Naphthoquinone fused diazepines targeting hyperamylasemia: potential therapeutic agents for diabetes and cancer.

Aim: Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.Materials & methods: Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established via preliminary screening against A549 based lung cancer cell line at 5 µM.Results & conclusion: Compound 4b exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC50 against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound 4p has been selected for further studies, as it demonstrated significant cytotoxicity, while compound 4b showed no effect on AKT gene expression but upregulated IGF-1R gene expression, suggesting a role in managing diabetes. Compound 4p exhibited the ability to decrease AKT expression and increase IGF-1R expression, indicating its potential for treating both diabetes and cancer.

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How Minimal Clinically Important Difference and Patient Acceptable Symptom State Relate to Patient Expectations and Satisfaction in Spine Surgery: A Review.

This narrative review seeks to enhance our comprehension of how Minimal Clinically Important Difference (MCID) and Patient Acceptable Symptom State (PASS) values in established Patient Reported Outcome Measures (PROMs) for spine surgery correspond with patient preoperative expectations and postoperative satisfaction. Through our literature search, we found that both MCID and PASS serve as dependable indicators of patient expectations. However, MCID may be more susceptible to a floor effect. This implies that PASS may offer a more accurate reflection of how patients anticipate surgery to address their symptoms. Nevertheless, it is crucial to recognize that achieving MCID or PASS may not be an absolute prerequisite for patients to be satisfied with their treatment.

Comparison of inflammatory markers in low-pressure pneumoperitoneum with deep neuromuscular block versus standard pressure pneumoperitoneum among patients undergoing laparoscopic cholecystectomy for gallstone disease: a randomized control trial.

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. METHODOLOGY: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. RESULTS: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. CONCLUSION: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings.

Case report: A case of pseudo-acute kidney injury due to cyclin-dependent kinase inhibitor.

Various classes of targeted therapies have emerged in the last few years, which have revolutionized cancer treatment, and improved the prognosis and survival of cancer patients. Unfortunately, these agents have serious toxic effects on the kidneys. Some of the toxic effects are hypertension, acute kidney injury (AKI), and proteinuria. One interesting phenomenon that has emerged recently is pseudo-acute kidney injury due to the interference with the tubular secretion of creatinine by some of the targeted therapeutic agents. Understanding this physiology is needed to avoid unnecessary investigation and withholding of lifesaving chemo regimen. Alternative methods to assess renal function such as cystatin C-based estimated glomerular filtration rate (eGFR) can differentiate true AKI from pseudo-AKI. Here, we describe one such case of pseudo-AKI from cyclin-dependent kinase (CDK) 4/6 inhibitor, abemaciclib, which inhibits tubular secretion of creatinine. Using cystatin-C-based eGFR revealed pseudo-AKI in this case.

Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity.

Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael's addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.

Clinical Characteristics of 96 Patients Presenting With Hematogenous Spinal Osteomyelitis- a Retrospective Study.

OBJECTIVE: To report clinical characteristics and course of care for patients diagnosed with hematogenous spinal osteomyelitis (HVO). METHODS: Medical records of patients presenting to two tertiary care centers with HVO were reviewed. RESULTS: 96 consecutive patients with HVO were identified. Mean follow-up was 8.9 months. Most infections occurred in the lumbar region (50.0%). Of the cultures taken, MRSA accounted for 9%; MSSA, 26%; Streptococcus species, 12%; other gram-positive bacteria, 23%; gram-negative, 17%; fungal, 2.6%; and 11.5% of cultures returned no growth. 57 patients underwent surgery. Of these, 79% of the patients had undergone a trial of empiric antibiotics (cefepime and vancomycin) of the day prior to surgery. 44% underwent secondary surgeries, typically due to a heavy wound burden of necrotic tissue and pus. Postoperative antibiotics were prescribed to all patients. 51.6% of the patients were prescribed antibiotic therapy >6 months. Overall mortality rate was 3.8%. Major cause of all deaths was septic shock. Post-infection sequelae occurred in 47.4% of patients. The most common sequelae were persistent or new sites of infection, sepsis, and abscess. CONCLUSIONS: Diabetes, hypertension, and renal failure appear to increase the risk of post-infection sequelae and death. While non-operative management was attempted in nearly 47%, ultimately 73% had surgery. This high rate may reflect our population of patients hospitalized in a tertiary care center. Available data suggests that patients presenting with hematogenous osteomyelitis be followed closely as failure of non-operative management, and resulting morbidity, was high.

