Evidence of microRNAs origination from chloroplast genome and their role in regulating Photosystem II protein N (psbN) mRNA.

The microRNAs are endogenous, regulating gene expression either at the DNA or RNA level. Despite the availability of extensive studies on microRNA generation in plants, reports on their abundance, biogenesis, and consequent gene regulation in plant organelles remain naVve. Building on previous studies involving pre-miRNA sequencing in Abelmoschus esculentus, we demonstrated that three putative microRNAs were raised from the chloroplast genome. In the current study, we have characterized the genesis of these three microRNAs through a combination of bioinformatics and experimental approaches. The gene sequence for a miRNA, designated as AecpmiRNA1 (A. esculentus chloroplast miRNA), is potentially located in both the genomic DNA, i.e., nuclear and chloroplast genome. In contrast, the gene sequences for the other two miRNAs (AecpmiRNA2 and AecpmiRNA3) are exclusively present in the chloroplast genome. Target prediction revealed many potential mRNAs as targets for AecpmiRNAs. Further analysis using 5' RACE-PCR determined the AecpmiRNA3 binding and cleavage site at the photosystem II protein N (psbN). These results indicate that AecpmiRNAs are generated from the chloroplast genome, possessing the potential to regulate mRNAs arising from chloroplast gene(s). On the other side, the possibility of nuclear genome-derived mRNA regulation by AecpmiRNAs cannot be ruled out.

Novel CHRNA3 variants identified in a patient with bladder dysfunction, dysautonomia, and gastrointestinal dysmotility.

Congenital anomalies of the kidney and urinary tract (CAKUT) are estimated to be responsible for 20%-50% of congenital anomalies and are also a leading etiology of early-onset renal disease. Primary CAKUT are caused by genetic factors that impair proper in-utero genitourinary tract development and secondary CAKUT result from the influence of environmental factors. The CHRNA3 gene, which encodes the Alpha-3 subunit of the nicotinic acetylcholine receptor, is hypothesized to be associated with Megacystis-microcolon-intestinal hyperperistalsis syndrome. More recently, pathogenic variants in CHRNA3 have been identified in individuals with CAKUT as well as individuals with panautonomic failure. Here we present a patient with neurogenic bladder, vesicoureteral reflux, mydriasis, and gastrointestinal dysmotility found to have novel compound heterozygous variants in CHRNA3. These findings support the consideration of CHRNA3 disruption in the differential for CAKUT with dysautonomia and gastrointestinal dysmotility.

Treating low- and intermediate-risk acute promyelocytic leukemia with and without chemotherapy: A comparison in a tertiary care center.

Background: Acute promyelocytic leukemia (APL) comprises approximately 10% of acute myeloid leukemia (AML) cases. Material and Methods: Both options of treatment (ATRA-ATO and ATRA-chemotherapy) were discussed with patients with low- and intermediate-risk APL, pros and cons explained in details, and treatment regimen selected after getting informed written consent. Results: Total 71 patients were included in the study; among these patients, 3 were negative for both FISH for t (15,17) and RT-PCR for promyelocytic leukemia retinoic acid receptor alpha, and 36 patients with APL had white blood cell count at diagnosis >10 × 109/l. Total 30 patients with newly diagnosed as low- and intermediate-risk-APL fulfilled all inclusion criteria, treated and followed for a minimum period of 2 years up to June, 2016. Fifteen patients liked to be treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), while rest of the 15 patients preferred treatment with ATRA and chemotherapy. Conclusion: Combination of ATRA and ATO is equally effective, less toxic, and more feasible in comparison to ATRA and chemotherapy for patients with low- and intermediate-risk APL and is a viable option for this subset of patients, especially in countries with limited resources.

Identification of potent histone deacetylase 2 (HDAC2) inhibitors through combined structure and ligand-based designs and molecular modelling approach.

