Combination therapy of nitazoxanide with oseltamivir compared with oseltamivir in hospitalized patients with seasonal influenza.

Antiviral combinations have been proposed as treatment for influenza in order to increase the antiviral activity by action at different sites of action as well as obviate the emergence of drug resistance to the commonly used antiviral agents like oseltamivir. Nitazoxanide has been found to exhibit anti-influenza viral activity with clinical benefit in a previous study. We recruited 242 cases of SARI, among whon 67 were confirmed to have influenza viral infection. In a randomized blinded fashion, 34 patients received a combination of nitazoxanide and oseltamivir whereas 33 cases received oseltamivir alone. Clinical parameters were followed in both groups and the nasal swabs were re-tested on day 6 for influenza positivity and the cycle threshold (CT) values. No significant differences were observed in terms of time for resolution of fever, other symptoms, and SOFA scores. Nine patients succumbed during the course of the illness that included three in the oseltamivir group and six in the combination group. All but one of those who expired had an underlying co-morbid illness. Our preliminary data suggest that the addition of nitazoxanide does not improve outcomes in hospitalized patients with influenza. Larger studies are recommended for statistically robust conclusions.

Nosocomial SARS-COVID-19 Outbreak During the Third Wave of COVID-19 in an Oncology Facility at a Tertiary Care Hospital in Kashmir, India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a life-threatening respiratory condition, especially in immunocompromised patients, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially detected in China in December 2019, the first case in India was diagnosed on January 30, 2020. Here we report a nosocomial COVID-19 outbreak among cancer patients and healthcare workers (HCWs) in a medical oncology unit of a tertiary care hospital from our region. MATERIALS AND METHODS: This was a descriptive study of the nosocomial COVID-19 outbreak and was conducted in the month of January 2022 at the medical oncology unit of a tertiary care hospital in Srinagar, Jammu and Kashmir (J&K), India. The study included 25 COVID-19 cases, including patients and HC/non-HCWs (NHCWs). The confirmation of diagnosis was done through real-time polymerase chain reaction (RT-PCR) using nasopharyngeal/oropharyngeal swabs as the test sample. RESULTS: Twenty-five COVID-19 cases, including 14 admitted patients, nine HCWs, and two NHCWs were confirmed by COVID-19 RT-PCR in a span of 11 days. The first case was a positive HCW. The patients were admitted for management of various hematological as well as solid organ malignancies. Of the 14 patients, eight were in the pediatric age group with a mean age of 6.9 years, and six were adults with a mean age of 55.2 years. Thirteen patients were on different chemotherapy protocols, and one was undergoing an autologous stem cell transplant. Of the 14 patients, four were asymptomatic for COVID-19 symptoms, eight had mild disease, and two had severe disease with respiratory failure. Two patients with severe diseases needed COVID-19-designated high-dependency unit (HDU) admission. There was one COVID-19-related death. Among the healthcare workers, the mean age was 33.8 years, of which six were males and three were females. All the HCWs and NHCWs had mild disease, and all of them recovered completely. CONCLUSION: Nosocomial COVID-19 illness is a new entity and is preventable. COVID-19 illness will remain in society after the pandemic is over, like the influenza B viral illness, and there can be seasonal flares in the future. Proper measures should be taken to prevent its clustering in hospital settings.

Clinicopathological Features and Status of Programmed Death Ligand-1 (PD-L1) Expression in Lung Cancer: A Single Centre Study From North India.

