148,396 patients in cohort 2 (mean age 66.1 years; 56.6% male). Identified risk factors for exacerbation (and associated 1-year absolute risk of severe, or combined moderate and severe exacerbation, respectively) included: Medical Research Council dyspnea scale score (15.9%/28.4%); COPD Assessment Test score (9.6%/25.3%); GOLD grade of airflow limitation (forced expiratory volume in 1 second % predicted; 13.6%/27.5%); and lung cancer (8.1%/23.6%). After adjustment for risk factors, these factors remained independently associated with severe exacerbation at 1, 3, and 5 years of follow-up. Conclusion: The identified risk factors may aid physicians in the early recognition of patients with COPD classified as GOLD group A or B at risk of first exacerbation.

Can a diagnosis of Leiomyosarcoma soft palate be missed in the era of commoner oral carcinomas? - Rare case report and review of literature.

Leiomyosarcomas (LMSs) of the head and neck are an extremely rare entity. Of all smooth muscle tumors, 4%-10% occur in the head and neck and only 0.06% in the oral cavity. Because of its infrequency, it has been associated with both delayed diagnosis and misdiagnosis. Here, we report the clinicopathological findings of a case of primary LMS of the soft palate in a 42-year-old male patient with an emphasis on the judicious use of ancillary diagnostic modalities to arrive at a definitive diagnosis. Intraorally, LMSs present as painless, lobulated, fixed masses of the submucosal tissues in middle-aged or older individuals. The treatment modalities and lymph nodal dissection criteria are dissimilar to more common oral carcinomas. Hence, definitive diagnosis is necessary.

Assessment of Operative Time for Lip and Oral Cancers: A Tool to Improve Operative Room Efficiency.

Operation theatre (OT) time utilisation rates can be improved with an assessment of the procedure time that will result in effective scheduling of cases. Our study is the first of its kind to audit the amount of OT time required for a particular surgery in lip and oral cavity cancers, depending on the various components of this complex procedure. This prospective cross-sectional study, based on an operative room database of 323 OT sessions, was conducted in the Department of Surgical Oncology at a tertiary care centre on lip and oral cancer patients from January 1st, 2019 to December 31st, 2020. Various components of the surgery, like the primary site, operating surgeon, type of neck dissection, bone resection, and reconstructive procedure, were noted. The time of entry and exit of the patient from the OT was noted. Operative time and OT time utilisation rates were calculated. SPSS 21.0 statistical tool; Students 'T', ANOVA and Games-Howell tests were applied. In 323 OT sessions, while 303 surgeries were done for primary cases (93.8%), the remaining 20 cases were for recurrent cases (6.2%). Buccal mucosa and the floor of the mouth were the most and least common sites, respectively. The mean OT time was 212.42 ± 73.83 min, the maximum being the primary at alveolus. The mean OT late start time was 70.03 ± 23.41 min and the mean OT runover time was 37.62 ± 43.53 min. The mean time varied significantly with the type of neck dissection, bone resection, and reconstructive surgery done and the operating surgeon. The mean OT time was highest for free flap reconstructive surgery (328.71 ± 62.02 min), but it didn't vary with its type. Considering only the lip and oral cancer surgeries, the OT time utilisation rate was 57.1%. Assessment and quantification of the operative duration of lip and oral cancer surgeries will help in accurate prediction of surgical duration, better OT list planning, and thus improved OT time utilisation rate. Our research not only provides data on the historical mean of procedures, but it may also encourage other centres to adopt our quantitative approach to OT scheduling.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

INTRODUCTION: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. METHODS: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75 years in COPD with initiation of long-acting anti-muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65 years of age. RESULTS: Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65 years preserved an additional 469.7 mL or 236.0 mL, 327.5 mL or 203.3 mL, or 213.5 mL or 137.5 mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65 years of age, respectively. CONCLUSIONS: This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Worst Pattern of Invasion as a Predictor of Nodal Metastasis in Early-Stage Oral Squamous Cell Carcinoma.

