Initial experience with 3D laparoscopic choledochal cyst (CDC) excision and hepatico-duodenostomy (HD) in 21 children.

INTRODUCTION: Minimal access surgery has gradually become the standard of care in the management of choledochal cysts (CDC). Laparoscopic management of CDC is a technically challenging procedure that requires advanced intracorporeal suturing skills, and hence, has a steep learning curve. Robotic surgery has the advantages of 3D vision, articulating hand instruments making suturing easy and thus is ideal. However, the non-availability, high costs and necessity for large-size ports are the major limiting factors for robotic procedures in the paediatric population. Use of 3D laparoscopy incorporates the advantage of 3D vision and at the same time allows the use of small-sized conventional laparoscopic instruments. With this background, we discuss our initial experience with the use of 3D laparoscopy using conventional hand instruments in CDC management. AIM: To study our initial experience in the management of CDC in paediatric patients with 3D laparoscopy in terms of feasibility and peri-operative details. MATERIALS AND METHOD: All patients under 12 years of age treated for choledochal cyst in a period of initial 2 years were retrospectively analysed. Demographic parameters, clinical presentation, intra-operative time, blood loss, post-operative events and follow-up were studied. RESULTS: The total number of patients were 21. The mean age was 5.3 years with female preponderance. Abdominal pain was the most common presenting symptom. All patients could be completed laparoscopically. No patient needed conversion to open procedure or re-exploration. The average blood loss was 26.67 ml. None of the patients required a blood transfusion. One patient developed a minor leak postoperatively and was managed conservatively. CONCLUSION: 3D laparoscopic management of CDC in the paediatric age group is safe and feasible. It offers the advantages of depth perception aiding intracorporeal suturing, with the use of small-sized instruments. It is thus a 'bridging the gap' asset between conventional laparoscopy and robotic surgery. LEVEL OF EVIDENCE: Treatment study level IV.

We are all aging, and here's why.

Here, through this review, we aim to serve this purpose by first discussing the statistics and aging demographics, including the life expectancy of the world and India, along with the gender life expectancy gap observed throughout the world, followed by explaining the hallmarks and integral causes of aging, along with the role played by senescent cells in controlling inflammation and the effect of senescence associated secretory phenotype on longevity. A few of the molecular pathways which are crucial in modulating the process of aging, such as the nutrient-sensing mTOR pathway, insulin signaling, Nrf2, FOXO, PI3-Akt, Sirtuins, and AMPK, and their effects are also covered in paramount detail. A diverse number of ingenious research methodologies are used in the modern era of longevity exploration. We have attempted to cover these methods under the umbrella of three broad categories: in vitro, in vivo, and in silico techniques. The drugs developed to attenuate the aging process, such as rapamycin, metformin, resveratrol, etc. and their interactions with the above-mentioned molecular pathways along with their toxicity have also been reviewed in detail.

An Unusual Case of Type A Posterior Cloaca Associated with 46XX Disorder of Sexual Differentiation with Y Duplication of Urethra.

We report an infant reared as a girl who presented with ambiguous genitalia and urine coming per rectum. On examination, she had minimal clitoromegaly with labial fusion and Y urethral duplication. On investigations, genetic, metabolic, and endocrine causes for disorder of sexual differentiation were ruled out. This girl was operated via a posterior sagittal approach. This case was unique in that the urogenital sinus was deviated posteriorly and opened in the anterior rectal wall and the accessory urethra opened in clitoris, along with ambiguity of external genitalia, thus making it a rare variant of the posterior cloaca. The diagnosis requires a high index of suspicion in clinician and a meticulous examination of the external genitalia. Very little literature is available for this rare anomaly. Few reports have classified them as female pseudohermaphroditism with cloacal and urogenital sinus defects. Hence, we hereby discuss and review the literature for previously reported cases.

Long-term experience with simultaneous prone video-assisted thoracoscopic anterior spinal release and posterior spinal fusion in severe rigid pediatric spinal deformities.