Minimal Clinically Important Difference and Patient-Acceptable Symptom State in Orthopaedic Spine Surgery: A Review.

¼: Minimal clinically important difference (MCID) and patient-acceptable symptom state (PASS) are both metrics at interpreting patient-reported outcome measures (PROMs). ¼: MCID values tend to vary significantly depending on the baseline pain and function in both acute and chronic symptom states while PASS thresholds are more stable. ¼: MCID values are more easily attainable than PASS thresholds. ¼: Although PASS is more relevant to the patient, it should continue to be used in tandem with MCID when interpreting PROM data.

Five-Year Outcomes of Sleeve Gastrectomy in Patients with Class I Obesity and Type 2 Diabetes Mellitus.

BACKGROUND: Several studies have reported short and medium-term outcomes of laparoscopic sleeve gastrectomy (LSG) in patients with class I obesity and type 2 diabetes mellitus (T2DM). However, literature on outcomes beyond three years is scarce. The present study discusses the 5-year results of a previously reported cohort of 20 patients with class I obesity and T2DM, who had undergone LSG between March 2012 and March 2015. MATERIALS AND METHODS: Patients were followed up in the bariatric clinic at yearly intervals as per institute protocol. Primary outcome was proportion of patients with a glycated haemoglobin (HbA1c) level of 6.5% or less, 5 years after LSG. Secondary outcomes were percentage total weight loss (%TWL), excess weight loss (EWL), weight regain and complications. RESULTS: Out of 20 patients, 9 (45%) were male and 11 (55%) were female. Mean age was 41.6 ± 9.5 years. Mean pre-operative weight and BMI were 94.8 ± 14.4 kg and 33.4 ± 1.2 kg/m2, respectively. Median duration of diabetes was 42 months. Mean pre-operative fasting plasma glucose (FPG) and HbA1c were 171.1 ± 56.8 mg/dL and 8.7 ± 1.6%, respectively. Of the 17 patients available for follow-up at 5 years, 9 (52.9%) achieved HbA1c < 6.5% without medication, while 7 (41.2%) patients had improvement of their glycaemic status. One patient had recurrence of diabetes after initial remission. Mean %TWL and %EWL were 18% and 65.1%, respectively. CONCLUSION: Laparoscopic sleeve gastrectomy is a reasonable option as a metabolic procedure for patients with T2DM and class I obesity.

Selective Detection of Picric Acid and Pyrosulfate Ion by Nickel Complexes Offering a Hydrogen-Bonding-Based Cavity.

This work describes the synthesis and characterization of three mononuclear nickel complexes supported with amide-based pincer ligands. All three complexes presented an H-bonding-based cavity due to the migration of amidic protons to the appended heterocyclic rings that formed H-bonds with the metal-ligated solvent molecule(s). These complexes functioned as the nanomolar chemosensors for the detection of picric acid and pyrosulfate ion as inferred by the detailed absorption and emission spectral studies while further supported with FTIR, NMR, and mass spectra of the isolated products. We also illustrate a few practical detection methods for the sensing of picric acid in the solution state as the naked-eye colorimetric methods and in the solid state by employing polystyrene films.

Capillary haemangioma of the heart presenting with pericardial effusion: A case report.

