Autosomal Dominant Pseudohypoaldosteronism Type 1 in a Newborn With Failure to Thrive.

Pseudohypoaldosteronism type 1 is a rare genetic disorder characterized by salt wasting and resistance to mineralocorticoids due to mutations in the NR3C2 gene which codes for the aldosterone receptor proteins in the kidneys. This case study involves an infant who presented with poor growth and significant hyponatremia. There was improvement in growth and correction of hyponatremia with sodium supplementation, later found to carry a new genetic variant causing autosomal dominant pseudohypoaldosteronism type 1. A 14-day-old newborn presented with failure to thrive, severe hyponatremia, mild hyperkalemia, and metabolic acidosis. The electrolyte abnormalities were corrected with intravenous fluid and sodium supplementation. Continued oral sodium supplementation led to improved weight gain. Clinical suspicion and subsequent diagnostic testing led to a diagnosis of the autosomal dominant renal form of pseudohypoaldosteronism type 1. Genetic testing revealed a novel mutation on the NR3C2 gene, c.556_557del (p.Met186Valfs*3). The baby was discharged home on supplemental sodium and high-calorie formula for catch-up growth. Outpatient follow-up is ongoing.

Serum Parathyroid Hormone and Vitamin D Levels as Predictors of Hypocalcemia after Total/ Near Total Thyroidectomy.

BACKGROUND: Post-operative Hypocalcaemia is the most-common complication of total and near-total thyroidectomy which is a selective treatment for benign and malignant thyroid diseases. Incidence ranges from 0.5-50%. OBJECTIVES: The role of vitamin-D and Parathyroid hormone(PTH) in incidence of Hypocalcemia after thyroidectomy has been taken into consideration. METHODS: This is a prospective interventional study is conducted in Kasturba Medical College and hospital, Manipal after taking written informed consent from the participants. It aimed at surveying the serum level of preoperative Vitamin D, PTH and calcium before total-thyroidectomy surgery and its relationship with the incidence of postoperative hypocalcemia after the surgery. The study was done on 70 patients who were-planned for total/near total thyroidectomy. Preoperative Vitamin D, PTH, calcium and Postoperative 4 hours-PTH, Calcium were measured on POD-1, POD-2-4, the results obtained were then analysed. RESULTS:  Considering the cut-off of calcium as 8.6mg/dl, 42 patients developed hypocalcemia on POD-1, 28 patients on POD-2. Preoperative calcium and postoperative PTH levels in people having hypocalcaemia where significantly less compared to the patients having normal calcium. 4-hours post-operative PTH measurements showed 51% sensitivity, 100% specificity and strong co-relation between postoperative hypocalcemia and drop in PTH levels- (p=<0.001). Out of 42 patients who developed hypocalcemia 28- (65%) patients had vitamin-D deficiency(p=0.5) on POD-1 and out of 51 patients with hypocalcemia on POD 2-4, 33(78%) had-vitamin-D-deficiency(p=0.3852). Which was not statically significant. CONCLUSION: 4 hours post-operative PTH level is a predictor of early postoperative hypocalcemia, by detecting this we can effectively manage postoperative hypocalcemia.

Ethical Considerations in Neonatal Research.

Children are considered a vulnerable population and have traditionally been excluded from research studies. This exclusion of children in general, and neonates in particular, from clinical research hampers the development of safe and effective therapies in this population. However, research involving children (including infants) is essential to guide therapy and optimize care. Neonatal research is complex, time intensive, difficult and expensive to conduct, and raises some unique ethical considerations. The complexity of research in this population is highlighted by the fear of causing harm to fragile sick infants which has led to the creation of special regulations on the degree of risk exposure permissible in research involving infants. This is further compounded by the inability of infants to provide informed consent or assent and the reliance on obtaining surrogate consent from parents who may themselves be vulnerable and overwhelmed by their infant's illness and the amount of information provided to them. In this review, we discuss the evolution of ethical regulations related to research, the justification for research in infants, and some of the ethical nuances of research in this population.