PURPOSE: While posterior-alone techniques have been successful for most pediatric spinal deformities, anterior spinal release may be useful for severe rigid deformities. Traditional lateral-positioned video-assisted thoracoscopic surgical release (VATSR) followed by prone posterior spinal fusion (PSF) has been criticized for adding extensive operative morbidity. We aimed to reduce its disadvantages by performing prone VATSR and PSF simultaneously and evaluate its long-term outcomes. METHODS: All consecutive patients from 1991 to 2012 undergoing VATSR and PSF at one institution were retrospectively reviewed. The inclusion criteria comprised severe rigid thoracic scoliosis (> 70°, bending correction > 45°) or kyphosis (> 75°, bolster correction > 45°), and a minimum 2 year follow-up. Demographics, operative data, hospital stay, and radiographic correction data were compared between patients who had undergone sequential VATSR followed by PSF and those who had undergone these procedures simultaneously. RESULTS: Of 153 patients who had undergone VATSR and PSF, 53 met the inclusion criteria (31 sequential, 22 simultaneous; average follow-up, 50 [range, 24-86] months). Age, preoperative measurements and flexibility, and perioperative complications did not differ significantly. The simultaneous group showed significantly lower operative time (449 vs. 618 min), blood loss (1039 vs. 1906 cc), and hospital stay (6.3 vs. 8.5 days) (all, p < 0.05). Postoperative radiographic correction and maintenance at the final follow-up showed a non-significant trend favoring the simultaneous group. CONCLUSION: Our simultaneous prone VATSR and PSF technique showed significantly lower operative time, blood loss, and hospital stay compared with the traditional sequential VATSR and PSF method, suggesting its value in treating rigid deformities.

Multidisciplinary Approach for Management of Pediatric Tumors: a Case Series.

Pediatric solid tumors have wide range of presentations. Multidisciplinary approach is often needed for their optimum management. There are no reports discussing such an approach to pediatric tumors involving pediatric surgeons, oncologists and cardiothoracic surgeons together for the management. We report 5 such cases being managed in our institution from 2010 to 2016. All cases needed chemotherapy followed by resection with a team of surgeons involving pediatric surgeon and cardiothoracic surgeon.

Posterior Sagittal Approach for Uterovaginal Anastomosis in a Case of Congenital Cervical Atresia with Anorectal Malformation.

Cervical atresia is a rare association with anorectal malformation (ARM) which can be missed till puberty in the presence of normal vaginal orifice. A 12-year-old girl operated for ARM in neonatal age presented with primary amenorrhea. She had a normal vaginal opening, short perineal body, and prolapsed anteposed anus and was diagnosed with cervical agenesis. As the posterior sagittal approach is standard to place the rectum in correct anatomical position, reconstruction of the anus along with adequate perineal body and uterovaginal anastomosis was performed through this approach. This report highlights the utility and versatility of this approach for the management of such complex cases.

Dysplasia Epiphysealis Hemimelica/Trevor Disease: Report of a Lesion Solely Involving the Lunate Bone: A Case Report.

CASE: We describe the case of a dysplasia epiphysealis hemimelica (DEH) lesion affecting uniquely the lunate bone in a 16-year-old boy causing pain, stiffness, and decreased range of motion. Surgical excision was performed, leading to resolution of primary symptoms with residual limitations in terminal wrist extension. CONCLUSIONS: From our review of the literature, we believe this case to be the first report of a DEH lesion affecting solely the lunate bone. Although conservative and surgical management have both been described with DEH cases, we report a positive outcome following the excision of a symptomatic lesion.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor with Activity against Pseudomonas aeruginosa.

DS86760016 is a new leucyl-tRNA-synthetase inhibitor at the preclinical development stage. DS86760016 showed potent activity against extended-spectrum multidrug-resistant Pseudomonas aeruginosa isolated from clinical samples and in vitro biofilms. In a murine catheter-associated urinary tract infection model, DS86760016 treatment resulted in significant eradication of P. aeruginosa from the kidney, bladder, and catheter without developing drug resistance. Our data suggest that DS86760016 has the potential to act as a new drug for the treatment of Pseudomonas infections.

In Vitro and In Vivo Activities of DS86760016, a Novel Leucyl-tRNA Synthetase Inhibitor for Gram-Negative Pathogens.

The emergence of multidrug-resistant (MDR) Gram-negative bacilli is a major concern in the treatment of nosocomial infections. Antibacterial agents with novel modes of action can be useful, as these pathogens have become resistant to almost all existing standard-of-care agents. GSK2251052, a leucyl-tRNA synthetase inhibitor, has a novel mode of action against Gram-negative bacteria. However, the phase 2 studies with this drug were terminated due to microbiological failures based on the rapid emergence of drug resistance during the treatment of complicated urinary tract infections. DS86760016 is a novel leucyl-tRNA synthetase inhibitor active against MDR Gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, with an improved pharmacokinetic profile. DS86760016 showed lower plasma clearance, longer plasma half-life, and higher renal excretion than GSK2251052 did in mice, rats, monkeys and dogs. DS86760016 also showed lower mutant prevention concentrations against P. aeruginosa than did GSK2251052. No resistant bacteria were observed in murine urinary tract infection models at a dose that maintained urinary concentrations above the mutant prevention concentration. DS86760016 also showed a lower risk of resistance development than did GSK2251052 in comparative in vivo studies with murine urinary tract infection models. These results suggest that DS86760016 has potential as a new drug for the treatment of MDR Gram-negative bacterial infections, with a lower risk of drug resistance development than that of GSK2251052.

