Role of oral melatonin in prevention of postoperative delirium in patients undergoing elective surgery under general anesthesia: A Randomized controlled trial.

Background: Postoperative delirium is a common complication in patients undergoing elective surgery under general anesthesia. We aimed to minimize the incidence with an oral dose of 3 mg of melatonin administered the night before surgery. Methods: Hundred and sixty-two patients aged 40-80 years posted for various urological and gastrointestinal surgeries under general anesthesia with no preoperative cognitive deficits were randomly distributed equally to melatonin or control groups. In the control group, routine premedication was done with tablet alprazolam (0.25 mg) and ranitidine (150 mg), but in the melatonin group, the patients were given 3 mg melatonin orally the night before surgery along with routine premedication. The CAM scale was used for diagnosis of postoperative delirium. Results: Incidence of delirium was significantly lower in the melatonin group, 23.5%, 8.6%, and 2.5% at 6, 24, and 48 hours, respectively, and the corresponding mean (SD) values of CAM scores were 1.37 (1.30), 1.07 (1.03), and 0.69 (0.80). In contrast, the incidence of delirium was 46.9%, 30.9%, and 16% at 6, 24, and 48 hours, respectively, in the control group. There was a significant reduction in anxiety, a lower incidence of cognitive dysfunction (i.e., MoCA score <26), and improvement in sleep quality in the melatonin group at 6, 24, 48, and 72 hours after the surgical intervention. The generalized estimating equations model (GEE) model was used to study change in MoCA and CAM scores over time between the two groups, and it showed a significant interaction between time and treatment groups (P < 0.001). Conclusions: Melatonin premedication reduced incidence of postoperative delirium and cognitive dysfunction and was associated with better sleep quality and anxiolysis.

Efficacy of melatonin in decreasing the incidence of delirium in critically ill adults: a randomized controlled trial / Eficácia da melatonina na redução da incidência de delirium em pacientes adultos graves: um ensaio clínico randomizado

ABSTRACT Objective: To determine whether enteral melatonin decreases the incidence of delirium in critically ill adults. Methods: In this randomized controlled trial, adults were admitted to the intensive care unit and received either usual standard care alone (Control Group) or in combination with 3mg of enteral melatonin once a day at 9 PM (Melatonin Group). Concealment of allocation was done by serially numbered opaque sealed envelopes. The intensivist assessing delirium and the investigator performing the data analysis were blinded to the group allocation. The primary outcome was the incidence of delirium within 24 hours of the intensive care unit stay. The secondary outcomes were the incidence of delirium on Days 3 and 7, intensive care unit mortality, length of intensive care unit stay, duration of mechanical ventilation and Glasgow outcome score (at discharge). Results: We included 108 patients in the final analysis, with 54 patients in each group. At 24 hours of intensive care unit stay, there was no difference in the incidence of delirium between Melatonin and Control Groups (29.6 versus 46.2%; RR = 0.6; 95%CI 0.38 - 1.05; p = 0.11). No secondary outcome showed a statistically significant difference. Conclusion: Enteral melatonin 3mg is not more effective at decreasing the incidence of delirium than standard care is in critically ill adults.

RESUMO Objetivo: Determinar se a melatonina enteral diminui a incidência de delirium em adultos em estado grave. Métodos: Neste estudo controlado e randomizado, os adultos foram admitidos à unidade de terapia intensiva e/ou receberam apenas o padrão de cuidado habitual (Grupo Controle) ou o tratamento combinado com 3mg de melatonina enteral uma vez ao dia às 21h (Grupo Melatonina). A ocultação da alocação foi feita por meio de envelopes selados opacos e numerados sequencialmente. O intensivista que avaliou o delirium e o pesquisador que realizou a análise dos dados foram cegados quanto à alocação do grupo. O desfecho primário foi a incidência de delirium dentro de 24 horas de internação na unidade de terapia intensiva. Os desfechos secundários foram a incidência de delirium nos dias 3 e 7, a mortalidade na unidade de terapia intensiva, a duração da internação na unidade de terapia intensiva, a duração da ventilação mecânica e o escore da escala de desfecho de Glasgow (na alta). Resultados: Foram incluídos 108 pacientes na análise final, com 54 sujeitos em cada grupo. Em 24 horas de internação na unidade de terapia intensiva, a incidência de delirium não foi diferente entre os Grupos Melatonina e Controle (29,6% versus 46,2%; RR = 0,6; IC95% 0,38 - 1,05; p = 0,11). Nenhum desfecho secundário apresentou diferenças estatisticamente significativas. Conclusão: Em adultos em estado grave, 3mg de melatonina enteral não foi mais eficaz que os cuidados padrão na redução da incidência de delirium.