Histone deacetylase 2 (HDAC2) is associated with various neuropathic degenerative diseases and is considered a novel target for Alzheimer's disease (AD). Elevated levels of HDAC2 trigger excitatory neurotransmission and reduce synaptic plasticity, synaptic number, and memory formation. In the current study, we identified HDAC2 inhibitors using an integrated structure and ligand-based approaches to drug design. Three pharmacophore models were generated by using different pharmacophoric features and validated using the Enrichment factor (EF), Güner-henry (GH) score, and percentage yield. The model of choice was used to screen a library of Zinc-15 compounds and interfering compounds were eliminated by using drug likeliness and PAINS filtering. Further, docking studies in three stages were carried out to obtain hits with good binding energies and were followed by ADMET studies yielding three virtual hits. The virtual hits, i.e. ZINC000008184553, ZINC0000013641114, and ZINC000032533141, were subjected to molecular dynamics simulation studies. Compound ZINC000008184553, identified as lead, was found to have optimal stability, low toxicity under simulated conditions, and may potentially inhibit HDAC2.Communicated by Ramaswamy H. Sarma.

Severe persistent marrow aplasia in chronic myeloid leukemia (CML): An unusual complication of imatinib.

Background: Imatinib has changed the treatment of chronic myeloid leukemia (CML) drastically since 15 years. It is usually well tolerated, but severe persistent marrow aplasia is an unusual complication of imatinib while using it in CML. The aim of this study is to describe our experience confronting this rare side effect and review the available data worldwide. Patients and Methods: It was a retrospective analysis conducted at a center from February 2002 to February 2015. This study was endorsed by our Institutional Review Board (IRB) and written consent was taken from all patients. Patients diagnosed as Philadelphia (Ph) chromosome-positive CML either in chronic phase (CP), accelerated phase (AP), or blastic crisis (BC) were included. There were a total of 1,576 patients with CML treated with imatinib during this period. Karyotyping and quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) were done at the time of pancytopenia for all patients. Results: In total, 11 (males = 5, females = 6) patients met our inclusion criteria from 1,576 patients of CML. The median age was 58 years (range 32-76). Out of 11 patients 8, 2, and 1 patients were in CP, AP, and BC phases, respectively. The median time of administration of imatinib was 3.3 months (range 1.5-6). The average time of marrow recovery was 10.4 months (range 5-15). Two patients expired (one from septicemia and the other from intracranial hemorrhage). BCR-ABL transcripts level by RT-PCR revealed the existence of the disease in all patients. Conclusion: Imatinib is a very well-tolerated tyrosine kinase inhibitor (TKI), but is associated with persistent myelosuppression when used in older age, advanced phase of the disease, and treated previously. After confirming persistent marrow aplasia, the treatment is mainly supportive. It is striking that the disease is still persistent, which is confirmed by RT-PCR. There is no consensus regarding recalling imatinib at lower doses or the use of second-generation TKI (nilotinib, dasatinib) in these patients.

Experience of Nivolumab Prior to Autologous Stem Cell Transplant for Relapsed Refractory Hodgkin Lymphoma.

Purpose Nivolumab is an anti-programmed cell death protein 1 (PD1) monoclonal antibody that is indicated in relapsed/refractory Hodgkin lymphoma (R/R HL) after autologous stem cell transplant (autoSCT). Purpose of our retrospective study was to assess safety and efficacy of Nivolumab in R/R HL as a bridge to autoSCT in patients who are refractory to ≥ 2 lines of chemotherapy. Methods Demographic data, number of chemotherapy regimens given previously, number of Nivolumab doses taken, and disease status on PET/CT were noted. Nivolumab was administered as a 3 mg/kg IV infusion every 2 weeks. The immunotherapy related adverse events (irAEs) were noted if any and documented. Results A total of 16 patients were included in the study. Ten patients were male and 6 were female. Median age was 22 years (range 3-32 years). The median number of treatment lines prior to Nivolumab was 3 (range 2-7). Nine patients had Complete Response (CR), 3 had Partial response (PR), 2 had Stable Disease (SD), 1 patient had pseudo-progression; classified as IR (3) and 1 expired before end of treatment evaluation. The drug was well tolerated, with mild irAEs noted. Twelve patients (75%) successfully underwent autoSCT. At a median follow up of 17.5 months (range 0.5-35 months), the progression- free survival (PFS) was 75% and overall survival (OS) was 87.5%. Conclusion Nivolumab is effective and safe in patients with R/R HL and is a good bridging therapy to autoSCT.

