Real-world experience of monoclonal antibodies in mild-to-moderate COVID-19 patients at a tertiary care center.

Background: Neutralizing antibodies cocktail (casirivimab and imdevimab) has received emergency use authorization recommendation by Food and Drug Administration (FDA) and WHO for mild-to-moderate COVID-19 infection in specific high-risk groups. Antibodies cocktail has shown promising results in preventing progression to severe disease, but the real-world experience is still evolving. Herein, we present a retrospective analysis of 22 patients who were administered the antibodies cocktail between August 2021 and March 2022 at our tertiary care center. Methods: We conducted an observational retrospective analysis of clinicoradiological, inflammatory parameters, progression of the disease, and outcome among 22 mild and moderate COVID-19 patients treated with antibodies cocktail. Results: The mean age was 67.7 years (SD ± 18.3) and comprised of 13 males (59%), while 9 were females (40.9%). Nine (40.9%) patients were fully vaccinated with two doses, nine (40.9%) were partially vaccinated with one dose while four patients (18.2%) were unvaccinated, and the rest were unvaccinated. Diabetes and hypertension were the commonest comorbidities; hematological and solid organ malignancies were other comorbidities. Eight patients had radiological opacities consistent with COVID-19 pneumonia and had shown significant regression in four patients after the therapy. None of our patients required supplemental oxygen or progressed to severe acute respiratory distress syndrome. All patients were discharged in a stable condition within 6 days of the therapy. Conclusions: The neutralizing antibodies cocktail has shown encouraging results in our analysis in preventing progression to severe disease in patients with high-risk conditions.

Sweetness and positivity together aren't a happy ending: Case controlled study amongst severe COVID-19 for impact of diabetes mellitus on survival.

Background: India is the epicenter of diabetes mellitus (DM). The relationship between COVID and DM in age/gender-matched non-diabetics has not been studied yet. The role of DM in predicting the disease severity and outcome in COVID patients might provide new insight for effective management. Methods: We conducted a prospective comparative study at a COVID care center from 25th April-31st May 2021. Among 357 severe-COVID patients screened, all consecutive diabetes (n-113) and age/gender-matched non-diabetes (n-113) patients were recruited. All diabetics and non-diabetics at admission were subjected to high resolution computed tomography (HRCT) chest and inflammatory markers (C-reactive protein (CRP), D-dimer, ferritin, interleukin-6 (IL-6), lactate dehydrogenase (LDH), Neutrophil-Lymphocyte Ratio (NLR)) before starting anti- COVID therapy. Statistical analysis was done using JMP 15·0 ver·3·0·0. Results: The prevalence of DM among the screened population (n-357) was 38·37%. The mean age of the study population was 61y with male preponderance (57%). There was no statistical difference in the HRCT-score or inflammatory markers in the two groups except for higher NLR (p-0·0283) in diabetics. Diabetics had significantly inferior overall survival (OS) (p-0·0251) with a 15d-OS of diabetics vs. non-diabetics being 58·87%, 72·67%, and 30d-OS of diabetics vs. non-diabetics being 46·76%, 64·61%, respectively. The duration of the hospital stay was not statistically different in the two groups (p-0·2). Conclusion: The mortality is significantly higher in severe-COVID patients with DM when compared to age/gender-matched non-diabetics. There was no significant difference in most inflammatory markers/CT at admission between the two groups.

Vitamin D, body mass composition and metabolic risk factors in healthy young Indians.

BACKGROUND: Studies have linked vitamin D to risk factors for cardiovascular disease. Obesity is a potential confounder in these studies. This study examined the relationship of 25 (OH) cholecalciferol (25[OH] D3) with insulin resistance, blood glucose, and lipid profile in lean male adults. METHOD: We enrolled two hundred and thirty four military recruits before beginning of military training. Demographic and anthropometric data were collected from them. The participants underwent body mass composition analysis by dual energy X ray absorptiometry. Fasting samples were collected for measurement of blood glucose, lipid profile, 25(OH) D3, serum parathormone (PTH) and insulin. RESULTS: Vitamin D deficiency and insufficiency was found in 47.7% (107/224) and 31.6% (71/224) of participants, respectively. Using Pearson's correlation coefficient 25(OH) cholecalciferol and fasting blood glucose (FBG) were inversely correlated (p = 0.023). However, similar relation was not found between 25(OH) D3 and total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, homeostatic model assessment of insulin resistance and levels of PTH. On body composition analysis, there was no correlation of 25(OH) cholecalciferol with body mass index or fat mass index. CONCLUSION: This study showed that in lean young male population, 25(OH) cholecalciferol and FBG are inversely correlated but no association of 25(OH) D3 with other cardiometabolic risk factors could be demonstrated.

