Technical and Anatomical Aspects of Retroperitoneoscopic Renal Surgery: A Summary of Tribulations and Resolutions Encountered at a Tertiary Care Institute of North India.

INTRODUCTION: Kidneys are a retroperitoneal organ but the widely practiced laparoscopic approach to renal surgery is transperitoneal due to the advantages of greater working space at the cost of entering the peritoneal cavity, risk of injury to intraperitoneal organs, and the increased risk of postoperative bowel complications. The classic open approach to kidney procedures has been the flank approach without violating the peritoneal cavity instead of the retroperitoneal approach to renal surgery with the advantages of direct access to the renal hilum, especially the renal artery. Being a technically challenging procedure, the retroperitoneoscopic approach is less practiced and needs an experienced surgical team. Through this study, we have tried to unveil the myths and illustrate the exact position of ports, which is the decisive initial step in retroperitoneoscopic surgery. MATERIAL AND METHODS: This retrospective study was conducted at a developing tertiary center in northern India with novice staff mainly to determine the technical and anatomical caveats pertaining to the retroperitoneoscopic approach for renal surgeries, the challenges faced, and their resolutions. The decision for the site of incision for primary or camera port was taken only after a proper anatomical study of the cadavers and ongoing retroperitoneal surgical experience while treating various patients suffering from renal diseases. The study comprised eight patients, during the period from June 2023 to March 2024. Various parameters, such as demographic variables, diagnosis, mean operative time, estimated blood loss, technical difficulties encountered and their resolution, complications, and reasons for conversion were studied. A total of 15 cadavers were dissected during the above time period to study finer anatomical details of port positioning and other details. RESULTS: After an elaborate study of 15 cadavers and thereafter performing surgery on eight patients during the above time period, surgery was successfully performed on six patients, and two patients needed conversion to open procedure due to dense adhesions and non-progression while complications occurred in two patients (peritoneal rent and renal vein injury), which were managed laparoscopically. CONCLUSION:  Nonetheless, restrictions of surgical space make retroperitoneoscopic space a challenging procedure but with elaborate experience, which we gained through cadaveric study, and surgical results obtained during the initial few cases such as the exact site of the primary port and technical intricacies, and handling of complications if and when faced, we hope our study will certainly make retroperitoneal space more amicable to urologists.

Bilateral Symmetric Absence of Lumbricals of the Foot: A Rare Case Report.

Variations of the lumbricals of the foot are not common, unlike the lumbricals of the hand. Few cases of unilateral absence of lumbricals of the foot have been reported. There have been far fewer cases of bilateral asymmetric absence of the lumbricals of the foot reported. The study reports the findings observed during the routine dissection for undergraduate medical students in the Department of Anatomy. We observed that the third lumbrical in both the feet was absent in an elderly male cadaver. The other features of both feet were usual. Externally, there was no apparent deformity, operation mark, or evidence of injury in any of the feet. Considering the functional role of the lumbricals in particular and other small intrinsic muscles in general, on the mechanics of foot movement, it is of much significance to have the knowledge of the possible variations and their clinical implications, which should be studied using different diagnostic tools such as imaging techniques, dynamometry, and other modalities.

Bilateral higher carotid termination with rare anomalous emergence of ventral branches of the external carotid arteries: A cadaver study.

The common carotid artery bifurcates into two terminal branches-the external and internal carotid arteries. The head, neck, and face regions principally get their blood supply from the external carotid artery and its branches. Some previous articles have mentioned the abnormal pattern of the external carotid artery branching and its variable origin. In this article, a rare case has been documented, having the combination of anomalies of the high carotid termination and bilateral variable origin of the ventral branches of the external carotid artery encountered during routine dissection of the head and neck region of a 55-year-old male cadaver in the Department of Anatomy. In this instance, on the right side of the neck, we observed the presence of a thyrolinguofacial trunk which arose from the ventral surface of the external carotid artery, and on the left side, the linguofacial trunk emerged from the ventral surface of the external carotid artery while the superior thyroid artery branched off directly from the left common carotid artery. This apart, there was bilateral high termination of the common carotid artery. Although the exact embryogenesis of such common arterial trunks anomalies and high carotid termination is not clear, detailed and precise anatomical knowledge of such a combination of anomalies will provide further insight for better radiological evaluation and to avert iatrogenic vascular injuries during any surgical procedures of the head and face region.

