Difficult venesections: An easy solution.

Venesection is common procedure performed in day to day life of every doctor. Conventional vein finders available are costly and not easily available. The present paper highlights the use of makeshift vein finder.

Dermoscopic Correlation of an Eccentric Case of Kindler Syndrome.

Kindler syndrome (KS) is a rare autosomal recessive skin condition. The FERMT1 gene mutates and causes symptoms such as blistering and epidermal atrophy, as well as an increased risk of cancer and poor wound healing. A male in his 20s sought treatment for his hyper-hypopigmentation over the body with poikiloderma of the face with thin wrinkled cigarette paper skin in association with photosensitivity. He gave a history of developing blisters all over the body during his childhood, which formed raw areas and eventually healed forming atrophic scars. The objective is to assess the correlation of clinical findings with dermoscopy in a case of KS. KS is a rare disorder with poikiloderma, photosensitivity, and acral bullae in infancy as predominant features. Dermoscopy proves to be a useful tool in the diagnosis of this rare disorder as it helps in the identification of poikiloderma, adermatoglyphia, and cigarette paper scarring.

Evaluating the cost of robotic-assisted total and unicompartmental knee arthroplasty.

As uptake of robotic-assisted arthroplasty increases there is a need for economic evaluation of the implementation and ongoing costs associated with robotic surgery. The aims of this study were to describe the in-hospital cost of robotic-assisted total knee arthroplasty (RA-TKA) and robotic-assisted unicompartmental knee arthroplasty (RA-UKA) and determine the influence of patient characteristics and surgical outcomes on cost. This prospective cohort study included adult patients (≥ 18 years) undergoing primary unilateral RA-TKA and RA-UKA, at a tertiary hospital in Sydney between April 2017 and June 2021. Patient characteristics, surgical outcomes, and in-hospital cost variables were extracted from hospital medical records. Differences between outcomes for RA-TKA and RA-UKA were compared using independent sample t-tests. Logistic regression was performed to determine drivers of cost. Of the 308 robotic-assisted procedures, 247 were RA-TKA and 61 were RA-UKA. Surgical time, time in the operating room, and length of stay were significantly shorter in RA-UKA (p < 0.001); whereas RA-TKA patients were older (p = 0.002) and more likely to be discharged to in-patient rehabilitation (p = 0.009). Total in-hospital cost was significantly higher for RA-TKA cases (AU$18580.02 vs $13275.38; p < 0.001). Robotic system and maintenance cost per case was AU$3867.00 for TKA and AU$5008.77 for UKA. Patients born overseas and lower volume robotic surgeons were significantly associated with higher total cost of RA-UKA. Increasing age and male gender were significantly associated with higher total cost of RA-TKA. Total cost was significantly higher for RA-TKA than RA-UKA. Robotic system costs for RA-UKA are inflated by the software cost relative to the volume of cases compared with RA-TKA. Cost is an important consideration when evaluating long term benefits of robotic-assisted knee arthroplasty in future studies to provide evidence for the economic sustainability of this practice.

Cinnamaldehyde attenuates TNF-α induced skeletal muscle loss in C2C12 myotubes via regulation of protein synthesis, proteolysis, oxidative stress and inflammation.

Inflammation is the primary driver of skeletal muscle wasting, with oxidative stress serving as both a major consequence and a contributor to its deleterious effects. In this regard, regulation of both can efficiently prevent atrophy and thus will increase the rate of survival [1]. With this idea, we hypothesize that preincubation of Cinnamaldehyde (CNA), a known compound with anti-oxidative and anti-inflammatory properties, may be able to prevent skeletal muscle loss. To examine the same, C2C12 post-differentiated myotubes were treated with 25 ng/ml Tumor necrosis factor-alpha (TNF-α) in the presence or absence of 50 µM CNA. The data showed that TNF-α mediated myotube thinning and a lower fusion index were prevented by CNA supplementation 4 h before TNF-α treatment. Moreover, a lower level of ROS and thus maintained antioxidant defense system further underlines the antioxidative function of CNA in atrophic conditions. CNA preincubation also inhibited an increase in the level of inflammatory cytokines and thus led to a lower level of inflammation even in the presence of TNF-α. With decreased oxidative stress and inflammation by CNA, it was able to maintain the intracellular level of injury markers (CK, LDH) and SDH activity of mitochondria. In addition, CNA modulates all five proteolytic systems [cathepsin-L, UPS (atrogin-1), calpain, LC3, beclin] simultaneously with an upregulation of Akt/mTOR pathway, in turn, preserves the muscle-specific proteins (MHCf) from degradation by TNF-α. Altogether, our study exhibits attenuation of muscle loss and provides insight into the possible mechanism of action of CNA in curbing TNF-α induced muscle loss, specifically its effect on proteolysis and protein synthesis.