The effect of vitamin D supplementation on cardiorespiratory fitness and muscle strength in male adults undergoing basic military training.

BACKGROUND: Vitamin D deficiency (VDD) is ubiquitous in the Indian subcontinent. VDD has been shown to impair muscle functions. However, the association of VDD with cardiorespiratory endurance is uncertain. Hence, we enrolled and supplemented vitamin D in military recruits with VDD with an aim to evaluate effect of supplementation on cardiorespiratory endurance and muscle strength. METHOD: We enrolled 90 military recruits with VDD and randomly allotted them to two groups equally. The group I received cholecalciferol granules 60,000 IU every fortnight for twelve weeks (cases), and the group II was observed as control. Muscle strength and cardiorespiratory endurance was assessed with a battery of tests (standing broad jump, bent arm hang test, 20 m shuttle run) at baseline and repeated at the end of training (nineteen weeks). Blood samples were collected for measurement of serum 25(OH)D and parathyroid hormone. RESULTS: In Group I and Group II, there was significant increase in 25(OH) D levels (25.8 ± 7.1 and 17.3 ± 3.5 ng/ml, respectively), and in VO2 max (9.8 ± 8.8 and 12.7 ± 8.6 ml/kg/min, respectively) compared with the baseline values. However, no significant change was observed in muscle strength after supplementation. There was no difference between the groups in VO2 max and muscle strength at baseline and at the end of training. CONCLUSION: Vitamin D supplementation did not improve muscle strength and cardiorespiratory endurance in military recruits with VDD. A significant rise in 25(OH) D was observed even in those not supplemented with vitamin D.

The ABC of diabetes. How many patients are able to achieve the goal laid down by American Diabetes Association?

BACKGROUND: To study the number of patients with Type 2 Diabetes Mellitus who achieve the glycemic, blood pressure and LDL-Cholesterol targets as per American Diabetes Association, Standard of Care for Management of Diabetes. METHODS: Hundred patients of Type 2 Diabetes mellitus were recruited from December 2008 to January 2009 from an Endocrinology OPD of tertiary care hospital and followed up for six months. Glycosylated hemoglobin (HbA1c), blood pressure (BP) and LDL-Cholesterol (LDL) were estimated at baseline and prevalence of those at target (HbA1c <7%, BP < 130/80 mm Hg, LDL < 100 mg/dl) was documented and repeated at three and six months to monitor improvement in the number of patients at target and trend in improvement of individual parameters. RESULTS: The percentage of patients at target at baseline and six months for HbA1c was (45% vs. 55% p = 0.101), BP < 130/80 mm Hg (27% vs. 25%) and LDL <100 mg/dl (37% vs. 40% p = 0.386). All three parameters were at target in one patient and three patients at six months period. Mean values at baseline and six months of HbA1c 7.46% (95% CI 7.17-7.75) vs 7.21% (95% CI 6.9-7.52), Systolic BP 138 mm Hg (95% CI 135-141), Diastolic BP 86 mm Hg (95% CI 84-86) and LDL 114 mg/dl (95%CI 107-121) vs. 110 mg/dl (95%CI 105-116) did not show significant improvement (p for trend). CONCLUSION: Standards of care for HbA1c, blood pressure and LDL remains to be achieved in majority of the diabetic patients.

The relationship between serum 25-hydroxy vitamin D, parathormone and bone mineral density in Indian population.

