QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.

BACKGROUND: Pazopanib hydrochloride (PZB) is a protein kinase inhibitor approved by the United States Food and Drug Administration and European agencies for the treatment of renal cell carcinoma and other renal malignancies. However, it exhibits poor aqueous solubility and inconsistent oral drug absorption. In this regard, the current research work entails the development and evaluation of the extrudates of pazopanib hydrochloride by the hot-melt extrusion (HME) technique for solubility enhancement and augmenting oral bioavailability. RESULTS: Solid dispersion of the drug was prepared using polymers such as Kollidon VA64, hydroxypropylmethylcellulose (HPMC), Eudragit EPO, and Affinisol 15LV in a 1:2 ratio by the HME process through a lab-scale 18 mm extruder. Systematic optimization of the formulation variables was carried out with the help of custom screening design (JMP Software by SAS, Version 14.0) to study the impact of polymer type and plasticizer level on the quality of extrudate processability by measuring the torque value, appearance, and disintegration time as the responses. The polymer blends containing Kollidon VA64 and Affinisol 15LV resulted in respective clear transparent extrudates, while Eudragit EPO and HPMC extrudates were found to be opaque white and brownish, respectively. Furthermore, evaluation of the impact of process parameters such as screw rpm and barrel temperature was measured using a definitive screening design on the extrude appearance, torque, disintegration time, and dissolution profile. Based on the statistical outcomes, it can be concluded that barrel temperature has a significant impact on torque, disintegration time, and dissolution at 30 min, while screw speed has an insignificant impact on the response variables. Affinisol extrudates showed less moisture uptake and faster dissolution in comparison to Kollidon VA64 extrudates. Affinisol extrudates were evaluated for polymorphic stability up to a 3-month accelerated condition and found no recrystallization. PZB-Extrudates using the Affinisol polymer (Test formulation A) revealed significantly higher bioavailability (AUC) in comparison to the free Pazopanib drug and marketed formulation.

Anti-factor H Autoantibody-Associated Hemolytic Uremic Syndrome: A Rare Entity in a Pediatric Patient.

An 11-year-old patient presented with the primary complaint of hematuria and vomiting. On further investigation and a series of diagnostic tests, including a biopsy and thrombotic microangiopathy (TMA) profile, the patient was diagnosed with thrombotic microangiopathy. TMA is a pathological process involving endothelial cell injury, leading to thrombocytopenia and microangiopathic hemolytic anemia. This case highlights the importance of considering TMA in pediatric patients presenting with nonspecific symptoms, such as loss of appetite. Further research is needed to understand the pathophysiology and optimal management strategies for pediatric TMA. This case adds to the growing body of literature on pediatric TMA and underscores the need for a high index of suspicion in similar clinical scenarios.

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study.

BACKGROUND AND OBJECTIVE: A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. METHODS: Male and female subjects (n = 135; age: 25-60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. RESULTS: CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants' vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. CONCLUSION: The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

A novel humanized mouse model for HIV and tuberculosis co-infection studies.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model. Methods: The irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis. Results: Our humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Conclusion: The humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.

Integrating 40-GEP Testing to Improve Clinical Recommendations for Adjuvant Radiation for Cutaneous Squamous Cell Carcinoma: Multidisciplinary Consensus Guidelines.

Early identification and intervention in patients with cutaneous squamous cell carcinoma (cSCC) who are at high risk for metastasis is important for optimal outcomes. Prognostic tools (e.g., American Joint Committee on Cancer, 8th edition [AJCC-8]) and management guidelines (National Comprehensive Cancer Network® [NCCN]) are useful in helping to identify high-risk patients with cSCC who might benefit from adjuvant therapies, such as radiation and/or immunotherapies; however, traditional staging and management guidelines rely on clinicopathologic risk factors to predict risk, which limits their prognostic accuracy. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help clinicians stratify risk in patients with cSCC. The validated 40-GEP test can accurately classify patients with at least one high-risk feature as being at low (Class 1), higher (Class 2A), or highest (Class 2B) biological risk of nodal or distant metastasis within three years of diagnosis. A multidisciplinary panel comprising radiation oncologists and dermatologists/Mohs micrographic surgeons with expertise in cSCC management convened in June 2023 to discuss the utility of 40-GEP testing in cSCC clinical decision-making in regard to adjuvant radiation therapy (ART). The panel identified gaps in clinical practice in which 40-GEP testing has particular utility: in escalation of care for lower-stage patients with high-risk tumors; in de-escalation of care for patients for whom the risks of ART may outweigh the benefits; and in decision-making regarding elective radiation to the nodal basin. The expert panel developed a risk-based clinical workflow for ART in patients with cSCC, utilizing 40-GEP testing within NCCN management guidelines and AJCC-8 staging.

