A rare differential diagnosis of aortic stenosis with a black aortic valve: A case report.

BACKGROUND: Cardiac ochronosis, presenting as a rare manifestation of alkaptonuria, an autosomal recessive disorder, is characterised by black pigmentation of calcified cardiac valves and atherosclerotic plaques. We report an intraoperative dilemma on the discovery on the black aortic valve in a case of an old lady with degenerative calcific aortic stenosis. CASE PRESENTATION: A 60-year-old lady was electively admitted for valve replacement with a bioprosthetic valve for severe aortic stenosis. She was symptomatic with complaints of headache and giddiness and had a pressure gradient of 113/17mmhg across the aortic valve. Intraoperatively, she was found to have cardiac ochronosis on the discovery of pigmented aortic intima extending to the valve leaflets and underwent valve replacement with a mechanical prosthetic valve. She was post-operatively evaluated for the same and diagnosed with alkaptonuria. Though the surgery went uneventful and the patient was discharged without any complication, she was advised to be on regular follow-up to assess valve gradients, paravalvular leaks and to monitor the disease progression. CONCLUSION: The presented case sheds light on the rare cardiac manifestation of alkaptonuria. In the absence of definitive pre-operative diagnosis, intraoperative findings played a pivotal role in guiding the surgical approach and choice of prosthetic valve. The decision to use a mechanical valve was influenced by the potential risks associated with bioprosthetic valves in the setting of ochronosis. Ongoing follow-up and monitoring are essential to assess the durability of the chosen prosthetic valve and to manage any long-term consequences of the underlying metabolic condition.

Outcome of Open Repair of Thoracoabdominal Aortic Aneurysm in Takayasu Arteritis: A Retrospective Analysis.

BACKGROUND: Takayasu Arteritis (TA) is an immune mediated arteritis causing inflammation of the aorta and its branches, which can result in aortic aneurysms. Our aim is to describe the outcome of surgical management in these patients who presented with Thoracoabdominal aortic aneurysm (TAAA). METHODS: Between 2003 and 2023, 40 TA patients with TAAA underwent operative repair. RESULTS: There were 24 females and 16 males, in the age group of 19-53 years, with hypertension in 20 patients. Raised Erythrocyte sedimentation Rate was present in 13 patients. According to Crawford classification, there were 2 patients with type I, 2 with type II, 17 with type III, 12 patients with type IV and 7 with type V aneurysm. Multiple steno-occlusive lesions of aortic branches were present in 21 patients, with majority affecting the renal artery. Femoral Artery Femoral Vein Partial cardiopulmonary bypass was used for types I, II, III and V. Separate bypass to visceral branches was done in eight patients, of whom five had multiple bypasses and three patients only had renal bypass. Twelve patients underwent reimplantation of branches, out of which nine had multiple vessel reimplantation. Four patients underwent staged repair of the aneurysm, which included visceral debranching in the first day, followed by repair of the aneurysm in the next day. In the immediate postoperative period, ten patients developed acute kidney injury and two required dialysis. Other morbidities included acute respiratory distress syndrome (ARDS), spinal cord dysfunction, bleeding, and wound complications. Three patients expired in the immediate postoperative period. Mean duration of intensive care unit stay was 4.1 days and hospital stay was 12.7 days. Comparison of disease activity with morbidity and mortality was statistically insignificant. Patients were on follow-up for a range of 6 months to 14 years and median follow-up of 25 months. Over this time period four patients expired and four developed anastomotic pseudoaneurysm requiring intervention. On comparing the disease activity at the time of surgery with the long-term arteritis related complications that required intervention, the P value was 0.653 and hence statistically not significant. The 10-year survival rate is 84.4%. CONCLUSIONS: Surgical repair has good and satisfactory outcome, with low early and late mortality rates. Progression of disease can occur at any stage of the disease, hence indicating the need for long term follow-up and frequent imaging.

