Rhino Orbital Cerebral Mucormycosis in Covid-19 Crisis.

Rhino-Orbital cerebral Mucormycosis (ROCM) an angioinvasive fungal infection commonly seen in diabetic and immunocompromised patients. In recent days, due to COVID 19 pandemic mucormycosis has been significantly increased (Smith et al. in Radiol Cardiothorac Imaging 2(5):e200280, 2020). In this study we evaluate the involvement, clinical features, contributing risk factors and outcome of post covid Rhino orbital cerebral mucormycosis. A cross sectional descriptive study was conducted on post covid rhino orbital cerebral mucormycosis patients from May 2021 to October 2021 in Otorhinolaryngology department of Stanley Medical college Chennai. We collected detailed history of Covid-19 hospital stay, treatment taken, co morbidities, Endoscopic findings, management and outcome. 243 cases analysed with median age 51 years (range 28-75 years) and male predominance with M:F ratio 1.6. The median time interval between covid and ROCM was 20 (15-35) days. Based on involvement 111 (46%) Stage-II, 87 (36%) Stage-I, 37 (15%) stage III and 8 (3%) stage IV disease observed. with overall mortality of 5.7%. Among which 230 (94.6%) patients had diabetes mellitus, 111 (45.8%) patients received steroid and 134 (54.3%) had immunomodulators during covid management. Despite of surgical debridement and antifungal therapy 14 (5.8%) patients died from mucormycosis. we conclude that covid be the predisposing factor for mucormycosis especially in patients with diabetes and increased usage of steroids. Treatment needs multimodality approach with antifungals and surgical debridement with surveillance fir good outcome.

Robotic Surgery in Head and Neck in Pediatric Population: Our Experience.

Robot assisted surgery of the head and neck is a relatively novel approach in the management of head and neck tumors. There are very few reported cases of robot-assisted surgery of the head and neck in pediatric population in the world literature and no report of such procedures in the Indian subcontinent. In this article we present three such cases we performed for the first time in the country. The first case is that of second branchial cleft cyst, the second is a 4-year-old boy with a tongue base cyst and the third patient is a 12-year-old girl with left parotid gland tumor. All the patients underwent successful Robotic surgeries. Case 1 underwent robotic excision of the cyst through a retroauricular hairline incision. Case 2 underwent transoral robotic excision of the tongue base cyst. Case 3 underwent robotic excision of the tumor through a modified facelift incision. The mean docking time for the robot was 12.33 min and approximate blood loss was less than 10 ml in all cases. The patient and their parents were extremely satisfied with the cosmetic outcomes of the scarless surgery. Robot assisted surgery has the advantage of performing minimally invasive procedures within constrained spaces especially in children. The multiarticulated endowrist movements of the robotic arms combined with higher magnification and three-dimensional depth perception allows a precise surgery with better visualization in otherwise inaccessible areas resulting in better surgical outcome. With exceptional advantages of scarless surgery, minimal blood loss and postoperative pain and better surgeon ergonomics, robotic technique is an effective and feasible option in Pediatric Head and neck Surgery.

Plasmodium falciparum: genetic polymorphism in apical membrane antigen-1 gene from Indian isolates.

A number of stage-specific antigens have been characterized for vaccine development against Plasmodium falciparum malaria. This study presents a comprehensive analysis of the sequence polymorphism in Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) in population samples from the eastern and western parts of India. This is the first study of its kind for the nearly full length PfAMA-1 gene from these regions in India. Our observations confirmed that sequence diversity of PfAMA-1 confines only to point mutations and shows 4-8% variation as compared to the prototypes. As opposed to the previous studies on PfAMA-1, our study revealed a greater degree of polymorphism in the Domain II region of PfAMA-1 protein, though signature for diversifying selection is seen throughout the gene. Our present investigation also indicates a very high degree of variation in the reported T- and B-cell epitopes of PfAMA-1. Few noteworthy and unique observations made in this study are the substitution of Cysteine residues responsible for the disulfide bond structure of the protein and the presence of premature termination after 595 amino acids in 3 of the 13 isolates under consideration. These crucial findings add new perspectives to the future of AMA-1 research and could have major implications in establishing AMA-1 as a vaccine candidate.

Indicators of lean body mass catabolism: emphasis on the creatinine excretion rate.