OBJECTIVES: Vitamin D deficiency (VDD) is a global problem. Not all patients with VDD have clinical manifestations or secondary hyperparathyroidism. We studied the interaction between serum 25-hydroxy vitamin D (25OHD), parathormone (PTH) and bone mineral density (BMD) in Indian adolescents and adults. DESIGN: Population survey. PATIENTS: A total of 1829 adolescents and 1346 adults aged 50 years and above were analysed in this study. MEASUREMENTS: Serum biochemistry, 25OHD, PTH and BMD were estimated. Subjects were grouped according to quartiles of serum PTH. VDD was defined as severe (25OHD ≤ 5 ng/ml), moderate (25OHD ≤ 10 ng/ml) and mild (25OHD ≤ 20 ng/ml) and secondary hyperparathyroidism (SHPT) when serum PTH levels >65 pg/ml. RESULTS: Only 30-40% of subjects with moderate and severe VDD, respectively, had SHPT. BMD decreased from Quartile 1 to Quartile 4 of PTH at all sites among adolescents and adults, with only a marginal decline in serum 25OHD levels between these quartiles. Further, within each PTH quartile, there was no difference in BMD according to categories of VDD. Analysing BMD in the different PTH quartiles, the PTH cut-offs beyond which BMD showed a significant decline, was 35 pg/ml in adolescents and 53 pg/ml in adults. CONCLUSIONS: Less than half of the subjects with VDD have SHPT. BMD levels start to decline at PTH values currently considered to be normal. These data suggest the need to redefine SHPT in different age groups keeping in mind the relationship between PTH and BMD. This may also influence the decision to supplement subjects with VDD.

Respiratory sinus arrhythmia in dogs. Effects of phasic afferents and chemostimulation.

We examined the hypothesis that respiratory sinus arrhythmia (RSA) is primarily a central phenomenon and thus that RSA is directly correlated with respiratory controller output. RSA was measured in nine anesthetized dogs, first during spontaneous breathing (SB) and then during constant flow ventilation (CFV), a technique whereby phasic chest wall movements and thoracic pressure swings are eliminated. Measurements of the heart rate and of the moving time averaged (MTA) phrenic neurogram during these two ventilatory modes were made during progressive hypercapnia and progressive hypoxia. RSA divided by the MTA phrenic amplitude (RSAa) showed a power-law relationship with both arterial carbon dioxide partial pressure (PaCO2) and oxygen saturation (SaO2), but with different exponents for different conditions. However, the power-law relation between RSAa and respiratory frequency had an exponent indistinguishable from -2 whether hypoxia or hypercapnia was the stimulus for increased respiratory drive, and during both CFV and spontaneous breathing (-1.9 +/- 0.4, hypoxia, SB; -1.8 +/- 0.7, hypoxia, CFV; -2.1 +/- 0.8, hypercapnia, SB; -1.9 +/- 0.7, hypercapnia, CFV). We conclude that respiratory sinus arrhythmia is centrally mediated and directly related to respiratory drive, and that changes in blood gases and phasic afferent signals affect RSA primarily by influencing respiratory drive.

Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: ascertainment methods and sample description.

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.

Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.

Tracheal perforation. A complication associated with transtracheal oxygen therapy.

A 73-year-old woman with a transtracheal oxygen catheter in place developed sudden onset of respiratory distress and subcutaneous emphysema. Bronchoscopy revealed the presence of three posterior tracheal wall perforations and a blind pouch arising from one of the perforations. Subsequent bronchoscopies revealed complete healing of the perforations. We believe that these perforations occurred during placement of the transtracheal catheter.

Catheter position and blood gases during constant-flow ventilation.

We studied the effect of catheter position and flow rate on gas exchange during constant-flow ventilation (CFV) in eight anesthetized, paralyzed dogs. The distal tips of the insufflation catheters were positioned 0.5, 2.0, 3.5, and 5.0 cm from the tracheal carina. Flow rates were varied between 10 and 55 l/min and steady-state arterial blood gases were measured. At a given flow rate, arterial CO2 pressure (PaCO2) decreased as CFV was administered further into the lung up to a distance of 3.5 cm from the carina; there were no significant differences in PaCO2 at 3.5 and 5.0 cm. For a given catheter position, PaCO2 decreased with increasing flow rate up to a flow rate of 40 l/min. Further increases in flow rate had no significant effect on PaCO2. Arterial O2 pressure (PaO2) was relatively constant at all flow rates and catheter positions. We conclude that, up to a point, CO2 elimination can be improved by positioning the catheters further into the lung; advancing the catheters further than 3.5 cm from the carina may cause over-ventilation of specific lung regions resulting in a relative plateau in CO2 elimination and relatively constant PaO2's. Positioning the catheters further into the lung permits the use of lower flow rates, thus potentially minimizing the risk of barotrauma.

