Efficacy and safety of fezolinetant for vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vasomotor symptoms (VMS), such as hot flashes and night sweats, are highly prevalent and burdensome for women experiencing menopausal transition. Fezolinetant, a selective neurokinin 3 receptor (NK3R) antagonist, is a potential therapeutic option for mitigating VMS. OBJECTIVES: Our aim is to assess the efficacy and evaluate the safety profile of fezolinetant compared with placebo in post-menopausal women suffering from VMS, by pooling all the relevant data and reflecting the most current evidence. SEARCH STRATEGY/SELECTION CRITERIA: An extensive literature search was performed in the PubMed, Medline and Cochrane Library databases from inception until June 2023 to identify relevant trials. DATA COLLECTION AND ANALYSIS: Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous outcomes. Risk ratios (RRs) were calculated for dichotomous outcomes. All statistical analyses were performed using R Statistical Software. MAIN RESULTS: A total of six randomized controlled trials were added. For the frequency of daily VMS, the combined pooled result favored the fezolinetant group over placebo (MD -2.38, 95% CI -2.64 to -2.12; P < 0.001, I2 = 0%). For the severity of daily VMS, fezolinetant was again found to be superior to the placebo group (MD -0.40, 95% CI -0.51 to -0.29; P < 0.001, I2 = 70%). Fezolinetant (120 mg) consistently demonstrated a significant reduction in the severity of daily moderate/severe VMS compared with other doses at both 4 and 12 weeks. Patient-reported outcomes (PROs) of Greene Climacteric Scale (GCS), PROMIS the Sleep Disturbance Short Form 8b and Menopause-Specific Quality of Life (MENQoL) scores indicated significant improvement with fezolinetant. No significant difference in efficacy of fezolinetant at 4 and 12 weeks were observed in any outcome. As for safety, no significant differences in the treatment emergent adverse events at 12 weeks were found between fezolinetant and placebo. CONCLUSIONS: Our study significantly favors fezolinetant over placebo regarding the primary efficacy outcomes of daily moderate to severe VMS frequency and severity, including PROs, while both the groups are comparable in terms of treatment emergent adverse events. Further studies are needed to confirm these findings.

Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Efficacy and safety of Ciprofol compared with Propofol during general anesthesia induction: A systematic review and meta-analysis of randomized controlled trials (RCT).

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.

Intestinal Inflammation and Regeneration-Interdigitating Processes Controlled by Dietary Lipids in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a disease of chronic inflammatory conditions of the intestinal tract due to disturbance of the inflammation and immune system. Symptoms of IBD include abdominal pain, diarrhea, bleeding, reduced weight, and fatigue. In IBD, the immune system attacks the intestinal tract's inner wall, causing chronic inflammation and tissue damage. In particular, interlukin-6 and interlukin-17 act on immune cells, including T cells and macrophages, to amplify the immune responses so that tissue damage and morphological changes occur. Of note, excessive calorie intake and obesity also affect the immune system due to inflammation caused by lipotoxicity and changes in lipids supply. Similarly, individuals with IBD have alterations in liver function after sustained high-fat diet feeding. In addition, excess dietary fat intake, along with alterations in primary and secondary bile acids in the colon, can affect the onset and progression of IBD because inflammatory cytokines contribute to insulin resistance; the factors include the release of inflammatory cytokines, oxidative stress, and changes in intestinal microflora, which may also contribute to disease progression. However, interfering with de novo fatty acid synthase by deleting the enzyme acetyl-CoA-carboxylase 1 in intestinal epithelial cells (IEC) leads to the deficiency of epithelial crypt structures and tissue regeneration, which seems to be due to Lgr5+ intestinal stem cell function. Thus, conflicting reports exist regarding high-fat diet effects on IBD animal models. This review will focus on the pathological basis of the link between dietary lipids intake and IBD and will cover the currently available pharmacological approaches.

Characterization of Sesuvium sesuvioides Using High-Performance Liquid Chromatography and Validation of Its In Vivo Anti-hyperthyroidism Effect via Suppressing Oxidative Stress and Inflammatory Markers.

