Novel Insights Into the Epidemiological and Clinico-Pathological Profile of Triple-Negative Breast Cancer: Dissection of an Aggressive Variant.

Objective Triple-negative breast cancer (TNBC) represents an aggressive and prognostically poor variant of breast cancer. Over the years, detailed research has been conducted and published in Western literature. However, there lacks a detailed account of TNBC cases from the perspective of a low-volume institution. This study aims to assess the clinical features of TNBC, as well as their prognostic implications in a tertiary care centre. Methods and materials This prospective observational study took place at a tertiary health centre for two years, spanning from 2021 to 2023. The study aimed to investigate various clinicopathological and epidemiological parameters, thereby highlighting the shortcomings in the existing knowledge about the subject in the context of a low-volume centre, as well as additional contributing factors in developing countries like India. A group of 150 participants diagnosed with TNBC through biopsy and immunohistochemistry and >40 years of age were included in the study. Patients who tested positive for hormonal receptors and who refused to give consent for participation were excluded from the study. The study subjects were categorized according to their clinical TNM (cTNM) stage and eventually segregated into two primary heads, namely pre-surgery chemotherapy with breast-conserving surgery (BCS) after a good response, or modified radical mastectomy (MRM) upfront. Important demographic details, including age, socioeconomic status, and education, were also recorded. A comprehensive follow-up assessment post-treatment was performed to detect early recurrence. After data collection, the recurrence rates were correlated with the TNBC status to establish the aggressiveness of the cancer. Statistical analysis of the data was done using the Statistical Package for Social Sciences (SPSS) -16version software. Results The average age of the 150 participants in the study was 52.21 years (SD±4.89 years). The highest recorded age was 64 years, while the lowest recorded age was 45 years. In the study, it was observed that 41% of the participants diagnosed with TNBC had stage III disease, whereas 33.5% had stage I disease, 22% had stage IV disease and 3.6% had stage II disease. A total of 27.5% of individuals with TNBC exhibited metastases in various anatomical sites, whereas the other 72.5% did not show any signs of metastasis. Conclusion Triple-negative breast cancer has earned its position as a unique subtype of breast cancer due to its unusual molecular characteristics, aggressive behavior, limited treatment options, and poor prognosis. The lower per-capita income and limited knowledge pertaining to this variant, along with the absence of more specific treatment options, contribute to the already high levels of morbidity and mortality associated with this illness. To effectively address this unique and very virulent ailment and customize our strategies, it is imperative to do further comprehensive investigations, thereby enabling us to deliver the highest quality of medical attention to individuals afflicted by this pathology.

Wunderlich Syndrome: A Seldom Presentation of a Relatively Ubiquitous Tumor.

Wunderlich syndrome (WS) is characterized by spontaneous renal or perinephric hemorrhage in the absence of known trauma. WS is much rarer than haemorrhage caused by iatrogenic or traumatic conditions. The classic WS presentation of Lenk's triad of acute onset flank pain, flank mass, and hypovolemic shock is seen in less than a quarter of patients. The majority of patients present with only isolated flank pain and are frequently imaged in the emergency department with an unenhanced computed tomography (CT). The underlying aetiology varies, with the majority of cases attributed to neoplasms, vascular disease, cystic renal disease, and anticoagulation. We hereby present a case of an 80-year-old female who presented with severe discomfort in her left flank for three days in the absence of trauma. The patient was brought in a state of hypovolemic shock. After a thorough evaluation, a diagnosis of WS secondary to angiomyolipoma was made, for which selective angioembolization of the left renal artery was performed. However, due to further deterioration, a left nephrectomy had to be performed. The patient had an uneventful recovery and showed no deterioration on follow-up. The treatment modalities are vivid depending on the hemodynamic status of the patient, ranging from conservative management to operative intervention, and should be tailored to the vital state on admission.

Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways.

A Study of the Degree of Gall Bladder Wall Thickness and Its Impact on Patients Undergoing Laparoscopic Cholecystectomy.