Introduction Programmed death ligand-1 (PD-L1) is an immunological checkpoint that supports the inhibition of the anti-tumor immune system. A higher level of PD-L1 expression was also discovered on the cell surfaces of several cancer cells, including non-small cell lung carcinoma (NSCLC). Identifying individuals who would benefit from PD-1/PD-L1 antibody immunotherapy is crucial in the era of precision medicine. The study's objective was to assess the distribution and degree of PD-L1 ligand expression in various forms of lung cancer and examine its link to clinicopathological variables. Methods This prospective, observational, cross-sectional study was done in a tertiary care hospital in North India over 2 years from 2019 to 2021. A total of 100 patients diagnosed with lung cancer through either endobronchial or image-guided biopsies were enrolled. The biopsy specimens of lung cancer patients have been subjected to immunohistochemistry (IHC) staining. PD-L1 expression was positive when at least 1% of tumor cells were stained. In our study, we used the rabbit monoclonal Anti-PD-L1 antibody (CAL10) (ab237726) (Abcam Plc, UK).  Results  Of the 100 patients, Squamous cell carcinoma (SQCC) was the predominant histological pattern. The mean age of the study group was 57.26 ± 10.53 years. High PDL-1 positivity (>50% ) is seen in a total of 10 patients, while low PD-L1 positivity (1-50%) is seen in 24 patients. Of all patients with high PD-L1 positivity (n=10), 80% had stage IV at the time of diagnosis. However, on similar lines, 71 % of patients with low PD-L1 positivity presented with stage IV at the time of diagnosis. (p value=0.09). Among 10 patients with epidermal growth factor receptor (EGFR) positive status, high PD-L1 positivity is seen in 20%. Among 3 patients with anaplastic lymphoma kinase (ALK) positive status, only one patient showed high PD-L1 positivity, whereas negative PDL-1 was seen in 2 patients, which was not statistically significant. Conclusion  The management of lung cancer is driven by precision medicine, including PDL-1 expression, which correlates with immune checkpoint inhibitor response. In our cohort, PD-L1 expression appears to be mostly linked to the squamous cell subtype of lung cancer, with elevated tumor stage and mediastinal lymphadenopathy in Kashmiri people. Other oncogenic driver mutations are not connected to PD-L1 expression. The function of PD-L1 expression in lung tumors requires more study.

Combination of vitamin C, thiamine and hydrocortisone added to standard treatment in the management of sepsis: results from an open label randomised controlled clinical trial and a review of the literature.

Background: Combination of vitamin C, hydrocortisone and thiamine have recently been used in sepsis but data of efficacy are conflicting and no data are available from developing countries. We sought to study the effect of addition of this combination to standard care in patients with sepsis/septic shock in a north Indian setting.Methods: In a prospective, open label, randomised fashion, 100 patients with sepsis/septic shock were recruited to receive either standard therapy alone (control group, n = 50) or a combination of vitamin C, thiamine and hydrocortisone (treatment group, n = 50) in addition. The patients were followed for various clinical and laboratory parameters, in-hospital and 30-day mortality, duration of vasopressor use, lactate clearance, duration of hospital stay, and change in serum lactate and the SOFA score over the first 4 days.Results: The 2 groups were matched for basic characteristics. The in-hospital mortality (28% in controls and 24% in treatment group, p = .82) and 30-day mortality (42% in controls and 40% in treatment group, p = 1.00) was not significantly different in the 2 groups. However, there was a significant difference in duration of vasopressor use (96.13 ± 40.50 h in control group v/s 75.72 ± 30.29 h in treatment group, p value = .010) and lactate clearance (control group: 41.81% v/s treatment group: 56.83%, p value =.031) between 2 groups.Conclusions: Addition of vitamin C, hydrocortisone, and thiamine into standard care of sepsis does not improve in-hospital or 30 day mortality. However lower vasopressor use and faster lactate clearance is observed with treatment.

Cost of Severe Chronic Obstructive Pulmonary Disease Exacerbations in a High Burden Region in North India.

BACKGROUND: Data on costs of acute exacerbations of COPD (AECOPD) in low-income countries are sparse. We conducted a prospective survey to assess direct and indirect costs of severe AECOPD in a tertiary care setting in a high prevalence area of North India. METHODS: We conducted face-to-face surveys using a semi-structured questionnaire among a convenience sample of 129 consenting patients admitted with AECOPD. Data were collected on out-of-pocket costs of hospitalization, consultation, medications, diagnostics, transportation, lodging, and missed work days for self and their attendants. Out-of-pocket costs were supplemented with World Health Organization-CHOICE estimates. Missed work-days were valued on per capita national income (Indian Rupees [INR] 68,748, US$1,145.8). Median total cost per exacerbation episode was INR 44,390 (Inter-quartile range [IQR]: INR 33,354-63,642; US$739.8, IQR: 555.9-1060.7). Hospital costs constituted the largest component of the costs (71%) followed by other costs directly borne by the patient himself (29%), medicine costs (14%), transportation charges (2%) and diagnostic tests (3%). Indirect costs to caregivers (median INR 1,544, IQR: INR 0-17,370 INR; US$25.7, IQR: US$0-289.5), calculated as financial loss due to missed work days, accounted for 4% of the total cost. Expenses were covered by family members in all but 11 patients. CONCLUSIONS: AECOPD in India are associated with substantial costs and strategies to reduce the burden of disease such as smoking cessation, influenza and pneumococcal vaccination, etc should be aggressively pursued.

