Tenofovir-Associated Kidney Dysfunction and Bone Fracture: A Case Report and Literature Review.

Tenofovir is an integral part of antiretroviral therapy used to treat HIV. Long-term use of tenofovir has been associated with decreased glomerular filtration rate, leading to chronic kidney disease, as well as acidosis, electrolyte imbalances, and tubular dysfunction. Tenofovir can also disrupt bone health by decreasing renal phosphate absorption, contributing to osteomalacia. This leads to disruption in mineral metabolism, elevated parathyroid hormone levels, and ultimately, low bone mineral density. Replacing tenofovir with alternative antiretroviral therapy can improve kidney function if done early in the course of the disease. Here, we discuss a case of a 65-year-old woman with HIV who presented with advanced renal failure and hypophosphatemia-induced bone fracture attributed to long-term use of tenofovir. We conclude monitoring kidney function and considering alternative antiretroviral therapy is important to prevent and manage these side effects in patients on long-term tenofovir therapy.

An Image-Guided Percutaneous Core Needle Biopsy for Accurate Assessment of Musculoskeletal Tumors: A Targeted Diagnosis.

Background Accurate diagnosis of musculoskeletal tumors is essential for guiding appropriate treatment strategies. Percutaneous core needle biopsy (PCNB) is increasingly recognized as a valuable method for obtaining tissue samples for histopathological examination. This study aims to evaluate the diagnostic accuracy and clinical utility of PCNB in diagnosing musculoskeletal tumors. Methodology A total of 152 cases suspected of musculoskeletal tumors underwent PCNB at our tertiary care center between 2020 and 2023. Pre-biopsy evaluation included comprehensive clinical assessment and imaging studies. Core biopsies were performed under image guidance, with specimens sent for histopathological examination and culture sensitivity analysis. Diagnostic yield, accuracy, and performance metrics of PCNB were assessed. Results PCNB demonstrated a diagnostic yield of 93.4%. However, in cases where initial biopsies were inconclusive, repeat core biopsy or open biopsy provided the necessary diagnostic clarity. PCNB demonstrated a remarkable diagnostic accuracy of 97.9%, with a specificity and positive predictive value of 100%. There were no post-biopsy complications and no instances of local recurrence from the biopsy tract. Conclusions PCNB can be a reliable method for diagnosing musculoskeletal tumors, offering high diagnostic accuracy and minimal complications. The utilization of image guidance enhances precision and reduces the risk of complications. PCNB proves effective in diagnosing both primary tumors and bone infections, facilitating timely and appropriate treatment strategies in orthopedic oncology.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis.

In this editorial we comment on the article by Wei et al, published in the recent issue of the World Journal of Clinical Oncology. The authors investigated the role of Transmembrane 9 superfamily member 1 (TM9SF1) protein in bladder cancer (BC) carcinogenesis. Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines. These cell lines were then subject to cell counting kit 8, wound-healing assay, transwell assay, and flow cytometry. Proliferation, migration, and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression. TM9SF1 silencing inhibited proliferation, migration and invasion of BC cells. The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

Selective transcriptomic dysregulation of metabolic pathways in liver and retina by short- and long-term dietary hyperglycemia.

A high glycemic index (HGI) diet induces hyperglycemia, a risk factor for diseases affecting multiple organ systems. Here, we evaluated tissue-specific adaptations in the liver and retina after feeding HGI diet to mice for 1 or 12 month. In the liver, genes associated with inflammation and fatty acid metabolism were altered within 1 month of HGI diet, whereas 12-month HGI diet-fed group showed dysregulated expression of cytochrome P450 genes and overexpression of lipogenic factors including Srebf1 and Elovl5. In contrast, retinal transcriptome exhibited HGI-related notable alterations in energy metabolism genes only after 12 months. Liver fatty acid profiles in HGI group revealed higher levels of monounsaturated and lower levels of saturated and polyunsaturated fatty acids. Additionally, HGI diet increased blood low-density lipoprotein, and diet-aging interactions affected expression of mitochondrial oxidative phosphorylation genes in the liver and disease-associated genes in retina. Thus, our findings provide new insights into retinal and hepatic adaptive mechanisms to dietary hyperglycemia.