Breast Cancer in the Arabian Gulf Countries.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of breast cancer in the GCC. Most of the studies reported a consistent increase in breast cancer incidence over the past decades, which was particularly attributed to the adoption of a Westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data on breast cancer risk factors in the GCC were limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50; an advanced stage at presentation; and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed toward elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

Autologous versus allogeneic blood transfusion: A comparative study of the peri-operative outcomes in a tertiary care hospital in South India amidst the COVID-19 pandemic.

Autologous blood transfusion is known to have advantages over allogeneic transfusion. The COVID-19 pandemic intensified the already existing shortage of allogeneic blood supply. We carried out a study during this period with the aim to elicit the effects of autologous blood collection and transfusion, to compare the peri-operative outcomes of autologous and allogeneic transfusion practices and also to assess the influence of the autologous transfusion programme in the Blood Centre inventory. It was prospective observational comparative study among neurosurgical and vascular surgical patients in a tertiary care centre in South India. 141 patients were allocated into Group I (n = 71) who received autologous transfusion and those who received conventional allogeneic transfusion were clustered as Group II (n = 72) for analysis. We employed Acute Normovolemic Hemodilution (ANH), Pre-deposit Autologous Donation (PAD) and Intra-operative Cell Salvage (ICS) as various modalities for autologous blood collection. In our study, 43 (60.6%) from Group I received exclusive autologous blood transfusion, whereas 28 (39.4%) required additional allogeneic transfusion. No significant difference in hemoglobin, hematocrit, platelet count and INR were observed between the groups post transfusion. Significant difference was observed in the thoracoabdominal aortic aneurysm (TAAA) patients with respect to duration of ICU stay (2.7 ± 1.1 days in Group I and 6.2 ± 0.8 days in Group II; p = 0.002) and re-exploration due to bleeding (16.7% in Group I and 40% in Group II; p = 0.048). Autologous blood transfusion is safe and effective. It can be employed as routine practice and also during any acute shortage or pandemic.

A rare case of retro-hepatic inferior vena caval leiomyosarcoma - Computed tomography, surgical and intraoperative echocardiography imaging.

Leiomyosarcoma of retro-hepatic portion of inferior vena cava (IVC) is a rare vascular tumor with poor prognosis if adequate surgical resection is not achieved. Surgical repair includes dissection of the tumor and reconstruction of the IVC with a tube graft. Establishing a normal flow and gradient in IVC and hepatic veins is imperative for a successful repair. We report a case of retro hepatic IVC leiomyosarcoma where the preoperative computed tomography described the anatomy and extension of the tumor whereas intraoperative transesophageal echocardiography helped in the assessment of adequacy of surgical repair.

The plant specialized metabolite epicatechin- 3-gallate (EC3G) perturbs lipid metabolism and attenuates fat accumulation in pigeonpea pod borer, Helicoverpa armigera.

Control of pod borer Helicoverpa armigera, a notorious polyphagous pest requires paramount attention with focus on environment-friendly management approaches. Overproduction of catechins (epigallocatechin-EGC and epicatechin-3-gallate-EC3G) in the pod borer-resistant pigeonpea wild relative, Cajanus platycarpus during continued herbivory prodded us to assess their underlying molecular effect on H. armigera. Significant reduction in larval and pupal growth parameters was observed when reared on artificial diet incorporated with 100 ppm EC3G vis a vis 100 ppm EGC and EGC + EC3G. Comparative RNAseq analyses of larvae that fed on normal and EC3G-incorporated diet revealed 62 differentially expressed genes dominated by detoxification and lipid metabolism. While lipase and fatty acid-binding protein 2-like were up-regulated, delta9-FADS-like involved in fatty acid synthesis was downregulated, indicating effect of EC3G on fat metabolism. Validation of RNAseq data by qPCR; midgut glutathione-S-transferase and esterase assays depicted increased lipolysis and reduced lipogenesis in EC3G-fed larvae. Additionally, differential accumulation of stearic acid and oleic acid in EC3G-fed and control larvae/adults ascertained perturbation in lipogenesis. Supported by modelling, molecular docking and simulations, we demonstrate the possible involvement of the insect adipokinetic hormone receptor (AKHR) in the EC3G-mediated response. The study demonstrates plant specialized metabolite EC3G as a potential candidate for H. armigera control.

