Xeroderma Pigmentosum-Associated Childhood Interstitial Lung Disease.

Chromosomal breakage syndromes are a group of genetic disorders that are ascribable to the autosomal recessive mode of inheritance. Xeroderma pigmentosum is one of the chromosomal breakage syndromes which is due to the involvement of deformity in the deoxyribonucleic acid's nucleotide excision repair. Xeroderma pigmentosum is a genetic disorder, which is autosomal recessive, heterogeneous, and more common in cases of consanguinity, caused by mutations in at least 10 genes and 9 complementation groups. The disorder is very rare. Patients experience photophobia and extreme photosensitivity and have pigmentary changes in ultraviolet light-exposed areas of the body with freckling, premalignant, and malignant skin lesions arising in keratinocytes soon after the fleeting exposure to sunlight. Patients are also oversensitive to environmental mutagens such as cigarette smoke and possibly to the widely used agricultural insecticide, diazinon. Progressive neurological abnormalities along with some rare complications are also noticed among these patients. Symptoms and thoracic high-resolution computed tomography are considered for diagnosis. Only corticosteroids can be given to limit the progression of the disease. Xeroderma pigmentosum-related interstitial lung disease is one of the rarest forms and we thereby report an interesting case.

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology.

Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.

Clinical Presentation of Cases with SARS-CoV-2 Reinfection/ Reactivation.

BACKGROUND: Reinfection/reactivation of SARS-CoV-2 has been a matter of great interest from the immunological and vaccine perspective. However, little is known about the clinical presentation of such reinfection/reactivation. We report a case series of 9 COVID-19 patients having experienced two clinically- and/or virologically-confirmed episodes of COVID-19. METHODS: Epidemiological and clinical characteristics of 9 healthcare workers (HCWs) with two episodes of SARS-CoV-2 are described. RESULTS: The incidence of reinfection/reactivation amongst the HCWs was 2% (9 out of 491) with an average remission period of 66 days (range 43-78 days). Amongst the cases of reinfection 4/9 were asymptomatic in first episode were symptomatic in second episode. There is negative correlation between numbers of days the patients took to become SARS-CoV-2 negative by RT-CPR and/or clinically recover in the first episode and the second episode irrespective for the time spent in remission. CONCLUSION: Shorter durations of SARS-COV-2 infection in the first episode are associated with longer time to recovery in the second episode in patients with re-infection/reactivation.

Clinical Characteristics, Management, and Short-Term Outcome of Neonates Born to Mothers with COVID-19 in a Tertiary Care Hospital in India.

INTRODUCTION: We describe the clinical characteristics, management, and short-term outcomes of SARS-CoV-2 neonates born to mothers with COVID-19 in a tertiary care hospital in Mumbai, India. METHODS: The study is a retrospective analysis of 524 neonates born to mothers with COVID-19 admitted from 14th April 2020 to 31st July 2020. RESULTS: SARS-CoV-2 infection was detected in 6.3% of the newborns of the mothers with COVID-19. No significant differences were observed between maturity at gestation, birth weight and sex of SARS-CoV-2 infected and noninfected newborns. The risk of sepsis was 4.09 [95% confidence interval (95% CI) 1.28-13.00] fold higher in the neonates with SARS-CoV-2 as compared to the noninfected group (p = 0.031). Poor feeding was significantly more common among SARS-CoV-2 infected neonates (12.1%) as compared to the noninfected neonates (2.7%) (p = 0.017). There was a total of 13 neonatal deaths, of which 3 deaths occurred in SARS-CoV-2 infected neonates (9%) while 10 (2.04%) in the SAR-CoV-2 negative group. The risk of neonatal death was higher in SARS-CoV-2 infected newborns [odds ratio (OR) 4.8; 95% CI 1.25-18.36]. CONCLUSION: Neonatal SARS-CoV-2 infection is observed in almost 6% of neonates born to mothers with perinatal COVID-19. There is a higher risk of adverse outcomes such as neonatal sepsis and death in the SARS-CoV-2 infected as compared to the noninfected neonates.

The current pandemic of COVID-19 has affected all the countries globally. However, the adverse impact of the pandemic is more seen in the low-income and middle-income countries (LMICs). Although there is evidence on the adverse impact of the SARS-CoV-2 on the health of mothers and neonates, the evidence is mainly from high-income countries. For reducing the mortality and morbidity due to COVID-19 in LMICs, there is a need to generate evidence from the LMICs. The present study is a part of the National Registry of pregnant women with COVID-19 in India (PregCovid registry). Our study demonstrates a higher risk of adverse outcomes such as neonatal sepsis and death in the SARS-CoV-2 infected as compared to the noninfected neonates. The study also showed the risk of SARS-CoV-2 infection in 6.3% of neonates born to mothers with COVID-19.