Potential diagnostic and prognostic biomarkers for breast cancer: A compiled review.

Breast cancer is one of the major reason for death of women worldwide. As per the International Agency for Research on Cancer (IARC) statistics, the number of cases of breast cancer is increasing year by year in many parts of the world. As per the recent global cancer burden figures, in 2020, there were 2.26 million incidences of breast cancer cases and it is one of the main causes of mortality due to cancer in women in the world. Biomarkers of breast cancer would prove to be very beneficial to screen women who are at higher risk and for detection of disease recurrence. Here, studies carried out on biomarkers of breast cancer and susceptibility to the disease have been reviewed. Various databases like Google Scholar, ScienceDirect and PubMed have been used for searching and majorly literature from the last 10 years have been considered. Potential biomarkers of breast cancer including blood based angiogenic factors, glycoprotein-based biomarkers, hormone receptor biomarkers and other biomarkers that were identified from various studies have been summarized.

Potential biomarkers in endometrial cancer: a narrative review.

CONTEXT: Every year, approximately 0.4 million women suffer from endometrial cancer (EC) worldwide and it has become the most common gynecological malignancy. Almost 66% of EC cases are diagnosed at an early stage and can be cured by performing surgery while those at an advanced stage turns out to be fatal. Biomarkers of endometrial cancer would be very valuable for screening of women who are at high risk and in detecting the chance of recurrence of disease. OBJECTIVE: The current article has reviewed studies published on expression of biomarkers and susceptibility to EC. METHODS: Google Scholar and PubMed were used as searching platforms and we have majorly considered the literature from last 10 years. RESULTS: Potential biomarkers of EC identified from various studies were summarised.

Transurethral lidocaine (100 mg) bladder irrigation (TULI100) reduces the incidence of catheter related bladder discomfort in transurethral resection of bladder tumors: A randomized, double blind, controlled trial.

BACKGROUND: Transurethral resection of bladder tumors (TURBT) surgeries requires post-resection catheterization for continuous irrigation of the bladder. This indwelling catheter is associated with distressing catheter-related bladder discomfort (CRBD) and increases postoperative pain and agitation. OBJECTIVES: To prove the hypothesis that transurethral 100 mg lidocaine irrigation at the end of TURBT can reduce the frequency of moderate-to-severe postoperative CRBD. METHODS: 116 patients scheduled for TURBT were screened, 94 were recruited and completed the study. American Society of Anesthesiologists Physical Status I-II adult patients, 20-75 years of age undergoing elective TURBT surgery under general anesthesia were included. Transurethral normal saline with 0.01% lidocaine (100 mg in 1 L NS) was used for irrigation 30 min before the completion of surgery in group L, while only normal saline was used for transurethral irrigation in group N. The main outcomes were frequency of CRBD, pain and patient satisfaction at 0, 1, 2, and 6 h postoperatively. RESULTS: A total of 94 patients were analyzed in the study. The incidence of moderate-severe CRBD was significantly lower in group L as compared to group C at 0, 1, and 2 h (65.9% vs. 31.9%, p = 0.01; 31.9% vs. 10.6%, p = 0.012; 21.3% vs. 2.1%, p = 0.004, respectively). At the 6-h mark, the incidence of CRBD was lower in group L, although this did not achieve statistical significance (6.38% vs. 2.1%; p = 0.613). CONCLUSION: Irrigation with 0.01% lidocaine (100 mg) towards the end of TURBT reduces the incidence of moderate-severe CRBD by 52% and increases patient satisfaction.

Normal Saline Versus Balanced Crystalloids in Renal Transplant Surgery: A Double-Blind Randomized Controlled Study.