A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV-Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/Mtb co-infection.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Unraveling Compositional Study, Chemometric Analysis, and Cell-Based Antioxidant Potential of Selective High Nutraceutical Value Amaranth Cultivars Using a GC-MS and NMR-Based Metabolomics Approach.

Amaranthus (family Amaranthaceae) is a potentially nutritious pseudocereal also known as a functional food owing to its high nutritional quality grains especially rich in essential amino acids. Emerging study, however, unambiguously indicates that apart from essential nutrients like protein, other phytochemicals present in amaranth seeds provide excellent health benefits. Squalene is one such phytonutrient found in Amaranthus seeds, which is also its largest vegetal source. In this research work, GC-MS and NMR spectroscopy-based metabolomics have been utilized for the compositional analysis of Amaranthus seeds coupled with a multivariate data set. Investigation of nonpolar and polar seed extracts of six different cultivars of amaranth identified 47 primary and secondary metabolites. One-way ANOVA showed significant quantitative metabolic variations in different cultivars of amaranth. Multivariate principal component analysis of both the GC-MS and NMR analyzed data broadly classified in two groups showed significant variations in the polar (lysine, arginine, GABA, and myoinositol) and nonpolar (squalene, tryptophan, and alkylated phenols, which are potential nutraceutical agents) metabolites. The squalene content estimated using HPLC varied significantly (1.61 to 4.72 mg g-1 seed dry weight) among six different cultivars. Positive correlations were found among the cellular antioxidant activity and squalene content. Cultivar AM-3 having the maximum squalene content showed the highest antioxidant activity evaluated on the cellular level over human embryonic kidney cells, clearly revealing potent intercellular reactive oxygen species scavenging capacity and strong membrane lipid peroxidation inhibition potential. Oxidative stress markers such as MDA, SOD, GSH, and CAT levels in cells further corroborated the research work. The study also indicated high concentrations of lysine (80.49 mg g-1 dry seeds) in AM-2, squalene (0.47% by weight) in AM-3, and 2,4-di-tert-butyl phenol (18.64% peak area) and myoinositol (79.07 mg g-1 dry seeds) in AM-5. This novel comparative metabolomic study successfully profiles the nutrient composition of amaranth cultivars and provides the opportunity for the development of nutraceuticals and natural antioxidants from this functional food.

Impose of KNDy/GnRH neural circuit in PCOS, ageing, cancer and Alzheimer's disease: StAR actions in prevention of neuroendocrine dysfunction.

The Kisspeptin1 (KISS1)/neurokinin B (NKB)/Dynorphin (Dyn) [KNDy] neurons in the hypothalamus regulate the reproduction stage in human beings and rodents. KNDy neurons co-expressed all KISS1, NKB, and Dyn peptides, and hence commonly regarded as KISS1 neurons. KNDy neurons contribute to the "GnRH pulse generator" and are implicated in the regulation of pulsatile GnRH release. The estradiol (E2)-estrogen receptor (ER) interactions over GnRH neurons in the hypothalamus cause nitric oxide (NO) discharge, in addition to presynaptic GABA and glutamate discharge from respective neurons. The released GABA and glutamate facilitate the activity of GnRH neurons via GABAA-R and AMPA/kainate-R. The KISS1 stimulates MAPK/ERK1/2 signaling and cause the release of Ca2+ from intracellular store, which contribute to neuroendocrine function, increase apoptosis and decrease cell proliferation and metastasis. The ageing in women deteriorates KISS1/KISS1R interaction in the hypothalamus which causes lower levels of GnRH. Because examining the human brain is so challenging, decades of clinical research have failed to find the causes of KNDy/GnRH dysfunction. The KISS1/KISS1R interactions in the brain have a neuroprotective effect against Alzheimer's disease (AD). These findings modulate the pathophysiological role of the KNDy/GnRH neural network in polycystic ovarian syndrome (PCOS) associated with ageing and, its protective role in cancer and AD. This review concludes with protecting effect of the steroid-derived acute regulatory enzyme (StAR) against neurotoxicity in the hippocampus, and hypothalamus, and these measures are fundamental for delaying ageing with PCOS. StAR could serve as novel diagnostic marker and therapeutic target for the most prevalent hormone-sensitive breast cancers (BCs).

Assessment of soft- and hard-tissue changes following combined anterior segmental bi-jaw orthognathic surgery.

