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BACKGROUND: While coronavirus disease 2019 (COVID-19) is no longer a public health emergency, certain patients remain at risk of severe outcomes. To better understand changing risk profiles, we studied the risk factors for patients with and without solid organ transplantation (SOT) through the various waves of the pandemic. METHODS: Using the National COVID Cohort Collaborative we studied a cohort of adult patients testing positive for COVID-19 between January 1, 2020, and May 2, 2022. We separated the data into waves of COVID-19 as defined by the Centers for Disease Control. In our primary outcome, we used multivariable survival analysis to look at various risk factors for hospitalization in those with and without SOT. RESULTS: A total of 3,570,032 patients were captured. We found an overall risk attenuation of adverse COVID-19-associated outcomes over time. In both non-SOT and SOT populations, diabetes, chronic kidney disease, and congestive heart failure were risk factors for hospitalization. For SOT specifically, longer time periods between transplant and COVID-19 were protective and age was a risk factor. Notably, asthma was not a risk factor for major adverse renal cardiovascular events, hospitalization, or mortality in either group. CONCLUSIONS: Our study provides a longitudinal view of the risks associated with adverse COVID-related outcomes amongst SOT and non-SOT patients, and how these risk factors evolved over time. Our work will help inform providers and policymakers to better target high-risk patients.
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Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-ß. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-ß, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.
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Molecular sub-characterization of triple-negative breast cancer (TNBC) has great therapeutic and possibly prognostic implications. The primary aim of this study was to investigate the incidence of luminal androgen receptor (LAR) subtype of TNBC and secondary aims were sub-categorization and clinico-pathologic correlation of LAR breast cancers. Retrospective study (January 2008 and 31st of December 2018) consisting of 157 TNBC patients. Androgen receptor (AR) expression was measured by immunohistochemical analysis. One percent cutoff was set as a positive expression. Sub-categorization was done on the basis of EGFR (> 15% of tumor cells) and Ki-67 expression (low- < 11%, intermediate- 11-20%, and high- > 21%). AR expression was correlated with various clinico-pathologic features and outcomes of the patients. The incidence of AR expression in TNBC was 24.8%. Considering different thresholds of > 5%, > 10%, and > 20% immunostaining, the incidence of AR positivity was 18.4, 15.2, and 11.5% respectively. The incidence of Ki-67 (p = 0.89) and EGFR (p = 0.643) expression did not differ significantly in AR-positive and -negative TNBC. Based on EGFR expression 19, 67 and 14% patients were categorized as low, intermediate, and high risk respectively. Low-risk (p ≤ 0.001) and low-grade (p = 0.014) tumors were more likely to have > 10% AR expression. Clinico-pathological profile, response to neoadjuvant chemotherapy, disease-free survival (p = 0.458), and overall survival (p = 0.806) did not significantly differ between AR expressing and negative TNBC. On multivariate analysis, only tumor staging was a significant predictor of survival (p = 0.012) and AR expression of > 10% revealed a trend towards improved survival (p = 0.07). When considering only AR-positive TNBC, AR expression of > 10% (p = 0.038), distant metastases (p = 0.003), and EGFR status (p = 0.024) were significantly associated with survival. AR expression does not seem to very strongly correlate with prognosis in TNBC and further studies could focus more on its predictive role in deciding anti-androgen therapy.
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BACKGROUND: Aspergillus flavus is an important agricultural and food safety threat due to its production of carcinogenic aflatoxins. It has high level of genetic diversity that is adapted to various environments. Recently, we reported two reference genomes of A. flavus isolates, AF13 (MAT1-2 and highly aflatoxigenic isolate) and NRRL3357 (MAT1-1 and moderate aflatoxin producer). Where, an insertion of 310 kb in AF13 included an aflatoxin producing gene bZIP transcription factor, named atfC. Observations of significant genomic variants between these isolates of contrasting phenotypes prompted an investigation into variation among other agricultural isolates of A. flavus with the goal of discovering novel genes potentially associated with aflatoxin production regulation. Present study was designed with three main objectives: (1) collection of large number of A. flavus isolates from diverse sources including maize plants and field soils; (2) whole genome sequencing of collected isolates and development of a pangenome; and (3) pangenome-wide association study (Pan-GWAS) to identify novel secondary metabolite cluster genes. RESULTS: Pangenome analysis of 346 A. flavus isolates identified a total of 17,855 unique orthologous gene clusters, with mere 41% (7,315) core genes and 59% (10,540) accessory genes indicating accumulation of high genomic diversity during domestication. 5,994 orthologous gene clusters in accessory genome not annotated in either the A. flavus AF13 or NRRL3357 reference genomes. Pan-genome wide association analysis of the genomic variations identified 391 significant associated pan-genes associated with aflatoxin production. Interestingly, most of the significantly associated pan-genes (94%; 369 associations) belonged to accessory genome indicating that genome expansion has resulted in the incorporation of new genes associated with aflatoxin and other secondary metabolites. CONCLUSION: In summary, this study provides complete pangenome framework for the species of Aspergillus flavus along with associated genes for pathogen survival and aflatoxin production. The large accessory genome indicated large genome diversity in the species A. flavus, however AflaPan is a closed pangenome represents optimum diversity of species A. flavus. Most importantly, the newly identified aflatoxin producing gene clusters will be a new source for seeking aflatoxin mitigation strategies and needs new attention in research.