Microbial etiology in hospitalized North Indian adults with community-acquired pneumonia.

BACKGROUND: There is a paucity of literature regarding the microbial etiology of community-acquired pneumonia (CAP) in India. The current study was aimed to study the microbial etiology of hospitalized adults with CAP. METHODS: The study was conducted in a 700-bedded North Indian hospital. Consecutive adults admitted with CAP over a period of 2 years from 2013 to 2015 were recruited for the study, and apart from clinical evaluation underwent various microbiological studies in the form of blood culture, sputum culture, urinary antigen for pneumococcus and Legionella, serology for Mycoplasma and Chlamydia and real-time reverse transcriptase polymerase chain reaction for influenza viruses. Radiographic studies were performed in all patients and repeated as required. The patients were treated with standard antibiotic/antiviral therapy and outcomes were recorded. RESULTS: A total of 225 patients (median age: 59 years) were enrolled. Streptococcus pneumoniae was the most common organism found (30.5%), followed by Legionella pneumophila (17.5%), influenza viruses (15.4%), Mycoplasma pneumoniae (7.2%), Chlamydia pneumonia (5.5%), Mycobacterium tuberculosis (4.8%), Klebsiella pneumoniae (4.8%), methicillin-resistant Staphylococcus aureus (3.5%), Pseudomonas aeruginosa (3.1%), methicillin-sensitive S. aureus (1.7%), and Acinetobacter sp. (0.8%) with 4% of patients having multiple pathogens etiologies. High Pneumonia Severity Index score correlated with the severity and outcome of the CAP but was not predictive of any definite etiological pathogen. In-hospital mortality was 8%. CONCLUSION: Streptococcus pneumoniae, Legionella, and influenza constitute the most common etiological agents for north Indian adults with CAP requiring hospitalization. Appropriate antibiotic therapy and preventive strategies such as influenza and pneumococcal vaccination need to be considered in appropriate groups.

Two-year mortality in survivors of acute exacerbations of chronic obstructive pulmonary disease: A North Indian study.

OBJECTIVES: Data about long-term mortality of Indian patients following acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are scant. We set out to study the 2-year mortality in north Indian patients following discharge after AECOPD. MATERIALS AND METHODS: One hundred and fifty-one (96 male) patients admitted for AECOPD and discharged were followed for 2 years at 3, 6, 12, 18, and 24 months for mortality. Statistical analysis was performed to identify risk factors associated with mortality. RESULTS: Sixty (39.7%) of the 151 recruited died during the 24 months of follow-up, 30 (19.8%) at 3-month, 43 (28.5%) at 6-month, 49 (32.4%) at 1-year, 55 (36.4%) at 18-month, and 60 (39.7%) at 2 years. There was no mortality in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I (0 of 6 cases), whereas it was 12.3% (n = 8 of 65 patients) in GOLD Stage II, 41.7% (n = 15 of 36 cases), in GOLD Stage III, and 84.1% (n = 37 of 4 cases), of patients with GOLD Stage IV. Mortality was associated with 6-min walk distance, oxygen saturation, low body mass index, history of congestive heart failure, and St. George Respiratory Questionnaire score. CONCLUSION: Indian patients discharged after AECOPD have a high 2-year mortality. Measures to reduce the frequency of exacerbations need to be routinely adopted in patients with COPD.

Osmotic demyelination syndrome following slow correction of hyponatremia: Possible role of hypokalemia.

A 47-year-old male presented with hyponatremia that was corrected slowly as per the recommended guidelines. The patient improved initially but went on to develop a quadriparesis with a locked-in state due to a central as well as extrapontine myelinolysis and subsequently succumbed to an intercurrent infective illness. The patient had associated hypokalemia. Hyponatremia can result in central pontine myelinolysis even when the electrolyte disorder is treated slowly, and the concomitant hypokalemia seems to play a contributory role in the pathogenesis of the neurological disorder.

Intrathoracic gossypiboma causing intractable cough.

A 45-year old woman presented with a 5-month history of coughing, eight months after surgery for post-tubercular fibrosis with bronchiectasis. Upon computerized tomography (CT) scanning, a sponge-like structure was seen in the pneumonectomy cavity near the stump of the right main bronchus. Bronchoscopic examination revealed a whitish mass blocking the right main bronchial stump which, upon attempted retrieval, yielded long threads of cotton fibres from a retained surgical gauze. The gossypiboma was removed surgically and the patient became symptom-free. Although rare after thoracic surgery, gossypibomas need to be considered in symptoms following surgery.