About one-third of early stage oral cancer patients have occult nodal metastasis. High grade worst pattern of invasion (WPOI) is associated with an increased risk of nodal metastasis and poor prognosis. However, it still remains unanswered whether to perform an elective neck dissection for clinically node-negative disease or not. This study aims to evaluate the role of histological parameters including WPOI in predicting nodal metastasis in early-stage oral cancers. This analytical observational study comprised 100 patients of early-stage, node-negative, oral squamous cell carcinoma, admitted in the Surgical Oncology Department from April, 2018 till the sample size was reached. The socio-demographic data, clinical history, and findings of clinical and radiological examination were noted. The association of nodal metastasis with various histological parameters like tumour size, degree of differentiation, depth of invasion (DOI), WPOI, perineural invasion (PNI), lymphovascular invasion (LVI) and lymphocytic response was determined. SPSS 20.0 statistical tool; student's 't' test and chi-square tests were applied. While the buccal mucosa was the commonest site, the rate of occult metastasis was highest in the tongue. Nodal metastasis was not significantly associated with age, sex, smoking and primary site. While the nodal positivity was not significantly associated with tumour size, pathological stage, DOI, PNI and lymphocytic response, it was associated with LVI, degree of differentiation and WPOI. Increasing WPOI grade correlated significantly with the nodal stage, LVI and PNI, but not with DOI. WPOI is not only a significant predictor of occult nodal metastasis but can also be a novel therapeutic tool in the management of early-stage oral cancers. In patients with an aggressive WPOI pattern or other high-risk histological parameters, the neck can be addressed with either elective neck dissection or radiotherapy after wide excision of the primary tumor; otherwise, an active surveillance approach can be followed.

An electrochemical impedance aptasensor based on selenomolybdate nanodot/antimonene hybrid for platelet-derived growth factor-BB.

The aim of the present study was to design a unique bioelectrode for the quantitative analysis of a potential cancer biomarker, platelet-derived growth factor-BB (PDGF-BB), which can be used for the early detection of cancer. We report the fabrication of succinic acid-capped selenomolybdate polyoxometalate nanodots, POM (SA), decorated antimonene hybrid film on glassy carbon as a suitable bioelectrode. Antimonene nanosheets, synthesized by the chemical exfoliation of antimony provided a large surface area for the symmetric dispersal of POM (SA) nanodots, resulting in site-specific covalent immobilization of the aptamer, PDGF-BB. A comprehensive electrochemical immunosensing investigation was performed on the electrode for sensing of a target antigen, Ag-PDGF-BB. The sensitivity, selectivity, and reproducibility of the bioelectrode were investigated using a best-fit equivalent circuit model that fitted the impedance response. The bioelectrode showed a linear impedimetric response in a broad range for Ag-PDGF-BB (10 pM to 100 nM in pH 7.4 PB) with a limit of detection of 3.5 pM and sensitivity of 80 Ω cm2 per decade. The response sensitivity of the POM(SA)/antimonene hybrid based bioelectrode toward PDGF-BB was approximately ∼1.8-fold higher than that of the POM(SA) only modified bioelectrode. The dissociation constant of immunoreaction between the aptamer-functionalized bioelectrode and target Ag-PDGF-BB was 76 nM, indicating a high binding affinity between the aptamer PDGF-BB and target Ag-PDGF-BB on the electrode surface.

Cancer insights from magnetic resonance spectroscopy of cells and excised tumors.

Multinuclear ex vivo magnetic resonance spectroscopy (MRS) of cancer cells, xenografts, human cancer tissue, and biofluids is a rapidly expanding field that is providing unique insights into cancer. Starting from the 1970s, the field has continued to evolve as a stand-alone technology or as a complement to in vivo MRS to characterize the metabolome of cancer cells, cancer-associated stromal cells, immune cells, tumors, biofluids and, more recently, changes in the metabolome of organs induced by cancers. Here, we review some of the insights into cancer obtained with ex vivo MRS and provide a perspective of future directions. Ex vivo MRS of cells and tumors provides opportunities to understand the role of metabolism in cancer immune surveillance and immunotherapy. With advances in computational capabilities, the integration of artificial intelligence to identify differences in multinuclear spectral patterns, especially in easily accessible biofluids, is providing exciting advances in detection and monitoring response to treatment. Metabolotheranostics to target cancers and to normalize metabolic changes in organs induced by cancers to prevent cancer-induced morbidity are other areas of future development.

Malignant solitary fibrous tumor of maxilla presenting as proptosis: A case report.

ABSTRACT: Solitary fibrous tumor (SFT) is a fibroblastic mesenchymal neoplasm that rarely metastasizes. SFTs was first described in relation to pleura. However, occurrence of this tumor type has been reported in other sites like peritoneum, liver, adrenal gland, meninges and oral cavity. In head and neck region, oral cavity is the most common site of involvement. Most of the solitary fibrous tumors are benign and present as an asymptomatic slow growing mass. Surgery remains the mainstay of treatment. Hereby, we describe a case of 71-year-old male with malignant solitary fibrous tumor arising from right maxilla invading the right orbit presenting as proptosis.

Characterization of lipomatous tumors with high-resolution 1H MRS at 17.6T: Do benign lipomas, atypical lipomatous tumors and liposarcomas have a distinct metabolic signature?

