Long-term quality of life and work ability among severe COVID-19 survivors: A multicenter study.

Background: Coronavirus disease 2019 (COVID-19), is known for its variable severity and high infectivity. Though fewer than 15% of infected cases develop severe disease, a major proportion had prolonged stay in the intensive care unit (ICU). Prolonged ICU stay is known to have a long-term impact on behavior and quality of life.8 Therefore, it is likely that patients discharged after severe COVID-19 have issues that persist for long term. The current study aimed to assess the long-term impact of severe COVID-19 on the Quality of life (QOL), sleep pattern, behavior, and workability. Methods: The current multicenter study adopted a cross-sectional design to analyze data from two tertiary care COVID-19 dedicated hospitals. All experimental procedures were approved by the ethics committee of the M.L.B Medical College. Participants were 20-60 age group who had been admitted to the ICU because of severe COVID-19 and had elapsed at least one and a half year since their discharge. After informed written consent the participants were assessed for: EUROHIS-QOL 8-item index; Workability Score; Quality of sleep; The major depression inventory (MDI) questionnaire; Generalized anxiety disorder 7 item scale (GAD-7); Current global health status score: an innovative subjective scale (1 -10) to determine the current global health status when 5 is the status before COVID-19. Findings: 491 participants were assessed, the median follow-up time after discharge from the hospital was 561·0 days (range, 548-580 days). The mean duration of ICU stay was 8.72 ± 2.85 days. There was significant reduction in the prevalence of obesity, diabetes, and hypertension as compared with discharge time. The mean of EUROHIS-QOL score, workability score, current global health status score was 3.28 ± 0.98, 6.87 ± 0.85, 4.53 ± 1.36 respectively. The mean MDI and anxiety scores were 4.12 ± 1.45 and 18.63 ± 3.28, respectively. Interpretation: Severe COVID-19 survivors have new-onset psychological disorders and sleep disturbances. Long term quality of life and work ability remains poor after prolong ICU admission secondary to severe COVID-19.

Antimicrobial consumption and bacterial resistance pattern in patients admitted in I.C.U at a tertiary care center.

BACKGROUND: Throughout the world multi drug resistant nosocomial infections are one of the leading causes of death and morbidity among hospitalized patients. Antimicrobial resistance [AMR] has become a major problem in treatment of such infections. High consumption of antimicrobials particularly in ICUs is often described as the most important factor leading to AMR. OBJECTIVE: The aim of the study was to study the magnitude of antimicrobial resistance amongst nosocomial pathogens and the antimicrobial prescription patterns of patients admitted in intensive care unit. METHODS: The study was conducted in I.C.U of a tertiary care government hospital in Delhi over a period of 4 months, on 100 patients admitted in I.C.U. Depending on clinical suspicion laboratory samples were collected and subjected to antimicrobial sensitivity testing. Antimicrobial prescription of these patients were collected from I.C.U records and analyzed. OBSERVATIONS: Staphylococcus aureus and Klebsiella species were the most common organism [23%]. Among patients where causative organism was isolated, two or more organisms were isolated from 50% of the samples. Most of the Klebsiella species and Acinetobacter species were resistant to beta lactam group of antibiotics such as cephalosporins and piperacillin-tazobactam. 60% of isolates of S. aureus were found to be MRSA while none of the S. aureus were resistant to linezolid and vancomycin. All patients were prescribed two or more antimicrobials while 66% patients were prescribed 3-5 antimicrobials. Commonest combination was beta lactam with metronidazole followed by levofloxacin with metronidazole with addition of aminoglycosides or linezolid as third drug. Total 20 antimicrobial agents were used in the treatment of the patients. Among these consumption [in DDD/100bed days] of metronidazole was highest [100.9] followed by fluconazole [76.6] and levofloxacin [62.7]. CONCLUSION: High usage of antimicrobial consumption has been noted in this study, prompting institution of measures to formulate and adherence to antimicrobial policy strictly.

Role of the Truview EVO2 laryngoscope in the airway management of elective surgical patients: A comparison with the Macintosh laryngoscope.