Cajanus platycarpus Flavonoid 3'5' Hydroxylase_2 (CpF3'5'H_2) Confers Resistance to Helicoverpa armigera by Modulating Total Polyphenols and Flavonoids in Transgenic Tobacco.

Pod borer Helicoverpa armigera, a polyphagus herbivorous pest, tremendously incurs crop damage in economically important crops. This necessitates the identification and utility of novel genes for the control of the herbivore. The present study deals with the characterization of a flavonoid 3'5' hydroxylase_2 (F3'5'H_2) from a pigeonpea wild relative Cajanus platycarpus, possessing a robust chemical resistance response to H. armigera. Though F3'5'H_2 displayed a dynamic expression pattern in both C. platycarpus (Cp) and the cultivated pigeonpea, Cajanus cajan (Cc) during continued herbivory, CpF3'5'H_2 showed a 4.6-fold increase vis a vis 3-fold in CcF3'5'H_2. Despite similar gene copy numbers in the two Cajanus spp., interesting genic and promoter sequence changes highlighted the stress responsiveness of CpF3'5'H_2. The relevance of CpF3'5'H_2 in H. armigera resistance was further validated in CpF3'5'H_2-overexpressed transgenic tobacco based on reduced leaf damage and increased larval mortality through an in vitro bioassay. As exciting maiden clues, CpF3'5'H_2 deterred herbivory in transgenic tobacco by increasing total flavonoids, polyphenols and reactive oxygen species (ROS) scavenging capacity. To the best of our knowledge, this is a maiden attempt ascertaining the role of F3'5'H_2 gene in the management of H. armigera. These interesting leads suggest the potential of this pivotal branch-point gene in biotic stress management programs.

Bedside Chest Ultrasound in Postoperative Pediatric Cardiac Surgery Patients: Comparison With Bedside Chest Radiography.

OBJECTIVE: The primary objective was to study the degree of agreement between the chest ultrasound (CUS) studies and chest x-ray (CXR) studies in postoperative pediatric cardiac surgical patients regarding the diagnosis of thoracic abnormalities, and also to compare the diagnostic performance of CUS in reference to CXR for the detection of thoracic abnormalities. The secondary objective was to compare the necessity for interventions done on the basis of CUS and CXR findings in the postoperative setting. DESIGN: A prospective observational study. SETTING: At a postoperative pediatric cardiac surgical intensive care unit in a tertiary-care center. PARTICIPANTS: One hundred sixty patients between the age of 2 months to 18 years undergoing elective cardiac surgery for various congenital heart diseases. INTERVENTIONS: After obtaining permission from the institutional ethics committee, 160 pediatric cardiac surgical patients were studied prospectively in the postoperative period. On the day of surgery (postoperative day [POD] 0), bedside CXR was done in the immediate postoperative period. After bedside CXR, CUS examination was performed and then interpreted by the principal investigator. The CXR was interpreted by the surgical team. Provisional diagnosis was made by the principal investigator and surgical team. Any intervention required was decided based on CXR or CUS findings or both. The procedure was repeated in the morning of POD 1. MEASUREMENTS AND MAIN RESULTS: The degree of agreement between CUS studies and CXR studies in detecting abnormalities was evaluated by Cohen's kappa (k) statistics. The diagnostic performance of CUS was compared with that of CXR using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy. Overall, kappa analysis (k) showed substantial agreement between the findings of the CUS and CXR studies (k = 0.749). The diagnostic performance of CUS, as compared with CXR, was found to have a sensitivity of 96.9%, specificity of 84.75%, PPV of 73.4%, NPV of 98.43%, and diagnostic accuracy of 88.44%. In 94 abnormal findings, the interventions were done based on CUS or CXR findings or both. Overall, there was a substantial agreement (k = 0.787) between CUS and CXR regarding the necessity for interventions. CONCLUSIONS: The degree of agreement between CUS and CXR studies was substantial for atelectasis, interstitial edema, and diaphragmatic weakness. The degree of agreement between CUS and CXR studies was almost perfect for pneumothorax and fair for pleural effusion. More CUS studies detected intrathoracic pathologies than CXR studies. The CUS also detected abnormalities earlier than CXR and was found to be useful for the early institution of intervention therapy in patients with interstitial edema and atelectasis. It would be reasonable to conclude that CUS may be considered in some instances as an alternative to CXR.