Dietary fish oil enriched in very-long-chain polyunsaturated fatty acid reduces cardiometabolic risk factors and improves retinal function.

Very-long-chain polyunsaturated fatty acids (VLCPUFAs; C24-38) constitute a unique class of PUFA that have important biological roles, but the lack of a suitable dietary source has limited research in this field. We produced an n-3 C24-28-rich VLCPUFA-oil concentrated from fish oil to study its bioavailability and physiological functions in C57BL/6J mice. The serum and retinal C24:5 levels increased significantly compared to control after a single-dose gavage, and VLCPUFAs were incorporated into the liver, brain, and eyes after 8-week supplementation. Dietary VLCPUFAs resulted in favorable cardiometabolic changes, and improved electroretinography responses and visual performance. VLCPUFA supplementation changed the expression of genes involved in PPAR signaling pathways. Further in vitro studies demonstrated that the VLCPUFA-oil and chemically synthesized C24:5 are potent agonists for PPARs. The multiple potential beneficial effects of fish oil-derived VLCPUFAs on cardiometabolic risk and eye health in mice support future efforts to develop VLCPUFA-oil into a supplemental therapy.

The Efficacy and Safety of Mechanical Thrombectomy in Posterior Circulation Large Vessel Occlusion as Compared to Anterior Circulation Large Vessel Occlusion: A Systematic Review.

Mechanical thrombectomy (MT) has been established as a standard of care for patients with stroke due to anterior circulation large vessel occlusion (AC-LVO). Due to a lack of robust evidence for the effectiveness of mechanical thrombectomy, intravenous thrombolysis (IVT) is still the only approved first-line acute reperfusion strategy for posterior circulation large vessel occlusion (PC-LVO). This systematic review analyzes and reports on the effectiveness and safety of MT in PC-LVO. A literature review was performed to identify all studies of patients with acute ischemic stroke due to PC-LVO who underwent MT with second-generation devices (stent retrievers and/or aspiration devices) that were reported between January 2017 and January 2023. The primary outcome was functional independence at 90 days, defined as a modified Rankin (mRS) score of ≤2. Secondary outcomes were successful recanalization (modified treatment in cerebral infarction score (mTICI) 2b/3), symptomatic intracerebral hemorrhage (sICH), and mortality at 90 days post-procedure. We looked at 13 studies with a total of 30,407 participants in four meta-analyses and 5951 participants in nine observational studies. In most studies, patients in the PC-LVO group were male and younger than the AC-LVO group. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score, lower rates of IVT, longer onset-to-groin puncture time, lower likelihood of sICH, higher 90-day mortality rates, and higher futile recanalization rates were frequently observed in the PC-LVO group with a large discrepancy in the likelihood of functional independence at 90 days with majority studies showing comparable rates. Hence, in patients with acute ischemic stroke caused by the PC-LVO, successful reperfusion can be achieved via MT, though at the cost of higher mortality rates. Such futile recanalization can be avoided with the refinement of procedures through technical improvements, skills training, and recognition of reliable predictors associated with it, which might help increase the efficacy of MT in PC-LVO. Additionally, future large-scale RCTs comparing patient selection and interventional strategies to avoid futile interventions are also needed.

Pre-Operative Predictors of Health-Related Quality of Life Two Years After Pediatric Epilepsy Surgery: A Prospective Cohort Study.