Identification and synthesis of novel inhibitors of mycobacterium ATP synthase.

A non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against M. smegmatis ATP synthase. Herein, we disclose our efforts to develop the structure activity relationship against Mycobacterium tuberculosis (Mtb.H37Rv strain) around the identified hit 1. A scaffold hopping approach was used to identify compounds 14a, 14b and 24a with improved activity against MTb.H37Rv.

Incidence of intrapartum stillbirth and associated risk factors in tertiary care setting of Nepal: a case-control study.

BACKGROUND: Each year, 1.2 million intrapartum stillbirths occur globally. In Nepal, about 50 % of the total number of stillbirths occur during the intrapartum period. An understanding of the risk factors associated with intrapartum stillbirth will facilitate the development of preventative strategies to reduce the associated burden of death. This study was conducted in a tertiary-care setting with the aim to identify risk factors associated with intrapartum stillbirth. METHODS: A case-control study was completed from July 2012 to September 2013. All women who had an intrapartum stillbirth during the study period were included as cases, and 20 % of women with live births were randomly selected upon admission to create the referent population. Relevant information was retrieved from clinical records for case and referent women. In addition, interviews were completed with each woman to determine their demographic and obstetric history. RESULTS: During the study period, 4,476 women were enrolled as referents and 136 women had intrapartum stillbirths. The following factors were found to be associated with an increased risk for intrapartum stillbirth: poor familial wealth quintile (Adj OR 1.8, 95 % CI-1.1-3.4); less maternal education (Adj OR, 3.2 95 % CI-1.8-5.5); lack of antenatal care (Adj OR, 4.8 95 % CI 3.2-7.2); antepartum hemorrhage (Adj OR 2.1, 95 % CI 1.1-4.2); multiple births (Adj. OR-3.0, 95 % CI- 1.9-5.4); obstetric complication during labor (Adj. OR 4.5, 95 % CI-2.9-6.9); lack of fetal heart rate monitoring per protocol (Adj. OR-1.9, 95 % CI 1.5-2.4); lack of partogram use (Adj. OR-2.1, 95 % CI 1.1-4.1); small-for-gestational age (Adj. OR-1.8, 95 % CI-1.2-1.7); preterm birth (Adj. OR-5.4, 95 % CI 3.5-8.2); and being born preterm with a small-for-gestational age (Adj. OR-9.0, 95 % CI 7.3-15.5). CONCLUSION: Being born preterm with a small-for-gestational age was associated with the highest risk for intrapartum stillbirth. Inadequate fetal heart rate monitoring and partogram use are preventable risk factors associated with intrapartum stillbirth; by increasing adherence to these interventions the risk of intrapartum stillbirth can be reduced. The association of the lack of appropriate antenatal care with intrapartum stillbirth indicates that quality antenatal care may improve fetal health and outcomes. TRIAL REGISTRATION: ISRCTN97846009.

Women living with HIV/AIDS (WLHA), battling stigma, discrimination and denial and the role of support groups as a coping strategy: a review of literature.

BACKGROUND AND OBJECTIVES: Women living with HIV/AIDS, in particular, have been positioned as a latent source of infection, and have captivated culpability and blame leading to a highly stigmatised and discriminated life. Despite the situation, women and their particular concerns have largely been ignored in HIV/AIDS research literature. This review aims to examine and analyze the feelings, experiences and perceptions of Women living with HIV/AIDS (WLHA) and will also access the role of support group as a coping strategy on the basis of 7 primary researches conducted in or on different parts of the world. METHODOLOGY: A systematic literature search was carried out on major data bases ASSIA, CINAHL, Science Direct, Web of Knowledge, Wiley Inter Science, AMED, Pub Med/Bio Med Central, MEDLINE and Cochrane Library. The articles included for review purpose were gauged against the pre-defined inclusion/exclusion criteria and quality assessment checklist resulting in a final 7 papers. FINDINGS/RESULTS: The findings were compiled into five thematic areas: (1) Disclosure as a sensitive issue; (2) Stigma and Discrimination associated with HIV/AIDS and the multidimensional effects on women's health and wellbeing; (3) Internalised Stigma; (4) Women living with HIV/AIDS experiences of being rejected, shunned and treated differently by physicians, family and close friends; (5) Support Group as among the best available interventions for stigma and discrimination. CONCLUSION: Support groups should be offered as a fundamental part of HIV/AIDS services and should be advocated as an effective and useful intervention. Further research is needed to examine the effect of support groups for women living with HIV/AIDS. A community based randomised controlled trial with support group as an intervention and a control group could provide further evidence of the value of support groups.