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Aflatoxinas , Aspergillus flavus , Genoma Fúngico , Familia de Multigenes , Metabolismo Secundario , Aspergillus flavus/genética , Aspergillus flavus/metabolismo , Aflatoxinas/genética , Aflatoxinas/metabolismo , Metabolismo Secundario/genética , Zea mays/microbiología , Zea mays/genética , Estudio de Asociación del Genoma Completo , Genes Fúngicos , Secuenciación Completa del Genoma , Variación GenéticaRESUMEN
African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n=58) and low (n=60) TAC troughs (N=515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12mg, respectively. Of 34,542 identified variants across 99 genes, 1,406 variants were suggestively associated with TAC troughs in univariate models (p-value <0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.
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BACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.
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Neoplasias de la Mama , Fluoresceína , Metástasis Linfática , Biopsia del Ganglio Linfático Centinela , Humanos , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Femenino , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Ganglio Linfático Centinela/patología , Axila , Biopsia Guiada por Imagen/métodosRESUMEN
Subgenome dominance has been reported in diverse allopolyploid species, where genes from one subgenome are preferentially retained and are more highly expressed than those from other subgenome(s). However, the molecular mechanisms responsible for subgenome dominance remain poorly understood. Here, we develop genome-wide map of accessible chromatin regions (ACRs) in cultivated strawberry (2n = 8x = 56, with A, B, C, D subgenomes). Each ACR is identified as an MNase hypersensitive site (MHS). We discover that the dominant subgenome A contains a greater number of total MHSs and MHS per gene than the submissive B/C/D subgenomes. Subgenome A suffers fewer losses of MHS-related DNA sequences and fewer MHS fragmentations caused by insertions of transposable elements. We also discover that genes and MHSs related to stress response have been preferentially retained in subgenome A. We conclude that preservation of genes and their cognate ACRs, especially those related to stress responses, play a major role in the establishment of subgenome dominance in octoploid strawberry.
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Fragaria , Genoma de Planta , Genoma de Planta/genética , Fragaria/genética , Cromatina/genética , Poliploidía , Mapeo CromosómicoRESUMEN
BACKGROUND: Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit. METHODS: This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18 years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded. RESULTS: A total of 332 children were included and their mean age was 14.6 ± 3.9 years (M:F = 1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies + associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6 ± 4.1 days. The number of cases increased significantly over 3 decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p = 0.04) and increase in VHL cases (p = 0.04) in the last decade though overall increase in familial cases was nonsignificant (p = 0.11). No perioperative mortality was observed except for 3% after adrenalectomy. CONCLUSION: A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery.