Comparison of effects of sevoflurane versus propofol on left ventricular longitudinal global and regional strain in patients undergoing on-pump coronary artery bypass grafting.

Background: Assessment of myocardial deformation by quantifying peak systolic longitudinal strain (PSLS) is a sensitive and robust index to detect subclinical myocardial dysfunction. We hypothesize that sevoflurane by virtue of anesthetic preconditioning preserves myocardial function better than propofol. Aims: The authors have assessed the effects of sevoflurane and propofol on global longitudinal strain (GLS) as a primary outcome in patients undergoing on-pump coronary artery bypass grafting. Our secondary aim was to assess the pattern of regional distribution of segmental PSLS between the groups. Materials and Methods: Fifty patients with normal left ventricular function undergoing coronary artery bypass grafting were analyzed in this prospective observational study. Consecutive patients received either propofol (P) or sevoflurane (S) anesthesia. Measurements: Trans-esophageal echocardiographic images (mid-esophageal four-chamber, two-chamber, and three-chamber (long-axis)) were recorded during the precardiopulmonary bypass (CPB) and post-CPB period. Strain analysis (GLS/segmental PSLS) was done offline by investigators blinded to the study. The inotropic score, duration of inotropic support, and mechanical ventilation required were recorded. Results: Following cardiopulmonary bypass and coronary revascularization, GLS reduced significantly in both the groups (P < 0.05). In the S-group, significant reduction in segmental strain was observed only in apical segments including apex, whereas in P-group significant reduction in segmental strain was seen in mid- and apical segments. The postoperative VIS, duration of inotropes/vasopressor required, and mechanical ventilation were similar in both the groups. Conclusions: There are no significant differences in global left ventricular function as assessed by GLS between patients anesthetized with sevoflurane or propofol. However, regional PSLS was better preserved in the S-group compared to P-group.

Comparison of Three Ultrasound Views for Internal Jugular Venous Cannulation in Patients Undergoing Cardiac Surgery: A Randomized Trial.

BACKGROUND: The quality of needle visualization during ultrasound-guided internal jugular vein (IJV) cannulation determines the ease of procedure, whereas posterior IJV wall puncture is the most common risk associated. The IJV can be imaged in different views, which offer certain advantages over each other. We compared three different ultrasound views for IJV cannulation short axis (SAX), long axis (LAX), and oblique axis (OAX) with respect to the quality of needle visualization, first pass success rate, and posterior IJV wall puncture. METHODS: Two hundred ten patients undergoing elective cardiac surgery were analyzed in this prospective randomized clinical trial. Patients were randomly assigned to one of the three groups: SAX (n = 70), LAX (n = 70), and OAX (n = 70). The quality of needle visualization, first pass success rate, and incidence of posterior IJV wall puncture in each of the three ultrasound views were studied. The Chi-square test and ANOVA were used for the comparison of means and proportion between the groups. RESULTS: The quality of needle visualization was graded as good in 90% patients in OAX group, 81.4% patients in LAX group, and 14.2% patients in SAX group, respectively (P < 0.0001). OAX group had the highest first pass success rate (94.2%) followed by SAX (88.5%), and then, LAX (82.8%), but it was statistically insignificant among the groups (P = 0.105). The mean IJV access time was longer in LAX group when compared to OAX and SAX group (P < 0.0001).The incidence of IJV posterior wall puncture was 14.2% patients in SAX group and none in other groups (P = 0.0011). CONCLUSION: The results suggest that OAX view can be adopted as standard approach during ultrasound-guided IJV cannulation as it safe and reliable.