BACKGROUND: The major stress response to critical illness leads to a catabolic state and loss of lean body mass. AIMS: To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process. DESIGN: Prospective observational study. METHODS: Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium. RESULTS: Seventeen patients were studied for 3-10 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >/=1 g/kg/day and energy intake was >/=50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine. CONCLUSION: Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

Uncovering the basis of a severe degree of acidemia in a patient with diabetic ketoacidosis.

In this teaching exercise, the goal is to demonstrate how an application of principles of physiology can reveal the basis for a severe degree of acidaemia (pH 6.81, bicarbonate <3 mmol/l (P(HCO(3))), PCO(2) 8 mmHg), why it was tolerated for a long period of time, and the issues for its therapy in an 8-year-old female with diabetic ketoacidosis. The relatively low value for the anion gap in plasma (19 mEq/l) suggested that its cause was both a direct and an indirect loss of NaHCO(3). Professor McCance suggested that ileus due to hypokalaemia might cause this direct loss of NaHCO(3), and that an excessive excretion of ketoacid anions without NH(4)(+) in the urine accounted for the indirect loss of NaHCO(3). In addition, he suspected that another factor also contributing to the severity of the acidaemia was a low input of alkali. He was also able to explain why there was a 16-h delay before there was a rise in the P(HCO(3)) once therapy began. The missing links in this interesting story, including a possible basis for the hypokalaemia, emerge during the discussion between the medical team and Professor McCance.

Plasmodium vivax: genetic diversity of the apical membrane antigen-1 (AMA-1) in isolates from India.

Malaria parasites exhibit sequence diversity for a number of stage specific antigens. Several studies have proved that apical membrane antigen-1 (AMA-1) is an effective target for eliciting a protective immune response in humans and other experimental animals. We have investigated the sequence variation in Plasmodium vivax AMA-1 (Pv AMA-1) from different Indian isolates. This is the first study of its kind for the nearly full length Pv AMA-1 from India. Our analysis reveals greater degree of genetic diversity in Pv AMA-1 than reported so far and identifies five novel haplotypes. This is significant to establish the antigenic repertoire of isolates in a malaria endemic country like India.

Physiological disposal of the potential alkali load in diet of the rat: steps to achieve acid-base balance.

The purpose of this study was to provide a better understanding of the physiological role of endogenous net organic acid production in rats consuming their usual diet. Balance studies were performed over 24 h, and urine was collected in the day and night portions of the diurnal cycle. A supplemented low-electrolyte diet(LED) was fed to determine whether urinary organic anions were identical to those in the diet. A titration procedure was developed to determine the pK of titratable groups in the urine of rats studied with and without an acid load. Although normal rats excreted net acid (NAE), the latter was inversely related to the amount of food consumed. The rates of excretion of bicarbonate (HCO3), citrate, unmeasured organic anions, and NH+4 were higher in the night portion of the diurnal cycle. NAE rose dramatically when alkali intake was decreased by consuming the LED. Dietary and urinary organic anions were not identical because rats fed the LED supplemented with potassium citrate excreted <10% of this alkali load as citrate and <25% as HCO3. In the 24 h after 3,000 ¿mol NH4Cl was given intraperitoneally, H+ did not appear to be retained, yet NAE rose by only close to 2,000 ¿eq. The rate of excretion of titratable groups with a pK in the 3 to 5 pH range fell by close to 1,000 ¿eq; most of these changes occurred in the first 7 h after NH4Cl was given. We conclude that rat chow provides a large net alkali load. There appear to be two types of endogenous acid production, a form associated with a rise in NAE (e.g., sulfuric acid) and dietary alkali-driven endogenous net acid production, which titrates this alkali. Renal excretion of organic anions makes these acids end products of metabolism.

Prevention of acute hyponatremia by mannitol: an unanticipated mechanism.