Diabetic Ketoacidosis and Acute Kidney Injury Associated With Enfortumab Vedotin for Urothelial Carcinoma: A Case Report.

Enfortumab vedotin is a novel breakthrough therapy that received accelerated US Food and Drug Administration approval in 2019 for the treatment of metastatic urothelial carcinoma in patients who have failed other lines of treatment. The characteristics of its adverse effects are not well understood. Diabetic ketoacidosis has been reported in 2 postmarketing reports presented as abstracts at the 2020 American Thoracic Society Conference and the 2021 American Society of Nephrology Conference. Both cases progressed rapidly and expired in <3 days. We present a similar case of a man in his late 50s with no history of diabetes who was diagnosed with urothelial carcinoma 2 years prior. Despite several lines of treatment, including platinum-based chemotherapy and immune checkpoint inhibitors, he developed metastasis and was started on enfortumab vedotin. After his second dose of enfortumab vedotin, he was admitted to the intensive care unit for diabetic ketoacidosis with an initial A1C level of 7.7%. He was intubated for airway protection, started on pressors, and developed oliguric acute kidney injury requiring continuous venovenous hemodialysis. Despite aggressive treatment, the patient died on hospital day 2. The lethality of this aggressive diabetic ketoacidosis despite therapy suggests some other effect of enfortumab vedotin on glucose metabolism in addition to insulin resistance and the need for prior diabetes screening.

UPR-Induced miR-616 Inhibits Human Breast Cancer Cell Growth and Migration by Targeting c-MYC.

C/EBP homologous protein (CHOP), also known as growth arrest and DNA damage-inducible protein 153 (GADD153), belongs to the CCAAT/enhancer-binding protein (C/EBP) family. CHOP expression is induced by unfolded protein response (UPR), and sustained CHOP activation acts as a pivotal trigger for ER stress-induced apoptosis. MicroRNA-616 is located within an intron of the CHOP gene. However, the regulation of miR-616 expression during UPR and its function in breast cancer is not clearly understood. Here we show that the expression of miR-616 and CHOP (host gene of miR-616) is downregulated in human breast cancer. Both miR-5p/-3p arms of miR-616 are expressed with levels of the 5p arm higher than the 3p arm. During conditions of ER stress, the expression of miR-616-5p and miR-616-3p arms was concordantly increased primarily through the PERK pathway. Our results show that ectopic expression of miR-616 significantly suppressed cell proliferation and colony formation, whereas knockout of miR-616 increased it. We found that miR-616 represses c-MYC expression via binding sites located in its protein coding region. Furthermore, we show that miR-616 exerted growth inhibitory effects on cells by suppressing c-MYC expression. Our results establish a new role for the CHOP locus by providing evidence that miR-616 can inhibit cell proliferation by targeting c-MYC. In summary, our results suggest a dual function for the CHOP locus, where CHOP protein and miR-616 can cooperate to inhibit cancer progression.

Nephrotic syndrome following COVID-19 vaccination: a systematic review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection has caused significant morbidity and mortality. Vaccines produced against this virus have proven highly effective. However, adverse events following vaccination have also been reported. One of them is nephrotic syndrome, that can be associated with different pathologic pictures. This review aims to provide a wider understanding of incidence, etiopathogenesis, and management of nephrotic syndrome following vaccination against SARS-CoV-2. METHODS AND RESULTS: A literature search was undertaken using appropriate keywords in various databases like PubMed, Google Scholar, Europe PMC, and Science Direct. Twenty-one articles were included following qualitative assessment. Data of 74 patients from these articles were included. DISCUSSION: The pathogenesis of nephrotic syndrome following COVID vaccination has been widely attributed to the activation of angiotensin-converting enzyme-2 receptors, leading to podocyte effacement. Relapses have also been reported in patients with prior history of nephrotic syndrome following COVID-19 vaccination. A renal biopsy is necessary to identify the histopathological picture. Management of COVID-19 vaccine-induced nephrotic syndrome was mainly reported as successfully attainable with corticosteroids and supportive management. CONCLUSION: Further investigations will help in establishing an early diagnosis and salvaging kidney function.