Background The importance of optimal acid-base balance during renal transplant surgeries cannot be stressed enough. Optimal preload and electrolyte balance is important in maintaining this. There has been a debate on the choice of perioperative crystalloids in renal transplant surgeries over the past decades. Normal saline (0.9% saline) is more likely to cause hyperchloremic acidosis when compared to balanced salt solutions (BSS) with low chloride content whereas BSS may cause hyperkalemia. We aim to compare the safety and efficacy of normal saline (NS), Ringer's lactate (RL) and Plasmalyte (PL) on acid-base balance and electrolytes during living donor kidney transplantation. Materials and methods Patients were randomized to NS group (n = 60), RL group (n = 60) and Plasmalyte group (n = 60). Arterial blood samples were collected for acid-base analysis after induction of anaesthesia (T0), prior to clamping the iliac vein (T1), 10 minutes after reperfusion of the donated kidney (T2) and at the end of surgery (T3). In addition, serum creatinine and 24-hour urine output were recorded on postoperative days one, two and seven. Results There was a statistically significant difference (p < 0.001) in the pH at the end of surgery between the three groups with the NS group being more acidotic (pH 7.29 ± 0.06, 95% CI 7.27-7.32), although this was not clinically relevant. This was explainable by the parallel increase in chloride in the NS group. Early postoperative graft functions in terms of serum creatinine, urine output and graft failure requiring dialysis were not significantly different between the groups. Conclusion Balanced salt solutions such as Plasmalyte and Ringer's lactate are associated with better pH and chloride levels compared to normal saline when used intraoperatively in renal transplant patients. This difference, however, does not appear to have any bearing on graft function. Plasmalyte seems to maintain a better acid-base and electrolyte balance, especially during the postreperfusion period.

Comparative evaluation of optic nerve sheath diameter in patients undergoing laparoscopic cholecystectomy using low and standard pressures of gas insufflations.

Background and Aims: Intra-abdominal insufflation of CO2 is associated with an increase of intracranial pressure (ICP). We conducted this randomized control trial to compare the impact of low vs standard pressure pneumoperitoneum on ICP through the ultrasonographic estimation of the optic nerve sheath diameter (ONSD). Material and Methods: Patients of age group 18-80 years planned for laparoscopic cholecystectomy were randomly allocated into two groups; group S (standard pressure of 12-16 mmHg) and group L (low pressure of 8-10 mmHg) on the basis of intra-abdominal pressures used for the surgery. All were administered general anesthesia and end-tidal carbon dioxide (ETCO2) was maintained between 35 and 40 mmHg and peak airway pressures less than 35 cmH2O. ONSD was measured in either eye at a point 3 mm posterior to the globe at following time intervals; baseline, 5 min after induction, 10 min after insufflation, 10 min after reverse Trendelenburg, intraoperatively during surgery and after exsufflation in the supine position. Results: The demographic profile and operative times were comparable. ONSD was measured in 100 patients in each group for both the eyes and no patient had values above the cutoff value of 5.0 mm. No significant difference in the ONSD was observed at the above mentioned time intervals between the groups. There was a statistically significant lower value of the heart rate and mean arterial pressure in the low-pressure group. Conclusion: Intra-abdominal insufflation of CO2 at standard and low pressures does not increase ICP in short duration surgeries and thus both the pressures can be safely used in adult patients operated in reverse Trendelenburg position. Advantages of low pressure were limited to better hemodynamic control.

Critical events during intra-hospital transport of critically ill patients to and from intensive care unit.

OBJECTIVES: Intensive care unit (ICU) patients are at an increased risk of many catastrophic events during intrahospital transport (IHT) for various procedures. This study was planned to determine the incidence and types of adverse events occurring during the transport of critically ill patients in a tertiary care hospital. METHODS: This prospective observational study was conducted in the ICU of a tertiary care hospital for 8 months after ethical clearance from the institute ethics committee. All patients transported out of the ICU during the audit period for diagnostic or therapeutic procedures were included in the study. Vitals and several study parameters were recorded before, during, and after shifting patients to and from the ICU. Various critical events were noted during transport and classified into major and minor critical events based on the presence and absence of potential consequences that lead to a change of therapy during transport. RESULTS: One hundred and sixty patients were studied for consecutive IHT to and from the ICU. The patients were transported for imaging studies (58.1%), minor surgery (31.8%), major surgery (2.5%), and other procedures (7.5%). A total of 248 critical events were observed in 104 IHTs (65%; 95% confidence interval [95% CI]: 57.4%-72.1%). Hence, an average of 2.38 critical events occurred per IHT. There were 31 major events among the 248 critical events (12.5%; 95% CI: 8.8%-17.1%). CONCLUSIONS: Standard guidelines about the accompanying personnel and monitoring need to be followed during IHT. Conduct of minor surgical procedures in the ICU and better bedside diagnostic procedures may be considered for the future.