PURPOSE: To evaluate the effectiveness and mode of action of the osmotic diuretic mannitol to prevent the development of acute hyponatremia in a setting designed to mimic the acute hyponatremia observed on the day of surgery. RESULTS: Hyponatremia (129+/-1 mM, fall of 10+/-1 mM, p <0.01) was induced by the intraperitoneal administration of half-isotonic saline plus DDAVP to rats (n = 8); hyponatremia was due to a positive balance of electrolyte-free water (EFW). Rats given mannitol (10 mmol/kg body wt) in addition to the hypotonic saline plus DDAVP had only a minor degree of hyponatremia (plasma [Na+] 136+/-1 mM, fall 3+/-2 mM, p >0.05). All the mannitol given was excreted over the 16 h of observation, but the urine volume was not higher in these rats. The higher rate of excretion of EFW was due to a marked reduction in the rate excretion of Na+ with mannitol. This antinatriuresis was also present when mannitol was given intravenously. CONCLUSIONS: Although mannitol increased the excretion of EFW, the mechanism required an enhanced renal reabsorption of Na+ rather than an increase in the urine flow rate.

Minimum urine flow rate during water deprivation: importance of the permeability of urea in the inner medulla.

We evaluated whether altering the rate of excretion of sodium (Na) and chloride (Cl) when antidiuretic hormone (ADH) acts would cause urea to behave as an 'effective' or 'ineffective' urinary solute. Urine composition was compared to that in the excised papillary tip in rats treated with DDAVP while on a normal or a low electrolyte diet; half the rats were given a urea load. Studies were also carried out in humans who were water restricted for 12 to 16 hours and given DDAVP. One group had a high rate of NaCl excretion induced by a thiazide diuretic, while the other group consumed a low salt diet to decrease the rate of excretion of electrolytes. Urea (3 mmol/kg) was ingested after the control urine samples were collected. On the high salt protocols, the urine flow rate was directly proportional to the rate of excretion of electrolytes ('non-urea' osmoles) and there was no change in the 'non-urea' osmolality despite large changes in Na and Cl excretion rates. After urea was administered, there was no change in urine flow rate, 'non-urea' osmolality, or 'non-urea' osmole excretion rate, whereas the urinary urea concentration, urine osmolality and the rate of excretion of urea were higher. The papilla of the salt-loaded rats had a similar urea concentration to that in the urine. In contrast, in the low electrolyte excretion protocols, the sum of the concentrations of 'non-urea' osmoles in the urine was much lower than that in the excised papilla, and the converse applied to urea. Similar changes were observed in the composition of the urine in human subjects with high and low rates of excretion of electrolytes. We conclude that urea appears to be an 'ineffective' urine osmole when there is a high rate of salt excretion, whereas urea is an 'effective' osmole when there is a low rate of excretion of electrolytes.

Acute hyponatremia in the perioperative period: insights into its pathophysiology and recommendations for management.

Our purpose is to review the topic of acute postoperative hyponatremia by focusing on pertinent aspects of the physiology of water and solute excretion. Four areas will be highlighted: an examination of the source of addition of electrolyte-free water, an exploration of the basis for the very large natriuresis that occurs during cerebral salt wasting following neurosurgery, possible reasons to explain why acute postoperative hyponatremia may pose a greater risk for young women [Ayus and Arieff 1996, Ayus et al. 1992, Arieff 1986, Wijdick et al. 1991], and issues related to treatment of acute hyponatremia.

Control of excretion of potassium: lessons from studies during prolonged total fasting in human subjects.

A deficit of K+ of close to 300 mmol develops in the first 2 wk of fasting, but little further excretion of K+ occurs, despite high levels of aldosterone and the delivery of ketoacid anions that are not reabsorbed in the distal nephron. Our purpose was to evaluate how aldosterone could have primarily NaCl-retaining, rather than kaliuretic, properties in this setting. To evaluate the role of distal delivery of Na+, four fasted subjects received an acute infusion of NaCl to induce a natriuresis. To assess the role of distal delivery of HCO3-, five fasted subjects were given an infusion containing NaHCO3. The natriuresis induced by an infusion of NaCl caused only a small rise in the rate of excretion of K+ (0.8 +/- 0.1 to 1.9 +/- 0.3 mmol/h); in contrast, when HCO3- replaced Cl- in the infusate, K+ excretion rose to 8.3 +/- 2.2 mmol/h, despite little excretion of HCO3- (urine, pH 5.8) and similar rates of excretion of Na+. The transtubular K+ concentration gradient was 19 +/- 3 with HCO3- and 6 +/- 2 with NaCl. We conclude that the infusion of NaHCO3 led to an increase in K+ excretion, likely reflecting an increased rate of distal K+ secretion. With a low distal delivery of HCO3-, aldosterone acts as a NaCl-retaining, rather than a kaliuretic, hormone.