Clinical course and outcome of patients with COVID-19 in Mumbai City: an observational study.

OBJECTIVE: To understand the outcome of hospitalised patients from Mumbai City, which had the highest number of COVID-19 cases in India. DESIGN: Observational study with follow-up. SETTING: Data extraction from medical records of patients with COVID-19 admitted to Nair Hospital & TN Medical College, Mumbai, India. PARTICIPANTS: 689 patients with COVID-19 were admitted in the hospital from 26 March 2020 to 11 May 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: In-hospital mortality; joint effect of comorbidity and age on the risk of dying. RESULTS: A total of 689 patients (median age 44 years) admitted with RT-PCR-confirmed COVID-19 were included in the study. Of these, 77.36% of patients were discharged alive while 22.64% died. 11.61% required some kind of oxygen support while 2.8% of patients required intensive care unit admissions. Older age (HR 2.88, 95% CI 2.09 to 3.98), presence of comorbidities (HR 2.56, 95% CI 1.84 to 3.55), history of hypertension (HR 3.19, 95% CI 1.67 to 6.08), and presence of symptoms at the time of admission (HR 3.21, 95% CI 1.41 to 7.26) were associated with increased risk of in-hospital mortality. Treatment with a combination of azithromycin with hydroxychloroquine, antiviral or steroid compared with no treatment did not alter the disease course and in-hospital mortality. The combined effect of old age and presence of comorbid conditions was more pronounced in women than men. CONCLUSIONS: In-hospital patients were younger, less symptomatic with lesser need of ventilators and oxygen support as compared with many western countries. TRIAL REGISTRATION: Not applicable (observational study, not a clinical trial).

Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study.

Background: Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, clinically presenting with common symptoms of fever, dry cough, and breathlessness within 14 days of exposure. Its severity ranges from mild to severe, latter manifesting into severe acute respiratory syndrome. As a part of multidisciplinary team, physiotherapy along with medical management was administered to patients with COVID-19 in an acute care setup. This retrospective study aims to explore various patient characteristics and will aid in identifying the impairments associated with the disease, giving a direction to the physiotherapy community in planning future management strategy to improve quality of life. Patients and methods: The present study is a unicentric study wherein prospective analysis of retrospective data of patients referred for physiotherapy from May 13 to July 31, 2020, was performed. (i) Characteristics of patients, (ii) associated comorbidities, (iii) hospital course since the time of admission to discharge, (iv) mode of oxygen delivery, (v) pre- and post-physiotherapy treatment values of oxygen saturation and heart rate, and (vi) physiotherapy treatment were recorded. The archived data were analyzed using the commercially available SPSS software version 24. Wilcoxon's matched pair test was used to compare pre- and post-treatment oxygen saturation and heart rate, and McNemar's test was used to compare mode of oxygen delivery and pre- and post-physiotherapy treatment. Results: Descriptive analysis of data showed a better outcome in terms of grade of dyspnea and rate of discharge on day 14 of physiotherapy treatment. Hence, a comparative analysis of day 1 and day 14 was performed for mode of oxygen delivery, oxygen saturation, and heart rate. A statistically significant improvement was observed in the heart rate (p = 0.001) and oxygen delivery (p = 0.000). However, no significant difference in the level of oxygen saturation was found (p = 0.6433). Conclusion: Physiotherapy treatment in conjunction with medical treatment can be effectively administered in patients with COVID-19 in acute care setup taking into consideration the health status and the hemodynamic stability of the patients. It emphasizes the role of physiotherapy in the alleviation of symptoms, facilitating early weaning and recovery enabling early discharge from the hospital. How to cite this article: Verma CV, Arora RD, Mistry HM, Kubal SV, Kolwankar NS, Patil PC, et al. Changes in Mode of Oxygen Delivery and Physiological Parameters with Physiotherapy in COVID-19 Patients: A Retrospective Study. Indian J Crit Care Med 2021;25(3):317-321.

Prevalence and profile of sleep-disordered breathing and obstructive sleep apnea in patients with interstitial lung disease at the pulmonary medicine department of a tertiary care hospital in Mumbai.