Background The gold standard management for symptomatic gallstone disease is elective laparoscopic cholecystectomy, which has replaced open cholecystectomy. The wall thickness of the gallbladder is an indicator of cholecystitis in patients who have presented with symptoms of gallstone disease. The aim of this study was to evaluate preoperative gall bladder wall thickness by ultrasonography and assess its impact on the outcome of laparoscopic cholecystectomy, including conversion rate, complications, operative time, and postoperative hospital stay. Method This prospective study was conducted on 350 patients with symptomatic gallstone disease, those who had undergone laparoscopic cholecystectomy in Dr. Sampurnanand Medical College, Jodhpur, and attached hospitals from July 2019 to November 2021. On the basis of ultrasonography findings of gallbladder wall thickness, patients were divided into four groups: normal thickness - up to 2 mm, mild thickness - 3-4mm, moderate thickness - 5-6mm, and severe wall thickness - more than 6mm). Up to 2 millimeters thickness was considered as normal. Results The incidence of conversion rate, as well as intra or postoperative complications, were higher in moderate and severe wall thickness groups. The maximum incidence of complication rate is seen in moderately thickened group (33.33%). In severely thickened group, complication was seen in 100% of patients. Operative time, as well as postoperative hospital stay, were more in higher thickness groups. There was a statistically significant correlation between gallbladder wall thickness and conversion rate, complications operative time, and postoperative length of stay. Conclusion Increased gallbladder wall thickness causes increased intra as well as postoperative complications, more conversion to open procedure rate, increased operative time, and enhanced postoperative hospital stay. Among the total study population, 29.71% of patients had increased gallbladder wall thickness. In our study, a positive correlation was seen among gallbladder wall thickness, complication rate, conversion rate, intraoperative time, and postoperative hospital stay.

Laparoscopic Versus Open Ventral Hernia Repair: Experience at a Tertiary Care Center in Western Rajasthan.

Background Ventral hernias are the second most common type of hernias accounting for 21-35% of all hernia types. Ventral hernia includes incisional, umbilical, epigastric, and Spigelian hernias, among others. Currently, patients and surgeons prefer laparoscopic repair of ventral hernias. This study aimed to compare laparoscopic with open hernia repair in terms of various operative and patient parameters. Methodology This was a prospective observational study conducted in the Department of General Surgery, Dr. Sampurnanand Medical College, Jodhpur. All patients admitted with a diagnosis of ventral hernia for mesh repair (open as well as laparoscopic) were included. Laparoscopic and open hernia repair were compared in terms of operative time, postoperative hospital stay, time to resume routine activity, postoperative complications, and recurrence. Results Among the 50 patients included in the study (25 patients each in the laparoscopic and open groups), the mean operative time was 57.52 ± 5.80 minutes in the laparoscopic group and 59.8 ± 11.15 minutes in the open group. The mean hospital stay in the laparoscopy and open groups was 7.4 ± 1.58 days and 9.88 ± 2.96 days, respectively (p-value = 0.0006; significant). Postoperative pain (using the visual analog scale score) was less in patients who underwent laparoscopic surgery (p-value = 0.001; significant). Seroma and surgical site infections were the most common complications which were observed more in the open hernia repair group. Recurrence was seen in one case operated by the open technique. Conclusions Laparoscopic ventral hernia repair is technically safer, effective, and feasible with better clinical outcomes in patients seeking treatment in a government hospital.

Molecular Subtypes As Emerging Predictors of Clinicopathological Response to Neoadjuvant Chemotherapy (NACT) in Locally Advanced Breast Cancer (LABC): A Single-Centre Experience in Western India.

INTRODUCTION: Locally advanced breast cancer (LABC) is a subset of breast cancer characterized by the most advanced breast tumours in the absence of distant metastasis. Treatment of LABC has evolved from a single modality treatment to multimodality management. Neoadjuvant chemotherapy (NACT) is increasingly being used to treat patients with LABC. This study assessed tumour response after NACT using clinical changes, Response Evaluation Criteria in Solid Tumors (RECIST) criteria and pathological report. METHODOLOGY: This study was a prospective as well as retrospective observational study carried out in the department of general surgery, Dr. Sampurnanand Medical College, Jodhpur. All the patients admitted with stage III (IIIA, IIIB, IIIC) were included in the study after obtaining approval from the institutional ethical committee. Clinical response was assessed by RECIST criteria (clinical complete response (cCR), clinical partial response (cPR), clinical progressive disease (cPD), and clinical stable disease (cSD)) and pathological response by histopathological report (pCR). Response of various molecular subtypes was noted. RESULTS: Among 31 patients included in the study, cCR observed in 22.58% cases, cPR observed in 61.29% cases while cPD and cSD seen in 3.22% and 12.90% cases, respectively. Pathological complete response (pCR) observed in 19.35% cases. Favourable response seen with human epidermal growth factor receptor 2 (HER2) overexpression (cCR = 50%, pCR = 37.50%) followed by triple negative (cCR = 25%, pCR = 25%) molecular subtypes. CONCLUSIONS: It can be concluded that molecular subtype determination helps in deciding treatment protocol in patients with LABC with HER2 overexpression and triple-negative breast cancers having a better clinicopathological response to NACT than luminal subtypes. NACT results in downstaging of tumours, thus, help in achieving surgically clear margins and elimination of micrometastases which decreases the recurrence rates and morbidity/mortality of patients.

