Squamous cell carcinoma arising from pilonidal sinus

Pilonidal sinus is usually present in the sacrococcygeal region. The common presentations are cellulitis, abscess or sinus. Rarely malignant change may be seen in chronic pilonidal sinus. We report a case of chronic pilonidal sinus complicated with squamous cell carcinoma.     

Neurofibromatosis 1 vasculopathy manifesting as a peripheral aneurysm in an adolescent

Arterial vasculopathy is a well-recognized but uncommon manifestation of neurofibromatosis type 1 (NF-1). It can manifest as stenoses, aneurysms or arteriovenous malformations. NF-1 vasculopathy typically involves the aorta, visceral arteries or carotid-vertebral circulation. Aortic and visceral vasculopathy typically presents as stenotic lesions, while aneurysms have been reported primarily in the subclavian/vertebral arteries. Aneurysms of the peripheral/extremity arteries are an extremely rare complication of NF-1 that may present as a mass or spontaneous rupture. We present the case of a teenage boy with an arm mass secondary to an aneurysm. We hope this case will increase recognition of the variable clinical manifestations of NF-1 vasculopathy among radiologists.     

Association of Interleukin 1 beta (IL‐1B) gene polymorphism with early pregnancy loss risk in the North Indian population

C+3953T IL‐1 B single‐nucleotide polymorphism (SNP) genotyping was carried out in 140 unrelated early pregnancy loss (EPL) patients and in 198 fertile healthy control women and in chorionic villous samples by PCR‐RFLP. In Indian population, this is the first report on association of IL‐1 B SNP C+3953T polymorphism and EPL.     

Lipid Lowering Activity of Guggulsterone from Commiphora mukul in Hyperlipaemic Rats

The lipid lowering action of guggulsterone, the active constituent of guggulipid, has been studied in triton and cholesterol fed hyperlipaemic rats. Serum lipids were found to be lowered by guggulsterone (50 mg/kg, b.w.) in triton WR-1339 induced hyperlipaemia. Chronic feeding of this drug (5 mg/kg, b.w.) in animals simultaneously fed with cholesterol (25 mg/kg, b.w.) for 30 days, caused lowering in the lipid and apoprotein levels of very low density and low density lipoproteins in experimental animals. Guggulsterone activates lipolytic enzymes in plasma and liver as well as stimulated receptor mediated catabolism of low density lipoprotein. The hypolipidaemic activity of this drug is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acid excretion and enhanced plasma lecithin:cholesterol acyltransferase activity.     

Therapeutic cooperation between auranofin,a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8^+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.     

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

Hippocampal and parahippocampal volumes vary by sex and traumatic life events in children

BackgroundChildhood trauma is reliably associated with smaller hippocampal volume in adults; however, this finding has not been shown in children, and even less is known about how sex and trauma interact to affect limbic structural development in children.MethodsTypically developing children aged 9 to 15 years who completed a trauma history questionnaire and structural T₁-weighted MRI were included in this study (n = 172; 85 female, 87 male). All children who reported 4 or more traumas (n = 36) composed the high trauma group, and all children who reported 3 or fewer traumas (n = 136) composed the low trauma group. Using multivariate analysis of covariance, we compared FreeSurfer-derived structural MRI volumes (normalized by total intracranial volume) of the amygdalar, hippocampal and parahippocampal regions by sex and trauma level, controlling for age and study site.ResultsWe found a significant sex × trauma interaction, such that girls with high trauma had greater volumes than boys with high trauma. Follow-up analyses indicated significantly increased volumes for girls and generally decreased volumes for boys, specifically in the hippocampal and parahippocampal regions for the high trauma group; we observed no sex differences in the low trauma group. We noted no interaction effect for the amygdalae.LimitationsWe assessed a community sample and did not include a clinical sample. We did not collect data about the ages at which children experienced trauma.ConclusionResults revealed that psychological trauma affects brain development differently in girls and boys. These findings need to be followed longitudinally to elucidate how structural differences progress and contribute to well-known sex disparities in psychopathology.     

Knowledge,attitude, and practice regarding COVID-19 among COVID-19 patients and their correlation with the outcomes: A cross-sectional study

Objective: To assess the knowledge, attitude, and practice (KAP) regarding COVID-19 among COVID-19 patients and their relation with the outcomes.Methods: This cross-sectional study was carried out among COVID-19 patients (18-year-old or older) consecutively admitted to a dedicated COVID-19 hospital located in northwest Rajasthan, India. Data regarding socio-demographic parameters, KAP, and primary composite outcome (admission to intensive care unit, mechanical ventilation, or in-hospital death) were collected. KAP scores were compared between different demographic variables and primary composite outcomes. Association between different demographic variables, primary composite outcomes, and KAP scores were determined through multivariate linear regression. Besides, the correlation among KAP scores was analyzed. Results: Out of the total 222 patients, most of them (65.76％) had average KAP scores towards COVID-19. The mean scores for knowledge were 7.88, with an overall correct rate of 71.63％; the mean attitude scores were 2.42, with an overall correct rate of 60.50％; the mean practice scores were 5.12, with an overall correct rate of 64.00％. Patients who met the primary composite outcomes had higher knowledge scores, but lower attitude and practice scores. The result showed a significant positive correlation between the level of education, socioeconomic class, and knowledge, attitude, and practice towards COVID-19. Knowledge towards COVID-19 was significantly associated with a positive attitude and good practice. Conclusions: Our findings show that adult COVID-19 patients have average KAP towards COVID-19 among COVID-19 patients. Poor attitude and practice towards COVID-19 are associated with adverse outcomes, so it is suggested to strengthen attitude and practice towards COVID-19 to improve the outcomes.