PURPOSE: Seizure freedom is an important predictor of health-related quality of life (HRQOL) after pediatric epilepsy surgery. This study aimed to identify the pre-operative predictors of HRQOL 2 years after epilepsy surgery in children with drug-resistant epilepsy. METHODS: This multicenter prospective cohort study assessed pre-operative predictors including child (demographics and clinical variables), caregiver (including caregiver depressive and anxiety symptoms) and family characteristics. HRQOL was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55 pre-operatively and 2-years after surgery. Univariable linear regression analyses were done to identify significant preoperative predictors of HRQOL 2-years after surgery, followed by multivariable regression. RESULTS: Ninety-five children underwent surgery, mean age was 11.4 (SD=4.2) years, and 59 (62%) were male. Mean QOLCE scores were 57.4 (95%CI: 53.8, 61.0) pre-operatively and 65.6 (95%CI: 62.0, 69.1) after surgery. Univariable regression showed fewer anti-seizure medications (ß=-6.1 [95%CI: -11.2, -1.0], p = 0.019), older age at seizure onset (ß=1.6 [95%CI: 0.8, 2.4], p<0.001), higher pre-operative HRQOL (ß=0.7 [95%CI: 0.5, 0.8], p<0.001), higher family resources (ß=0.6 [95%CI: 0.3, 0.9], p<0.001), better family relationships (ß=1.7 [95%CI: 0.3, 3.1], p = 0.017) and lower family demands (ß=-0.9 [95%CI: -1.5, -0.4], p<0.001) were associated with higher HRQOL after surgery. Caregiver characteristics did not predict HRQOL after surgery (p>0.05). Multivariable regression showed older age at seizure onset (ß=4.6 [95%CI: 1.6, 7.6], p = 0.003) and higher pre-operative HRQOL (ß=10.2 [95%CI: 6.8, 13.6], p<0.001) were associated with higher HRQOL after surgery. CONCLUSION: This study underscores the importance of optimizing pre-operative HRQOL to maximize HRQOL outcome after pediatric epilepsy surgery.

Prevalence of Depression and Coping Strategies Among Head and Neck Cancer Patients: A Hospital-Based Study.

Background The burden of cancer is increasing in all countries and so is in India. Among Indian males, lung, mouth, and tongue are very common cancers. Cancer is a life-threatening stressful condition, and cancer survivors report negative effects which decrease the quality of life because of long-term post-treatment effects. When cancer treatment is ongoing, patients express mixed emotion which is happiness and relief. This study aimed to find out the prevalence of depression and assess the coping strategies among the same head and neck cancer patients. Material and methods This cross-sectional study was conducted at the outpatient level in the Department of Radiotherapy, Sri Devaraj Urs Medical College (SDUMC), Sri Devaraj Urs Academy of Higher Education and Research (SDUAHER), Kolar, for a period of three years. The sample size was calculated based on the previous study. Head and Neck cancer patients who are more than 18 years old and histologically diagnosed with cancer were included in the study, and head and neck cancer patients with previously diagnosed mental illness or patients with mental health medications or chronically debilitated cancer were excluded. For sociodemographic details, a pretested semi-structured questionnaire was used. To assess depression Zung Depression Scale was used. To assess coping strategy the Cancer Coping Questionnaire was used. All data collected by interview technique which will last not less than 20 minutes. All data were entered in a Microsoft Excel sheet and analyzed using SPSS version 22 (Armonk, NY: IBM Corp.). To compare between groups, t-test and ANOVA were used with a statistically significant p<0.05. Results Of 188 head and neck cancer patients, 117 (62.2%) aged 31-60 years, 136 (72.3%) were females, 121 (64.4%) belonged to rural background, 143 (76.1%) were illiterates, 105 (55.9%) belonged to joint family, and 110 (58.5%) belonged to class IV modified BG Prasad classification. This study showed 16% of head and neck cancer patients had depression according to the Zung Depression Scale. With respect to the coping domain, cancer patients from rural backgrounds had higher coping scores, and illiterate had higher scores. With respect to the positive focus coping subdomain, male cancer patients had higher scores compared, to rural cancer patients, who had higher scores, and illiterate had higher scores. With respect to the diversion domain, rural cancer patients had higher scores, illiterate patients had higher scores, and this difference was statistically significant. With respect to the interpersonal scale domain, rural patients, patients belonging to joint families, patients aged more than 60 years, and illiterate patients had higher scores compared with literates, and these were statistically significant with p<0.05. This study demonstrated that the presence of depression had no impact on coping domains, and there was no significant correlation between depression and coping scores. Conclusion Mental health must be thoughtfully considered among cancer patients as cancer with depression may have a negative impact on their experience with cancer. Cancer keeps growing as a public health problem and all cancer-treating hospitals should work on various preventable measures for reducing the future burden of various health dimensions affected by cancer. The very intention of treating cancer should be improving the survival of the diagnosed case and this needs targeted mental health intervention.