Recovery of Latent HIV-1 from Brain Tissue by Adoptive Cell Transfer in Virally Suppressed Humanized Mice.

Defining the latent human immunodeficiency virus type 1 (HIV-1) burden in the human brain during progressive infection is limited by sample access. Human hematopoietic stem cells (hu-HSCs)-reconstituted humanized mice provide an opportunity for this study. The model mimics, in measure, HIV-1 pathophysiology, transmission, treatment, and elimination in an infected human host. However, to date, brain HIV-1 latency in hu-HSC mice during suppressive antiretroviral therapy (ART) was not studied. To address this need, hu-HSC mice were administered long acting (LA) ART 14 days after HIV-1 infection was established. Animals were maintained under suppressive ART for 3 months, at which time HIV-1 infection was detected at low levels in brain tissue by droplet digital polymerase chain reaction (ddPCR) test on DNA. Notably, adoptive transfer of cells acquired from the hu-HSC mouse brains and placed into naive hu-HSC mice demonstrated viral recovery. These proof-of-concept results demonstrate replication-competent HIV-1 reservoir can be established in hu-HSC mouse brains that persists during long-term ART treatment. Hu-HSC mice-based mouse viral outgrowth assay (hu-MVOA) serves as a sensitive tool to interrogate latent HIV-1 brain reservoirs.

Humanized Mice for Infectious and Neurodegenerative disorders.

Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.

Ex-foliar application of glycine betaine and its impact on protein, carbohydrates and induction of ROS scavenging system during drought stress in flax (Linum usitatissimum).

Crop plants have an innate capacity to acclimatize and survive myriad stresses in field conditions. This acclimatization to stress enhances crop stand in field and productivity of plant. Inter alia field crops withstand drought stress (hydropenia) by inducing synthesis or accumulation of osmolytes such as (i) proline and other amino acids, (ii) glycine betaine (GB), (iii) soluble carbohydrates, and (iv) reactive oxygen species (ROS) scavenging system as intrinsic drought antagonizing molecules. Precise in vivo induction of osmolytes and their effect on ROS scavenging system in flax/linseed has not been elucidated. The investigation was carried out to identify a tolerant and susceptible cultivar of flax from a core collection of 53 core accessions and evaluate the role of compatible osmolytes in Linum usitatissimum under hydropenia. We screened eight morphometrically diverse flax genotypes in field under irrigated and un-irrigated condition and classified them as tolerant and susceptible genotypes. Further, we examined the effect of ex-foliar glycine betaine application - a signature molecule involved in drought tolerance, on selected tolerant and susceptible varieties. Our results showed stimulatory impact of glycine betaine on accumulation of ROS scavenging antioxidants, total soluble protein and on its own accumulation. While the ex-foliar application had no inhibitory effect on the growth of plants; accumulation of free proline, amino acids and carbohydrates are inhibited par se in flax. Our findings reveal, flax is a non-accumulator of glycine betaine and exogenous application of glycine betaine enhances its own levels during drought stress.

Adjuvant chemotherapy in uterine carcinosarcoma: Comparison of a doublet and a triplet chemotherapeutic regimen.