BACKGROUND: The Truview EVO2(C) laryngoscope (TL) is a recently introduced optical device designed to provide an unmagnified anterior image of the glottic opening and allow indirect laryngoscopy. AIM: This study is designed to determine whether the TL is a better alternative to the Macintosh laryngoscope (ML) for routine endotracheal intubations in patients with usual airway characteristics. METHODS: We compared the Truview EVO2(C) and MLs in 140 elective surgical patients requiring general anaesthesia and intubation in a prospective crossover fashion. The two blades were compared in terms of Cormack and Lehane grades, time required for intubation, anaesthetists' assessment of ease of intubation, intubation difficulty score, attempts at intubation, success rate, soft tissue damage and arterial oxygen saturation during laryngoscopy. The Student t test and Chi-square test were used to determine the statistical significance of parametric data and categorical data, respectively. RESULTS: The Truview EVO2(C) blade provided a better laryngoscopic view than the Macintosh blade as suggested by improved Cormack and Lehane grades (in 48 patients), but required a longer time for intubation than the Macintosh blade (34.1 vs. 22.4 s), i.e., an improved view at the cost of longer mean intubation time. In spite of lower intubation difficulty scores, Truview EVO2(C) was considered as difficult to use on subjective assessment by the anaesthesiologist when compared with Macintosh. There was no difference observed between the two groups in attempts at intubation, success rate, soft tissue damage and arterial oxygen saturation during laryngoscopy. CONCLUSION: We opine that although Truview provides a better laryngoscopic view than Macintosh in difficult cases, it does not have an extra benefit over Macintosh otherwise, further indicating the need for more experience with the use of a Truview laryngoscope.

Evaluation of postoperative analgesic efficacy of transversus abdominis plane block after abdominal surgery: A comparative study.

BACKGROUND: The transversus abdominis plane (TAP) block is an effective method of providing postoperative analgesia in patients undergoing midline abdominal wall incisions, by blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit. We evaluated its analgesic efficacy in patients during the first 48 postoperative hours after abdominal surgery, in a randomized, controlled single-blind clinical trial. MATERIALS AND METHODS: Sixty patients (mean age 36.2 ± 9.6 years) of either sex of ASA grade 1 and 2 who underwent major gynecological or surgical operation were randomized either to receive standard care, including patient-controlled tramadol analgesia (n = 30), or to undergo TAP block (n = 30) in addition to standard care. After completion of surgery, 20 ml of 0.375% levobupivacaine was deposited into the transversus abdominis neurofascial plane via the bilateral lumbar triangles of Petit. Each patient was assessed in the postanesthesia care unit and at 2, 4, 6, 12, 24, and 48 h postoperatively. RESULTS: The TAP block reduced Visual Analog Scale pain scores at most (2, 4, 6, 12, 24 h), but not at all time (36, 48 h) points assessed. Patients undergoing TAP block had reduced tramadol requirement in 24 h (210.05 ± 20.5 vs. 320.05 ± 10.6; P < 0.01) and 48 h (508.25 ± 20.6 vs. 550.25 ± 20.6; P < 0.01), and a longer time to the first PCA tramadol request (in minutes), compared to the control group (178.5 ± 45.6 vs. 23.5 ± 3.8; P < 0.001). CONCLUSION: The TAP block provided highly effective postoperative analgesia in the first 24 postoperative hours after major abdominal surgery, and no complications due to the TAP block were detected.

Safety and efficacy of low-molecular-weight heparins in prophylaxis of deep vein thrombosis in postoperative/ICU patients: A comparative study.

BACKGROUND: Venous thromboembolism (VTE), although a very common problem in everyday clinical practice, remains asymptomatic in most cases. Clinical diagnosis helps identify those who are going to have thromboembolic episode. A combination of clinical scoring systems like Wells' score and D-dimer assay provide a useful diagnostic tool. Trauma (surgical or accidental) and critically ill patients are found to have greatest risk. Enoxaparin and dalteparin are amongst the most common low-molecular-weight heparins (LMWHs) used for deep venous thrombosis (DVT) prophylaxis in such patients. AIM: The present study is designed to compare their role in preventing DVT in postoperative or critically ill patients and to determine their relative safety profiles. MATERIALS AND METHODS: The study included 36 critically ill adult patients. All the patients were allocated into three groups of 12 patients each. Group I patients received no prophylaxis, group II received inj. enoxaparin s/c 0.6-0.8 mg/kg twice daily, and group III received inj. dalteparin s/c 125-250 units/kg once daily. Routine investigations and coagulation profile were recorded on admission to intensive care unit (ICU) and at every third day thereafter. Patients were daily assessed for pretest probability of DVT using Wells' scoring, and D-dimer test was done on the 7(th) day. Occurrence of any bleeding (visible or occult) was noted, and incidence of DVT was determined in each group using positive results of D-dimer test and the clinical assessment with Wells' score. RESULTS: A significant difference in Wells' score (P < 0.05) was found between groups I and III on day 5 and day 7. A lower, but insignificant difference in the incidence of DVT was found between the study and control groups. No significant difference in major bleeding or other side effects was found. Better hemodynamic status and arterial blood gases in the study groups may indirectly refer to absence of asymptomatic DVT or silent pulmonary embolism in this group. CONCLUSION: The present study suggests that LMWHs, namely, enoxaparin and dalteparin, provide effective means of preventing DVT in high-risk, critically ill or postoperative patients, without causing any significant increase in the risk of bleeding or other side effects. Dalteparin appears to be unaffected by low creatinine clearance as explained by its clearance by a non-saturable mechanism. Still, a more extensive study with larger population is needed to make the outcomes worthwhile.