Assessing the Rates and Reasons of Elective Surgical Cancellations on the Day of Surgery: A Multicentre Study from Urban Indian Hospitals.

BACKGROUND: Cancellations of elective surgeries on the day of surgery (DOS) can lead to added financial burden and wastage of resources for healthcare facilities; as well as social and emotional problems to patients. These cancellations act as barriers to delivering efficient surgical services. Optimal utilisation of the available resources is necessary for resource-constrained low-and-middle-income countries (LMIC). This study investigates the rate and causes of cancellations of elective surgeries on the DOS in various surgical departments across ten hospitals in India. METHODS: A research consortium 'IndSurg' led by World Health Organisation Collaboration Centre (WHOCC) for Research in Surgical Care Delivery in LMICs, India conducted this multicentre retrospective cross-sectional study to analyse the cancellations of elective/planned surgical operations on DOS across urban secondary and tertiary level hospitals. We audited surgical records of a pre-decided period of six weeks for cancellations, documented relevant demographic information and reasons for cancellations. RESULTS: We analysed records from the participating hospitals, with an overall cancellation rate of 9.7% (508/5231) on the DOS for elective surgical operations. Of these, 74% were avoidable cancellations. A majority (30%) of these 508 cancellations were attributed to insufficient resources, 28% due to patient's refusal or failure to show-up, and 22% due to change in patient's medical status. CONCLUSION: We saw a preponderance of avoidable reasons for elective surgery cancellations. A multidisciplinary approach with adequate preoperative patient counselling, timely communication between the patients and caregivers, adequate preoperative anaesthetic assessment, and planning by the surgical team may help reduce the cancellation rate.

PPAR-γ activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) results in periventricular inflammation, hypomyelination of the white matter, and hydrocephalus in premature infants. No effective therapy exists to prevent these disorders. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists reduce inflammation, alleviate free radical generation, and enhance microglial phagocytosis, promoting clearance of debris and red blood cells. We hypothesized that activation of PPAR-γ would enhance myelination, reduce hydrocephalus, and promote neurological recovery in newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH; autopsy brain samples from premature infants with and without IVH were analyzed. We found that IVH augmented PPAR-γ expression in microglia of both preterm human infants and rabbit kits. The treatment with PPAR-γ agonist or PPAR-γ overexpression by adenovirus delivery further elevated PPAR-γ levels in microglia, reduced proinflammatory cytokines, increased microglial phagocytosis, and improved oligodendrocyte progenitor cell (OPC) maturation in kits with IVH. Transcriptomic analyses of OPCs identified previously unrecognized PPAR-γ-induced genes for purinergic signaling, cyclic adenosine monophosphate generation, and antioxidant production, which would reprogram these progenitors toward promoting myelination. RNA-sequencing analyses of microglia revealed PPAR-γ-triggered down-regulation of several proinflammatory genes and transcripts having roles in Parkinson's disease and amyotrophic lateral sclerosis, contributing to neurological recovery in kits with IVH. Accordingly, PPAR-γ activation enhanced myelination and neurological function in kits with IVH. This also enhanced microglial phagocytosis of red blood cells but did not reduce hydrocephalus. Treatment with PPAR-γ agonist might enhance myelination and neurological recovery in premature infants with IVH.

Early Extended Neonatal Screening for Congenital Cytomegalovirus Infection: A Quality Improvement Initiative.