Quantification of Right Atrial-Indexed End-Systolic Volumes and Emptying Fraction in Children Undergoing Cardiac Surgery With Two-Dimensional Transesophageal Echocardiography: A Prospective Observational Study.

OBJECTIVES: The primary objective of this study was to establish "normal" right atrial (RA)-indexed end-systolic volumes (ESVs) and emptying fraction (EF) in children undergoing ventricular septal defect (VSD) repair using two-dimensional (2D) transesophageal echocardiography (TEE). Secondary objectives were to obtain RA-indexed ESV and EF in children with RA/right ventricular (RV) volume overload (atrial septal defect [ASD]) and RV pressure overload (tetralogy of Fallot [TOF]) and to determine whether baseline differences existed in these indices among the three lesions. DESIGN: A prospective observational study. SETTING: Tertiary referral center and a university level teaching hospital. PARTICIPANTS: The study comprised 90 children (30 in each cohort) >3 kg and <14 years old admitted for elective repair of either VSD, TOF, or ASD. MEASUREMENTS AND MAIN RESULTS: RA ESV and EF were measured in the midesophageal four-chamber view using the area-length and the modified Simpson's methods with 2D TEE in the prebypass period. Mean RA- indexed ESV (area-length method) in the VSD cohort was 24.2 ± 6.7 mL/m2, whereas it was significantly greater in the TOF (31.9 ± 9.8 mL/m2; p = 0.0008) and ASD (52 ± 12.9 mL/m2; p < 0.0001) cohorts. RA EF in the TOF cohort was 48.4% ± 7.6%, which was significantly more than in the VSD (41.5% ± 11.8%; p = 0.0093) and ASD (39.1% ± 12.3%; p = 0.0008) cohorts. CONCLUSIONS: This was the first study using 2D TEE to measure RA indices in children with and without right-sided heart dilation undergoing cardiac surgery. In this study, RA, ESV, and EF were considerably different in children with congenital heart disease causing RV pressure or volume overload. Additional studies can examine how these values can be used for risk stratification in this cohort of patients or how they correlate with measures of ventricular performances.

Prospective Comparative Evaluation of Noninvasive and Invasive Mechanical Ventilation in Patients of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure Type II.

INTRODUCTION: Acute respiratory failure is a potential complication of chronic obstructive pulmonary disease (COPD) that severely affects the health of the patient and may require mechanical ventilation. We compared noninvasive and invasive mechanical ventilation in COPD patients with acute respiratory failure type II to validate clinical outcome based on biochemical analysis of arterial blood gases (ABGs) and pulmonary parameters in terms of duration of mechanical ventilation, period spent in intensive care unit (ICU) and mortality. MATERIALS AND METHODS: After approval of institutional ethical committee 100 patients were selected for randomized prospective controlled trial and divided into two groups of 50 each according to mode of mechanical ventilation. Group-I patients managed with noninvasive ventilation (NIV) Group-ll managed with invasive ventilation. RESULTS: Demographic data between two groups were comparable. ABG parameters were better at 2 h and 6 h interval in NIV as compared to invasive ventilation (P < 0.05). The duration of ventilation and total time spent in ICU was 106±10 hours and 168±8 hours respectively in NIV group and 218 ± 12 and 280 ± 20 in invasive group. On intergroup comparison these were significantly less in noninvasive group (P < 0.05). Hospital acquired pneumonia occurred in 10% of patients in invasive group whereas no incidence of pneumonia found in noninvasive group. Mortality rate was 12% in invasive groups and 2% in noninvasive groups. CONCLUSION: NIV leads to significant improvement in ABG and pulmonary parameters and it reduces duration of ventilation and total period of hospital stay so it can be used as an alternative to invasive ventilation as first-line treatment in COPD.