Background: Anterior segmental Bi-jaw orthognathic surgery is indicated primarily for the correction of dentoalveolar protrusion. They are also indicated for correcting apertognathia, closing interproximal spaces between segments and can be incorporated with other osteotomies to obtain better results. Aim: The aim of this study was to analyze and compare the soft- and hard-tissue changes in patients who underwent combined anterior segmental bi-jaw orthognathic surgery. Settings and Design: To compare and evaluate soft- and hard-tissue changes before and after combined anterior segmental bi-jaw orthognathic surgery by assessing (a) parameters in vertical dimension and (b) parameters in horizontal dimension and patient satisfaction was also assessed following surgery at 6 months' time interval. Materials and Methods: It is a prospective, single center and analytical study with sample size of 20 patients. It required routine setup for orthognathic surgery and manual tracing of lateral cephalograms. The surgical outcomes were assessed by hard tissue (Sella Nasion Point A (SNA) angle, Sella Nasion Point B (SNB) angle, Point A Nasion Point B (ANB) angle, NAPg, U1-NF, L1-MP angles; NA, NB, B-Pg, Nasion-Anterior nasal spine (N-ANS) distance, Anterior nasal spine-Gnathion (ANS-Gn) distance, and overjet and overbite) and soft tissue (facial convexity, NL, LM angles; LM fold, UL and LL protrusions, Upper lip length (ULL), Lower lip length (LLL), Sn-A, Si-B, Pg-Pg*, Ls-U1, Li-L1 distances, interlabial gap, and U1 exposure) variables pre and postsurgery. Statistical Analysis: Descriptive statistics involved the mean and standard deviation, and recorded data were subjected to the statistical analysis using IBM SPSS 20 statistical package. The paired t-test, Pearson correlation coefficient were used. The level of significance P < 0.05 was taken as statistically significant and P < 0.01 as very significant. Results: Overall improvement after surgery in both hard- and soft-tissue parameters was observed and significant changes were seen in every variable, except Si-B (P > 0.05). Correlations between soft- and hard-tissue changes were significant in both sagittal and vertical planes. Patients' satisfaction score showed that all patients had the high overall rate of satisfaction. Conclusions: Our study concludes that combined anterior segmental bimaxillary orthognathic surgery is a simple technique with minimal postoperative complications and limited relapse. The changes in facial esthetics and occlusion following orthognathic surgery depend highly on the stability achieved during the postoperative period.

Single linear miniplate versus rectangular grid plate in the treatment of mandibular angle fractures: A prospective, clinico-radiographic, comparative study.

Study Design: Randomized Control Trial. Objective: A prospective, clinico-radiographic, comparative study was planned to evaluate the treatment outcome and postoperative complications in isolated mandibular angle fractures using 2.0-mm system single linear 4 hole with gap miniplate versus 4 hole rectangular grid plate, both stabilized with 4 8-mm monocortical screws. Methods: Thirty patients with isolated mandibular angle fractures were randomly categorized into two groups with 15 patients each. Group 1 patients were treated with single 2.0 mm × 4 hole linear miniplate along the superior border and Group 2 patients were treated with a 2.0 mm × 4 hole rectangular grid plate on lateral cortex of mandible. Pain, swelling, occlusion, bite force, maximum inter-incisal opening, intraoperative time, facial nerve injury, fracture stability, and postoperative complications were assessed and compared at regular intervals up to 12 months. Results: There was no major difference in terms of treatment outcome in both systems and both were equally effective without any statistically significant difference in any of the parameters. None of the patients presented with any of the complications except for postoperative infection which was reported by 1 patient from each group at 3 months postoperatively and were managed conservatively. Conclusion: Both plating systems are equally effective; however, the rectangular grid plate could be a safe and effective alternative to the single miniplate when adaptation and fixation is not possible along the external oblique ridge of the mandible (e.g., fracture with bone loss along the superior border).

Incorporation of the 40-Gene Expression Profile (40-GEP) Test to Improve Treatment Decisions in High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients: Case Series and Algorithm.