BACKGROUND: Identification of congenital cytomegalovirus (cCMV) infection in neonates is important for early diagnosis of sensorineural hearing loss. Therefore, a quality improvement project was designed with an aim to improve newborn CMV screening by 25% from a baseline rate of 22%. METHODS: This project was conducted across two hospital sites at one medical center with two tertiary care newborn nurseries and neonatal intensive care units. Symptomatic neonates with suggestive findings of cCMV, who had failed the newborn hearing screen, who had not had a hearing screen performed by 10 days of age, or who were infants of HIV-positive mothers were screened for cCMV. Serial interventions (formalized teaching sessions using an algorithm and involving a nurse educator, creation of electronic medical record order sets, huddle board reminders, and regular audits) were conducted, and statistical process control p-charts were used to identify any signals and to determine if there was any special cause variation. RESULTS: Of 5,817 infants born in 2018, 903 were eligible for screening. Small for gestational age (46%) was the most common indication for screening. After multiple interventions, the median screening rate increased from a baseline of 22% in 2016 to 74% during the one-year study period. Four infants had positive CMV screen and received appropriate treatment as a result of these interventions. CONCLUSION: Multidisciplinary quality improvement initiatives can improve newborn screening for cCMV infection in a tertiary care environment.

Reduced Hippocampal Dendrite Branching, Spine Density and Neurocognitive Function in Premature Rabbits, and Reversal with Estrogen or TrkB Agonist Treatment.

Preterm-born children suffer from neurological and behavioral disorders. Herein, we hypothesized that premature birth and non-maternal care of preterm newborns might disrupt neurobehavioral function, hippocampal dendritic arborization, and dendritic spine density. Additionally, we assessed whether 17ß-estradiol (E2) replacement or the TrkB receptor agonist, 7,8-dihydroxyflavone (DHF), would reverse compromised dendritic development and cognitive function in preterm newborns. These hypotheses were tested by comparing preterm (E28.5) rabbit kits cared and gavage-fed by laboratory personnel and term-kits reared and breast-fed by their mother doe at an equivalent postconceptional age. Neurobehavioral tests showed that both premature-birth and formula-feeding with non-maternal care led to increased anxiety behavior, poor social interaction, and lack of novelty preference compared with term-kits. Dendritic branching and number of total or mushroom dendritic spines were reduced in the CA1 field of preterm-kits compared with term controls. While CDC42 and Rac1/2/3 expression levels were lower, RhoA-activity was higher in preterm-kits compared with term controls. Both E2 and DHF treatment reversed prematurity-induced reduction in spine density, reduced total RhoA-GTPase levels, and enhanced cognitive function. Hence, prematurity and non-maternal care result in cognitive deficits, and reduced dendritic arbors and spines in CA1. E2 replacement or DHF treatment might reverse changes in dendritic spines and improve neurodevelopment in premature infants.

Adenocarcinoma of the duodenojejunal flexure presenting as a stricturous lesion.

A 50-year-old woman was referred with a colicky upper abdominal pain of 3 months duration. She experienced an increase in pain 2 weeks prior to presentation. This was associated with bilious vomiting about 5-6 times/day with no change in bowel habits. She had no history of any abdominal pathology. A review of systems showed she had a weight loss of 20 kg over a period of 4 months with recent onset of loss of appetite. Physical examination revealed a soft distended upper abdomen with non-radiating pain in the epigastrium. CT of the abdomen showed a heterogeneously enhancing stricturous growth in the proximal part of the jejunum with gross dilation of the stomach and duodenum. She underwent resection and anastomosis of the proximal jejunum. Histopathology revealed the lesion to be an adenocarcinoma.

Primary colonic signet ring cell carcinoma in a young patient.

A 28-year-old woman presented with colicky abdominal pain for 3 months. Pain was associated with episodes of vomiting, abdominal distension and constipation. She also had loss of weight for this duration. General physical examination was unremarkable and the abdomen was soft, with no palpable organomegaly. A CT of the abdomen showed small bowel and ascending colon dilation with multiple air fluid levels. There was also a short segment of circumferential bowel wall thickening and luminal narrowing in the hepatic flexure with sudden transition of bowel diameter. She underwent a right hemicolectomy after necessary preoperative investigations. Histopathology revealed signet ring cell carcinoma (SRCC). This case highlights the importance of detecting such a lesion in a young, otherwise fit woman. The challenge lies in early diagnosis and awareness of general practitioners about this aggressive form of colonic tumours.