Constant-flow ventilation in pigs.

Constant-flow ventilation (CFV) is a ventilatory technique in which physiological blood gases can be maintained in dogs by a constant flow of fresh gas introduced via two catheters placed in the main-stem bronchi (J. Appl. Physiol. 53: 483-489, 1982). High-velocity gas exiting from the catheters can create uneven pressure differences in adjacent lung segments, and these pressure differences could lead to gas flow through collateral channels. To examine this hypothesis, we studied CFV in pigs, animals known to have a high resistance to collateral ventilation. In three pigs we examined steady-state gas exchange, and in six others we studied unsteady gas exchange at three flow rates (20, 35, and 50 l/min) and three catheter positions (0.5, 1.5, and 2.5 cm distal to the tracheal carina). During steady-state runs we were unable to attain normocapnia; the arterial CO2 partial pressure (PaCO2) was approximately 300 Torr at all flow rates and all catheter positions, compared with 20-50 Torr at similar flows and positions in dogs studied previously. The initial unsteady gas-exchange experiments indicated no consistent effect of catheter position or flow rate on the rate of rise of PaCO2. In three other pigs, the rates of rise of PaCO2 were compared with the rates observed with apneic oxygenation (AO). At the maximum flow and deepest position, the rate of rise of PaCO2 was lower during CFV than during AO. These data suggest that flow through collateral channels might be important in producing adequate gas transport during CFV; however, other factors such as airway morphometry and the effects of cardiogenic oscillations may explain the differences between the results in pigs and dogs.

Velocity profiles in central airways with endotracheal intubation: a model study.

Steady inspiratory velocity profiles were measured at two flow rates in a 3:1 scale model of the human central airways in the presence of five modes of endotracheal intubation. The presence of an orifice or a short endotracheal tube had no significant effect on the velocity profiles distal to the carina. Long endotracheal tubes change the profiles in both main bronchi. A significant peak occurred in the frontal plane near the walls, and the maximum velocity in the airway was almost identical to the endotracheal tube center-line velocity. The flow impinging on the medial wall of the main bronchus was redirected up around the anterior and posterior walls yielding bipeak velocity profiles in the sagittal plane. A tube placed eccentrically in the trachea over the right main bronchus did not alter the velocity profiles in the left main bronchus, suggesting a redirection of flow over the carina into the left lung. An endobronchial tube at the mouth of the right main bronchus did change the shape of the velocity profiles in the left main bronchus. In the left upper lobar bronchus the presence of trachea intubation had no effect on the velocity profiles. However, in the right upper lobar bronchus, the long endotracheal tube flattened the velocity profiles from the strongly skewed ones seen in the absence of the endotracheal inserts. These results not only are relevant to distribution of ventilation and aerosol particle deposition, but also have strong implications in intrapulmonary gas mixing, especially when high-frequency low tidal-volume ventilation is involved.

Effect of the larynx on oscillatory flow in the central airways: a model study.

Measurements were made of the effect of the larynx on the oscillatory flow profiles in a 3:1 scale model of the human central airways. A fixed glottic aperture corresponding to the shape and size at midinspiration was used. Oscillatory airflows at peak Reynolds numbers, similar to those obtained during spontaneous breathing and panting, were studied. The flow distribution to the five lobar bronchi was maintained by distally placed linear resistors. A hot-wire anemometer probe was used to measure the local velocity along two perpendicular diameters at six stations distributed through the model. Near the proximal end of the trachea, the flat velocity profiles at the beginning of the flow cycle peaked at maximum flow because of the jet created by the glottic aperture. This peaked structure was conserved during the latter half of the inspiratory cycle. Close to the carina, the jet had almost dissipated and the entry conditions into the main bronchi corresponded to those in the absence of the laryngeal model. The effect of the glottic aperture on the mean velocity was not felt beyond the carina, and the characteristic skewed profiles seen in oscillatory flows, in the absence of the larynx, were present in the main and lobar bronchi.

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.