Background: Distinguishing between some benign lipomas (BLs), atypical lipomatous tumors (ALTs), and dedifferentiated liposarcomas (DDLs) can be challenging due to overlapping magnetic resonance imaging characteristics, and poorly understood molecular mechanisms underlying the malignant transformation of liposarcomas. Purpose: To identify metabolic biomarkers of the lipomatous tumor spectrum by examining human tissue specimens using high-resolution 1H magnetic resonance spectroscopy (MRS). Materials and methods: In this prospective study, human tissue specimens were obtained from participants who underwent surgical resection for radiologically-indeterminate lipomatous tumors between November 2016 and May 2019. Tissue specimens were obtained from normal subcutaneous fat (n=9), BLs (n=10), ALTs (n=7) and DDLs (n=8). Extracts from specimens were examined with high-resolution MRS at 17.6T. Computational modeling of pattern recognition-based cluster analysis was utilized to identify significant differences in metabolic signatures between the lipomatous tumor types. Results: Significant differences between BLs and ALTs were observed for multiple metabolites, including leucine, valine, branched chain amino acids, alanine, acetate, glutamine, and formate. DDLs were distinguished from ALTs by increased glucose and lactate, and increased phosphatidylcholine. Multivariate principal component analysis showed clear clustering identifying distinct metabolic signatures of the tissue types. Conclusion: Metabolic signatures identified in 1H MR spectra of lipomatous tumors provide new insights into malignant progression and metabolic targeting. The metabolic patterns identified provide the foundation of developing noninvasive MRS or PET imaging biomarkers to distinguish between BLs, ALTs, and DDLs.

One-Year Outcomes with Use of Anti-T-Lymphocyte Globulin in Patients Undergoing Kidney Transplantation: Results from a Prospective, Multicentric, Observational Study from India.

INTRODUCTION: Large-scale Indian data on the use of anti-T-lymphocyte globulin (ATLG) (Grafalon®) as induction therapy in kidney transplantation (KT) patients is lacking. The aim of this study was to determine the 1-year patient and graft survival outcomes with the use of ATLG as induction regimen in KT. METHODS: In a prospective, multicentric, observational study, adult patients who underwent ABO-compatible KT and had received ATLG as a part of induction were included in the study. The primary outcome measure was overall survival and death-censored graft survival at 12 months. The primary safety outcome was assessed by development of infectious complications and graft rejection. RESULTS: In total, 359 patients were included in this study. The mean age was 42.77 ± 12.30 years and 83% were male. The average ATLG dose per patient was 6.2 ± 2.2 mg/kg whereas average cumulative dose per patient was 389.6 ± 149.8 mg. The rate of graft dysfunction was 13.4% of patients and 6.7% had biopsy-proven acute rejection (BPAR). There were a total of 12 (3.3%) deaths and one graft loss. Overall survival and death-censored graft survival at 12 months were 96.65% and 99.44%, respectively. The rate of infections was 13.6% with urinary tract infections being most common. CONCLUSION: ATLG at an average dose of 6 mg/kg is an effective and safe induction regimen immunosuppressant for ABO-compatible KT with favourable impact on survival and graft function in Indian patients.

'It's helped me to learn to deal with it': a mixed methods service evaluation of a multicomponent fibromyalgia service.

OBJECTIVES: To evaluate the Royal London Hospital for Integrated Medicine (RLHIM) multicomponent fibromyalgia service. METHODS: Mixed methods approach consisting of the completion of validated quantitative outcome measures (Patient Health Questionnaire-9; Generalised Anxiety Disorder-7; Pain Catastrophising Scale; Patient Self-Efficacy Questionnaire) pre- and post-treatment to explore the impact of treatment; and qualitative focus groups with patients at their follow-up appointments to explore patients' experiences and perspectives on the service. RESULTS: 138 fibromyalgia patients attended the RLHIM group fibromyalgia service during the period of the evaluation. Baseline scores demonstrate that patients were significantly impaired pre-treatment according to all outcome measures. At the end of the course of treatment, scores for all outcome measures showed clinically and statistically significant improvements. These improvements were maintained at both 6- and 9-month follow-up appointments. Qualitative analysis indicated that those participating valued the multicomponent treatment approach, and perceived the service as having a positive impact on their fibromyalgia and overall quality of life, enabling patients to effectively manage their condition. CONCLUSIONS: Patients attending the RLHIM multicomponent fibromyalgia service appear to have demonstrable improvements in presenting symptoms, and quality of life. The findings support a multicomponent approach to the treatment of fibromyalgia.

Outcome of Atypical & Complex Clubfoot Managed by Modified Ponseti Method-A Prospective Study.