Cardiac haemangiomas (CH) are rare benign primary tumours of the heart and constitute nearly 2.8% of primary cardiac tumours. In a-48-year-old female, a cardiac tumour mass over right ventricular out flow area and main pulmonary artery was detected during diagnostic workup for aetiology of recurrent pericardial effusion. Echocardiograhy and pericardial fluid findings were non conclusive. Contrast enhanced Computed tomography (CECT) and Positron emission tomography (PET) scan imaging found the exophytic, moderately hypermetabolic, heterogeneous mass lesion posterolateral to main pulmonary trunk. We did partial resection of lesion without cardiac reconstruction and open incisional biopsy through midline sternotomy incision. Histopathological analysis confirmed this as a case of Capillary type of haemangioma of heart.

Preoperative patient-reported outcome score thresholds predict the likelihood of reaching MCID with surgical correction of adult spinal deformity.

BACKGROUND CONTEXT: Preoperative (pre-op) identification of patients likely to achieve a clinically meaningful improvement following surgery for adult spinal deformity (ASD) is critical, especially given the substantial cost and comorbidity associated with surgery. Even though pain is a known indication for surgical ASD correction, we are not aware of established thresholds for baseline pain and function to guide which patients have a higher likelihood of improvement with corrective surgery. PURPOSE: We aimed to establish pre-op patient-reported outcome measure (PROM) thresholds to identify patients likely to improve by at least one minimum clinically important difference (MCID) with surgery for ASD. STUDY DESIGN: This is a retrospective cohort study using prospectively collected data. PATIENT SAMPLE: We reviewed 172 adult patients' charts who underwent corrective surgery for spinal deformity. OUTCOME MEASURES: Included measures were the Visual Analog Scale for pain (VAS), Oswestry Disability Index (ODI), and Scoliosis Research Society-22 (SRS-22). Our primary outcome of interest was improvement by at least one MCID on the ODI and SRS-22 at 2 years after surgery. METHODS: As part of usual care, the VAS, ODI, and SRS-22 were collected pre-op and re-administered at 1, 2, and 5 years after surgery. MCIDs were calculated using a distribution-based method. Determining significant predictors of MCID at two years was accomplished by Firth bias corrected logistic regression models. Significance of predictors was determined by Profile Likelihood Chi-square. We performed a Youden analysis to determine thresholds for the strongest pre-op predictors. RESULTS: At year two, 118 patients (83%) reached MCID for the SRS and 127 (75%) for the ODI. Lower pre-op SRS overall, lower pre-op SRS pain, and higher pre-op SRS function predicted a higher likelihood of reaching MCID on the overall SRS (p < 0.05). Higher pre-op ODI, lower SRS pain and self-image, and higher SRS overall predicted a higher likelihood of reaching MCID on the ODI (p < 0.05). An ODI threshold of 29 predicted reaching MCID with a sensitivity of 0.89 and a specificity of 0.64 (AUC = 0.7813). An SRS threshold of 3.89 predicted reaching MCID with a sensitivity of 0.93 and specificity of 0.68 (AUC = 0.8024). CONCLUSIONS: We identified useful thresholds for ODI and SRS-22 with acceptable predictive ability for improvement with surgery for ASD. Pre-op ODI, SRS, and multiple SRS subscores are predictive of meaningful improvement on the ODI and/or SRS at 2 years following corrective surgery for spinal deformity. These results highlight the usefulness of PROMs in pre-op shared decision-making.

Is it safe to stop at C7 during multilevel posterior cervical decompression and fusion? - multicenter analysis.