Evaluation of Intranasal Dexmedetomidine as a Procedural Sedative for Ophthalmic Examination of Children With Glaucoma.

PRECIS: This study evaluated 2 doses of intranasal dexmedetomidine (IND) (3.0 and 3.5 µg/kg) as a procedural sedative for postoperative examination of children with glaucoma. A dose of 3.5 µg/kg was more efficacious and obviated the need for repeated general anesthesia. PURPOSE: This study was carried out to determine the safety and effective dose of IND as a procedural sedative for postoperative follow-up examinations after glaucoma surgery in children in place of repeated examination under anesthesia. MATERIALS AND METHODS: In this prospective randomized double-blinded interventional study, consecutive children aged 6 months to 6 years were randomized to receive 3.0 and 3.5 µg/kg IND using a mucosal atomizer device in the preoperative area of the operating room, under continuous monitoring of vital signs. Intranasal midazolam 0.25 mg/kg was used as a rescue agent in case of inadequate sedation, and general anesthesia was administered in case of persistent failure. All infants underwent a complete anterior and posterior segment evaluation including intraocular pressure and corneal diameter measurements. RESULTS: A total of 30 and 31 children aged 23.9±15.0 and 19.2±10.1 months, respectively, received 3.0 and 3.5 µg/kg IND. Adequate sedation was possible in 18 of 30 (60%) children receiving 3.0 µg/kg and 24 of 31 (77.4%) receiving 3.5 µg/kg IND alone (P=0.17). In combination with midazolam, successful sedations were 86.6% versus 100%, respectively (P=0.052). One patient in the 3.5 µg/kg group had ventricular arrhythmia, reversed with dextrose-saline infusion and injection glycopyrrolate. CONCLUSIONS: IND appears to be a safe and effective procedural sedative for postoperative follow-up examinations of pediatric glaucoma patients at doses of 3 and 3.5 µg/kg. The dose of 3.5 µg/kg was successful in more children.

Comparison of Air-QⓇ insertion techniques in pediatric patients with fiber-optic bronchoscopic assessment: a prospective randomized control trial.

BACKGROUND: Air-QⓇ laryngeal mask airway (LMA) is a second-generation supraglottic airway device (SAD) providing adequate airway control despite the unfavorable airway anatomy in children. Several studies have assessed it as a conduit for tracheal intubation and compared its efficacy with that of other SADs, but there are no studies comparing the laryngeal view with midline and rotational insertion techniques of Air-Q. Therefore, this study compared the fiber-optic bronchoscopic (FOB) assessment of the Air-Q position using these two insertion techniques. METHODS: This randomized controlled trial included 80 patients of the American Society of Anesthesiologists physical status I/II of either sex (age group 5-12 years, weight 10-30 kg), who were scheduled for elective surgery in the supine position under general anesthesia. The patients were randomly subjected to rotational and midline technique groups (n = 40, each), and appropriate sized Air-Q, based on the weight of the patient, was inserted using the technique allocated to each patient. Time taken and number of attempts for successful insertion of the devices and any complications after removal of device were studied. RESULTS: FOB grade 1 (ideal position) was seen in 29/40 (72.5%) and 19/40 (47.5%) children subjected to the rotational and classic midline techniques, respectively (P = 0.045). The time taken to successfully insert the Air-Q was significantly lesser in the rotational technique group (7.2 ± 1.5 s) than in the classic midline technique group (10.2 ± 2.1 s) (P < 0.001), whereas complications were similar in both groups. CONCLUSIONS: The rotational technique was associated with better FOB view, and was faster than the classic midline technique of Air-Q insertion in pediatric patients.