Safety and Efficacy of Atezolizumab-Bevacizumab in Real World: The First Indian Experience.

Background: Atezolizumab-bevacizumab (atezo/bev) combination is a recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). There are no studies from India reporting the safety and efficacy of this drug in real-world settings where most patients present in an advanced stage. Methods: In this retrospective study from two centers in India, we included patients with uHCC who received atezo/bev as first-line systemic therapy. Comparison of overall survival (OS) among the different Child-Turcotte-Pugh (CTP) classes was the primary objective, while progression-free survival (PFS), radiologic response, and adverse events to the therapy were secondary objectives. Results: The median age of the 67 patients who received atezo/bev therapy was 61 (29-82) years, and 86% were males. Nonalcoholic steatohepatitis (55.2%) was the commonest cause of cirrhosis, and most patients belonged to BCLC-C (74.6%%). There were 24 patients in CTP A, 36 in CTP B, and 7 in CTP C. The median OS was 12 (95%CI, 8.16-15.83) months in the cohort. The median OS in CTP class A, B, and C was 21 (95%CI, 0-42.06) months, 9 (95%CI, 5.46-12.53) months, and 4 (95%CI, 2.14-5.85) months, respectively (P < 0.001). The median PFS in the whole cohort was 8 (95%CI, 6.03-9.96) months. The median PFS in Child A, B, and C was 18 (95%CI, 0.16-35.84) months, 8 (95%CI, 6.14-9.85) months, and 2 (95%CI, 1.77-2.23) months (P < 0.001). On mRECIST evaluation, 12.9% had achieved a complete response, 25.8% had a partial response, 27.41% had stable disease, and the rest had progressed. The objective response rate was 38.7%, and the disease control rate was 66.12%. Of the 64% who developed adverse events, 13.43% discontinued the drug. The incidence of grade ≥3 events was significantly higher in CTP C (85.7%) compared to CTP A (12.5%) and CTP B (14%) (P < 0.001). Conclusions: Atezolizumab-bevacizumab is safe and effective in uHCC in real-world settings. Candidate selection is of utmost importance in treating uHCC with atezolizumab-bevacizumab to achieve a good response. Current evidence strongly suggests limited use of atezolizumab-bevacizumab in patients with CTP C, and such individuals should not be considered for this combination therapy.

Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice.

Both monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) play important roles in lipid metabolism, and diets enriched with either of these two fatty acids are associated with decreased cardiovascular risk. Conventional soybean oil (CSO), a common food ingredient, predominantly contains linoleic acid (LA; C18:2), a n-6 PUFA. Recently, a modified soybean oil (MSO) enriched in oleic acid (C18:1), a n-9 MUFA, has been developed, because of its improved chemical stability to oxidation. However, the effect of the different dietary soybean oils on cardiovascular disease remains unknown. To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (w/w) LA-rich CSO or high-oleic MSO for 12 weeks. Both soybean oils contained a similar amount of linolenic acid (C18:3 n-3). The CSO diet decreased plasma lipid levels and the cholesterol content of VLDL and LDL by approximately 18% (p < 0.05), likely from increased hepatic levels of PUFA, which favorably regulated genes involved in cholesterol metabolism. The MSO diet, but not the CSO diet, suppressed atherosclerotic plaque size compared to the Western control diet (Control Western diet: 6.5 ± 0.9%; CSO diet: 6.4 ± 0.7%; MSO diet: 4.0 ± 0.5%) (p < 0.05), independent of plasma lipid level changes. The MSO diet also decreased the ratio of n-6/n-3 PUFA in the liver (Control Western diet: 4.5 ± 0.2; CSO diet: 6.1 ± 0.2; MSO diet: 2.9 ± 0.2) (p < 0.05), which correlated with favorable hepatic gene expression changes in lipid metabolism and markers of systemic inflammation. In conclusion, supplementation of the Western diet with MSO, but not CSO, reduced atherosclerosis development in LDLR-KO mice independent of changes in plasma lipids.