BACKGROUND CONTEXT: Despite a number of studies addressing the anatomical and biomechanical challenges of long segment, posterior cervical fusion surgery, recommendations for appropriate caudal "end level" vary widely. PURPOSE: Compare revision rates, patient reported outcomes and radiographic outcomes in patients in whom 3+ level posterior fusions ended in the cervical spine versus those in whom the fusion was extended into the thoracic spine. STUDY DESIGN: Multicenter retrospective analysis. OUTCOME MEASURES: Visual analog scale (VAS), Oswestry disability index (ODI), cervical lordosis, C2-C7 sagittal plumbline, T1 slope, and revision rate. METHODS: We assembled a radiographic and clinical database of patients that had undergone three or more level posterior cervical fusions for degenerative disease from January 2013 to May 2015 at one of four busy spine centers. Only those patients with at least 2 years of postoperative (postop) follow-up were included. Patients were divided into two groups: group I (fusion ending at C6 or C7) and group II (fusion extending into the thoracic spine). All radiographic measurements (cervical lordosis, T1 slope, and C2-C7 sagittal plumbline) were performed by an independent experienced clinical researcher. RESULTS: Two hundred and sixty-four patient cases were reviewed and sorted into the two outlined groups, Group I (n=168) and Group II (n=96). Demographically, mean age, percentage of females, non-smokers and anterior support were greater in Group II than in Groups I (p<.05). Mean estimated blood loss (EBL), operative time (OR) and length of hospital stay (LOS) were significantly higher in Group II (p<.05). Rate of revision was not clinically or statistically significantly different (p>.05) between Group I (11.1%) and Group II (9.4%). The majority of the revision surgeries occurred between 2 to 5 years postop. A greater number of subjacent degeneration/spondylolisthesis events were noted in Group I compared with Group II (3.6% vs. 1.2%). There were significant improvements in mean clinical outcomes (ie, VAS and ODI) at two years postop in both groups, but there were no statistically significant differences between the groups (p>.05). Mean cervical lordosis at 2 years postop improved in all groups (12.8° vs. 14.1°); however, there was no significant statistical difference in change for mean cervical lordosis (2 weeks vs. 2 year postop) between the two groups. Similary, there were no significant statistical differences in change for mean C2-C7 sagittal plumbline and T1 slope (2 weeks vs. 2 year postop) between the two groups(p>.05). CONCLUSIONS: Caudal end level did not significantly affect revision rates, patient reported outcomes or radiographic outcomes. Higher EBL, OR, and LOS in group II suggest that, absent focal C7-T1 pathology, extension of posterior cervical fusions into the thoracic spine may not be necessary. Extension of posterior cervical fusions into the thoracic spine may be recommended for higher risk patients with limitations to strong C7 bone anchorage. In others, it is safe to stop at C7.

Correction to: Impact of Bariatric Surgery on Clinical, Biochemical, and Hormonal Parameters in Women with Polycystic Ovary Syndrome (PCOS).

In the original article the name of author Mohd Ashraf Ganie was presented incorrectly. It is correct here.

Impact of Bariatric Surgery on Clinical, Biochemical, and Hormonal Parameters in Women with Polycystic Ovary Syndrome (PCOS).

There is limited data on the impact of bariatric surgery on polycystic ovarian syndrome (PCOS) especially in the Indian population. BACKGROUND: To study the impact of bariatric surgery in women with PCOS in terms of clinical, hormonal, and radiological aspects of polycystic ovarian syndrome. METHODS: A prospective observational study of 50 women who underwent bariatric surgery at our tertiary care center. Evaluation of anthropometric data and menstrual cyclicity as well as markers of hyperandrogenism was done preoperatively and at 3- and 6-month and 1-year follow-up. RESULTS: Eighteen (36%) women were diagnosed to have PCOS. % EWL at 3-months (n = 14), 6-month (n = 14), and 1-year (n = 11) follow-up was 31%, 49%, and 63% respectively among women with PCOS. All females regained their normal menstrual cycle at 3 months of follow-up. Hirsutism resolved completely among 44% (5/11) with a decline in median hirsutism score from 11 to 9 at 1-year follow-up. Mean serum testosterone decreased from 0.83 ± 0.38 ng/ml preoperatively to 0.421 ± 0.25 ng/ml at 1-year follow-up (p Ë‚ 0.01), whereas changes in levels of serum LH and FSH were not significant. Seventy-seven percent of females (14/18) had polycystic ovaries preoperatively on USG; out of which, 55% (i.e., 4/7) showed complete resolution at 1-year follow-up. Metabolic syndrome resolved completely at 1-year follow-up in both PCOS and non PCOS group. CONCLUSIONS: Bariatric surgery results in an effective and sustained weight loss with improvement in clinical, hormonal, and radiological parameters associated with PCOS.