BACKGROUND: Uterine carcinosarcoma (UCS) is a rare and aggressive malignancy, and there are no existing standard guidelines for adjuvant therapy. Doublet chemotherapy regimens are most favored in adjuvant setting; however, given the early chances of distant recurrences, does a triple-drug adjuvant chemotherapy improve disease-free survival (DFS), remains to be seen. Our aim of the study is to compare and review different adjuvant regimens used in UCS. METHODS: Retrospective chart analysis included 37 optimally staged UCS patients. Each of them had either received paclitaxel plus carboplatin (PC) or paclitaxel, ifosfamide, and cisplatin (TIP). A toxicity analysis was charted as per common terminology criteria for adverse events (CTCAE) 4 criteria. A survival analysis was done by the Kaplan-Meier method, and log-rank test was used for comparison of two variables. RESULTS: Incidence of UCS was 4.1% and mean age (standard deviation) was 58.73 ± 6.3 (range 42 - 71) years. TIP and PC chemotherapies were given to 22 and 15 patients, respectively. Five-year DFS and overall survival for TIP versus PC were 38.2% versus 35.9% (P = 0.118) and 49% versus 50.3% (P = 0.306), respectively, and for Stage I, II versus Stage III was 78.8% versus 12.7%(P = 0.001) and 92.3% versus 34.2% (P = 0.002), respectively. However, in advanced disease (Stage III), there is a trend toward DFS advantage of triple-drug adjuvant regimen (Hazards ratio (HR) = 0.35, 95% confidence interval (CI) = 0.12-1.07). Grade 3 and 4 toxicities were seen in 54.5% patients of TIP chemotherapy group and in 13.3% patients of the PC chemotherapy (P = 0.012). CONCLUSION: Triple-drug adjuvant chemotherapy (TIP) confers no survival advantage over doublet chemotherapy (PC), and in turn, increases the grade 3/4 toxicity in the adjuvant setting of optimally staged UCS patients.

Internal Jugular Vein Cannulation Using a 3-Dimensional Ultrasound Probe in Patients Undergoing Cardiac Surgery: Comparison Between Biplane View and Short-Axis View.

OBJECTIVE: To compare the clinical performance in terms of procedure time, success rate, and cannulation attempts between ultrasound biplane view (BPX) and short-axis (SAX) view for internal jugular vein cannulation (IJV) in patients undergoing cardiac surgery. DESIGN: Prospective, observational pilot study. SETTING: University level tertiary referral hospital. PATIENTS: The study comprised 100 patients between ages 18 and 75 years undergoing elective cardiac surgery. INTERVENTIONS: One hundred patients were divided into 2 groups of 50 (BPX group and SAX group) by assigning the study participants alternatively to each group. IJV cannulation was performed using a 3-dimensional ultrasound probe in all patients with either BPX view (BPX group, n = 50) or the SAX view (SAX group, n = 50) by an experienced anesthesiologist. MEASUREMENTS AND MAIN RESULTS: Time required for imaging, time for IJV puncture, time for guidewire confirmation, number of needle punctures and needle redirections, and incidence of posterior wall puncture were noted in both groups. In addition, the quality of needle visualization and the incidence of complications were recorded. The time taken for imaging was significantly greater in the BPX group than in the SAX group (9.52 ± 2.69 s v 7.94 ± 2.55 s; p = 0.0034), whereas the time taken for IJV puncture (10.39 ± 2.33 s v 23.7 ± 2.46 s; p < 0.0001), time taken for confirmation of guidewire (32.94 ± 4.50 s v 57.64 ± 7.14 s; p < 0.0001), and the incidence of posterior wall puncture (4% v 26%; p = 0.0022) were significantly less in the BPX group than in the SAX group. The total number of attempts taken to puncture the IJV was fewer in the BPX group than in the SAX group (55 v 78). Successful puncture of the IJV occurred on the first attempt in 90% of patients in the BPX group, whereas it was only 50% in the SAX group (p < 0.0001). The quality of needle visualization was good in 90% of patients in the BPX group, whereas it was only 6% in the SAX group. The number of needle redirections for IJV puncture was less in the BPX group than in the SAX group (48 v 116). The incidence of complications was not significant between the 2 groups. CONCLUSION: The results suggested that the BPX view may be a safer, feasible and more reliable method than the SAX view for IJV cannulation in cardiac surgical patients.

HIV-1-Associated Left Ventricular Cardiac Dysfunction in Humanized Mice.