Pancreatic cancer presenting as a Sister Mary Joseph's nodule.

A 69-year-old man presented with a painful umbilical nodule of 1 month duration. On examination the nodule was blackish in colour with a serous discharging fluid and was 2×2 cm in size, tender and fixed to the skin. There were no scars or sinuses at the umbilicus and no palpable mass or organomegaly on systemic examination. The patient underwent wide local excision of the skin nodule and on histopathology was reported as metastatic adenocarcinoma of the skin. A CT of the abdomen was performed to look for the primary site, which showed a 5×4 cm lesion in the tail of the pancreas. A biopsy from the pancreatic lesion was taken which was reported as an adenocarcinoma. CA19-9 was more than 1000 U/mL. The patient was advised palliative chemotherapy with gemcitabine. He was unwilling to take any further treatment in view of the advanced nature of the disease.

Endometriosis of extra-pelvic round ligament, a diagnostic dilemma for physicians.

A 49-year-old multiparous woman presented with a swelling in the left groin of 6 months duration. The swelling was associated with a dull aching pain. The patient reported increase in size of the swelling during lifting of heavy weights. Menstrual history was normal and there was no increase in pain over the swelling during menstruation. She underwent a caesarean section 20 years ago and the scar had healed by primary intention. She was provisionally diagnosed to have a left-sided inguinal hernia. Ultrasonography showed a multiloculated cyst measuring 5.3×1.5×5.2 cm within the inguinal canal. The patient had excision of the cyst under spinal anaesthesia. Intraoperatively the cyst was found to arise from the left round ligament. It measured 7×6 cm extending to the left lateral vaginal wall. Histopathology revealed endometriosis of the round ligament. Her gynaecological assessment was normal and they recommended no further treatment. On follow-up the patient was asymptomatic and wound had healed well.

Jejuno-jejunal intussusception: an unusual complication of feeding jejunostomy.

The jejuno-jejunal intussusception is a rare complication of jejunostomy tube placement. We are reporting a case of 33-year-old man who was suffering from absolute dysphagia due to carcinoma of cricopharynx with advanced metastatic disease, who underwent Stamms feeding jejunostomy as a part of palliative care. After 1 month he presented with colicky type of pain in the abdomen and vomiting. Sonogram of abdomen revealed a target sign and a feeding tube in a dilated jejunum. Abdominal CT proved the sonographic impression of jejuno-jejunal intussusception. He, therefore, underwent exploratory laparotomy and resection and anastomosis of the intussuscepted bowel. New feeding jejunostomy (FJ) was done distally from the anastomotic site. As per the literature this complication has been reported in Witzels jejunostomy. In our case the patient had undergone Stamms jejunostomy with placement of a Ryle's tube. Intussusception should be considered if a patient comes with abdominal pain and vomiting following FJ.

Portal pyaemia secondary to open haemorrhoidectomy: need for prophylactic broad spectrum antibiotics.

A 70-year-old man presenting with long standing grade 3 Haemorrhoids, underwent open haemorrhoidectomy under spinal anaesthesia. The patient passed stools on subsequent day and there was no bleeding per rectum. On day 5, he complained of dull aching upper abdominal pain. On physical examination, the abdomen was soft and there was mild tenderness in the epigastric region. Subsequently, he developed high temperature with chills and rigors. His condition failed to improve and the abdominal pain increased in severity. There was no pain in the perianal region and per rectum examination was normal. Leucocyte count rose to 12×10(9)/L and there were toxic changes on peripheral smear. Blood culture grew Staphylococcus aureus. Liver enzymes were mildly elevated. Coagulation profile was deranged. Fibrin degradation products were positive. D-dimer was high. CT revealed acute thrombosis of left portal vein and microabscesses suggestive of portal pyaemia.