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Neoplasias de las Glándulas Suprarrenales , Procedimientos Quirúrgicos Endocrinos , Enfermedades del Sistema Endocrino , Feocromocitoma , Cirujanos , Humanos , Niño , Adolescente , Estudios Retrospectivos , Feocromocitoma/cirugía , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/cirugía , Neoplasias de las Glándulas Suprarrenales/cirugíaRESUMEN
Introduction: Indocyanine green (ICG) angiography is the 'real-time intraoperative imaging' technique used to reduce the chances of hypoparathyroidism in post-thyroidectomy patients. In our study, the authors predicted the risk of early post-thyroidectomy hypocalcemia by intraoperative evaluation of parathyroid gland perfusion by ICG angiography. Materials and methods: In patients who underwent total thyroidectomy, ICG angiography was done using the SPY PHI imaging system (Stryker). Post-thyroid specimen removal, scoring of parathyroids was done in spy contrast mode. All 4 or <4 visualized parathyroids were scored for vascularity with the highest score of 8. Serum ionized calcium was done 6 h postsurgery and on the morning and evening of postoperative days 1 and 2. Calcium supplements were given to only those who developed clinical or severe biochemical hypocalcemia. Results: Out of 60, postoperative hypocalcemia was noted in 41 patients. Total ICG score ≤5 was seen in 34 patients, out of which 28 developed postoperative hypocalcemia showing PPV 82.3% and diagnostic accuracy of 68.3% while iPTH (4.28 pmol/l) showed PPV 76.7 and diagnostic accuracy 70 %. In eight patients, none of the glands was scored as 2 (White) and all these patients developed hypocalcemia requiring calcium infusion. Conclusion: The absence of visualization of at least 1 well-perfused (score 2) gland on ICG angiography is highly predictive of hypocalcemia and the majority of patients with total ICG score ≤5 developed hypocalcemia in the immediate postoperative period. ICG is a good predictor of the absence of hypoparathyroidism after thyroidectomy and is comparable to iPTH in the prediction of post-thyroidectomy hypocalcemia.
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Vacunas contra la COVID-19 , COVID-19 , Mieloma Múltiple , SARS-CoV-2 , Vacunación , Humanos , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios LongitudinalesRESUMEN
INTRODUCTION: Noise in the operating room is an ongoing problem that impacts the outcome of any surgery. Noise as a stressor can produce a startling reaction and activate the fight or flight response of the autonomic and endocrine systems. The psychobiology of stress as assessed by salivary cortisol level is a sensitive measure of allostatic load. This study aims to correlate, both subjectively and objectively, the salivary cortisol levels of the surgeon with noise level measurement in an endocrine surgery operating room (OR). MATERIALS AND METHODS: A prospective observational study was conducted in the Endocrine surgery OR of a tertiary care center. We recorded the noise from the shifting in of patients in the OR to shifting out using a digital sound level meter. The operating surgeon (S) provided two salivary cortisol samples (normal salivary cortisol <5 nmol/L), one baseline and another after the procedure. The questionnaire for the assessment of distraction during thyroidectomy was filled in by the S at the end of the procedure. Salivary cortisol levels were analyzed using SLV-4635 (formerly SLV-2930) DRG Instruments GmbH German using the ELISA technique. Statistical analysis was performed using SPSS 22.0. RESULTS: A total of 37 procedures with 74 salivary cortisol samples and 259 questionnaire responses from S were analyzed. All patients with only benign FNAC were operated upon (64.9% colloid). Mean TSH levels were 3.5 ± 6.7 mIU/L. The majority had a solitary thyroid nodule (STN) (25/37, 67.6%). Nineteen patients (51.3%) underwent open hemithyroidectomy, 10 patients total thyroidectomy, and eight patients endoscopic hemithyroidectomy. The mean noise level in the OR was 70 db. The maximum and minimum noise level in the OR was 90.06 and 51.81 dB, respectively. A total of 74 salivary cortisol samples from the S were collected (baseline and post-noise exposure) and mean cortisol levels were recorded. The surgeon was more significantly affected by surrounding noise, especially during critical phases 3 of surgery, mainly, RLN dissection and parathyroid dissection as recorded by their responses in the questionnaire (p = 0.003). The maximum value of post-operative salivary cortisol of surgeon was recorded as 23. 48 ng/mL and the minimum value recorded was 0.49 ng/mL. The difference in baseline cortisol and post-noise exposure cortisol levels of surgeon was found to be significant (p < 0.001). Maximum and mean noise levels were significantly associated with post-noise exposure salivary cortisol elevation in the surgeon (p = 0.032 and 0.014, respectively). The noise levels during RLN dissection were borderline significant with the post-noise exposure salivary cortisol of the surgeon (p = 0.055). CONCLUSION: Our research is the first such study which has been done to assess noise levels and their effect on thyroidectomy using objective salivary cortisol measurement. It challenges the misconstrued notion that visceral surgeries requiring lesser instruments are not associated with noise-related stress. Noise is a major distraction and the effect of long-term effect on the entire surgical team needs to be studied.
