ADVANCEMENTS IN MINIMALLY INVASIVE SURGERY: A COMPREHENSIVE ANALYSIS OF ROBOTIC SURGERY, ENDOSCOPIC TECHNIQUES, AND NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY.

The term "Natural Orifice Transluminal Endoscopic Surgery" (NOTES) defines a surgical approach that leverages the body's natural orifices to access the abdominal cavity, presenting a patient-centric perspective by highlighting its potential to eliminate abdominal wall aggression, mitigate postoperative discomfort, and offer benefits comparable to laparoscopic surgery. This comprehensive paper aims to not only review the existing landscape of NOTES techniques but also to propose advancements in flexible tools augmenting established endoscopic platforms, while also exploring the revolutionary concept of robotic structures grounded in micromechatronics and communication technologies. The thorough analysis encompasses the assessment of advantages and limitations associated with flexible devices and robotic platforms, coupled with an in-depth evaluation of the current array of devices used in NOTES, informed by pertinent literature. The authors' comprehensive approach entails scrutinizing technological breakthroughs and offering viable solutions, fostering a comprehensive understanding. Furthermore, the study encompasses an exhaustive evaluation and juxtaposition of state-of-the-art NOTES devices, supplemented by a nuanced discourse on the merits and demerits of flexible devices and robotic platforms, with a focused emphasis on their inherent strengths and weaknesses. Within this context, the discourse extends to strategic suggestions aimed at refining extant designs and cultivating robust, dependable autonomous robotic platforms purpose-built for NOTES. This narrative encapsulates the multifaceted exploration of benefits, challenges, and potential remedies directed towards enhancing prevailing designs and forging a dependable foundation for the future of NOTES.

Non-collagen genes role in digenic Alport syndrome.

BACKGROUND: Alport syndrome is a clinically heterogeneous nephropathy characterized by severe symptomatology at kidney level due to ultrastructural lesions of the glomerular basement membrane (GBM) as consequence of mutations in COL4 genes. The disease has been linked to COL4A3/COL4A4/COL4A5 mutations, which impair GBM functionality and can be inherited in a dominant, recessive or X-linked transmission. Although a targeted Next Generation Sequencing approach has allowed identifying families with pathogenic mutations in more than one COL4 α3-α4-α5 heterotrimer encoding genes, leading to conclude for a digenic pattern of inheritance, the role of non-collagen genes in digenic Alport syndrome has not yet been established. METHODS: We employed a whole-exome sequencing approach on three families in whom a digenic pattern of transmission could be suspected because of a likely biparental contribution or an unexplained phenotype in the proband. RESULTS: We identified in the three probands hypomorphic LAMA5 mutations co-inherited with pathogenic COL4 α4-α5 chains mutations. Segregation analysis revealed that the combination of LAMA5/COL4 variants co-segregate with a fully penetrant phenotype in line with a digenic inheritance. In one of the three probands an hypomorphic variant in NPHS2 was also found, suggesting that role of other kidney disease related-genes as modifiers. CONCLUSION: These findings validate the impact of LAMA5 mutations in digenic ATS and highlight the role of extracellular matrix's genes, basement membrane, slit diaphragm and podocyte cytoskeleton in ATS. This underline the need for a more extensive panel approach in the presence of a digenic ATS, in order to better define clinical severity and recurrence risk for family members.

Ectopic adrenocorticotropic hormone syndrome in a case of duodenal neuroendocrine tumor presenting with liver metastasis.

Ectopic adrenocorticotropic hormone (ACTH) syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS). Duodenal carcinoids are rare, indolent tumors usually associated with a benign progression. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET) presenting with liver metastasis. A 37-year-old female presented with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic lesion in the left lobe of the liver, suggestive of neoplasia. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml) and 87.56 µg/dl (n < 7.5 µg/ml), respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 µg/dl (n < 1.8 µg/ml), respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion with bilateral adrenal enlargement. A diagnosis of ectopic ACTH-dependent CS was made. Intraoperatively, a duodenal lesion of 0.5 cm × 0.5 cm was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. She underwent a Whipple's surgery, cholecystectomy, and left hepatic lobectomy. Postoperatively, she showed clinical and biochemical remission. Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis.