The molecular cause(s) for early onset heart failure in people living with HIV-1 infection (PLWH) remains poorly defined. Herein, longitudinal echocardiography was used to assess whether NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice reconstituted with human hematopoietic stem cells (Hu-NSG mice) and infected with HIV-1ADA can recapitulate the salient features of this progressive human disease. Four weeks post infection, Hu-NSG mice of both sexes developed left ventricular (LV) diastolic dysfunction (DD), with 25% exhibiting grade III/IV restrictive DD with mitral regurgitation. Increases in global longitudinal and circumferential strains and declines in LV ejection fraction and fractional shortening were observed eight weeks post infection. After twelve weeks of infection, 33% of Hu-NSG mice exhibited LV dyskinesia and dyssynchrony. Histopathological analyses of hearts seventeen weeks post infection revealed coronary microvascular leakage, fibrosis and immune cell infiltration into the myocardium. These data show for the first time that HIV-1ADA-infected Hu-NSG mice can recapitulate key left ventricular cardiac deficits and pathophysiological changes reported in humans with progressive HIV-1 infection. The results also suggest that HIV-1 infected Hu-NSG mice may be a useful model to screen for pharmacological agents to blunt LV dysfunction and associated pathophysiologic causes reported in PLWH.

Amplification of Replication Competent HIV-1 by Adoptive Transfer of Human Cells From Infected Humanized Mice.

Detection of latent human immunodeficiency virus type 1 (HIV-1) in "putative" infectious reservoirs is required for determining treatment efficiency and for viral elimination strategies. Such tests require induction of replication competent provirus and quantitative testing of viral load for validation. Recently, humanized mice were employed in the development of such tests by employing a murine viral outgrowth assay (mVOA). Here blood cells were recovered from virus infected antiretroviral therapy suppressed patients. These cells were adoptively transferred to uninfected humanized mice where replication competent virus was recovered. Prior reports supported the notion that an mVOA assay provides greater sensitivity than cell culture-based quantitative VOA tests for detection of latent virus. In the current study, the mVOA assays was adapted using donor human hematopoietic stem cells-reconstituted mice to affirm research into HIV-1 elimination. We simulated an antiretroviral therapy (ART)-treated virus-infected human by maintaining the infected humanized mice under suppressive treatment. This was operative prior to human cell adoptive transfers. Replication-competent HIV-1 was easily detected in recipient animals from donors with undetectable virus in plasma. Moreover, when the assay was used to investigate viral presence in tissue reservoirs, quantitative endpoints were determined in "putative" viral reservoirs not possible in human sample analyses. We conclude that adoptive transfer of cells between humanized mice is a sensitive and specific assay system for detection of replication competent latent HIV-1.

Ultrasound-guided Modified Parasternal Intercostal Nerve Block: Role of Preemptive Analgesic Adjunct for Mitigating Poststernotomy Pain.

BACKGROUND AND AIM: To assess the quality and effectiveness of postoperative pain relief after fast-tracking tracheal extubation in cardiac surgery intensive care unit, effected by a single-shot modified parasternal intercostal nerve block compared with routine in-hospital analgesic protocol, when administered before sternotomy. DESIGN: A prospective, randomized, double-blinded interventional study. SETTING: Single-center tertiary teaching hospital. PARTICIPANTS: Ninety adult patients undergoing elective coronary artery bypass grafting surgery under cardiopulmonary bypass. MATERIALS AND METHODS: Patients were randomized into two groups. Patients in the parasternal intercostal block group (PIB) (n = 45) received ultrasound-guided modified parasternal intercostal nerve block with 0.5% levobupivacaine after anesthesia induction at 2nd-6th intercostal space along postinduction using standardized anesthesia drugs with routine postoperative hospital analgesic protocol with intravenous morphine. Patients in the group following routine hospital analgesia protocol (HAP) (n = 45) served as controls, with standardized anesthesia drugs and routine hospital postoperative analgesic protocol with intravenous morphine. The primary study outcome aimed to evaluate pain at rest and when doing deep breathing exercises with spirometry, coughing expectorations using a 11-point numerical rating scale. RESULTS: The postoperative pain score at rest and during breathing exercises was compared between the two groups at different time durations (15 min after extubation and every 4th hourly for 24 h). Patients in the PIB group had significantly lower pain scores and better quality of analgesia during the entire study period at rest and during breathing exercise (P < 0.0001). Furthermore, the side effect profile and need of rescue analgesics were better in the PIB group than the HAP group at different time intervals. CONCLUSION: PIB is safe for presternotomy administration and provided significant quality of pain relief postoperatively, as seen after tracheal extubation for a period of 24 h, on rest as well as with deep breathing, coughing, and chest physiotherapy exercises when compared to intravenous morphine alone after sternotomy. This study further emphasizes the role of preemptive analgesia in mitigating postoperative sternotomy pain and it's role as a plausible safe analgesic adjunct facilitating fast tracking with sternotomies on systemic heparinization.