Procedural sedation in children for fractionated radiation treatment: Intranasal dexmedetomidine versus oral midazolam and ketamine.

Background and Aims: Sedation in paediatric cancer for fractionated radiation treatment (RT) is unique as the child has to be still for accurate delivery of RT, monitoring of the child is from a remote location and sedation is repeated for multiple sessions of RT. The present study was undertaken to compare the efficacy of intranasal dexmedetomidine with oral midazolam and ketamine combination for repeated sedation during fractionated RT in paediatric oncology. Methods: Ninety children aged between 3-6 years, planned for 21 fractions of RT, were randomised to receive intranasal dexmedetomidine 2 µg/kg (group D) or oral midazolam 0.2 mg/kg and ketamine 5 mg/kg (group MK). The 21 sessions of fractionated radiotherapy were divided into three subgroups of seven consecutive exposures 1-7, 8-14 and 15-21 for comparison. The primary endpoint was to determine the incidence of successful sedation. The sedation score achieved, time to satisfactory sedation and discharge, rescue ketamine required, and side effects were secondary endpoints. Results: The incidence of successful sedation in the three successive RT subgroups; sessions: 1-7, 8-14 and 15-21, was 82%, 75.6% and 66.7% in group D, as compared to 40%, 24.4% and 13.3% in group MK, respectively. (P < 0.001). A decrease in successful sedation was noted in the successive subgroups. Time to successful sedation and discharge was earlier in group D in comparison to MK (P = 0.000). More patients in group MK required rescue ketamine (P = 000). Conclusion: Intranasal dexmedetomidine produces more satisfactory sedation as compared to oral ketamine with midazolam for fractionated RT.

Bilateral High Trifurcation of the Common Carotid Artery and Variable Emergence of the Lower Branches of the External Carotid Artery: A Cadaveric Case Report.

Trifurcation of the common carotid artery in the neck region is a rare anatomical variation. In the present study, we reported a rare case having the combination of anomalies of the bilateral high common carotid arteries trifurcation and variable origin of lower branches of the external carotid artery during routine dissection of the head and neck region of a 60-year-old male cadaver in the Department of Anatomy. Both on the left and right sides of the neck region, the common carotid artery gave off three terminal branches: internal carotid artery, external carotid artery, and ascending pharyngeal arteries. Further, we also observed the presence of bilateral linguofacial trunks (common arterial trunks) that emerged from the external carotid arteries and also the left superior thyroid artery that originated directly from the left common carotid artery. Even though the embryogenesis of the variable origin of such arterial trunks is not apparent, it is very indispensable to have sound knowledge and better comprehension of the accurate anatomical architecture of such a rare combination of carotid arterial system anomalies for correct interpretation of the vascular imaging that pave the pathway for successful execution of surgical interventions in the neck region because of its utmost clinical implication.

The deleterious impact of a non-synonymous SNP on protein structure and function is apparent in hypertension.

Essential hypertension (EH) is a significant health issue around the globe. The indifferent therapy regimen suggests varied physiological functions due to the lifestyle and genetic presentations of an individual. The endothelial nitric oxide synthase (NOS3) gene is a crucial vascular system marker in EH that contributes significantly to the phenotype. Hence, the present study aimed to employ the candidate gene approach and investigate the association between NOS3 single nucleotide polymorphism (SNP) E298D (G894T/rs1799983) by applying several in silico tools and validation through human samples screening. We corroborated computational findings through a case-control study comprising 294 controls and 299 patients; the 894T allele emerged significantly as the risk allele (odds ratio=2.07; P=6.38E-05). The in silico analyses highlighted the significance of E298D on the native structure and function of NOS3. The dynamics simulation study revealed that the variant type 298D caused structural destabilization of the protein to alter its function. Plasma nitrite levels were reduced in patients (P=0.0002), and the same correlated with the 894T allele. Furthermore, correlations were apparent between clinical, genotype, and routine biochemical parameters. To conclude, the study demonstrated a perceptible association between the SNP E298D and NOS3 protein structure stability that appears to have a bearing on the enzyme's function with a deleterious role in EH.

Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude.