Enhancing neonatal survival: what can we do today?

OBJECTIVE: Neonatal deaths account for 44% of the world's under-5 child mortality. Over half of all neonatal deaths globally occur in preterm babies. Therefore, improving care of a preterm baby is particularly important to reduce under-5 mortality. The objective of this study was to spell out components of care of preterm/low birth weight babies at first level health facility and at first referral unit (FRU) in low resource settings. STUDY DESIGN: We have analyzed weight-wise survivals at two hospitals attached to medical colleges, J.J. Hospital, Mumbai and General Hospital, Talegaon, and at Rural Hospital, Dahanu. There were three-tier interventions: (i) warmth+ feeding and antibiotics, (ii) improved care at birth plus increased oxygen availability and (iii) use of dopamine. J.J. Hospital went through all these stages one after another; General Hospital had all three going simultaneously. The Rural Hospital had a 1+2. RESULTS: During 1978 to 1984, J.J. Hospital saved 50 to 55% very low birth weight (VLBW) babies by providing warmth, feeding and antibiotics. This percentage increased to 56 to 58%, when adequate oxygen and good care at birth was available (1984 to 1989). For babies in the moderately low birth weight category (MLBW), 1500 to 2000 g at birth, the corresponding figures were 56 to 58% and 84 to 86%. The same interventions led to statistically significant decline in MLBW and VLBW categories at General Hospital, Talegaon (2010 to 2013). The Rural Hospital, Dahanu (1987 to 1992) achieved better survival rates in VLBW (61.5%) and MLBW (92.5%) categories with identical interventions and less staff. CONCLUSION: On the basis of our results, we suggest that in resource-limited settings, the first level health facility may be able to look after short-stay babies that weigh more than 1500 g and that have no respiratory distress. The FRU may look after MLBW babies, with or without respiratory distress, and VLBW babies without respiratory distress by giving special care.

Transitional B lymphocytes are associated with protection from kidney allograft rejection: a prospective study.

Recent cross-sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody-mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation. When modeled as a time-dependent covariate, transitional B cell frequencies (but not total B cells or "regulatory" T cells) were associated with protection from acute rejection (any Banff grade; HR: 0.60; 95% CI: 0.37-0.95; p = 0.03). No association between transitional B cell proportions and either de novo donor-specific or nondonor-specific antibody (dnDSA; dnNDSA) formation was evident, although preserved transitional B cell proportions were associated with reduced rejection rates in those patients developing dnDSA. Three episodes of ABMR occurred, all in the context of nonadherence, and all associated with in vitro anti-HLA T cell responses in an ELISPOT assay (p = 0.008 versus antibody-positive patients not experiencing ABMR). This prospective study supports the potential relevance of transitional ("regulatory") B cells as a biomarker and therapeutic intervention in transplantation, and highlights relationships between humoral immunity, cellular immunity and nonadherence.

Meeting report: 3rd international transplant conference: how much risk can you take?

The 3rd International Transplant Conference took place on 31st October and 1st November 2014 at the University of Warwick, Coventry, UK. Key focal points of the meeting were the exploration of the molecular basis of antibody-antigen interactions and their relation to clinical practice and to share experiences and knowledge regarding strategies to transplant the 'high-risk' patient. In addition, lively debate sessions were hosted where controversial clinical and immunological themes were discussed by leading experts in the field.

P-selectin antagonism reduces thrombus formation in humans.