Clinical spectrum and molecular basis of recessive congenital methemoglobinemia in India.

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH-cytochrome b5 reductase (NADH-CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were identified which included 11 missense mutations causing single amino acid changes (p.Arg49Trp, p.Arg58Gln, p.Pro145Ser, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, p.Ala179Thr, p.Thr238Met, and p.Val253Met), one stop codon mutation (p.Trp236X) and one splice-site mutation (p.Gly76Ser). Seven of these mutations (p.Arg50Trp, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, and p.Thr238Met) were novel. Two mutations (p.Gly76Ser and p.Trp236X) were identified for the first time in the homozygous state globally causing type II RCM. We used the three-dimensional (3D) structure of human erythrocyte NADH-CYB5R to evaluate the protein structural context of the affected residues. Our data provides a rationale for the observed enzyme deficiency and contributes to a better understanding of the genotype-phenotype correlation in NADH-CYB5R deficiency.

Plating, nailing, external fixation, and fibular strut grafting for non-union of humeral shaft fractures.

PURPOSE: To compare various treatment modalities (plating, Ilizarov external fixation, and non-vascular fibular cortical strut grafting) for non-union of humeral shaft fractures. METHODS: Records of 9 women and 26 men aged 24 to 71 (mean, 42) years who presented with non-union of humeral shaft fractures were reviewed. The humeral shaft fractures were secondary to low-energy trauma (n=22) or vehicular accidents (n=13) and involved the proximal (n=9), middle (n=15), and distal (n=11) regions. 13 of the fractures were open. Infection was evident in 8 of the non-unions. For non-unions with infection (n=8), a 2-stage procedure entailing temporary Ilizarov fixation followed by plating was used. For non-unions without infection (n=23), one-stage plating and cancellous bone grafting was used. For non-unions of osteoporotic bone (n=4), one-stage non-vascularised fibular strut grafting was used. Outcome was measured using the Disabilities of the Arm, Shoulder and Hand (DASH) scoring system. RESULTS: The 35 patients were followed up for a mean of 16 (range, 6-60) months. All achieved bone union except for one (who had persistent infection). Respectively for non-unions with infection, nonunions without infection, and non-unions of osteoporotic bone, the mean times to bone union were 6.5 (range, 4-10), 5 (range, 4-8), and 10 (range, 6-14) months, the mean improvement in DASH score was 30, 43, and 18, and malalignment was noted in 5, 2, and one patient. Three patients had a preoperative radial nerve palsy for which standard tendon transfer was performed 6 weeks after treatment for non-union. CONCLUSION: Compression plating achieved the best results. An external fixator may be used temporarily for infected non-unions. Fibular strut grafting may be used when non-unions warrant additional stability.

A new simple approach for the determination of pyrimidine 5'-nucleotidase activity in human erythrocytes using an ELISA reader.

INTRODUCTION: Pyrimidine 5' nucleotidase type I (P5'N-1) deficiency is the most frequent abnormality of cell nucleotide metabolism causing hereditary non spherocytic hemolytic anemia (HNSHA). The aim of this study was to develop a simple method of determination of P5'N-1 activity in human erythrocytes using an ELISA reader METHODS: Determination of P5'N-1 activity is based on the liberation of inorganic phosphorus (Pi) after incubation with uridine monophosphate/cytidine monophosphate. Inorganic phosphorus (Pi), a product of the enzymatic reaction is directly quantitated from its ultraviolet absorbance. Purine/Pyrimidine nucleotides ratio (OD 260: OD 280) was also measured RESULTS: P5'N-1 deficient patients showed reduction in P5'N-1 activity (Mean ± SD; 4.06 ± 0.66 using an ELISA reader & 6.25 ± 1.37 using a spectrophotometer) as compared to the normal control group (ELISA reader: 13.24 ± 3.42 & Spectrophotometer: 18.25 ± 3.20). Heterozygotes showed intermediate activity (ELISA reader: 6.06 ± 0.48 & Spectrophotometer: 8.06 ± 1.28), however they would have been missed on screening using the Purine/Pyrimidine nucleotides ratio CONCLUSION: Determination of P5'N-1 activity by using an ELISA reader is a new, simple, less time consuming and reliable method. It also avoids the use of radioactive material or HPLC which is a significant advantage.