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Cirujanos , Nódulo Tiroideo , Humanos , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Quirófanos , Hidrocortisona/análisis , Nódulo Tiroideo/cirugíaRESUMEN
OBJECTIVE: To describe determinants of persisting humoral and cellular immune response to the second COVID-19 vaccination among patients with myeloma. METHODS: This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID-19 vaccination dates. Myeloma patients had an Anti-S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. RESULTS: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti-S antibody levels (<50 IU/mL) doubled during this interval (p = .023) and, in the 47 participants with T-spot data, there was a 25% increase negative T-spot tests (p = .008). Low anti-S antibody levels prior to the third vaccination were predicted by lower Anti-S antibody level and negative T-spot status after the second vaccine. Independent determinants of a negative T-spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti-S antibody levels. CONCLUSIONS: Negative T-spot results predict low Anti-S antibody levels (<50 IU/mL) following a second COVID-19 vaccination and a number of biomarkers predict T cell responses in myeloma patients.
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COVID-19 , Mieloma Múltiple , Humanos , Linfocitos T , COVID-19/prevención & control , Vacunas contra la COVID-19 , Mieloma Múltiple/terapia , Anticuerpos , Vacunación , Anticuerpos Antivirales , Inmunidad CelularRESUMEN
Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.
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Carpas , Evolución Molecular , Animales , Poliploidía , Genoma/genética , Epigénesis Genética , Genoma de PlantaRESUMEN
Introduction Cavitary lung disease has a wide range of differential diagnoses, which include both benign and malignant lesions. Imaging differentiation of benign from malignant cavitary lesions has always been a challenge due to overlapping imaging findings. The present study describes the most accurate multidetector computed tomography (MDCT) findings that could help in differentiating benign from malignant conditions in correlation with the histopathological reports. Methods This retrospective study was carried out on diagnosed cases of cavitary lung lesions on MDCT from January 2022 to February 2023. We evaluated the number of cavitary lung lesions, their location with respect to lung segment/lobe, the maximum diameter of the largest lesion, the maximum wall thickness of the largest cavity, and additional findings associated with these lesions. Measurements of the maximum wall thickness were plotted on a graph. Statistical analysis was done, and a receiver operating characteristic curve (ROC) was calculated to find the accurate cut-off wall thickness for malignant and non-malignant lesions. These findings were then correlated with the histopathological report. Results A review of the MDCT scans of 47 patients was done; 30 (63.8%) of those were male with a mean age of 47.93±14.68 (SD) years while 17 (36.2%) were female with a mean age of 52.53 ±18.38 (SD) years. Out of 47 patients, 27 (57.4%) had benign lesions and 20 (42.5%) had malignant lesions. Significant differences (p<0.05) were found between benign and malignant lesions while comparing the averages of maximum wall thickness (8.1 mm and 14.5 mm, respectively) and the irregular inner margin of the largest cavitary lesions. The presence of consolidation and centrilobular nodules correlated significantly (p<0.05) with the benign nature of cavitary lung lesions. The maximum cut-off wall thickness was <6 mm and >17 mm for the differentiation of benign from malignant lung lesions, respectively. Conclusions The maximum wall thickness and irregular inner margin of cavitary lung lesions was a good indicator for the differentiation of benign and malignant etiologies on MDCT while consolidation and centrilobular nodules favoured the benign etiology more.
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Background: Breast self-examination (BSE) plays an important role in the early diagnosis of breast cancer in India owing to the stigma attached to cancer. The authors compared the efficacies of animation video versus simulation techniques in BSE. Methods: Women with no previous history of conditions affecting the breasts were included in this prospective observational study and divided into an animation or simulation arm. The latter was further divided into three subgroups as per the simulation models used : the German (Delta Healthcare), British (Health Edco), and Indian (low-cost, validated) models used for teaching BSE. The hybrid animation video had a 9 min runtime with a lecture on BSE and a virtual character performing BSE. In both the arms, participants filled in a validated modified patient satisfaction questionnaire. Results: A total of 500 women participated. The mean age of the participants in the animation video arm was 20.21±3.88 years and 19.34±2.27, 22.94±9.6, and 18.97±1.31(20.41±5.99) years in the Indian, German, and British simulation models arm, respectively. The age difference between the two arms was statistically significant (P<0.05). Both animation video and simulation models were found to be useful by the participants. The participants' response to animation video being a better organized tool for learning BSE was statistically significant (90.48±7.98 vs. 84.02±15.09 P≤0.001) when compared to simulation models. The younger women (≤20 years) found these tools significantly more useful than those aged >20 years. Conclusions: All models had good efficiency and utility as learning tools for BSE. However, large studies in BSE set up with combination models are needed.