BACKGROUND: Sleep-disordered breathing (SDB), predominantly obstructive sleep apnea (OSA), is a frequent phenomenon in interstitial lung disease (ILD) and may be associated with significant morbidity and mortality. METHODOLOGY: A prospective, observational, hospital-based study was conducted in a tertiary care hospital after ethics committee permission. The study group consisted of 100 consecutive ILD patients diagnosed by a multidisciplinary diagnosis. They were evaluated for the prevalence of SDB with a polysomnography after a comprehensive history, detailed clinical examination, calculation of various pretest probability scores, and relevant prerequisite workup. RESULTS: Out of the total 100 ILD patients, 44 were male (44%) and 56 were female (56%). SDB was present in 57 (57%) patients. Of these, 29 (29%) were found to have only nocturnal oxygen desaturation (NOD), while 28 (28%) had OSA. The 28 cases of OSA were distributed as 15 mild OSA (53.57%), 10 moderate OSA (35.71%), and 3 severe OSA (10.71%). The patients were divided into the following four groups: total study Group (A), patients with OSA (Group B), patients with NOD without OSA (Group C), and no SDB (Group D). The mean forced vital capacity values predicted in the four groups were 53.67%, 50%, 45.56%, and 57.87%, respectively. The mean body mass index in the four groups was 24.56, 27, 26.98, and 24.89 kg/m2, respectively. The mean 6-min walk distance in the four groups was 280.7, 250, 256.65, and 311.4 m, respectively. The mean partial pressure of oxygen in the four groups was 65.65, 60, 62.10, and 75.66 mmHg, respectively. The mean apnea-hypopnea index in the study group was 2.98/h, 8.6/h with mild OSA, 21.69/h with moderate OSA, 48.78/h with severe OSA, 3.89/h in patients having NOD without OSA, and 2.54/h in patients with no SDB. CONCLUSION: SDB in ILD is associated with a significant impact on the cardinal determinants of functional capacity, lung function, and quality of life.

Appraisal of Critically Ill COVID-19 Patients at a Dedicated COVID Hospital.

PURPOSE: To study the pattern of severe COVID-19 to reduce morbidity and mortality. METHODS: It was an observational cohort study for comprehensive clinical analysis of critically ill COVID-19 patients at a dedicated COVID public hospital. RESULTS: Total 373(13.6%) patients were critically ill with 254(68.1%) males and 119(31.9%) females (including 25 pregnant) and death occurred in 69(18.5%) patients. Mean of parameters associated with critical COVID illness and having significant difference among dead and recovered were; age (47.08,p= 5.67E- 09), SpO2 (86.08), blood sugar(168.47,p= 1.86E-08), IL-6(210.5,p=0.0058) D-dimer(0.753,p= 0.00178). All the patients were given oxygen by non invasive technique, in 46(12.3%) intubation and invasive ventilation required. Use of hydroxychloroquin in 284(76.1%) (p=0.041,OR0.555,95%CI 0.314-0.981), lopinavir/ ritonavir in 283(75.9%) (p=4.222E-009,OR0.198, 95%CI0.114-0.345), tocilizumab in 124(33.2%) patients, (p=3.27E006, OR0.150, 95%CI0.063-0.358) were associated with recovery. Factors that influenced mortality were presence of co-morbidities (p=0.088,OR1.784,95%CI0.911-3.492), hypertension(p=0.0031,OR2.432,95% CI1.370 -4.318), low SpO2 (p=3.91E-010,OR0.017,95%CI0.002-0.137), high blood sugar(p=7.75E-009,OR8.514,95%CI 3.776-19.201), high LDH(p=0.00064,OR2.7 22,95%CI1.545-4.798) high ferritin(p=0.00014,OR4.606,95%CI 2.035-10.422), high D-dimer(p=2.85E-007,OR4.090,95%CI 2.371-7.056), low PFR(p=4.84E-008), and endotracheal intubation(p=3.14E-043,OR165.936,95%CI48.160-571.731). Using binary logistic regression, elevated IL-6(0.02441), low PFR(0.00082), and endotracheal intubation(2.04E-10) were statistically significant predictors of death. CONCLUSION: "Happy Hypoxia", hyperglycemia, high inflammatory markers (IL-6, ferritin), and ARDS were hallmark of critical COVID-19, early detection of factors associated with severity and mortality and starting the multipronged management with oxygen in prone position, hydroxychloroquin, antiviral, methylprednisolone, anticoagulants, tocilizumab early may help in halting the worsening of COVID and reduce morbidity and mortality.

Emerging trends of nosocomial pneumonia in intensive care unit of a tertiary care public teaching hospital in Western India.