Thrombospondin-1 (THBS1) levels elevate under hypoxia and have relevance in several cardiovascular disorders. The association of THBS1 with endothelial dysfunction implies its important role in hypertension. To establish the hypothesis, we screened patients with hypertension and their respective controls from the two different environmental regions. Cohort 1 was composed of Ladakhis, residing at 3500 m above sea level (ASL), whereas Cohort 2 was composed of north-Indians residing at ~200 m ASL. Clinical parameters and circulating THBS1 levels were correlated in the case-control groups of the two populations. THBS1 levels were significantly elevated in hypertension patients of both cohorts; however, the levels were distinctly enhanced in the hypertensive patients of HA as compared to normoxia (p < 0.002). The observation was supported by the receiver operating curve analysis with an area under curve of 0.7007 (0.627-0.774) demonstrating the discriminatory effect of hypobaric hypoxia on the levels as compared to normoxia (p < 0.011). Significant correlation of THBS1 and mean arterial pressure was observed with upraised positive correlations in the hypertensive highlanders as compared to the hypertensive patients from sea-level. The prevalence of differential distribution of THBS1 and CD47 genes variants, their interactions, and association with the THBS1 levels were also determined. Genotype-interactions between THBS1 rs2228263 and CD47 rs9879947 were relevant and the regression analysis highlighted the association of risk genotype-interactions with increased THBS1 levels in hypertension. Genetic studies of additional thrombospondin pathway-related genes suggest the complex role of THBS1 in the presence of its family members and the related receptor molecules at HA.

Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy.

The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously derived T cells are a major contributor to therapy failure. To interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the premanufacture T cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-sequencing analysis on sorted T-cell subsets from all 71 patients, followed by paired Cellular Indexing of Transcriptomes and Epitopes (CITE) sequencing and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on T cells from six of these patients. We found that chronic IFN signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naïve T-cell state, but is maintained in effector T cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function. SIGNIFICANCE: To improve clinical outcomes for CAR T-cell therapy, there is a need to understand the molecular determinants of CAR T-cell persistence. These data represent the largest clinically annotated molecular atlas in CAR T-cell therapy to date, and significantly advance our understanding of the mechanisms underlying therapeutic efficacy.This article is highlighted in the In This Issue feature, p. 2113.

Lingering effects of chemotherapy on mature T cells impair proliferation.

Engineered T-cell therapies have demonstrated impressive clinical responses in patients with hematologic malignancies. Despite this efficacy, many patients have a transient persistence of T cells, which can be correlated with transient clinical response. Translational data on T cells from pediatric cancer patients shows a progressive decline in chimeric antigen receptor (CAR) suitability with cumulative chemotherapy regardless of regimen. We investigated the effects of chemotherapy on surviving T cells in vitro, describing residual deficits unique to each agent including mitochondrial damage and metabolic alterations. In the case of cyclophosphamide but not doxorubicin or cytarabine, these effects could be reversed with N-acetylcysteine. Specifically, we observed that surviving T cells could be stimulated, expanded, and transduced with CARs with preserved short-term cytolytic function but at far lower numbers and with residual metabolic deficits. These data have implications for understanding the effects of chemotherapy on mature T cells later collected for adoptive cell therapy, as chemotherapy-exposed T cells may have lingering dysfunction that affects ex vivo adoptive cell therapy manufacturing techniques and, ultimately, clinical efficacy.

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6-8 weeks old healthy infants: A phase III, randomized, single blind, non-inferiority study.

BACKGROUND: A liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6-8 weeks old healthy infants. METHODS: A total of 405 healthy infants aged 6-8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4-6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period. RESULTS: Out of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4-6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated. CONCLUSION: After assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6-8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine. Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.

Estrogen receptor α and ß gene polymorphism in relation to bone mineral density and lipid profile in Northeast Indian women.

Estrogen regulates bone homeostasis and has a cardio-protective effect. Its physiological functions are mediated through receptors (ER) whose expression can be regulated by presence or absence of polymorphisms. However, the association between ER polymorphisms and BMD as well as lipids are inconsistent. The aim of the study was to investigate whether polymorphisms in ESR are associated with bone mineral density (BMD) and lipids in a cohort of Indian women. We studied PvuII, XbaI polymorphisms in ESR1 and AluI, RsaI polymorphisms in ESR2 genes and their association with bone mineral density (BMD) and lipids in premenopausal (n = 293, mean age: 33.01 ±â€¯5.23 years) and postmenopausal (n = 145, mean age: 56.91 ±â€¯7.1 years) women from Northeast India. AluI and RsaI polymorphisms in ESR2 gene were associated with BMD in postmenopausal women. Logistic regression analysis adjusted for age, BMI, tobacco and alcohol consumption revealed that xx genotype in XbaI polymorphism is associated with osteopenia at spine (OR = 3.3, 95% CI = 1.067-10.204) in postmenopausal women suggesting that allele X is protective (OR = 0.419, 95% CI = 0.177-0.991). Genotype aa in AluI polymorphism, seemed to be protective (OR = 0.092 for osteopenia; OR = 0.152 for osteoporosis) at spine whereas A allele was associated with osteopenia at femur (OR = 2.123, 95% CI = 1.079-4.166) in postmenopausal women. Allele r of RsaI polymorphism, was associated with osteoporosis at spine (OR = 3.222, 95% CI = 1.302-7.96). Thus, AIuI polymorphism of ESR2 gene was associated with spinal and femoral BMD whereas RsaI only with spinal BMD in postmenopausal women and ESR genotypes were not associated with lipids.

