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.

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.

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.

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.

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.

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.

Immune reactivity of spleen cells in advanced stages of tumor growth.

In a syngeneic tumor model by an indirect migration inhibition technique, using spleen cells from mice bearing large tumors (ATB-SC) no detectable amounts of migration inhibition factor (MIF) was found in response to either tumor cells or tumor extract. Although lymphokine production was suppressed, ATB-SC were able to respond to exogenous MIF and also to transfer a positive delayed foot-pad reaction (DFR) when co-inoculated with both forms of antigen into normal mice. These observations showed that in advanced stages of tumor development, when the ability of spleen cells to produce MIF toward tumor cells or tumor extract is lost, neither their capability to transfer a positive DFR not their responsiveness to MIF-rich culture supernatants were impaired.

Anganwadi worker's participation in rural newborn care.

Anganwadi worker was involved in rural newborn care as a link between a dai and a health worker. She was trained to ensure that, (i) borderline LBW/preterm baby was kept warm at home and (ii) a very small baby was referred to hospital. The training was conducted during routine monthly meetings and cost of equipping each anganwadi worked out to be Rs 110. Newborn survival, infant survivals and overall MCH performance improved. Thus, newborn care formed an ideal entry point into MCH activities.

PIP: The Rural Neonatal Care Program was initiated in January 1988 in Ganjad Primary Health Center, Dahanu, India, with the training of dais in care of the newborn. Later in the year training was conducted for anganwadi workers, who would follow-up newborn care until the child was 6 years of age. The anganwadi worker was a link between the dai and health worker and the health center. Home visits were made on the day of birth. The infant was measured and an health assessment made. If the infant was preterm or low birth weight and with a foot length of between 6.5 and 7 cm, repeat home visits were made to assess the breast feeding progress, the infant activity level, and general signs of health, as reflected in warm and pink feet. Training was conducted at monthly meetings at the block level, at the primary health care level, and during field visits to show how to care for hypothermic babies. A training manual and record book were developed and used. Footprints were made, and referrals were made to the hospital for those with feet under 6.5 to 7 cm. General observations were that birth registration improved, and infants were more easily identified for immunization. Newborn referral improved, and infant mortality declined. There was an important role for the anganwadi worker in providing continuity of care, identification of referrals, and training in the home for how to keep a baby warm. The number of referrals averaged 1-2 per month and 1-2 with special home attention. The training of the anganwadi worker in newborn care was included in the normal course of training and cost about Rs. 110 per worker.

Non-sucrose sweetener for pain relief in sick newborns.

A prospective controlled blind study was carried out in the Special Care Unit for Newborns to assess the effect of commercially available sweetener on pain relief in newborns. Response to intramuscular injection and the pain stimulus was studied in twenty-five sick newborns, 13 preterm and 12 term, in a blinded fashion. Pain score, duration of cry, heart rate and oxygen saturations were studied. Basal response, responses with sterile water or sweetener were recorded in each baby. Responses to sweetener versus no solution and sweetener versus sterile water were compared by applying paired t-test. The reduction in pain score with sweetener was significant when compared with no solution. The difference was not significant when compared with sterile water. Similarly, duration of cry and heart rate with sweetener were significantly less when compared to sterile water or to no solution. However, the difference in oxygen saturation was not significantly different. Sweetener has an analgesic effect in sick babies. This can minimise adverse effects associated with painful procedures.

Neonatal care during a residents' strike.

Medical officers from a primary health centre and rural hospital were posted at our neonatal care unit during the residents' strike that lasted 69 days. They were trained in labour room care and in special care of high-risk babies. Four weeks later they were to be first-on-call. During the pre-strike, strike and post-strike period, there was no significant difference in the number of high-risk deliveries and admissions and deaths at the special care unit (SCU). The low-tech neonatal care that we followed, can be practised at the first referral centre in rural areas of developing countries by the team led by a medical officer.

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.

Oropharyngeal delivery of oxygen to children.

Oropharyngeal oxygen was administered to 13 patients with rapid breathing and hypoxaemia, six of whom were newborns. Feeding tube, No. 8F, was used in newborns for delivery of oxygen and No. 1 OF for others. Oxygen flow rate, 0.5 litre/min for four newborns and 1 litre/min, for the rest, was adequate to maintain oxygen saturations 90% and above. There were no instances of tube blockage or displacement.

Intraosseous access using butterfly needle.

Butterfly needle (18 G) was used for intraosseous administration of fluids and drugs in 22 children with shock. All except one patient could be stabilized successfully. Fifteen children had severe dehydration because of diarrhoea. The intraosseous route needs to be popularized as an option for rehydration in areas, where diarrhoeal dehydration continues to be an important cause of child mortality.

Adequacy of solar energy to keep babies warm.

OBJECTIVE: Solar energy could be used as an alternate energy source for keeping neonates warm especially in tropical countries. The present study investigated the efficacy of solar powered room heating system. SETTING: Referral center for neonatal care. INTERVENTION: A fluid system heated by solar panels and circulated into a room was used to maintain room temperature. A servocontrolled heating device was used to regulate and maintain desired room temperature. MAIN OUTCOME MEASURES: Neonatal rectal temperature and room temperature. RESULT: Infants between 1750-2250 g were observed to require a mean room temperature of 32.5 degrees C to maintain normothermia. In 85 infants less than 1500 g, of the 5050 infant temperature records, only 3% showed a record less than 36 degrees C. CONCLUSIONS: Solar powered room heating is effective in maintaining infant temperature and is cost-effective as compared to the existing warming devices.

Clinical profile of severe birth asphyxia.

In this retrospective analysis, 56 babies with Apgar score 3 and less were studied. In 33, successful bag-mask ventilation was carried out. Seventeen babies received endotracheal IPPV. In 9 out of them bag-mask ventilation was never tried whereas in 8 bag-mask ventilation had failed. In 6 babies physical stimulation and blast of oxygen on the face was adequate. Following this experience, in the subsequent years, endotracheal intubation was required mainly in extremely low birth weight babies or babies with Apgar score 0 at birth. During the study period, drugs were used in about 50% babies. In subsequent years this figure has come down to 10%, that too in special situations. This study helped us to evolve a policy in resuscitations severely asphyxiated babies. Bag-mask ventilation is the first choice. Failure to achieve progressively improving Apgar score by 1 minute, usually 4-5, is an indication for endotracheal intubation. Drugs are required in special situations only.