BACKGROUND: Nosocomial pneumonia poses great challenge to an intensivist. Detailed information about hospital-acquired pneumonia (HAP) and ventilator-acquired pneumonia (VAP) is crucial for prevention and optimal management, thus improving quality Intensive Care Unit (ICU) care. Hence, we aimed to study the current trend of nosocomial pneumonia in ICU. MATERIALS AND METHODS: It was a prospective observational cohort study, conducted in the ICU of a tertiary care teaching public hospital over a period of 18 months. We studied clinical profile and outcome of 120 adult patients who developed VAP/HAP during the study period. We also analyzed the causative organisms, antibiotic sensitivity, and resistance pattern in these patients. RESULTS: Out of 120 patients, 29 patients were HAP and 91 patients were VAP. Mortality was 60% (72), and development of VAP and requirement of mechanical ventilation showed significant association with mortality (P < 0.00001). Most common organism causing HAP was Staphylococcus aureus (43.4%) and VAP was Klebsiella pneumoniae (49%). Maximum antibiotic sensitivity was found to piperacillin + tazobactam (58.8%), followed by imipenem (49.5%) and meropenem (41.8%), whereas maximum antibiotic resistance was found to cefepime (95.1%), followed by ceftazidime and amoxicillin (91.2%). CONCLUSION: Nosocomial pneumonia showed high incidence (17.44%) and mortality (60%). Common organisms identified were S. aureus and K. pneumoniae. Resistance was high for commonly used antibiotics and high antibiotic sensitivity for piperacillin + tazobactam and carbapenem. Contexte: La pneumonie nosocomiale pose un grand défi à un intensiviste. Des informations détaillées sur la pneumonie acquise dans les hôpitaux (HAP) et la pneumonie acquise par le ventilateur (VAP) sont essentielles pour la prévention et la gestion optimale, améliorant ainsi les soins de soins intensifs de qualité (UTI). Par conséquent, nous avons cherché à étudier la tendance actuelle de la pneumonie nosocomiale en UTI. Matériaux et méthodes: il s'agissait d'une étude de cohorte observationnelle prospective menée dans l'UCI d'un hôpital public d'enseignement tertiaire sur une période de 18 mois. Nous avons étudié le profil clinique et le résultat de 120 patients adultes qui ont développé le VAP / HAP pendant la période d'étude. Nous avons également analysé les organismes responsables, la sensibilité aux antibiotiques et le modèle de résistance chez ces patients. Résultats: Sur 120 patients, 29 patients étaient HAP et 91 patients étaient VAP. La mortalité était de 60% (72), et le développement du VAP et l'exigence de ventilation mécanique ont montré une association significative avec la mortalité (P < 0,00001). L'organisme le plus fréquent causant HAP était Staphylococcus aureus (43,4%) et VAP était Klebsiella pneumoniae (49%). Une sensibilité antibiotique maximale a été observée chez la pipéracilline + tazobactam (58,8%), suivie de l'imipénème (49,5%) et du méropénem (41,8%), alors que la résistance antibiotique maximale a été observée à cefépime (95,1%), suivie de ceftazidime et de l'amoxicilline (91,2%) . CONCLUSION: la pneumonie nosocomiale a montré une incidence élevée (17,44%) et la mortalité (60%). Les organismes communs identifiés étaient S. aureus et K. pneumoniae. La résistance était élevée pour les antibiotiques couramment utilisés et une forte sensibilité aux antibiotiques pour la pipéracilline + le tazobactam et le carbapénème.

Modern approaches to a rapid diagnosis of tuberculosis: promises and challenges ahead.

The limitations of the conventional methods for diagnosing tuberculosis have spurred multi-faceted research activities in this field throughout the world. Chromatographic methods appear promising but may not be widely available in the developing countries. Immuno-diagnostic methods using combinations ("cocktails") of antigens have high sensitivity and specificity and can easily be applied in the peripheral laboratories and in the field settings. Though expensive, molecular methods for diagnosis of tuberculosis have advantages of speed, sensitivity, and specificity. Adequate training of the eligible personnels in molecular methods and prevention of laboratory-dependent contamination may help reduce false positive results. Although, there are no clear guidelines, so far on how to make out the best from the gene amplification methods, yet their use may be encouraged with adequate quality controls, because of the inherent ingenuity and promises of these methods. Phage-based molecular methods provide rapid results in susceptibility tests for anti-tubercular drugs. In future, many sophisticated techniques are expected to hit the market for a rapid diagnosis of tuberculosis. In the developing countries, it is necessary to evaluate availability of suitable infrastructure and trained personnels before adopting modern diagnostic methods.