Vitamin d toxicity in adults: a case series from an area with endemic hypovitaminosis d.

Vitamin D deficiency state is endemic to the Kashmir valley of the Indian subcontinent. Physicians often treat patients with high doses of vitamin D for various ailments and on occasion the prescribed doses far exceed the requirements of the patients. Ten cases of hypercalcemia due to vitamin D intoxication are presented with features of vomiting, polyuria, polydipsia, encephalopathy and renal dysfunction. All the patients had demonstrable hypercalcemia and vitamin D levels were high in nine of the 10 cases. The patients had received high doses of vitamin D and no other cause of hypercalcemia was identified. Treatment of hypercalcemia resulted in clinical recovery in nine cases. We conclude that hypervitaminosis D must be considered in the differential diagnosis of patients with hypercalcemia in endemically vitamin D deficient areas. A careful history and appropriate biochemical investigation will unravel the diagnosis in most of the cases.

Comparison and agreement between venous and arterial gas analysis in cardiopulmonary patients in Kashmir valley of the Indian subcontinent.

BACKGROUND: Arterial blood gas (ABG) analysis is routinely performed for sick patients but is fraught with complications, is painful, and is technically demanding. OBJECTIVE: To ascertain agreement between the arterial and peripheral venous measurement of pH, pCO(2), pO(2), and bicarbonate levels in sick patients with cardiopulmonary disorders in the valley of Kashmir in the Indian subcontinent, so as to use venous gas analysis instead of arterial for assessment of patients. SETTING: Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, a 650-bedded tertiary care hospital in North India located at an altitude of 1584 m. METHODS: One hundred patients who required ABG analysis were admitted. Peripheral venous blood was drawn within 5 min of an ABG measurement, and the samples analyzed immediately on a point of care automated ABG analyzer. Finger pulse oximetry was used to obtain oxygen (SpO(2)) saturation. Data were analyzed using Pearson correlation and bias (Bland Altman) methods. RESULTS: The venous measurements of pH, pCO(2), pO(2) and bicarbonate, and the digital oxygen saturation were highly correlated with their corresponding arterial measurements. Bland Altman plots demonstrated a high degree of agreement between the two corresponding sets of measurements with clinically acceptable differences. The difference in pO(2) measurements was, however, higher (-22.34 ± 15.23) although the arterial saturation and finger oximetry revealed a good degree of agreement with clinically acceptable bias. CONCLUSION: Peripheral venous blood gas assessment in conjunction with finger pulse oximetry can obviate the routine use of arterial puncture in patients requiring ABG analysis.

An elderly male with tubercular osteomyelitis of the chest wall.

Primary tuberculosis of the ribs is rare. A 70-year-old male presented with a 6-month history of a chest wall swelling that ruptured over few weeks to lead to a chronic discharging sinus. He had been administered multiple antibiotics, but the discharge continued. Clinical examination revealed anaemia, cervical lymphadenopathy and a 2-cm splenomegaly. Investigations revealed a normochromic and normocytic anaemia (Hb 7.0 g/dl), an ESR of 60 and a positive tuberculin sensitivity test of 25 mm. Surgical excision of the sinus along with the underlying revealed a caseous rib with histopathological features of a caseating granuloma. The patient was put on antitubercular therapy and is doing well on follow-up.

Kaposi Sarcoma in a Non HIV Patient.

We report a case of a 45 year old non HIV infected female, who presented with multiple painful, livid reddish brown plaques, papules and nodules on both lower limbs and left index finger. The cutaneous nodular lesions on biopsy showed characteristic features of Kaposi's sarcoma. This case is reported due to paucity of Kapsi's sarcoma in non HIV Persons. It is typically a disease of older men from European and Mediterranean region. Here we present a case report of classic Kaposi's Sarcoma in a young Indian female.

Familial hypercholesterolemia.

Familial homozygous hypercholesterolemia is a rare autosomal disorder characterized by high levels of cholesterol, extensive tendon xanthomatosis and premature development of atherosclerotic disease. Early coronary artery disease with myocardial infarctions and sudden deaths are common. We reported a family of familial hypercholesterolemia from the Kashmir valley of the Indian subcontinent. The appearance and the severity of the cutaneous xanthomas was found to be age related suggesting a role for the duration of hypercholesterolemia in the development of xanthomatosis.