Pycnodysostosis: an anaesthetic approach to this rare genetic disorder.

Pycnodysostosis (the Toulouse-Lautrec syndrome) is a rare autosomal-recessive disorder of osteoclast dysfunction. This disorder was first described by Maroteaux and Lamy in 1962. We describe anaesthetic management of a 35-year-old female having pyknodysostosis with fracture shaft left femur with anticipated difficult intubation. Therefore, spinal anesthesia was planned for her fracture fixation. The intra- and postoperative period remains uneventful.

Sphaeranthus indicus induces apoptosis through mitochondrial-dependent pathway in HL-60 cells and exerts cytotoxic potential on several human cancer cell lines.

PURPOSE: The study was designed to screen Sphaeranthus indicus, Ganoderma lucidum, and Urtica dioica for their anticancer activity against human cancer cell lines. Phytochemical screening of active extracts was also planned. METHODS: Petroleum ether, ethanolic, and aqueous extracts of S indicus Linn, G lucidum P Karst, and U dioica Linn were subjected to cytotoxicity studies using 7 different cancer cell lines. Potent cytotoxicity was noted in petroleum ether extract of S indicus (SIP), which inhibited proliferation of various cancer cell lines. Growth inhibition was determined by sulforhodamine B assay. Two biochemical markers, namely ß-sitosterol and 7-hydroxyfrullanolide were isolated and characterized using high-performance thin layer chromatography, melting point, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass analysis. Cytotoxicity of isolated ß-sitosterol and 7-hydroxyfrullanolide were also determined. The IC(50) of SIP was calculated in the HL-60 cells and was found to be 53 µg/mL. Furthermore, SIP induced apoptosis in human leukemia HL-60 cells as measured by several biological end points. Cell cycle analysis and change in mitochondrial membrane potential was quantified by flow cytometry. Subsequently, using annexin V/PI assay, proportion of cells actively undergoing apoptosis was determined. Changes in DNA were observed by DNA ladder assay. RESULTS: SIP induced apoptotic bodies formation, induced DNA laddering, enhanced annexin-V-FITC binding of the cells, increased sub-G(0) DNA fraction, and induced loss of mitochondrial membrane potential (ΔΨm) in HL-60 cells. SIP also elevated the caspase 3 and caspase 9 levels in the HL-60 cells, which clearly indicates the involvement of the intrinsic proteins in inducing apoptosis. DISCUSSION: All the above parameters revealed that SIP induced apoptosis through the mitochondrial-dependent pathway in HL-60 cells. The criterion for anticancer activity in cytotoxicity assay was ≥70% growth inhibition at 100 µg/mL against at least 4 cell lines. As G lucidum and U dioica did not exhibit appreciable inhibitory activity against human cancer cell lines (less than 50%), they were not included in the study thereafter. The results established that SIP has apoptosis-inducing effect against HL-60 cells in vitro and is a promising candidate for further anticancer study. ß-Sitosterol and 7-hydroxyfrullanolide can be considered to be potent anticancer compounds isolated from SIP on the basis of present studies.

2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers.

A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and 5e) have exhibited potent cytotoxicity specifically against human leukemia HL-60 cell lines with IC(50) values in the range of 0.08-0.70 µM. All these compounds were tested for their effects on the cell cycle perturbations and induction of apoptosis. Morphological evidences of apoptosis, including fragmentation of nuclei and inter nucleosomal DNA laddering formation were clearly observed after 24h exposure to compound 4i. Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. These compounds trigger the mitochondrial apoptotic pathway that results in the loss of mitochondrial membrane potential through activation of multiple caspases followed by activation of caspase-3, and finally cleavage of PARP. Further the mechanism of cell death was analysed by fluorescent microscopic analysis and also by scanning electron microscopy. The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds.

Design and synthesis of spiro derivatives of parthenin as novel anti-cancer agents.