Laparoscopic repair of recurrent traumatic diaphragmatic hernia.

Laparoscopic repair of recurrent diaphragmatic hernia is infrequently reported. We report successful laparoscopic management of such a case in a 23-year-old male who presented with recurrent vomiting and hiccoughs. He had suffered a gun-shot injury to the chest 2 years ago, following which a primary diaphragmatic repair was done by laparotomy and thoracotomy. The patient developed recurrent left diaphragmatic hernia, which was repaired using polypropylene mesh using a laparoscopic approach. At 6 months of follow-up, the patient is doing well, and his symptoms have resolved. Laparoscopic repair of recurrent diaphragmatic hernia is feasible.

Relationship Between Preoperative Plasma Fibrinogen Concentration, Perioperative Bleeding, and Transfusions in Elective Adult Spinal Deformity Correction.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: This study sought to investigate the relationship between preoperative (preop) fibrinogen, bleeding, and transfusion requirements in adult spinal deformity corrections. SUMMARY OF BACKGROUND DATA: Blood loss after major spinal reconstruction increases the risks and costs of surgery. Preoperative fibrinogen levels may predict intra- and postoperative blood loss. METHODS: Data were collected from clinic charts and hospital medical records of all 142 of a single surgeon's consecutive adult spine patients undergoing 7 or more levels deformity correction surgeries from January 2011 to December 2014. t tests were used to compare perioperative variables between patients with total blood loss in the upper quartile (≥1,000 mL) and the remaining patients. Similarly, patients receiving >2 units of packed red cells (PRCs) were compared with others. Analysis of variance was used to compare the blood loss between the patients' groups (quartiles) based on their preoperative fibrinogen concentration. RESULTS: Mean total blood loss was 847.9 (±543.6) mL. Overall, mean preoperative fibrinogen concentration was 254.8 (±82.9) mg/dL. Patients with lower fibrinogen concentration (<193 mg/dL) experienced significantly higher blood loss than those with higher concentrations (p < .05). Patients with transfusion >2 units PRC had significantly greater number of spinal levels treated, higher mean operative time, total blood loss and lower mean preoperative fibrinogen than those transfused 2 or fewer units PRC (p < .05). Total blood loss correlated significantly with preoperative fibrinogen concentration (r = -0.51, p < .05). All the thromboelastography (TEG) variables (G, K, and Angle) correlated significantly with preoperative fibrinogen (p < .05). CONCLUSIONS: In our cohort undergoing correction of adult spinal deformity, patients with preoperative fibrinogen level lower than 193 mg/dL had significantly higher bleeding than their counterparts. Perioperative transfusion requirements correlated moderately both with the blood loss and preoperative fibrinogen concentration. Incorporation of preoperative fibrinogen allows better prediction of total perioperative blood loss and may therefore guide the treatment team in use of ameliorating therapies. LEVEL OF EVIDENCE: Level IV.

Ambidextrous techniques in cardiac surgery.

Ambidexterity is the state of being equally adept in the use of both the left and right hands. It is advantageous in surgeons, but the degree of ambidexterity found among them varies greatly. It is a very desirable attribute in laparoscopic surgery. It provides the surgeon with additional options for performing critical surgical steps when positioning and space are constrained, as is often the case in cardiac surgery and even more so in minimally invasive cardiac surgery. Mentoring for ambidexterity training can be initiated as early as during medical school.  In this tutorial we demonstrate ambidextrous surgical techniques such as the 'all in one hand' technique of using two forceps in one hand, Gilbert's technique of left internal mammary harvest, and a proximal anastomosis technique in aortocoronary bypass.