Synthesis and Biophysical Characterization of RNAs Containing 2'-Fluorinated Northern Methanocarbacyclic Nucleotides.

2'-Fluorinated Northern methanocarbacyclic (2'-F-NMC) nucleosides and phosphoramidites, based on a bicyclo[3.1.0]hexane scaffold bearing all four natural nucleobases (U, C, A, and G), were synthesized to enable exploration of this novel nucleotide modification related to the clinically validated 2'-deoxy-2'-fluororibonucleotides (2'-F-RNA). Biophysical properties of the 2'-F-NMC-containing oligonucleotides were evaluated. A duplex of 2'-F-NMC-modified oligonucleotide with RNA exhibited thermal stability similar to that of the parent RNA duplex, 2'-F-NMC-modified oligonucleotides had higher stability against 5'- and 3'-exonucleolytic degradation than the corresponding oligonucleotides modified with 2'-F-RNA, and 2'-F-NMC-modified oligonucleotides exhibited higher lipophilicity than the corresponding RNA oligonucleotides as well as those modified with 2'-F-RNA.

Naïve T-cell Deficits at Diagnosis and after Chemotherapy Impair Cell Therapy Potential in Pediatric Cancers.

Translational data on chimeric antigen receptor (CAR) T-cell trials indicate that the presence of naïve T cells in the premanufacture product is important to clinical response and persistence. In anticipation of developing CAR trials for other tumors, we investigated the T-cell distribution from children with solid tumors and lymphomas at diagnosis and after every cycle of chemotherapy. We found that patients with T cells enriched for naïve and stem central memory cells expanded well in vitro, but the majority of tumor types showed chemotherapy-related depletion of early lineage cells with a corresponding decline in successful ex vivo stimulation response. Unexpectedly, many pediatric patients with solid tumors had low numbers of naïve T cells prior to any therapy. These data indicate the ex vivo manufacture of CAR T cells may need to be customized based on the nature of T cells available in each disease type. SIGNIFICANCE: Cumulative chemotherapy cycles deplete naïve T cells in many pediatric cancer regimens, reducing expansion potential associated with successful adoptive cellular therapies. Naïve T-cell deficits can be seen at diagnosis as well, implying immune deficits that exist prior to chemotherapy, which may also affect the development of immune-based therapies.See related commentary by Leick and Maus, p. 466.This article is highlighted in the In This Issue feature, p. 453.

Feminization imprinted by developmental growth hormone.

Previously, we identified early developmental exposure to growth hormone (GH) as the requisite organizer responsible for programming the masculinization of the hepatic cytochromes P450 (CYP)-dependent drug metabolizing enzymes (Das et al., 2014, 2017). In spite of the generally held dogma that mammalian feminization requires no hormonal imprinting, numerous reports that the sex-dependent regulation and expression of hepatic CYPs in females are permanent and irreversible would suggest otherwise. Consequently, we selectively blocked GH secretion in a cohort of newborn female rats, some of whom received concurrent GH replacement or GH releasing factor. As adults, the feminine circulating GH profile was restored in the treated animals. Two categories of CYPs were measured. The principal and basically female specific CYP2C12 and CYP2C7; both completely and solely dependent on the adult feminine continuous GH profile for expression, and the female predominant CYP2C6 and CYP2E1 whose expression is maximum in the absence of plasma GH, suppressed by the feminine GH profile but more so by the masculine episodic GH profile. Our findings indicate that early developmental exposure to GH imprints the inchoate CYP2C12 and CYP2C7 in the differentiating liver to be solely dependent on the feminine GH profile for expression in the adult female. In contrast, adult expression of CYP2C6 and CYP2E1 in the female rat appears to require no GH imprinting.