Cutaneous squamous cell carcinoma (cSCC) has become a significant public health issue due to its rapidly rising incidence and an estimated 1.8 million newly diagnosed cases annually. As with other cancers, treatment decisions for patients with cSCC are based primarily on a patient's risk for poor outcomes. There has been improvement in clinicopathologic factor-based risk assessment approaches, either through informal methods or ever evolving staging approaches. However, these approaches misidentify patients who will eventually have disease progression as low-risk and conversely, over classify patients as high-risk who do not experience relapse. To improve the accuracy of risk assessment for patients with cSCC, the 40-gene expression profile (40-GEP) test has been validated to show statistically significant stratification of a high-risk cSCC patient's risk of nodal or distant metastasis, independent of currently available risk-assessment methods. The 40-GEP test allows for a more accurate classification of metastatic risk for high-risk cSCC patients, with the aim to influence appropriate allocation of clinician time and therapeutic resources to those patients who will most benefit. The objective of this article is to present a treatment algorithm in which clinicians can easily integrate the results of the 40-GEP test into their current treatment approaches to tailor patient care based on individual tumor biology. The following modalities were considered: surveillance imaging, sentinel lymph node biopsy (SLNB), adjuvant radiation therapy (ART), and clinical follow-up. The authors have contributed their own cases for discussion as to how they have seen the beneficial impact of 40-GEP test results in their own practice. Overall, clinicians can identify risk-aligned treatment pathway improvements with the use of the 40-GEP test for challenging to manage, high-risk cSCC patients.

Comparative evaluation of efficacy of C-reactive protein versus total leucocyte count as marker for monitoring patients with orofacial space infection of odontogenic origin.

Objective: To compare and evaluate the efficacy of C-Reactive Protein and total leucocyte count as markers for monitoring patients of odontogenic space infection. Materials and Methods: Blood samples were taken preoperatively and post-operatively at day 1, day 2, day 3 and day 7 for measuring the levels of CRP and TLC. The trends of CRP and TLC were analysed against the Clinical Severity Scale (CSS). The study was carried out on patients of odontogenic space infection, and minimum of 50 patients were selected for this study. Comparative evaluation of C-reactive protein (CRP) versus total leucocyte count (TLC) was performed. Results: Data were analysed using Statistical Package for Social Sciences (SPSS) version 21. Inferential statistics were performed using Spearman Correlation. The level of statistical significance was set at 0.05. The result of the study demonstrates that the C-reactive protein (CRP) was found to be more consistent indicator for monitoring the patients of odontogenic space infection than TLC, Differential Leucocyte Count (DLC) and erythrocyte sedimentation rate (ESR). Conclusion: We conclude that CRP should be incorporated as monitoring tool, and it serves as a better indicator than TLC for managing patients with orofacial space infections of odontogenic origin.

Surgical Approaches to Cavernous Sinus: A Narrative Review of the Literature with Anatomical Drawings.

IIntroduction. The cavernous sinus (CS) is a paired venous sinus in the human brain that is classified as a true dural venous sinus rather than a venous plexus. The entire CS is separated by septa into two small cavities called caves. The CS has a very close resemblance to various key structures present in the head. The CS is a blood compartment that contains ligaments, endothelium, and trabeculae. It is clinically significant because of its position and relationship with several cranial nerves. Clinical implications. For effective management and treatment of CS syndrome, CS thrombosis, carotid-cavernous fistula, and other CS-related problems, CS surgery became necessary. As a result of the lack of sophisticated surgical techniques in the past, CS surgery was exceedingly challenging, complicated, and deadly. The surgery of CSs can benefit from a variety of surgical procedures, including extradural and intradural, endoscopic endonasal, rhomboid, and temporopolar trans cavernous approaches. In this review, numerous surgical procedures for CS are discussed along with their intended uses. Conclusions. A greater understanding of the CS was made possible by the quick modifications and improvements in surgical methods, which aided in neurosurgery procedures.

A Prospective Study on Autotransplantation of Mandibular Third Molars With Complete Root Formation.

Study Design: Autotransplantation, if possible, is a viable option for replacing a missing tooth when a donor tooth is available. The most typical tooth transplant is the transfer of a third molar to a first molar site. No immune reaction results from transplants of this nature. It restores the proprioceptive function and normal periodontal healing; thus, the patient can have a natural chewing feeling and natural biological response. Objective: This study aims to evaluate the prognosis of autotransplanted mandibular third molar and also to evaluate the cost effectiveness of the treatment performed when compared to the other treatment modalities for prosthetic rehabilitation. Methods: A prospective study was done in the Department of Oral & Maxillofacial Surgery, Sardar Patel Post Graduate Institute of Dental & Medical Sciences, Lucknow, UP, India, with over 20 patients to evaluate the prognosis of autotransplanted mandibular third molars with complete root formation after atraumatic extraction of first or second mandibular molar, which were randomly selected irrespective of race, sex, caste, and socio-economic status. Regular clinical and radiographical examinations were performed over a period of 1 year and the patients were assessed for pain, swelling, infection, dry socket, periodontal pocket depth, ankylosis, root resorption, tooth mobility, and level of buccal bone in relation to cementoenamel junction (CEJ). Results: Eighteen out of 20 transplants were successful; only 2 mandibular transplants were extracted because of abnormal horizontal and axial mobility and the reason of failure was attributed to fact that the roots of transplant were short and conical and there was lack of alveolar bone height at the recipient site in one patient, while root resorption was the reason for failure of transplant in the other patient. Conclusions: This study assessed the efficacy of autotransplantation of molars and the viability of the procedure to replace unrestorable molar teeth; it also supports the hypothesis that transplantation of a mandibular third molar for replacement of a lost or seriously damaged molar tooth could be a reasonable alternative.