Noncoding RNA: An Insight into Chloroplast and Mitochondrial Gene Expressions.

Regulation of gene expression in any biological system is a complex process with many checkpoints at the transcriptional, post-transcriptional and translational levels. The control mechanism is mediated by various protein factors, secondary metabolites and a newly included regulatory member, i.e., noncoding RNAs (ncRNAs). It is known that ncRNAs modulate the mRNA or protein profiles of the cell depending on the degree of complementary and context of the microenvironment. In plants, ncRNAs are essential for growth and development in normal conditions by controlling various gene expressions and have emerged as a key player to guard plants during adverse conditions. In order to have smooth functioning of the plants under any environmental pressure, two very important DNA-harboring semi-autonomous organelles, namely, chloroplasts and mitochondria, are considered as main players. These organelles conduct the most crucial metabolic pathways that are required to maintain cell homeostasis. Thus, it is imperative to explore and envisage the molecular machineries responsible for gene regulation within the organelles and their coordination with nuclear transcripts. Therefore, the present review mainly focuses on ncRNAs origination and their gene regulation in chloroplasts and plant mitochondria.

Post-transplant Hemophagocytic Lymphohistiocytosis in Benign Hematological Disorders: Experience of 4 Cases with Review of Literature.

Post transplant Hemophagocytic lymphohistiocytosis (HLH) is a form of secondary HLH, which can be either early onset or late onset and is associated with significant morbidity and mortality. With the increasing popularity of post transplant cyclophosphamide based haploidentical stem cell transplantation (SCT), post transplant HLH is becoming a significant complication especially in benign hematological disorders. Methods: We present 4 cases of post transplant HLH occurring in 2 cases of severe aplastic anemia (post haploidentical SCT) and 2 cases of thalassemia major (post matched sibling SCT). All 4 cases had early onset variety with dismal prognosis. Conclusion: Post-transplant HLH is an important entity in benign hematological disorders, which needs to be identified early and treated promptly with steroids, monoclonal agents or immunosuppressive therapy. Serum ferritin levels are an important biomarker and help in monitoring response.

Pediatric chronic myeloid leukemia: A single-center experience.

BACKGROUND: The rationale of this study is to reveal the statistics of pediatric chronic myeloid leukemia (CML) patients. SUBJECTS AND METHODS: It is a retrospective analysis conducted to assess pediatric CML data from January 1998 to December 2014. There are 65 (3.2%) pediatric CML patients out of entire 2008 patients of CML. Data were analyzed regarding epidemiological characteristics, clinical presentations, response and side effects of imatinib, event-free survival, and overall survival of the pediatric CML patients. RESULTS: The median age of diagnosis was 11.84 years, and 76.9% patients were male and 23.07% patients were female. Sixty (92.3%) patients were in CML-chronic phase, 3 (4.6%) patients in CML-accelerated phase, and 2 (3.07%) patients in CML-blastic crisis. Most common initial symptoms and signs are weakness (60.0%), abdominal pain (55.38%), splenomegaly (100%), and hepatomegaly (86.5%). 67.3% of patients have white blood counts <100 × 109/L and 92.3% had platelets >150 × 109/L. In the initial months of 2002, imatinib was available and utilized in 54 patients. Of 54 patients, complete hematological response at 3 months, partial cytogenetic response at 6 months, complete cytogenetic response at 12 months, and major molecular response (MMR) at 18 months were 77.77%, 59.2%, 48.14%, and 40.74%, respectively. MMR at 36 months was 62.96% ( n = 34). Most common imatinib-related side effects are gastrointestinal upset and myelosuppression. CONCLUSION: Pediatric CML in India is comparable with Western countries regarding epidemiological characteristic, clinical presentations, and tolerance of imatinib. As there is a paucity of universal literature regarding pediatric CML (especially data from Southeast Asian region), this article may fill up that space.