Prevalence and Impact of Preexisting Comorbidities on Overall Clinical Outcomes of Hospitalized COVID-19 Patients.

COVID-19 risk increases with comorbidities, and the effect is magnified due to the contribution of individual and combined comorbidities to the overall clinical outcomes. We aimed to explore the influence of demographic factors, clinical manifestations, and underlying comorbidities on mortality, severity, and hospital stay in COVID-19 patients. Therefore, retrospective chart reviews were performed to identify all laboratory-confirmed cases of SARS-CoV-2 infection in Apollo Hospitals, Hyderabad, between March 2020 and August 2020.A total of 369 confirmed SARS-CoV-2 cases were identified: 272 (73.7%) patients were male, and 97 (26.2%) were female. Of the confirmed cases, 218 (59.1%) had comorbidities, and 151 (40.9%) were devoid of comorbidities. This study showed that old age and underlying comorbidities significantly increase mortality, hospital stay, and severity due to COVID-19 infection. The presence of all four comorbidities, diabetes mellitus (DM) + Hypertension (HTN) + coronary artery disease (CAD) + chronic kidney disease (CKD), conferred the most severity (81%). The highest mortality (OR: 44.03, 95% CI: 8.64-224.27) was observed during the hospital stay (12.73 ± 11.38; 95% CI: 5.08-20.38) in the above group. Multivariate analysis revealed that nonsurvivors are highest (81%) in (DM + HTN + CAD + CKD) category with an odds ratio (95% CI) of 44.03 (8.64-224.27). Age, gender, and comorbidities adjusted odds ratio decreased to 20.25 (3.77-108.77). Median survival of 7 days was observed in the (DM + HTN + CAD + CKD) category. In summary, the presence of underlying comorbidities has contributed to a higher mortality rate, greater risk of severe disease, and extended hospitalization periods, hence, resulting in overall poorer clinical outcomes in hospitalized COVID-19 patients.

Gut Microbiota and Inflammatory Disorders.

The gut has been colonized with bacteria, fungi, viruses, archaea, eukarya. The human and bacterial cells are found in a 1:1 ratio, while the variance in the diversity of gut microbiota may result in dysbiosis. Gut dysbiosis may result in various pathological manifestations. Beneficial gut microbiota may synthesize short-chain fatty acids like acetate, butyrate, propionate. Gram-negative organisms are the primary source of LPS, a potent pro-inflammatory mediator. Both gut microbiota and microbial products may be involved in immunomodulation as well as inflammation. Prebiotics and probiotics are being explored as therapeutic agents against various inflammatory and autoimmune disorders. Here, we discuss the molecular mechanisms involved in gut bacteria mediated modulation of various inflammatory and autoimmune disorders.

A Rare Case of Fractured Posterior Facet of the Talus in Association With Open Medial Subtalar Dislocation.

Subtalar or peritalar dislocation is the loss of contact between the articular surface of the talus distally and the calcaneum and navicular. In this paper, a case of open medial type of subtalar dislocation associated with fractured posterior facet of the talus in a 27-year-old man with a history of road traffic accident was reported. Immediate wound irrigation and open reduction under general anesthesia at the emergency room operation theater was successful followed by cast immobilization. At one-year follow-up, the patient was walking and carrying out his daily activities with mild restriction of inversion and eversion movements. Extensive wound debridement followed by immediate reduction and, when required, stabilization are the principal features of management. Open subtalar dislocation is an extremely rare injury and often poses a treatment dilemma. Early debridement and open reduction of the dislocation like in our case can give good functional outcome for an open medial subtalar dislocation at one-year follow-up. Temporary stabilization of dislocation in the form of Kirschner wires maybe needed in some cases only.

An investigation of vitamin D status in alopecia areata.