Atypical or complex clubfoot constitutes a small number of cases. Due to the difference in complexity of anatomy, standard deformity correction by Ponseti is not effective. Hence a modified Ponseti method was advised which focuses on deformity differences for treatment. We conducted a prospective study to analyze the outcome in atypical or complex clubfoot treated with the modified Ponseti method. All the children of age less than 1 year were included in the study with atypical or complex clubfoot. Every case was treated according to the modified Ponseti method and tenotomy. Pirani scores were measured at pretreatment, each visit, before application of a brace, and at the latest follow-up. Statistical analysis of all continuous and categorical variables was done. A total of 30 patients (47 feet) were included in the study. Mean Pirani score improved from 5.69 at presentation to 0.45 at time of brace application and latest follow-up 0.34 (p < .001). Six patients (9 feet) had a relapse which was managed with recasting. The mean Pirani score of relapse was 0.72, which after correction reduced to 0.11 (p = .008). Six patients had cast-related complications which were managed with conservative treatment. With an increase in popularity of the Ponseti method, a greater number of complex clubfoot cases are seen due to inadequate reduction or slippage of cast or improper cast application techniques. All these need to be identified at an early age. This helps in proper treatment and improves the quality of life as well as foot appearance.

Distribution of Cutaneous Malignancies in Eastern Rajasthan: A Five-Year Study.

Background: Cutaneous malignancies are rare with respect to other malignancies. The distribution of various histologies of these malignancies is not uniform. We aimed to study the distribution of these malignancies and their epidemiological pattern in Eastern Rajasthan with the data collected from various pathology labs in Jaipur. Methods: In this retrospective chart review we analysed the data of 453 patients presenting with histopathologically proven cutaneous malignancies to four major pathology departments and labs in Jaipur, Rajasthan. We recorded the distribution of these histologies according to incidence, age of presentation, gender and site predilection. The data was subsequently analysed using statistical methods. Results: Squamous cell carcinoma (36%)was the most common histology which was closely followed by basal cell carcinoma(31%). Malignant melanoma (13%) was the third most common histology to present. Other less common histologies to present were dermatofibrosarcoma, Kaposi sarcoma, non hidgkin lymphoma etc. The age range varied from 14 to 90 years. The mean age of presentation was 54.3 years. Male had a slight preponderance (1.36 times more than females)overall. Except Bcc, which had a female preponderance. Head and neck(38.41%) was the most common site to be affected overall followed by lower limbs(31.56%). Interpretation: The idea of distribution of these rare malignancies in our part of the country will not only help us in proper surgical management but also in educating the public about the possible causes and the need for early intervention leading to better prognosis.

A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19.

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.

Brain metabolites in cholinergic and glutamatergic pathways are altered by pancreatic cancer cachexia.

BACKGROUND: Cachexia is a major cause of morbidity in pancreatic ductal adenocarcinoma (PDAC) patients. Our purpose was to understand the impact of PDAC-induced cachexia on brain metabolism in PDAC xenograft studies, to gain new insights into the causes of cachexia-induced morbidity. Changes in mouse and human plasma metabolites were characterized to identify underlying causes of brain metabolic changes. METHODS: We quantified metabolites, detected with high-resolution 1 H magnetic resonance spectroscopy, in the brain and plasma of normal mice (n = 10) and mice bearing cachexia (n = 10) or non-cachexia (n = 9) inducing PDAC xenografts as well as in human plasma obtained from normal individuals (n = 24) and from individuals with benign pancreatic disease (n = 20) and PDAC (n = 20). Statistical significance was defined as a P value ≤0.05. RESULTS: The brain metabolic signature of cachexia-inducing PDAC was characterized by a significant depletion of choline of -27% and -21% as well as increases of glutamine of 13% and 9% and formate of 21% and 14%, relative to normal controls and non-cachectic tumour-bearing mice, respectively. Good to moderate correlations with percent weight change were found for choline (r = 0.70), glutamine (r = -0.58), and formate (r = -0.43). Significant choline depletion of -38% and -30%, relative to normal controls and non-cachectic tumour-bearing mice, respectively, detected in the plasma of cachectic mice likely contributed to decreased brain choline in cachectic mice. Similarly, relative to normal controls and patients with benign disease, choline levels in human plasma samples of PDAC patients were significantly lower by -12% and -20% respectively. A comparison of plasma metabolites from PDAC patients with and without weight loss identified significant changes in glutamine metabolism. CONCLUSIONS: Disturbances in metabolites of the choline/cholinergic and glutamine/glutamate/glutamatergic neurotransmitter pathways may contribute to morbidity. Metabolic normalization may provide strategies to reduce morbidity. The human plasma metabolite changes observed may lead to the development of companion diagnostic markers to detect PDAC and PDAC-induced cachexia.