A Prospective Open-Label Randomized Controlled Trial to Compare Intrathecal 1% 2-Chloroprocaine Versus 0.5% Bupivacaine in Ambulatory Elective Surgeries.

BACKGROUND: For an outpatient surgery, an ideal anesthetic drug should have a faster onset and shorter duration of action and minimal side effects. Although Bupivacaine is a drug of choice in spinal anesthesia but is not suitable for ambulatory surgeries. We aimed to compare 1% 2-chloroprocaine (2-CP) which is considered to be a short-acting agent with 0.5% hyperbaric bupivacaine as a spinal anesthetic agent in ambulatory surgeries. MATERIALS AND METHODS: The study includes a prospective analysis of 60 patients who underwent ambulatory surgeries of <60 min and were randomly divided into two groups of 30 each: Group I - intrathecal injection of preservative-free formulation of 1% 2-CP 40 mg (4 mL) given and Group II - intrathecal injection of 0.5% hyperbaric bupivacaine 10 mg (2.0 mL) given time to reach surgical anesthesia, time for resolution of motor block, time for end of anesthesia, time to requirement of first postoperative analgesic, time to unassisted ambulation, time for micturition, and time to reach discharge readiness criteria, which were recorded. RESULTS: We observed that in the CP group, onset time is early and there was more fast regression of surgical anesthesia in the CP group resulting in less time required for unassisted ambulation and less time for discharge from the hospital. CONCLUSION: We concluded that 2-CP can be used for spinal anesthesia in shorter duration surgeries with early recovery from anesthesia and hence early discharge from the hospital.

Primary Central Nervous System Burkitt Lymphoma in HIV Positive Pediatric Patient: A Rare Case Report.

Burkitt lymphoma is a high-grade B-cell lymphoma with aggressive course of disease and primarily systemic nodal involvement. Primary Burkitt lymphoma with isolated central nervous system (CNS) involvement and that too in pediatric population has been rarely reported. Here, we present a case of a primary Burkitt lymphoma involving brain in an human immunodeficiency virus-positive pediatric patient who was on antiretroviral therapy. Currently, there are no established protocols or guidelines for management of primary CNS Burkitt lymphoma thus posing challenges in the management of such cases. Our patient was successfully treated by surgical resection followed by chemotherapy and radiotherapy.

Clinical and epidemiological profile of neuroendocrine tumors: An experience from a regional cancer center from Western India.

BACKGROUND: Most of the data on neuroendocrine tumors (NETs) are from the Western literature. Indian studies regarding clinicopathological characteristics and treatment outcomes are lacking. METHODS: This is a prospective observational study of all new patients with NETs (except small-cell lung cancer) registered at our tertiary care cancer institute from November 2014 to November 2016. A total of 97 new patients were registered, of which 20 were lost to follow-up before starting any planned treatment. Epidemiological and clinicopathological features of all these 97 patients were studied, and the remaining 77 patients were analyzed for treatment response and survival analysis. RESULTS: The median age at diagnosis was 49 years (20-74 years) with male preponderance (M: F = 1.85:1). The most common primary site of origin was pancreas (34/97 = 35%), followed by unknown primary origin (19%), small intestine (9%), and pulmonary (6%). Of 97 patients, 91 (93.8%) presented with nonfunctional symptoms, 3 (3.1%) had purely functional symptoms, and 3 (3.1%) presented with both functional and nonfunctional symptoms. The most common presenting symptom was abdominal pain (59.7%), followed by jaundice (9.3%), whereas watery diarrhea (83.3%) and flushing (66.7%) were the most common functional symptoms. Sixty-six percent (64/97) of cases were metastatic at presentation. A strong correlation was noted between the primary site of origin and metastatic presentation (P = 0.016). Chemotherapy was the most common primary therapy (40.2%), followed by surgery (28.6%), watchful waiting (15.6%), and somatostatin analogs (11.7%). The median event-free survival was highest for patients undergoing surgery (10 months). CONCLUSIONS: The clinicopathological profile of NETs in the Indian population differs from Western countries. Majority of patients present with metastatic disease, thus representing a need for creating awareness among patients and medical fraternity and formulating Indian guidelines for optimized treatment.