Alopecia areata (AA) is a type of non-scarring, recurrent patchy loss of hair in hair-bearing areas and is mostly of autoimmune origin. Previous studies have suggested that some autoimmune diseases were found to be associated with vitamin D deficiency. The current study was designed to assess the levels of serum 25-hydroxy vitamin D and C-reactive protein in AA, as compared with controls and to further identify the association between vitamin D levels and disease severity in patients with AA. This cross-sectional study included 45 patients with AA and 45 healthy volunteers. Clinical and anthropometric parameters were recorded, according to a pre-designed proforma. Serum 25-hydroxy vitamin D and high-sensitivity C-reactive protein were estimated using ELISA kits. The severity of AA was determined using Severity of Alopecia Tool (SALT) score. We observed a significant rise in systemic inflammation as seen by elevated high-sensitive C-reactive protein levels and lowered 25-hydroxy vitamin D levels in patients with alopecia areata, compared to controls (p = 0.001). The levels of 25-hydroxy vitamin D showed a significant negative correlation with disease severity, while hs-CRP levels showed a significant positive correlation with disease severity (ρ = - 0.714, p = 0.001 and ρ = 0.818, p = 0.001). Our results suggest significant systemic inflammation and vitamin D deficiency in alopecia areata, more so with increasing disease severity. This gains particular importance in the treatment of alopecia areata in future, as supplementing vitamin D to AA patients would result in reducing the disease severity and inducing remission.

Intraluminal migration of gossypibioma.

BACKGROUND: Surgical sponge retained in the abdominal cavity following surgery, is a serious but avoidable complication. Common symptoms and signs of transmural migration of gossypibioma may include abdominal pain, vomiting, and bleeding. Transmural migration of surgical swab is a very rare phenomenon. CASE SERIES: We report a series of three such cases which presented to us with small bowel obstruction and laparotomy with extraction of gossypibioma was performed. RESULTS: All three patients recovered well with no morbidity. CONCLUSION: Gossypibioma is a surgical mishap which can be avoided if guidelines for operative theatre record keeping are seriously followed. CECT abdomen is very useful in its diagnosis. Exploratory laparotomy or laparoscopy is mandatory. This series also discusses the approach to migratory surgical gossypibioma in terms of clinical manifestations, diagnosis, treatment and prevention protocol.

Study of Ischemia Modified Albumin as a Biomarker in Acute Ischaemic Stroke.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of mortality and long-term disability. Prompt diagnosis and treatment of stroke are crucial for a better outcome. A blood test, which serves as a biomarker in rural areas will help in immediately transferring patients to a hospital for thrombolytic therapy. The aim of the present study was to examine the role of ischemia modified albumin (IMA) as a screening biomarker in acute ischaemic stroke. MATERIALS AND METHODS: Serum samples were collected from 50 patients with acute ischaemic stroke within one, 24, 48, 72 and 144 h of time of admission for IMA. We compared patients' 1st-hour value with age- and sex-matched controls by independent sample t test. p value < 0.05 was considered significant. RESULTS: The serum IMA levels of patients 1st hour (108 ± 8.9) were significantly higher than those of the controls (79 ± 6.3) p < 0.05. The IMA levels showed a steady decline at 1 h (108 ± 8.9), 24 h (94 ± 4.2), 48 h (82 ± 6.1), 72 h (77 ± 5.6) and 144 h (76 ± 3.8) of admission in patients. CONCLUSION: We observed that serum IMA was significantly higher in stroke patients as compared to controls. IMA was elevated in the acute phase of stroke and had a gradual graded decline over 1 week. We concluded that IMA may be a sensitive and rapid biomarker for screening of early ischaemic stroke in rural settings.

Multifocal spinal meningeal melanocytoma: an illustrated case review.

Primary melanocytic tumors of the central nervous system are rare. In this article the authors describe a case of C1C2 intradural extramedullary melanocytoma in a 43-year-old patient who presented with neck pain. C1-3 laminectomy was performed followed by excision of the lesion and an adjoining satellite nodule, along with the dural attachment. The histopathological features were consistent with a meningeal melanocytoma despite the presence of a satellite nodule. The patient has no evidence of recurrence during the six month follow up period. A brief review of literature pertaining to the radiological features, pathological findings, management and prognosis of this rare tumor is discussed.