Factors contributing to the degree of polyuria in a patient with poorly controlled diabetes mellitus.

Polyuria due to a glucose-induced osmotic diuresis is common in patients with hyperglycemia. This diuresis usually abates when the plasma glucose level approaches its renal threshold; the usual time course is less than 8 hours after commencing therapy. A 69-year-old man with non-insulin-dependent diabetes mellitus maintained hyperglycemia (540 mg/dL) and polyuria (4.7 L/24 hr) for 40 hours. Because there was no external supply of glucose, a balance study was conducted between the third and 40th hour after commencing treatment. In this interval, the overall concentration of glucose in the urine was less than 100 mmol/L and the urine osmolality was 378 mOsm/kg H2O. To evaluate the expected composition of the urine during a glucose-induced osmotic diuresis, urine was analyzed in normal rats infused with glucose plus urea and in untreated BB diabetic rats (plasma glucose and urea similar to that in our patient) as well as in 29 patients with hyperglycemia and polyuria. Glucose accounted for 60% of the urinary osmoles in rats and humans. Two subgroups of patients had a much lower urine glucose: one had an impaired concentrating ability (n = 6) and the other had an increased rate of renal glucose reabsorption (n = 5). In conclusion, in polyuria caused by hyperglycemia, the urine glucose should be 300 to 400 mmol/L with normal renal function. In the case we report, both the concentration of glucose and its excretion rate were much lower than expected with steady-state hyperglycemia (540 mg/dL) due to the high rate of excretion of NaCl, a concentrating defect, and excessive renal reabsorption of glucose.

Hyponatremia in the rat in the absence of positive water balance.

The purpose of this report is to determine the mechanisms that lead to hyponatremia when isotonic saline was the only fluid infused into rats given antidiuretic hormone (ADH), and what might minimize the degree of this hyponatremia. Normal rats were deprived of food and water for the 24-hr study period. They received an infusion of isotonic saline to expand their extracellular fluid (ECF) volume with and without exogenous ADH administration (N = 8 in each of the four groups). Similar studies were also carried out in 32 rats fed a low electrolyte diet for 72 hr before the experiment. An additional control group was fed the low electrolyte diet supplemented with sodium (Na), potassium (K), and chloride (Cl). Hyponatremia developed over 24 hr in rats fed their usual diet if treated with ADH and isotonic saline (fall, 13 +/- 2 mM, P < 0.01). The hyponatremia was caused by negative balance for Na + K salts. Hyponatremia did not develop after the saline + ADH treatment if rats were pretreated for 3 days with a low electrolyte diet. Two factors were required to develop this hyponatremia--generation of electrolyte-free water as a result of the excretion of a large quantity of Na + K salts at a high concentration in the urine, and prevention of the excretion of this electrolyte-free water by ADH. Increasing the avidity for Na reabsorption by the kidney prevented this type of hyponatremia from developing.

Postoperative hyponatremia despite near-isotonic saline infusion: a phenomenon of desalination.

BACKGROUND: It is widely presumed that the development of postoperative hyponatremia (which may be severe) results from administration of hypotonic fluids while antidiuretic hormone is acting. OBJECTIVE: To show that hyponatremia would occur in patients 24 hours after surgery if only near-isotonic solutions are given and to evaluate the mechanisms responsible for hyponatremia in this setting. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: 22 women who were having uncomplicated gynecologic surgery with infusion of near-isotonic solutions only (sodium chloride, 154 mmol/L, or Ringer lactate [sodium, 130 mmol/L, and potassium, 4 mmol/L]). MEASUREMENTS: Plasma electrolyte levels were measured at the time of induction of anesthesia and 24 hours later. Data on the balance of water and electrolytes were obtained for the same 24-hours period. RESULTS: At the time of induction of anesthesia, the plasma sodium concentration was 140 +/- 1 mmol/L; 24 hours later, it decreased in 21 of 22 patients (mean decrease, 4.2 +/- 0.4 mmol/L [P < 0.001]; lowest level, 131 mmol/L in 2 patients). The urine remained hypertonic (peak sodium plus potassium concentration in urine, 294 +/- 9 mmol/L) in all patients for the first 16 hours after induction of anesthesia. CONCLUSIONS: Postoperative hyponatremia occurred within 24 hours of induction of anesthesia when only near-isotonic fluids were infused. Hyponatremia was generally caused by generation of electrolyte-free water during excretion of hypertonic urine-a desalination process. This electrolyte-free water was retained in the body because of the actions of antidiuretic hormone. If the pathophysiology of this hyponatremic state is understood, recommendations for its prevention and treatment can be deduced.