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Monoclonal antibodies have been successfully utilized in a variety of animal models to treat auto-immune illnesses for a long time. Immune system responses will either be less active or more active depending on how the immune system is operating abnormally. Immune system hypoactivity reduces the body's capacity to fight off various invading pathogens, whereas immune system hyperactivity causes the body to attack and kill its own tissues and cells. For maximal patient compliance, we will concentrate on a variety of antibody therapies in this study to treat Type 1 diabetes (an autoimmune condition). T cells are responsible for the auto-immune condition known as T1D, which causes irregularities in the function of ß-cells in the pancreas. As a result, for the treatment and prevention of T1D, immunotherapies that selectively restore continuous beta cell-specific self-tolerance are needed. Utilizing monoclonal antibodies is one way to specifically target immune cell populations responsible for the auto-immune-driven disease (mAb). Numerous mAbs have demonstrated clinical safety and varied degrees of success in modulating autoimmunity, including T1D. A targeted cell population is exhausted by mAb treatments, regardless of antigenic specificity. One drawback of this treatment is the loss of obtained protective immunity. Immune effector cell function is regulated by nondepleting monoclonal antibodies (mAb). The antigen-focused new drug delivery system is made possible by the adaptability of mAbs. For the treatment of T1D and T cell-mediated autoimmunity, different existing and potential mAb therapy methods are described in this article.
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BACKGROUND: Myelolipomas are benign tumors usually found in adrenal glands. They can also be found extra-adrenally, either in 1 or multiple locations. Perinephric transplant myelolipoma has rarely been reported in the English literature. There's only been 1 instance of such a case reported in a kidney transplant patient, which was found on the explanted kidney. We report a case involving an asymptomatic patient with an ill-defined perinephric transplant mass. METHODS: The mass was then identified as myelolipoma on biopsy. The patient was then managed conservatively with serial imaging and laboratory testing. RESULTS: At the time of our report, the patient continues to have stable renal function and is doing well 24 months after the mass was first identified. CONCLUSIONS: We report the first case of perinephric transplant myelolipoma in a patient with ongoing stable renal allograft function. Based on our case report, we recommended that conservative management with serial imaging and routine testing be considered for patients with perinephric transplant myelolipoma.
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BACKGROUND: Margin assessment is an essential component of breast conservation surgery (BCS). Re-excision of infiltrated margin(s) detected on paraffin section histology (PSH) needs reoperation, adding time, inconvenience and cost. Intra-operative assessment of margins using frozen section histology (IFSH) can potentially obviate need for re-operation, thus facilitating one-step oncologically complete BCS. METHODS: IFSH and PSH reports of consecutive patients undergoing BCS (2010-2020) were reviewed. Accuracy and cost-efficacy of IFSH were assessed, considering PSH as gold standard. Cost of achieving oncologically complete BCS in whole cohort with IFSH (Scenario-A) was calculated and compared using appropriate statistical tests, with hospital costs for the cohort in a hypothetical Scenario-B, where IFSH was presumed not to have been used and all patients with infiltrated margin(s) on PSH would have been re-operated. RESULTS: Of the 367 patients screened, 39 were excluded due to incomplete IFSH data. Of 328 patients analyzed, 59 (18%) had one or more margins were reported infiltrated on IFSH, managed by re-excision or mastectomy in the same sitting, thus avoiding a reoperation. Additional 8 (2.4%) had involved margins on PSH (False negative IFSH). Significantly higher number of reoperations (p < 0.001) would have been needed in scenario-B. Average cost of the first operation with use of IFSH was Indian Rupees (INR) 25791 which included INR660 as IFSH cost. The average cost of reoperation was INR23724 which could be avoided in 59 (18%) by use of IFSH. The average cost per patient to achieve oncologically complete surgery in scenario A utilizing IFSH was significantly lower (p = 0.001) by INR3101 (11.7%), c.w. that in scenario B. Significant cost-saving with IFSH was maintained in cost-efficacy analysis undertaken with various higher and lower costs assumptions. CONCLUSIONS: Use of IFSH facilitates one-step oncologically complete BCS in majority of patients and results in considerable cost saving, resulting in avoidance of reoperations, besides preventing patient anxiety and delay in adjuvant treatment. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI/2021/08/035896).