Acute myeloid leukemia with RAM immunophenotype: A new underdiagnosed entity.

INTRODUCTION: Acute myeloid leukemia (AML) with RAM immunophenotype is a distinct subtype of AML, as described by the Children's Oncology Group (COG), with characteristic morphological and immunophenotypic properties. It is characterized by strong CD56 expression with dim to negative CD45, HLA-DR, and CD38 expression. It is an aggressive leukemia with a poor response to induction chemotherapy and/or frequent relapses. METHODS: Seven cases with the characteristic RAM immunophenotype were identified in this retrospective analysis of newly diagnosed pediatric AML cases from January 2019 to December 2021. Herein, we have critically analyzed their clinical, morphological, cytochemical, immunophenotyping, cytogenetic, and molecular profiles. The patients were traced and followed for their current disease and treatment status. RESULTS: Of 302 cases of pediatric AML (age <18 years), seven cases (2.3%) with the distinct RAM phenotype were observed, with age ranging from 9 months to 5 years. Two patients were misdiagnosed earlier as small round cell tumor because of the strong CD56 positivity and the absence of leukocyte common antigen (LCA), but they were later correctly identified as granulocytic sarcoma. The bone marrow aspirate showed blasts with unusual cohesiveness and clumping with nuclear moulding, mimicking non-hematologic malignancies. Flow cytometry revealed blasts with low side scatter, dim to negative CD45 and CD38, negative cMPO, CD36, and CD11b; moderate to bright CD33, CD117, and bright CD56. The Mean fluorescence intensity (MFI) of CD13 expression was significantly lower as compared to the internal controls. Cytogenetic and molecular studies did not show any recurrent abnormalities. Reverse transcription polymerase chain reaction for CBFA2T3-GLIS2 fusion was performed in 5/7 cases, with one positive result. On clinical follow-up, two patients were refractory to chemotherapy. Six of the seven cases had succumbed to death (duration of survival: 3-343 days after initial diagnosis). CONCLUSION: AML with RAM immunophenotype, a distinct form of pediatric AML with a poor prognosis, may pose a diagnostic challenge if presented as a soft tissue mass. A comprehensive immunophenotypic evaluation, including stem cell and myeloid markers, is critical for an accurate diagnosis of myeloid sarcoma with the RAM-immunophenotype. Our data demonstrated weak CD13 expression as an additional immunophenotypic finding.

RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity.

BACKGROUND: Endocrine-resistant breast cancers have elevated expression of XBP1, where it drives endocrine resistance by controlling the expression of its target genes. Despite the in-depth understanding of the biological functions of XBP1 in ER-positive breast cancer, effectors of endocrine resistance downstream of XBP1 are poorly understood. The aim of this study was to identify the XBP1-regulated genes contributing to endocrine resistance in breast cancer. METHODS: XBP1 deficient sub-clones in MCF7 cells were generated using the CRISPR-Cas9 gene knockout strategy and were validated using western blot and RT-PCR. Cell viability and cell proliferation were evaluated using the MTS assay and colony formation assay, respectively. Cell death and cell cycle analysis were determined using flow cytometry. Transcriptomic data was analysed to identify XBP1-regulated targets and differential expression of target genes was evaluated using western blot and qRT-PCR. Lentivirus and retrovirus transfection were used to generate RRM2 and CDC6 overexpressing clones, respectively. The prognostic value of the XBP1-gene signature was analysed using Kaplan-Meier survival analysis. RESULTS: Deletion of XBP1 compromised the upregulation of UPR-target genes during conditions of endoplasmic reticulum (EnR) stress and sensitized cells to EnR stress-induced cell death. Loss of XBP1 in MCF7 cells decreased cell growth, attenuated the induction of estrogen-responsive genes and sensitized them to anti-estrogen agents. The expression of cell cycle associated genes RRM2, CDC6, and TOP2A was significantly reduced upon XBP1 deletion/inhibition in several ER-positive breast cancer cells. Expression of RRM2, CDC6, and TOP2A was increased upon estrogen stimulation and in cells harbouring point-mutants (Y537S, D538G) of ESR1 in steroid free conditions. Ectopic expression of RRM2 and CDC6 increased cell growth and reversed the hypersensitivity of XBP1 KO cells towards tamoxifen conferring endocrine resistance. Importantly, increased expression of XBP1-gene signature was associated with poor outcome and reduced efficacy of tamoxifen treatment in ER-positive breast cancer. CONCLUSIONS: Our results suggest that RRM2 and CDC6 downstream of XBP1 contribute to endocrine resistance in ER-positive breast cancer. XBP1-gene signature is associated with poor outcome and response to tamoxifen in ER-positive breast cancer.