Immunosuppressive therapy for aplastic anemia: a single-center experience from western India.

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CsA) is the first-line therapy for acquired aplastic anemia (AA) in those not suitable for bone marrow transplant. Horse ATG (hATG) is preferred for this purpose, but its use is often impeded by shortages and costs. Being a rare disease, there is limited data on this therapy. This study aimed to evaluate this therapy in a large cohort of AA patients from western India. We retrospectively analyzed AA patients who received an indigenous preparation of hATG along with CsA as first-line treatment, between 2012 and 2015, at our center and evaluated the response, survival, and occurrence of adverse events. The response was further assessed separately for adults and children. During the period, 91 AA patients (4 non-severe, 57 severe and 30 very severe) were treated with IST. At 2 years, 23.5% adults and 39.1% children showed complete response and an overall of 68.1% cases became transfusion independent. More than half of the patients developed febrile neutropenia while roughly one sixth of the patients developed gum hypertrophy and/or hypertension. Two patients had clonal evolution. Mortality rate was calculated to be 31%; most common causes of death were infection and intracranial hemorrhage. The results of the study substantiate the effectiveness of IST in AA, using an inexpensive indigenous preparation of hATG along with CsA.

A study of the use of peripherally inserted central catheters in cancer patients: A single-center experience.

Effective and reliable venous access is one of the cornerstones of modern medical therapy in oncology. The focus of this prospective observational research is to study the various indications of a peripherally inserted central catheter (PICC) in different solid and hematological malignancies and the various complications and outcomes in the pediatric and adult cancer patients. This study was conducted in a prospective observational study design and collected data of patients with a diagnosis of any cancer, at a tertiary care oncology hospital in Ahmadabad, Gujarat, India, during a 2-year period. The PICC was inserted in 352 patients and most commonly used in hematological conditions (n = 295, 83.8%), followed by solid malignancies 57 (16.2%). In the hematological malignancy group, acute myeloid leukemia (48.01%) was the most common indication, and in the solid malignancies group, osteosarcoma (n = 9, 2.55%) was the most common indication for PICC insertion. PICCs were inserted most commonly in the left side of the venous system in 70.7% cases. The complications in the PICC study group included infections (12.5%), thrombosis (4.82%), catheter blockage (4.82%), arrhythmias (4%), premature catheter removal (3%), bleeding (2.55%), and pneumothorax (2.55%). The median days of the PICC use in situ were 152 days. To conclude from our study, PICCs are most commonly indicated in malignancies that are requiring long-term chemotherapy, such as hematological malignancy, especially acute myeloid leukemia, and solid malignancies, usually osteosarcoma, and these catheters are associated with complications such as infection, thrombosis, catheter blockage, arrhythmia, bleeding, and pneumothorax. The most disturbing aspect of the treatment of a cancer patient is multiple painful venipunctures made for administration of cytotoxic agents, antibiotics, blood products, and nutritional supplements. From this study, we can infer that PICC lines can be used for various malignancies that require long-term chemotherapy.

Clinical and microbiological profile of infections during induction phase of acute myeloid leukemia.

BACKGROUND: The primary objective of this study is to describe clinical and microbiological profile of infections during induction phase of acute myeloid leukemia (AML). PATIENTS AND METHODS: We reviewed the case records of 50 hospitalized patients with AML undergoing standard dose induction chemotherapy from January to December 2015. RESULTS: Out of 50 cases, 34 were males 16 females with median age of 30 years. Most common presenting symptoms were fever followed by bleeding diathesis. The clinical sites of infections were gastrointestinal tract including oral cavity (48%), respiratory tract (4%), skin/soft tissue (4%) and genitourinary tract (4%). Clinically (58%) or microbiologically (30%) documented infections were 88%, while 12% had fever without identifiable source. Overall, in 21 episodes microorganisms were isolated. Common sites of isolates were blood stream (11), stool (8), sputum (1) and urine (1). Gram negative infections accounted for 81% of total isolates; Escherichia coli (E. coli) being the commonest. Gram positive microorganisms were isolated in 19% of which methicillin resistant staphylococcus aureus (MRSA) was the most common. Gram negative bacterial infections were associated with higher mortality. CONCLUSION: Gastrointestinal tract is the most common clinical site of infection. Blood stream infection is the most common site for positive bacterial isolates. Gramnegative bacilli were the predominant cause of infections with E. coli being the most common pathogen isolated. Empiric antibiotic treatment for febrile neutropenia should be tailored to the locally prevalent pathogens and their susceptibility patterns.