Several novel spiro derivatives of parthenin (1) have been synthesized by the dipolar cycloaddition using various dipoles viz; benzonitrile oxides, nitrones and azides with exocyclic double bond of C ring (α-methylene-γ-butyrolactone). Majority of the compounds exhibited improved anti-cancer activity compared to the parthenin, when screened for their in vitro cytotoxicity against three human cancer cell lines viz., SW-620, DU-145 and PC-3. In vivo screening of select analog revealed improved anti-cancer activity with low mammalian toxicity as compared to parthenin. The results of the cytotoxicity pattern of these derivatives reveals the SAR of these sesquiterpinoid lactones and possible role of α,ß-unsaturated ketone of parthenin in inhibiting NF-kB. A mechanistic correlation of anti-cancer activity along with in vivo and western blotting experiments has been described.

A propionyloxy derivative of 11-keto-ß-boswellic acid induces apoptosis in HL-60 cells mediated through topoisomerase I & II inhibition.

Boswellic acids have invariably been reported for their antiproliferative potential in various cell systems. In the present study the growth inhibitory effect of propionyloxy derivative of 11-keto-ß-boswellic acid (PKBA; a semisynthetic analogue of 11-keto-ß-boswellic acid) on HL-60 promyelocytic leukemia cells is being reported for the first time. In the preliminary studies, in vitro cytotoxicity of PKBA was investigated against eight human cancer cell lines viz., IMR-32, SF-295 (both neuroblastoma), PC-3 (prostate), Colo-205 (colon), MCF-7 (breast), OVCAR-5 (ovary), HL-60, Molt-4 (both leukemia) and their respective IC(50) values were found to be 5.95, 7.11, 15.2, 14.5, 15, 15.9, 8.7 & 9.5µg/ml, respectively. For determining the mechanism of cell death in HL-60 cells, PKBA was subjected to different mechanistic studies. DNA relaxation assay of PKBA revealed inhibition of both topoisomerases I & II. The fragmentation analysis of DNA revealed typical ladders indicating the cytotoxic effect to be mediated by induction of apoptosis. The morphologic studies of PKBA showed the presence of true apoptotic bodies. Apoptosis was confirmed further by flow-cytometric detection of sub-G(1) peaks and enhanced annexin-V-FITC binding of the cells. The activation of apoptotic cascade by PKBA in HL-60 cells was found to be associated with the loss of mitochondrial membrane potential, release of cytochrome c, activation of initiator and executioner caspases and cleavage of poly ADP ribose polymerase (PARP). In vivo studies of PKBA revealed anti-tumoral activity against both ascitic and solid murine tumor models. These studies thus demonstrate PKBA to induce apoptosis in HL-60 cells due to the inhibition of topoisomerases I and II.

Natural antioxidants synergistically enhance the anticancer potential of AP9-cd, a novel lignan composition from Cedrus deodara in human leukemia HL-60 cells.

Antioxidants have been used as adjuvant with anticancer therapy to synergize the potential of the anti-neoplastic therapeutics. Based on the fact, we have studied the effect of three natural antioxidants curcumin, silymarin and acteoside on AP9-cd (standardized lignan composition from Cedrus deodara) induced cytotoxicity in human leukemia HL-60 cells. The antioxidant potential of individual test compounds was first evaluated with ferric reducing antioxidant power (FRAP) test, which revealed that all four molecules behave as antioxidants. The apoptotic potential of AP9-cd was significantly enhanced in HL-60 cells in the presence of curcumin, silymarin and acteoside. It was confirmed by using various models like MTT assay, DNA fragmentation, nuclei condensation, sub-Go DNA population, Annexin-V-FITC binding, ROS depletion and immunoblotting in HL-60 cells. AP9-cd and individual antioxidants alone at low doses (10µg and 10µM, respectively) have meager or no cytotoxicity in HL-60 cells, whereas in mutual combinations, there were 2-3 times enhancement in Annexin-V-FITC and sub-Go DNA population. Moreover, prominent DNA ladders were observed at low doses of AP9-cd in combinations with various antioxidants. The Hoechst staining of the nucleus also revealed the same results for the HL-60 cells treated with AP9-cd and different antioxidants. The molecular diagnostics revealed that the combinations induced a strong antioxidant effect which was correlated with the downregulation of NF-κB expression in the nucleus. Out of the three antioxidants, curcumin was found to be more potent than acteoside and silymarin in terms of enhancing the apoptotic potential of AP9-cd. These results propose an important role of natural antioxidant as adjuvant to enhance the anticancer potential of AP9-cd and more likely other anti-neoplastic therapeutics.