The utility of limited trans-thoracic echocardiography in the stratification of pulse pressure variation: A feasibility study in major open abdominal surgery.

BACKGROUND AND AIM: Limitation in use of pulse pressure variation (PPV) in predicting fluid responsiveness (FR) in hypotensive patients is encountered when values are in the "gray zone" (8-13%). Dynamic arterial elastance (E adyn= PPV/SVV) can be used in such situations to predict arterial pressure response to volume expansion (VE). In our study, we used respiratory variation of ascending aorta velocity time integral (AoVTI) calculated from suprasternal window as a surrogate of stroke volume variation (SVV). Fluids/vasopressors were administered to hypotensive patients intraoperatively based on value of E adyn. Aim was to assess feasibility and utility of suprasternal echocardiography in the above-mentioned subset of patients. MATERIALS AND METHODS: Hemodynamic data were monitored and respiratory variation in AoVTI was recorded using suprasternal echocardiography at all time points when patients developed hypotension (systolic blood pressure <90 mm Hg/<20% of baseline for 5 min) and at randomly selected time intervals when hemodynamic stability was maintained. VE with 250 ml of Ringer lactate (RL) was done in hypotensive patients with PPV value of 8-13% and E adyn>0.9. Increase of >15% in AoVTI after VE defined "fluid responsiveness." RESULTS: Twenty-eight patients were enrolled, but three were excluded in view of left ventricular systolic dysfunction detected during preinduction echocardiography. Hemodynamic and echocardiographic data were recorded at 538 observation points in 25 adults. Hypotension occurred in 247 data sets, and in 168 data sets, value of PPV was 8-13%. VE was carried out in only those 131 data sets in which the value of E adyn was >0.9. Area under the curve (AUC) for VE as an intervention in the indeterminate (PPV 8-13%) group was 0.574 (0.49-0.68, 95% CI, P < 0.049), and in the observation set with PPV >13, the AUC value was 0.7 (0.59-0.98, 95% CI, P < 0.01). CONCLUSIONS: Echocardiography using the suprasternal window in the operating room during abdominal surgery is feasible, but the utility of E adyn in stratification of patients with PPV 8-13% is inconclusive.

Overtreatment in the United States.

BACKGROUND: Overtreatment is a cause of preventable harm and waste in health care. Little is known about clinician perspectives on the problem. In this study, physicians were surveyed on the prevalence, causes, and implications of overtreatment. METHODS: 2,106 physicians from an online community composed of doctors from the American Medical Association (AMA) masterfile participated in a survey. The survey inquired about the extent of overutilization, as well as causes, solutions, and implications for health care. Main outcome measures included: percentage of unnecessary medical care, most commonly cited reasons of overtreatment, potential solutions, and responses regarding association of profit and overtreatment. FINDINGS: The response rate was 70.1%. Physicians reported that an interpolated median of 20.6% of overall medical care was unnecessary, including 22.0% of prescription medications, 24.9% of tests, and 11.1% of procedures. The most common cited reasons for overtreatment were fear of malpractice (84.7%), patient pressure/request (59.0%), and difficulty accessing medical records (38.2%). Potential solutions identified were training residents on appropriateness criteria (55.2%), easy access to outside health records (52.0%), and more practice guidelines (51.5%). Most respondents (70.8%) believed that physicians are more likely to perform unnecessary procedures when they profit from them. Most respondents believed that de-emphasizing fee-for-service physician compensation would reduce health care utilization and costs. CONCLUSION: From the physician perspective, overtreatment is common. Efforts to address the problem should consider the causes and solutions offered by physicians.

Novel synthetic analogs of diallyl disulfide triggers cell cycle arrest and apoptosis via ROS generation in MIA PaCa-2 cells.