Profound natriuresis, extracellular fluid volume contraction, and hypernatremia with hypertonic losses following trauma.

A young male sustained very serious head and soft tissue injuries in a motor vehicle accident (MVA). Three interesting problems developed in the sodium (Na) and water area in the second week in hospital. First, on day 11 after the MVA, his urine output increased to 3 liters per day; the urine osmolality was 1000 mOsm/kg H2O and Na and Cl were the principal urine osmoles. There appeared to be a salt wasting syndrome because he had a very large natriuresis (close to 900 mmol/24 hr) at a time when his central venous pressure was low. To help identify the nephron site responsible for a natriuresis with a high urine osmolality, additional studies were carried out in normal volunteers who took a loop or a thiazide diuretic on different occasions while ADH was acting. The pattern of natriuresis in the patient was similar to that after the thiazide but not the loop diuretic. The second problem concerned his hypernatremia (153 mM) because his urine was hypertonic and his intravenous therapy was isotonic saline. To explain hypernatremia while receiving more electrolyte-free water, we speculated that there was a water shift into cells resulting from particles generated and retained in his intracellular fluid. Given the large shift of water required, a lesion in muscle was suspected, a form of rhabdomyolysis. The third problem concerned the rate of catabolism of lean body mass. The metabolic consequences of generating these intracellular particles and the large amount of urea that was excreted could reflect a large degree of protein catabolism.

What is the impact of potassium excretion on the intracellular fluid volume: importance of urine anions.

Hyponatremia is a common electrolyte abnormality that causes symptoms as a result of swelling of brain cells. We evaluated the impact of a negative balance for sodium (Na) and potassium (K) salts on the intracellular fluid (ICF) volume, emphasizing the role of anions excreted with K. Rats (N = 10) were deprived of food and water for 24 hours. They received half-isotonic saline to expand their extracellular fluid (ECF) volume by 20%; a long acting antidiuretic hormone (DDAVP) preparation was given to prevent the excretion of electrolyte-free water. The concentration of Na in plasma fell from 139 +/- 1 mM to 120 +/- 2 mM 24 hours after the infusion of hypotonic saline (P < 0.01). Since these rats had a small negative balance for water (4 +/- 1 ml), hyponatremia was due to their negative balances for Na (2.2 +/- 0.3 mmol) and K (2.2 +/- 0.1). There were negative balances for Cl (2.4 +/- 0.2 mmol) and phosphate (0.7 +/- 0.05 mmol). Despite the negative balance for NaCl, the ECF volume as assessed by 3H-inulin space was not contracted. In this model for acute hyponatremia, its basis was electrolyte loss, but the ECF volume was not contracted, suggesting that water shifted from the ICF to the ECF. Hyponatremia is associated with cell swelling only if its cause is positive water balance and/or is loss of Na from the ECF. It is critical to examine the urine anions to determine the compartment of origin of particles excreted with K and thereby whether hyponatremia will result in overall expansion or contraction of the ICF volume.

Urea recycling: an aid to the excretion of potassium during antidiuresis.

Urea absorption in the inner medullary collecting duct provides a mechanism to elevate the concentration of urea in the papillary interstitial fluid and thereby permit the excretion of urea with as little water as possible. Urea reabsorption may have another important effect - to aid in the excretion of potassium (K). K excretion depends on two processes: first, factors such as aldosterone which cause the concentration of K in the luminal fluid of the cortical distal nephron to be high and, second, factors which augment the flow rate through those nephron segments. Since, the osmolality of the luminal fluid in the cortical collecting duct (CCD) and plasma are equal when antidiuretic hormone acts, the flow rate in the CCD is dependent on solute delivery. Urea is a major solute in the lumen of the CCD and thereby plays an important role in maintaining the CCD flow rate. Since urea and K are often found in the same foods, having urea help the excretion of K is potentially advantageous. If the excretion of urea was low, the flow rate in the terminal CCD would decline. In this circumstance, the luminal K concentration would have to rise in proportion to the fall in flow rate or there would be a diminished rate of excretion of K and, possibly, hyperkalemia.