Increased tongue use enhances 5-HT2C receptor immunostaining in hypoglossal motor nucleus.

Hypoglossal (XII) motoneurons are activated by type 2 receptors for serotonin (5-HT). This activation is especially strong during wakefulness which facilitates diverse motor functions of the tongue, including the maintenance of upper airway patency in obstructive sleep apnea (OSA) patients. We tested whether 5-HT2 receptor levels in the XII nucleus vary with intensity of tongue use. Three groups of rats were housed overnight under conditions of increasing oromotor activity: W-water available ad lib; S-sweetened water to stimulate drinking; S + O-sweetened water + oil applied on fur to increase grooming. After the exposures, immunostaining for 5-HT2C, but not 5-HT2A, receptors was higher in the XII nucleus in S + O than in W rats (65 ± 1.8 (SE) vs. 60 ± 2.0 arbitrary units; p = 0.008). In the medullary raphé obscurus region, the percentage of c-Fos-positive 5-HT cells was 13% higher (p = 0.03) in S + O than in W rats. The positive feedback between tongue use and 5-HT2C receptor immunostaining reveals a novel mechanism potentially relevant for OSA and neuromuscular disorders.

Injectable Biomimetic Hydrogels as Tools for Efficient T Cell Expansion and Delivery.

Biomaterial-based scaffolds are promising tools for controlled immunomodulation. They can be applied as three dimensional (3D) culture systems in vitro, whereas in vivo they may be used to dictate cellular localization and exert spatiotemporal control over cues presented to the immune system. As such, scaffolds can be exploited to enhance the efficacy of cancer immunotherapies such as adoptive T cell transfer, in which localization and persistence of tumor-specific T cells dictates treatment outcome. Biomimetic polyisocyanopeptide (PIC) hydrogels are polymeric scaffolds with beneficial characteristics as they display reversible thermally-induced gelation at temperatures above 16°C, which allows for their minimally invasive delivery via injection. Moreover, incorporation of azide-terminated monomers introduces functional handles that can be exploited to include immune cell-modulating cues. Here, we explore the potential of synthetic PIC hydrogels to promote the in vitro expansion and in vivo local delivery of pre-activated T cells. We found that PIC hydrogels support the survival and vigorous expansion of pre-stimulated T cells in vitro even at high cell densities, highlighting their potential as 3D culture systems for efficient expansion of T cells for their adoptive transfer. In particular, the reversible thermo-sensitive behavior of the PIC scaffolds favors straightforward recovery of cells. PIC hydrogels that were injected subcutaneously gelated instantly in vivo, after which a confined 3D structure was formed that remained localized for at least 4 weeks. Importantly, we noticed no signs of inflammation, indicating that PIC hydrogels are non-immunogenic. Cells co-delivered with PIC polymers were encapsulated within the scaffold in vivo. Cells egressed gradually from the PIC gel and migrated into distant organs. This confirms that PIC hydrogels can be used to locally deliver cells within a supportive environment. These results demonstrate that PIC hydrogels are highly promising for both the in vitro expansion and in vivo delivery of pre-activated T cells. Covalent attachment of biomolecules onto azide-functionalized PIC polymers provides the opportunity to steer the phenotype, survival or functional response of the adoptively transferred cells. As such, PIC hydrogels can be used as valuable tools to improve current adoptive T cell therapy strategies.

Association of high-density lipoprotein, triglycerides, and homocysteine with bone mineral density in young Indian tribal women.