A Shepherd's Crook Deformity of Proximal Femur Treated by Valgus Osteotomy and Bone Grafting.

The Shepherd's crook deformity of the proximal femur is a characteristic radiologic feature of fibrous dysplasia. It may be limited to a single bone, which is called monostotic, or may be polyostotic involving multiple bones as seen in McCune-Albright Syndrome. We report a case of a 19-year-old male patient who presented to us with pain in the right hip for one year. He had dysmorphic facies and multiple café-au-lait spots over the back, which were suggestive of McCune-Albright Syndrome. The radiographs of the hip showed varus deformity of the proximal femur. A lateral closing wedge osteotomy was done and the defect was filled with morselised femoral head allografts and fibular strut allografts. At the 14-month follow-up, the patient remained functionally active without any symptoms. The use of morselised femoral head allograft combined with strut fibular allograft ensures both stability and improved biology at the site of the lesion without any donor site morbidity.

Hoffa's Fracture with Associated Injuries Around the Knee Joint: An Approach to a Rare Injury.

Fractures of the distal femur typically occur in the axial and sagittal planes. A Hoffa fracture is a coronal plane fracture of the femoral condyle, which accounts for 8.7% to 13% of distal femoral fractures. It is usually associated with other injuries around the knee joint and hence is often missed. We conducted a comprehensive systematic review of papers published in the English language using PubMed, Web of Science, Scopus, and the Cochrane Database, which reported Hoffa's fracture associated with other injuries around the knee joint. We selected 11 eligible papers for final analysis and review. These papers had 12 patients with Hoffa's fracture, with associated injuries around the knee joint. The associated injuries with Hoffa's fracture were in the ipsilateral distal femur, proximal tibia fractures, patellar dislocation, patella fracture, and patellar tendon incarceration. The management principles for Hoffa's fracture with associated injuries around the knee joint are: having a high clinical index of suspicion for these injuries, obtaining all trauma series radiographs and computed tomography of the knee, achieving complete articular incongruity, and restoring the functions of the knee joint.

Effector gene expression underlying neuron subtype-specific traits in the Motor Ganglion of Ciona.

The central nervous system of the Ciona larva contains only 177 neurons. The precise regulation of neuron subtype-specific morphogenesis and differentiation observed during the formation of this minimal connectome offers a unique opportunity to dissect gene regulatory networks underlying chordate neurodevelopment. Here we compare the transcriptomes of two very distinct neuron types in the hindbrain/spinal cord homolog of Ciona, the Motor Ganglion (MG): the Descending decussating neuron (ddN, proposed homolog of Mauthner Cells in vertebrates) and the MG Interneuron 2 (MGIN2). Both types are invariantly represented by a single bilaterally symmetric left/right pair of cells in every larva. Supernumerary ddNs and MGIN2s were generated in synchronized embryos and isolated by fluorescence-activated cell sorting for transcriptome profiling. Differential gene expression analysis revealed ddN- and MGIN2-specific enrichment of a wide range of genes, including many encoding potential "effectors" of subtype-specific morphological and functional traits. More specifically, we identified the upregulation of centrosome-associated, microtubule-stabilizing/bundling proteins and extracellular guidance cues part of a single intrinsic regulatory program that might underlie the unique polarization of the ddNs, the only descending MG neurons that cross the midline. Consistent with our predictions, CRISPR/Cas9-mediated, tissue-specific elimination of two such candidate effectors, Efcab6-related and Netrin1, impaired ddN polarized axon outgrowth across the midline.

Fistulization of Peritoneal Hydatid Cyst to the Gastrointestinal Tract: An Unusual Cause of Subacute Intestinal Obstruction.