Interdigitating dendritic cell tumor: A rare case report with review of literature.

Interdigitating dendritic cell tumor/sarcoma (IDCT) is a very rare and aggressive neoplasm arising from antigen-presenting cells. It usually involves lymph nodes, but extranodal sites can also be involved. Because of the rarity of the disease, consistent standard treatment guidelines have not been established till date. We report a case of a 35-year-old female who presented with right-sided neck swelling and anterior mediastinal mass. Histopathology revealed large mononucleated cells with background of mixed polymorphous inflammatory cells suspicious of Hodgkin's lymphoma. Hence, to confirm the diagnosis, immunohistochemistry was done. Immunohistochemistry revealed that the tumor was CD30 - negative, CD10 - negative, CD2 - negative, leukocyte common antigen - positive, vimentin - positive, and S-100 - positive, diagnostic of IDCT. Patient was treated with eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen chemotherapy followed by involved field radiotherapy and showed dramatic response with complete resolution of mediastinal mass.

Treatment of breast cancer in a patient of Alport syndrome-induced chronic renal failure: A triumph story.

Alport syndrome is a hereditary disease of the glomerular basement membrane, characterized by the familial occurrence of progressive, hematuric nephropathy with sensorineural deafness. We are reporting here a young adult female, suffering from Alport syndrome with significant family history and on maintenance twice-weekly hemodialysis (HD), had been diagnosed with triple negative earlystage right-sided breast cancer. The patient was managed successfully with surgery and adjuvant chemotherapy with 3 cycles of 5-flurouracil, doxorubicin, and cyclophosphamide and 3 cycles of docetaxel. In this case, our clinical challenge was dose reduction of chemotherapeutic agents according to creatinine clearance and timing of HD in each cycle of chemotherapy. We confronted this by dose reduction of cyclophosphamide and timing of chemotherapy was at least 12 h after HD for each and every cycle. Patient is in regular follow-up in our department since 20 months without any recurrence of the disease.

Experience of Sorafenib as First-Line Treatment in Metastatic Renal Cell Carcinoma in a Tertiary Care Centre.

Background: Metastatic renal cell carcinoma is chemoresistant and radioresistant disease with poor survival historically, but outcome has improved in past decade after introduction of tyrosine kinase inhibitors like sunitinib and sorafenib. Sorafenib has not been tested in Indian patients with metastatic RCC till now. Material and Methods: This is a single arm, prospective, observational study done in unselected population of 60 patients with metastatic RCC treated with sorafenib as first- line therapy to assess efficacy and safety. Results: Twenty three out of 60 patients (38.33%) continued sorafenib by the end of the study. Overall response rates (ORR), stable disease (SD) and disease control rates (DCR) were 35%, 43.33% and 78.33%, respectively. Median progression- free survival (PFS) and overall survival (OS) were 6 and 8 months, respectively and associated with histopathology, Memorial Sloan Kettering Cancer Centre (MSKCC) risk groups, Heng risk groups and performance status. Best tolerated dose was 400 mg per day which was half of standard dose. Fatigue, diarrhea, rashes and hand foot syndrome were common side effects while hypertension was rare. Conclusion: Sorafenib, as first-line therapy, is an effective and safe treatment in Indian patients with metastatic RCC with poor tolerance to dose more than 400 mg per day. Side effects are mostly manageable.