This study investigated association between lipids and homocysteine (Hcy) with bone mineral density (BMD) in young women as opposed to previous studies on elderly women. HDL, triglyceride, and Hcy are significantly associated with BMD in young women and tobacco and alcohol consumption have no effect on this association. PURPOSE: The present study investigates whether the association of serum lipids and homocysteine (Hcy) with bone mineral density (BMD) reported mostly in elderly population can be generalized to young or premenopausal women, consequently suggesting screening of young women with low BMD for dyslipidemia or any cardiovascular events and vice versa. METHODS: Women (n = 293, aged 20-47 years) from Northeast India belonging to Tibeto-Burman origin were enrolled. Information about their physical and clinical attributes were collected by a structured questionnaire. Their BMDs at lumbar spine and femur were measured by dual-energy X-ray absorptiometry (DXA) and sera were profiled for lipid parameters and Hcy by auto-analyzer and ELISA, respectively. Women consuming tobacco and/or alcohol were grouped as consumers and others as non-consumers for the analysis. RESULTS: Positive correlation of BMD with HDL (spine and femur r = 0.38, p < 0.0001) and triglyceride (spine r = 0.534, p < 0.0001; femur r = 0.423, p < 0.0001) was observed, whereas Hcy correlated negatively with BMD (spine r = - 0.189, p = 0.0026; femur r = - 0.273, p < 0.0001). LDL showed a weak negative correlation with BMD (spine r = - 0.128, p = 0.0283; femur r = - 0.199, p = 0.0006). However, after adjusting for age, BMI, and consumption, HDL, triglyceride, and Hcy continued to show significant correlation with BMD at both the sites. Logistic regression analyses indicated that HDL, triglyceride, and Hcy were significant predictors of osteopenia and osteoporosis in our study cohort; however, consumption did not contribute to its prediction. CONCLUSION: Low levels of HDL and triglyceride and high levels of Hcy are significantly associated with osteopenia and osteoporosis in young Northeast Indian women.

Role of dexmedetomidine as an anaesthetic adjuvant in breast cancer surgery as a day-care procedure: A randomised controlled study.

BACKGROUND AND AIMS: Breast cancer surgery can be carried out as day-care procedure to increase patient turnover, decrease disease progression and financial burden. The present study was carried out to assess the role of dexmedetomidine in breast cancer surgery as a day-care procedure. METHODS: This prospective randomised, double-blind study was carried out on 100 patients screened for day-care breast cancer surgery. They were divided into two groups of 50 each; who received either normal saline (Group NS) or 0.6 µg/kg/h dexmedetomidine (Group D) infusion from 10 min before induction until skin closure. All patients were given general anaesthesia. The incidence of discharge, post-operative pain (POP), average rescue analgesia (fentanyl) required and side effects were noted. Statistical analysis was performed using Student's t-test and Chi-square test. RESULTS: Incidence of discharge in group NS was 60% compared to 88% in Group D (P = 0.001). Average rescue analgesia requirement by group NS was 136.07 ± 43.06 µg, whereas it was 77.5 ± 29.86 µg in Group D (P = 0.01). The incidence of POP in 6 h and within 2 h of expected discharge time in Group NS was 56% and 28%, respectively, and in Group D, it was 8% in both the periods (P < 0.001 and 0.01). Side effects such as post-operative nausea, vomiting and bleeding were encountered in eight and two patients, respectively, in Group NS and two and one patients, respectively, in Group D. CONCLUSION: Dexmedetomidine as an anaesthetic adjuvant makes breast cancer surgery feasible on day-care basis.

Newborn Screening for Hemoglobinopathies and Red Cell Enzymopathies in Tripura State: A Malaria-Endemic State in Northeast India.

Hemoglobinopathies are a group of inherited single gene disorders. There are reports on hemoglobin (Hb) variants identified in the tribal and non-tribal populations of Tripura State in northeastern India. This study aimed to determine the spectrum of hemoglobinopathies and enzymopathies by newborn screening in Tripura State and assess the extent of neonatal jaundice. A total of 2400 cord blood samples were collected and analyzed by high performance liquid chromatography (HPLC). Further confirmation of any abnormal HPLC was done by DNA analysis. The samples were also screened for deficiency of enzymopathies, glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase. Of 2400 cord blood samples screened, 225 (9.3%) were Hb E (HBB: c.79G>A) heterozygotes, 80 (3.3%) were Hb E homozygotes and one carried Hb E-ß-thalassemia (ß-thal). Other Hb abnormalities were also detected including 15 Hb S (HBB: c.20A>T) heterozygotes, two Hb D-Punjab (HBB: c.364G>C) heterozygotes and two compound heterozygotes for Hb D-Punjab and Hb E. Of the 80 homozygous Hb E babies, four were non-tribal and 76 babies were tribal, and 225 patients carried Hb E trait, 141 were tribal, while 84 were non-tribal. Of 40 G6PD deficient babies identified, 13 had coinherited Hb E and two babies had pyruvate kinase deficiency. α Genotyping was performed in 162 affected babies, 50 of them carried α gene deletions. Newborn screening programs for Hb E, other hemoglobinopathies and G6PD deficiency must be encouraged in the malaria-endemic northeastern region of India. Drug-induced hemolysis can also be avoided by screening for G6PD deficiency at birth.