CD34 negative HLA-DR negative acute myeloid leukaemia: A higher association with NPM1 and FLT3-ITD mutations.

INTRODUCTION: CD34 and HLA-DR negativity is often used as a characteristic immunophenotypic feature of acute promyelocytic leukaemia (APL) that differentiates APL from other subtypes of acute myeloid leukaemia (AML). However, other subtypes of AML, without expression of CD34 and HLA-DR antigens, have also been reported. METHODS: We analysed the HLA-DR negative de novo non-APL AML cases by dividing HLA-DR negative non-APL group into 2 sub-groups based on CD34 expression and compared the characteristics of CD34 negative HLA-DR negative with CD34 positive HLA-DR negative non-APL AML cases with respect to morphologic, immunophenotypic, molecular and clinical parameters. RESULTS: There were 70 cases (8.54%) which were CD34 negative HLA-DR negative and 52 cases (6.34%) were CD34 positive HLA-DR negative. The median age at diagnosis was higher in CD34 negative HLA-DR negative AML than in CD34 positive HLA-DR negative AML group (38 years vs. 12 years, p < 0.001). DIC rate was higher in CD34 negative HLA-DR negative group than the other group (p < 0.001). Median total leucocyte count was higher with higher blast count in peripheral blood and bone marrow in CD34 negative HLA-DR negative AML cases than the other group (p < 0.05). CD34 negative HLA-DR negative AML was more associated with normal karyotype (96.2% vs. 38.5%; p < 0.001), NPM1 mutation (67.8% vs. 8.3%; p < 0.001) and FLT-ITD mutation (37.3% vs. 13.9%; p < 0.05). In CD34 negative HLA-DR negative group, 16 cases had co-occurrence of NPM1 and FLT3-ITD mutations, whereas no case of CD34 positive HLA-DR negative group had such dual mutation positivity. There was poor median overall survival [3.8 months (95%CI: 2.3-7.8 months) vs. 20.4 months (95% CI: 12.8-25.7 months); p = 0.0148] in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases. CONCLUSION: We found that the CD34 negative HLADR negative non APL AML is highly associated with NPM1 and FLT3-ITD mutation, older age at diagnosis, DIC, higher total leucocyte count, higher blast counts and normal karyotype in comparison to CD34 positive HLA-DR negative AML group. Co-occurrence of NPM1 and FLT3-ITD mutation was also exclusively seen in CD34 negative HLA-DR negative group. There was poor overall survival in CD34 positive HLA-DR negative AML than CD34 negative HLA-DR negative AML cases.

miRNA-378 Is Downregulated by XBP1 and Inhibits Growth and Migration of Luminal Breast Cancer Cells.