Role of Maintenance Gemcitabine in Advanced Carcinoma Gallbladder.

Objective The aim of this study is to investigate the effects of gemcitabine maintenance on progression-free survival (PFS) in patients with metastatic gallbladder cancer (GBC). Materials and Methods Sixty patients with unresectable or metastatic GBC having ongoing response to treatment with initial six cycles of gemcitabine and a platinum-based doublet chemotherapy were prospectively randomized on day 21 of the 6th cycle in 1:1 fashion to receive either maintenance gemcitabine 1 g/m 2 intravenously on day 1 and day 8 of three weekly cycle or observation. Survival analysis was performed using the Kaplan-Meier method and comparisons by the log-rank test. A p -value < 0.05 was considered as statistically significant. Results Of 60 patients, a total of 56 were available for final analysis. The median PFS was 4.7 months (3.1-6.3) in gemcitabine arm and 2.6 months (2.4-2.8) in observation arm, hazard ratio (HR) 0.196 (95% confidence interval [CI]: 0.1-0.39), p < 0.001. Median overall survival in gemcitabine arm was 12.4 months (9.15-15.6) as opposed to 9.9 months (8.29-11.5) in observation arm, HR 0.76 (95% CI: 0.43-1.35), p = 0.354. The grade 3 or 4 side effects in maintenance arm were transaminitis (17.9%), thrombocytopenia (17.8%), neutropenia (14.2%), and febrile neutropenia (7.1%). Conclusions Maintenance gemcitabine therapy in unresectable/metastatic GBC patients responding to first-line gemcitabine and platinum treatment contributes to increase PFS with minimal and manageable side effects.

Nab-paclitaxel: An effective third-line chemotherapy in patients with advanced, unresectable gallbladder cancer.

BACKGROUND & OBJECTIVES: Gallbladder (GBC) is an aggressive form of cancer and most patients present with advanced unresectable disease due to lack of early signs and symptoms. This retrospective study was conducted to present the treatment outcomes with three lines of chemotherapies in a subset of patients with advanced, unresectable GBC with the primary objective to determine the response rates with nab-paclitaxel as the third-line chemotherapy after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 (oxaliplatin, leucovorin and 5-FU) therapy. Another objective was to evaluate the toxicity, progression-free survival (PFS) and overall survival (OS). METHODS: Treatment-naive patients with histologically proven inoperable GBC treated with gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel as the first-, second- and third-line chemotherapy were included in this study. The dose of gemcitabine and cisplatin or carboplatin was 1 g/m[2] on days 1 and 8 and 75 mg/m[2] (or target AUC of 5) on day 1, in a 21-day cycle. FOLFOX-4 was administered every two weeks and nab-paclitaxel was administered as 125 mg/m[2] on days 1, 8 and 15 in a 28-day cycle. RESULTS: There were eight men and 13 women with a median age of 57 yr who received nab-paclitaxel therapy. The overall response rate of the first-, second- and third-line chemotherapy was 61.9, 57.1 and 52.4 per cent, respectively. The median PFS for the gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy was 5.5, 5.4 and 2.9 months, respectively. The median OS with three lines of therapies was 14.0 months. Common Terminology Criteria (CTC) grade 3 or 4 haematological toxicities were observed in 28.6, 38.1 and 23.8 per cent of patients on gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy, respectively. INTERPRETATION & CONCLUSIONS: Our study suggests the clinical benefit of nab-paclitaxel chemotherapy in prolonging OS in a selected subgroup of advanced, unresectable GBC patients after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 therapy.