Re-intervention percutaneous balloon mitral valvuloplasty in a patient with left atrial appendage thrombus: a case report.

Background: Percutaneous balloon mitral valvuloplasty (PBMV) using an Accura balloon is an effective method for management of rheumatic mitral stenosis. Case summary: Herein, we present a case of a 43-year-old female, who had undergone a previous PBMV, who presented with very severe mitral re-stenosis with Type Ia left atrial (LA) clot, in atrial fibrillation and New York Heart Association functional Class III. We used the modified septal puncture and over-the-wire technique, avoiding inadvertent manipulation of the LA clot for PBMV. The mitral valve was successfully dilated from 0.9 to 1.5 cm2, and the patient had an uneventful post-procedure recovery. Discussion: The presence of LA clot and mitral re-stenosis in a previously intervened valve are considered unfavourable characteristics for a PBMV procedure, and patients are usually advised surgical intervention. These patients are also high-risk candidates for surgery due to late presentation with advanced disease and poor functional capacity. Our patient underwent successful re-intervention with PBMV despite having suboptimal characteristics.

AIH in HIV: A Very Much Possible Entity.

Autoimmune Hepatitis (AIH) is a chronic liver disease Characterized by interface hepatitis, lymphoplasmacytic infiltrate, and hepatic rosettes. HIV infection is a state of immunosuppression; hence, the possibility of AIH is relatively rare, especially in patients with low CD4 counts. Therefore, we present an interesting case series of four patients with autoimmune liver disease with myriad presentations for the first time from India. We propose that despite the rarity of this presentation with immunosuppression, one should never miss such a treatable cause of liver disease leading to good clinical outcomes.

A Ganglion Cyst on the Posterior Cruciate Ligament.

This case report describes a 29-year-old medical student, a junior resident in orthopaedic surgery who reported intermittent right knee pain due to an increase in mileage throughout his training. The posterior cruciate ligament was diagnosed with a ganglion cyst using diagnostic imaging. The purpose of this article is to describe the clinical and diagnostic aspects of a ganglion cyst found on the posterior cruciate ligament and to raise awareness among doctors of this uncommon condition and its diagnosis.

Role of Hemoglobin Content of Reticulocyte to Evaluate Anemia in Patients with Malignancy.

Anemia is common in patients with cancer and it's pathophysiology is complex and multifactorial . Conventional methods (Serum Iron, serum ferritin, TIBC, TSAT) to diagnosing iron deficiency anemia in cancer patients is affected by cancer type, duration, treatment, infection and inflammation related to cancer. RET-He measure the recent functional availability of iron and the correlation well with iron deficient / restricted erythropoiesis, and it is not affected by infection and inflammation related to cancer so it can be useful marker to rapidly rule out iron deficiency in cancer patients. Material: This is observation longitudinal study and study subjects including all type of diagnosed cancer patients with anemia (Hb <13 gm % in males and <12gm% in females) with or without treatment. Study duration was 18 month and 200 sample size was taken. Complete blood count (Hb, TLC, platelets, MCV, MCH, MCHC, reticulocyte hemoglobin) were analysed on SYSMEX XN 1000i. Serum Ferritin was estimated using AVANTOR CL-1000i and Serum iron, TIBC, TSAT was run on EBRA MANHEIN CHEM 5X machine. Bone marrow examination was done for diagnosis / staging . Iron stores were evaluated by Perl's Prussian blue stain and graded as per criteria laid down by Gale et al. Observation: At a cut off of 28.4 pg, RET-He achieved sensitivity of 96.77 % and specificity of 81.66% with NPV of 99.3% and PPV of 49.2% for iron deficient state in cancer patients. This cut off value rules out iron deficient erythropoiesis, reduces unnecessary iron studies and encourage early treatment of iron deficiency. There is also moderate agreement exist between iron stores of bone marrow and RET-He with Kappa 0.411 and p value <.0001. Conclusion: RET-He is better indicator of IDA in cancer patients as compared to other conventional methods of diagnosing IDA.This study also revealed a direct correlation between RET-He and bone marrow iron stores. In future it is advisable to use RET-He as a predictor of IDA, which is sensitive and specific at particular cut off points in routine evaluation in IDA in cancer patients.