X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR), a cellular stress response pathway involved in maintaining protein homeostasis in the endoplasmic reticulum (EnR). While the role of XBP1 in UPR is well-characterised, emerging evidence suggests its involvement in endocrine resistance in breast cancer. The transcriptional activity of spliced XBP1 (XBP1s) is a major component of its biological effects, but the targets of XBP1s in estrogen receptor (ER)-positive breast cancer are not well understood. Here, we show that the expression of miR-378 and PPARGC1B (host gene of miR-378) is downregulated during UPR. Using chemical and genetic methods, we show that XBP1s is necessary and sufficient for the downregulation of miR-378 and PPARGC1B. Our results show that overexpression of miR-378 significantly suppressed cell growth, colony formation, and migration of ER-positive breast cancer cells. Further, we found that expression of miR-378 sensitised the cells to UPR-induced cell death and anti-estrogens. The expression of miR-378 and PPARGC1B was downregulated in breast cancer, and higher expression of miR-378 is associated with better outcomes in ER-positive breast cancer. We found that miR-378 upregulates the expression of several genes that regulate type I interferon signalling. Analysis of separate cohorts of breast cancer patients showed that a gene signature derived from miR-378 upregulated genes showed a strong association with improved overall and recurrence-free survival in breast cancer. Our results suggest a growth-suppressive role for miR-378 in ER-positive breast cancer where downregulation of miR-378 by XBP1 contributes to endocrine resistance in ER-positive breast cancer.

Comedone Extractor with Multiple Variable Sized Holes for Mass Comedone Extraction.

Conventional comedone extractor has only one or two holes of fixed or variable sizes. This conventional extractor is not suitable for mass comedone extraction and that too of variable sizes. We tried to made an attempt to overcome this problem.

Role of Psychological Assessment in Aesthetic Procedures.

The psychology behind an aesthetic procedure needs to be understood and assessed by the attending cosmetologist for the satisfactory outcome of the procedure. Being alert about certain psychiatric conditions can help in deferring certain procedures, which prevent us from correcting something that is actually not required and will protect us from future trouble. The incorporation of the user-friendly body dysmorphic disorder (BDD) screening questionnaire in preaesthetic procedure workup as a routine can help in excluding psychologically unstable patients, who can be a contraindication for conducting the procedure per se.

Blastic plasmacytoid dendritic cell neoplasm: A clinicopathological diagnostic dilemma report of three cases with review of literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematologic neoplasm and classified under acute myeloid leukemia. Here, we describe the clinicopathological features of three cases of BPDCN: two with classical and one uncommon immunophenotype. A-35-year-old female (case 1) presented with complaint of nasal mass and generalized lymphadenopathy. Biopsy from axillary lymph node showed infiltration by cells with scant cytoplasm which were immunopositive for LCA, CD4, CD43, and ALK1. Flowcytometry showed positivity for CD45, CD4, CD33, and CD123 while negative for rest all markers. The other two cases have classical immunophenotype. In clinical practice, nasal mass with lymphadenopathy suggests natural killer T-cell/peripheral T-cell lymphoma. Again immunohistochemical positivity for CD4, CD43, and ALK while negativity for CD3 suggests anaplastic large cell lymphoma. In this case, morphology and extensive bone marrow involvement raise the suspicion. Fowcytometry positivity for HLADR, CD123, and CD33 helps in making diagnosis.

The miR-17-92 cluster: Yin and Yang in human cancers.

MicroRNAs (miRNAs) are non-coding RNAs which modulate gene expression via multiple post-transcriptional mechanisms. They are involved in a variety of biological processes, including cell proliferation, metastasis, metabolism, tumorigenesis, and apoptosis. Dysregulation of miRNA expression has been implicated in human cancers, and they may also serve as biomarkers of disease progression and prognosis. The miR-17-92 cluster is one of the most widely studied miRNA clusters, which was initially reported as an oncogene, but was later reported to exhibit tumour suppressive effects in some human cancers. This review summarizes the recent progress and context-dependant role of this cluster in various cancers. We summarize the known mechanisms which regulate miR-17-92 expression and molecular pathways that are in turn controlled by it. We discuss examples where it acts as an oncogene or a tumour suppressor along with key targets affecting hallmarks of cancer. We discuss how cellular contexts regulate the biological effects of miR-17-92. The plausible mechanisms of its paradoxical roles are explained, and mechanisms are described that may contribute to cell fate regulation by miR-17-92. Further, we discuss recently developed strategies to target miR-17-92 cluster in human cancers. MiR-17-92 may serve as a potential biomarker for prognosis and response to therapy as well as a target for cancer prevention and therapeutics.