BACKGROUND: Interaction of P-selectin with its glycoprotein ligand (P-selectin glycoprotein ligand type 1) mediates inflammatory processes that may also include vascular thrombosis. Platelet P-selectin expression is increased in patients with coronary heart disease, and its antagonism represents a potential future therapeutic target for the prevention and treatment of atherothrombosis. AIM: To investigate the effects of the novel small molecule P-selectin antagonist PSI-697 on thrombus formation in humans. METHODS AND RESULTS: In a double-blind randomized crossover study, thrombus formation was measured in 12 healthy volunteers, using the Badimon ex vivo perfusion chamber under conditions of low and high shear stress. Saline placebo, low-dose (2 m) and high-dose (20 m) PSI-697 and the glycoprotein IIb-IIIa receptor antagonist tirofiban (50 ng mL(-1)) were administered into the extracorporeal circuit prior to the perfusion chamber. As compared with saline placebo, blockade of platelet glycoprotein IIb-IIIa receptor with tirofiban produced 28% and 56% reductions in thrombus formation in the low-shear and high-shear chambers, respectively. PSI-697 caused a dose-dependent, but more modest, reduction in thrombus formation. Low-dose PSI-796 (2 m) reduced total thrombus area by 14% (P = 0.04) and 30% (P = 0.0002) in the low-shear and high-shear chambers, respectively. At the high dose (20 m), PSI-697 reduced total thrombus area by 18% (P = 0.0094) and 41% (P = 0.0008) in the low-shear and high-shear chambers, respectively. CONCLUSIONS: P-selectin antagonism with PSI-697 reduces ex vivo thrombus formation in humans. These findings provide further evidence that P-selectin antagonism may be a potential target for the prevention and treatment of cardiovascular disease.

Declining seroprevalence of HIV infection among paediatric inpatients.

An unlinked anonymous testing for HIV infection among consecutive paediatric admissions at Cama and Albless Hospital, Mumbai, was performed in 1998-99 and again in 2003-04. The seroprevalence declined from 5.5% (24/535) to 2.2% (10/447). Greater awareness, enhanced antenatal detection and measures taken to prevent mother-to-child transmission (MTCT) seem to have contributed to the declining seroprevalence. We believe that paediatric inpatients reflect the extent of MTCT in the community.

Sustainable decline in mortality among severely malnourished children with local resources.

Sustainability of survival among malnourished children is a challenge. Over a period of four years, we achieved a significant decline in mortality, using locally available food, medicines and simple protocols.

Antiretroviral therapy in children: Indian experience.

BACKGROUND: There is a paucity of reports on Highly Active Antiretroviral therapy (HAART) in children. We studied feasibility and effectiveness fixed dose combination (FDC) of lamivudine, nevirapine and stavudine in HIV infected children. DESIGN: Interventional study. SETTING: A Tertiary care center. SUBJECTS: Twenty five consecutive HIV positive antiretroviral naive children older than 18 months. METHODS: The study subjects were started on weight-appropriate doses of the FDC and followed up for 6 months. Weight, CD4 counts, absolute lymphocyte count (ALC) and number of episodes of illness were assessed before and after HAART. Adherence and barriers to adherence were studied. RESULTS: Mean weight increased from 15.2 to 16.8 kg (P < 0.001) while mean CD4 counts increased from 488/cmm to 765/cmm (P < 0.001). Only 2 cases of drug associated adverse event were encountered. Improvement in Center for Disease Control (CDC) immunological classification of the subjects was significant while that in World Health Organization (WHO) clinical staging was not statistically significant. Follow up visits were 95% of the expected 175 visits. The average distance traveled by the patient for every visit was 72 km (one way). CONCLUSIONS: Use of FDC in weight specific dosages is feasible and effective for treatment of Pediatric HIV in resource scarce setting. These preliminary results need to be tested in a different setting.

Hodgkins lymphoma with HIV infection.

The association between Hodgkins Lymphoma (HL) with HIV is common in adults but rare in children. A 5 year old boy, known case of HIV on antiretroviral therapy, presented with prolonged fever, multiple enlarged lymph nodes along with hepatosplenomegaly. A diagnosis of Hodgkins lymphoma was entertained on histopathological examination; further subtyping was done by immunohistochemistry.

Leptospirosis in children.

Leptospirosis has a broad spectrum of clinical manifestations varying, from inapparent influenza like illness to fulminant fatal disease with hepato-renal dysfunction and hemorrhagic phenomena. Our cases had fever, puffiness, respiratory distress and bleeding diathesis as leading manifestations. Leptospirosis was suspected in view of epidemic situation prevailing in the city. We report four cases here, three of which survived and one died.