Extrahepatic hydatid disease within the abdomen is uncommon, the most common site being the peritoneum. The alimentary tract is a rare site for hydatid cysts. Fistulization of abdominal hydatid cysts to the bowel lumen is a rare occurrence with few cases reported in existing literature. We report a rare case of fistulization of a peritoneal hydatid cyst to the stomach and duodenum with disseminated peritoneal and retroperitoneal hydatidosis, presenting with features of subacute intestinal obstruction. We briefly review the existing literature and discuss the confounding factors that we encountered during the diagnostic evaluation of this rare phenomenon.

Single-cell transcriptome profiling of the Ciona larval brain.

The tadpole-type larva of Ciona has emerged as an intriguing model system for the study of neurodevelopment. The Ciona intestinalis connectome has been recently mapped, revealing the smallest central nervous system (CNS) known in any chordate, with only 177 neurons. This minimal CNS is highly reminiscent of larger CNS of vertebrates, sharing many conserved developmental processes, anatomical compartments, neuron subtypes, and even specific neural circuits. Thus, the Ciona tadpole offers a unique opportunity to understand the development and wiring of a chordate CNS at single-cell resolution. Here we report the use of single-cell RNAseq to profile the transcriptomes of single cells isolated by fluorescence-activated cell sorting (FACS) from the whole brain of Ciona robusta (formerly intestinalis Type A) larvae. We have also compared these profiles to bulk RNAseq data from specific subsets of brain cells isolated by FACS using cell type-specific reporter plasmid expression. Taken together, these datasets have begun to reveal the compartment- and cell-specific gene expression patterns that define the organization of the Ciona larval brain.

Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers.

Dengue fever (DF) is a major global health burden with a pathophysiology that is still incompletely understood. Biomarkers that predict and explain susceptibility to DF and its progression to its more severe hemorrhagic form are much needed. DF is endemic in tropical and subtropical regions of the world, with a rapidly increasing incidence of disease severity. We conducted a clinical biomarker discovery study using both a case-control and longitudinal study design. Plasma proteome alterations in patients with DF (n = 12) and dengue hemorrhagic fever (DHF, n = 24) were analyzed in comparison to healthy controls (HCs, n = 16), using the isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics methodology (false discovery rate of 1%, ≥2 peptides). Several proteins such as the alpha-2 macroglobulin, angiotensinogen, apolipoprotein B-100, serotransferrin, and ceruloplasmin were upregulated (fold change >1.2) in all DHF cases, and downregulated in DF (fold change <0.83), compared with HCs. Plasma cytokine profiling (8 DF, 8 DHF, and 8 HC) on two consecutive time points, at day 0 (day of admission) and days 5-7, found significant elevation in IL-1RA, IL-7, TNF-α, MCP1-MCAF, and MIP-1ß levels, but only in the DHF cases, which is the severe disease, and not in DF, compared with HCs (p < 0.05). These new observations on changes in the plasma proteome and cytokine profiles in patients with dengue infection identify several putative molecular leads for future biomarker development and precision medicine in relation to forecasting DF disease severity.

Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

Membranous IVC Obstruction Presenting with Antegrade/Retrograde Respiratory Flow in the Intrahepatic Segment in Doppler Imaging and Prostatic and Urethral Congestion.

BACKGROUND: Obstruction of the inferior vena cava (IVC) is infrequent, membranous obstruction of the IVC (MOIVC) being one of its rare causes. Early diagnosis is important, as it can lead to hepatic congestion, cirrhosis and Budd-Chiari syndrome (BCS) and can predispose to development of hepatocellular carcinoma (HCC) in severe cases. CASE REPORT: We report a case of membranous IVC obstruction at the junction of hepatic and suprahepatic segments in a young male with extensive collateralization and venous aneurysms. Unique findings involved antegrade and retrograde flow during respiration in the upper part of intrahepatic IVC proximal to a large collateral vein as well as prostatic and urethral congestion leading to intermittent urinary hesitancy, which have not yet been described in such cases. CONCLUSIONS: MOIVC is a rare cause of IVC obstruction with typical radiological features. Early diagnosis and management is required due to risk of cirrhosis and HCC. Antegrade and retrograde flow may be seen in incomplete MOIVC above the level of a large collateral vein and it may lead to prostatic and urethral congestion.

Primary aneurysmal bone cyst of talus.

Aneurysmal bone cyst (ABC) of the talus is an extremely rare lesion; less than 20 cases have been reported in PubMed till 2012. We report a primary ABC of the talus in a 20-year-old male that was managed by extended intralesional curettage with phenol as an adjuvant and autologous cancellous iliac crest bone grafting. The patient had excellent functional outcome and there was no recurrence at 2 years of follow-up.