BACKGROUND: Diallyl disulfide (DADS), a principal organosulfur component of garlic, is known for its medicinal properties including anti-cancer activity. Prior studies have demonstrated that the compounds containing Diallyl disulfide moieties exhibited diverse therapeutic potential with promising biological activities. In the present study, we have investigated the in vitro anticancer activity of Diallyl disulfide derivatives (5a-5l and 7e-7m) against human cancer cell lines. METHODS: The effect of DADS analogs on different cancer cell lines was measured through MTT assay. Cell cycle progression, apoptosis, DNA fragmentation and levels of ROS were analyzed through FACS and confocal imaging. RESULTS: Bis[3-(3-fluorophenyl)prop-2-ene]disulfide (compound 5b) was the most potent compound among the tested DADS derivatives. FACS analysis revealed that increase in ROS generation by compound 5b was accompanied by cell cycle arrest in the G2/M phase and apoptosis in MIA PaCa-2 cells. Further, the apoptosis was confirmed by TUNEL assay. Western blot analysis showed that compound 5b induces G2/M phase arrest via ROS mediated DNA-damage, which in turn, induces phosphorylation of Chk1/Cdc25c/Cdc2 pathway. Furthermore, altered levels of ROS triggers intrinsic apoptotic cascade, as evidenced by dissipated mitochondrial membrane potential (ψ), decrease in Bcl-2/Bax ratio, cytochrome c release and cleavage of procaspase-3. Scavenging of ROS by antioxidant N-acetyl-cysteine (NAC) reversed the compound 5b induced augmented intracellular ROS levels and cell death. CONCLUSION: Taken together, the anti-proliferative effects of compound 5b were attributed to intracellular ROS accumulation, which in turn, triggers apoptosis by mediating DNA damage-induced G2/M phase arrest and evoking mitochondrial apoptotic pathway in MIA PaCa-2 cells.

Evidence for overuse of medical services around the world.

Overuse, which is defined as the provision of medical services that are more likely to cause harm than good, is a pervasive problem. Direct measurement of overuse through documentation of delivery of inappropriate services is challenging given the difficulty of defining appropriate care for patients with individual preferences and needs; overuse can also be measured indirectly through examination of unwarranted geographical variations in prevalence of procedures and care intensity. Despite the challenges, the high prevalence of overuse is well documented in high-income countries across a wide range of services and is increasingly recognised in low-income countries. Overuse of unneeded services can harm patients physically and psychologically, and can harm health systems by wasting resources and deflecting investments in both public health and social spending, which is known to contribute to health. Although harms from overuse have not been well quantified and trends have not been well described, overuse is likely to be increasing worldwide.

Anti-N-Methyl-D-Aspartate-Receptor Encephalitis in Young Females.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an immune-mediated disease commonly associated with ovarian teratoma. Anti-NMDA-receptor autoantibodies disrupt NMDA function leading to the development of psychosis, seizures and autonomic dysfunction. The treatment includes underlying tumour resection and immunosuppression. Slow recovery and unpredictable clinical course makes intensive care management of these patients challenging. We report the management of two young female patients with anti-NMDA-receptor encephalitis associated with ovarian teratoma.

Randomised controlled trial of central venous catheterisation through external jugular vein: A comparison of success with or without body manoeuvres.

BACKGROUND AND AIMS: The external jugular vein (EJV), often used for resuscitation, has been underutilised for central venous catheterisation (CVC) in view of an unpredictable success rate. There is an encouraging literature on the improved success rate of CVC through EJV with the inclusion of certain body manoeuvres. This prospective randomised controlled study was conducted with the aim of evaluating the efficacy of body manoeuvres in improving the success rate of CVC through EJV. METHODS: One hundred patients aged 18-50 years, scheduled for elective surgery requiring CVC, were randomly assigned to either undergo CVC using Seldinger technique with body manoeuvres or a control group undergoing CVC without body manoeuvres. The primary outcome was the success rate of CVC, as observed in the post-procedure chest radiograph. Secondary outcomes included quality of central venous pressure waveform, catheterisation attempts, total time for CVC, complications. RESULTS: CVC was achieved in 98% (49/50) of patients in study group and 80% (40/50) of patients in control group (P = 0.008). Mean catheterisation time was significantly lower in the study group (151.06 ± 40.50 s) compared to control group (173.50 ± 50.66 s) (P = 0.023). The incidence of catheter misplacement and failure to cannulate were lower in the study group (0%, 2% vs. 20%, 12.5%, respectively). Groups did not differ in a number of catheterisation attempts and incidence of haematoma. CONCLUSION: Inclusion of various body manoeuvres to Seldinger technique significantly improves the success rate of CVC through EJV.