Field test results of the motherhood method to measure maternal mortality.

BACKGROUND & OBJECTIVES: Measuring maternal mortality in developing countries poses a major challenge. In Nepal, vital registration is extremely deficient. Currently available methods to measure maternal mortality, such as the sisterhood method, pose problems with respect to validity, precision, cost and time. We conducted this field study to test a community-based method (the motherhood method), to measure maternal and child mortality in a developing country setting. METHODS: Motherhood method was field tested to derive measures of maternal and child mortality at the district and sub-regional levels in Bara district, Nepal. Information on birth, death, risk factors and health outcomes was collected within a geographic area as in an unbiased census, but without visiting every household. The sources of information were a vaccination registry, focus group discussions with local health workers, and most importantly, interview in group setting with women who share social bonds formed by motherhood and aided by their peer memory. Such groups included all women who have given birth, including those whose babies died during the measurement period. RESULTS: A total of 15,161 births were elicited in the study period of two years. In the same period 49 maternal deaths, 713 infant deaths, 493 neonatal deaths and 679 perinatal deaths were also recorded. The maternal mortality ratio was 329 (95%CI: 243-434)/100,000 live birth, infant mortality rate was 48 (44-51)/1000LB, neonatal mortality rate was 33 (30-36)/1000LB, and perinatal mortality rate was 45 (42-48)/1000 total birth. INTERPRETATION & CONCLUSIONS: The motherhood method estimated maternal, perinatal, neonatal and infant mortality rates and ratios. It has been field tested and validated against census data, and found to be efficient in terms of time and cost. Motherhood method can be applied in a time and cost-efficient manner to measure and monitor the progress in the reduction of maternal and child deaths. It can give current estimates of mortalities as well as averages over the past few years. It appears to be particularly well-suited to measuring and monitoring programmes in community and districts levels.

Intraluminal migration of surgical sponge: gossypiboma.

Surgical mop retained in the abdominal cavity following surgery is a serious but avoidable complication. The condition may manifest either as an exudative inflammatory reaction with formation of abscess, or aseptically with a fibrotic reaction developing into a mass. Intraluminal migration is relatively rare. We report the case of a 23 year old woman who presented after a previous caesarean section with intestinal obstruction. Plain abdominal radiograph and computed tomography confirmed the presence of gossypiboma. The patient underwent laparatomy and sponge removal. This report discusses the approach to, and manifestations of, migratory surgical gossypiboma.

Spectrum of novel mutations in the human PKLR gene in pyruvate kinase-deficient Indian patients with heterogeneous clinical phenotypes.

Eighteen unrelated pyruvate kinase (PK)-deficient Indian patients were identified in the past 4 years with varied clinical phenotypes ranging from a mild chronic haemolytic anaemia to a severe transfusion-dependent disorder. We identified 17 different mutations in the PKLR gene among the 36 mutated alleles. Ten novel mutations were identified: 427G>A, 499C>A, 1072G>A, 1180G>T, 1216G>A, 1220A>G, 644delG, IVS5 (+20) C>A, IVS9 (+44) C>T, and IVS9 (+93) A>C. A severe syndrome was commonly associated with some mutations, 992A>G, 1436G>A, 1220A>G, 644delG and IVS9 (+93) A>C, in the PKLR gene. Molecular graphics analysis of human red blood cell PK (RPK), based on the crystal structure of human PK, shows that mutations located near the substrate or fructose 1,6-diphosphate binding site may change the conformation of the active site, resulting in very low PK activity and severe clinical symptoms. The mutations target distinct regions of RPK structure, including domain interfaces and catalytic and allosteric sites. In particular, the 1216G>A and 1219G>A mutations significantly affect the interdomain interaction because they are located near the catalytic site in the A/B interface domains. The most frequent mutations in the Indian population appear to be 1436G>A (19.44%), followed by 1456C>T (16.66%) and 992A>G (16.66%). This is the first study to correlate the clinical profile with the molecular defects causing PK deficiency from India where 10 novel mutations that produce non-spherocytic haemolytic anaemia were identified.