Sesuvium sesuvioides was used to treat inflammation, arthritis, gout, and thyroid dysfunction. The current study evaluated the antihyperthyroidism effect of S. sesuvioides to consolidate its traditional use. High-performance liquid chromatography (HPLC) analysis of S. sesuvioides methanol extract revealed the presence of phenolics such as gallic acid (0.73 ppm/mg), benzoic acid (11.22 ppm/mg), p-coumaric acid (3.12 ppm/mg), ferulic acid (5.47 ppm/mg), cinnamic acid (3.54 ppm/mg), and sinapic acid (3.17 ppm/mg). In vivo hyperthyroidism was induced using thyroxine in vivo, which increased T3 (triiodothyronine), T4 (tetraiodothyronine), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. However, it reduced thyroid stimulating hormone (TSH), superoxide dismutase (SOD), and reduced glutathione (GSH). S. sesuvioides methanol extract alleviated thyroxine-induced intoxication in a dose-dependent manner. At a 750 mg/kg (SsCr3) dose, it reduced T3, T4, MDA, IL-6, and TNF-α by 61.23, 41.29, 45.17, 44.66, and 62.03%, respectively, and elevated TSH, SOD, and GSH by 365.52, 94.45, and 95.12%, respectively, relative to the diseased group. Further confirmation was done by histopathological examination, which showed normal thyroid histology where follicles were filled with colloids with more cytoplasmic concentrations. This activity is undoubtedly correlated to the richness of the extract by phenolic acids, as revealed by HPLC. In silico ADME/TOPKAT prediction performed on the secondary metabolites identified in S. sesuvioides methanol extract revealed acceptable pharmacodynamic, pharmacokinetic, and toxicity potential. Thus, S. sesuvioides could serve as a promising source for alleviating hyperthyroidism, which could be further incorporated into pharmaceutical preparations.

Dysregulated Liver Metabolism and Polycystic Ovarian Syndrome.

A significant fraction of couples around the world suffer from polycystic ovarian syndrome (PCOS), a disease defined by the characteristics of enhanced androgen synthesis in ovarian theca cells, hyperandrogenemia, and ovarian dysfunction in women. Most of the clinically observable symptoms and altered blood biomarker levels in the patients indicate metabolic dysregulation and adaptive changes as the key underlying mechanisms. Since the liver is the metabolic hub of the body and is involved in steroid-hormonal detoxification, pathological changes in the liver may contribute to female endocrine disruption, potentially through the liver-to-ovary axis. Of particular interest are hyperglycemic challenges and the consequent changes in liver-secretory protein(s) and insulin sensitivity affecting the maturation of ovarian follicles, potentially leading to female infertility. The purpose of this review is to provide insight into emerging metabolic mechanisms underlying PCOS as the primary culprit, which promote its incidence and aggravation. Additionally, this review aims to summarize medications and new potential therapeutic approaches for the disease.

Non-alcoholic fatty liver disease and liver secretome.

Metabolism of carbohydrates and lipids and protein degradation occurs in the liver and contributes to the body's homeostasis by secreting a variety of mediators. Any imbalance in this homeostasis due to excess fat consumption and the pathologic events accompanying lipotoxicity, autophagy dysregulation, endoplasmic reticulum stress, and insulin resistance may cause disturbances in the secretion of the proteins from the liver and their physiologic modifications and interactions with others. Since the liver secretome plays a role in the regulation of fuel metabolism and inflammation not only in the liver per se but also in other organs, the proteins belong to the utmost targets for treating metabolic and inflammatory diseases (e.g., COVID-19), depending on the available and feasible approaches to controlling their biological effects. However, in this era, we still come across new liver-derived proteins but are yet unable to entirely understand the pathologic basis underlying disease progression. This review aims to provide an updated overview of liver secretome biology with explanatory mechanisms with regard to the progression of metabolic and inflammatory liver diseases.

The Impact of Delayed Surgical Care on Patient Outcomes With Alimentary Tract Perforation: Insight From a Low-Middle Income Country.

Introduction In-patient delay is associated with increased mortality in patients with alimentary tract perforations. Access to surgical care is a glaring health issue in low-middle income countries (LMICs), where patient presentation is also delayed for a myriad of reasons, which can be broadly categorized as social/cultural, financial, and structural in their nature. The impact these delays have on surgical outcomes in low-middle income countries is not known. Methods A retrospective cohort study of patients who underwent emergency laparotomy for alimentary tract perforation from July 2015 to June 2018 was conducted at a tertiary care hospital in Karachi, Pakistan. Time was recorded in two variables: symptom onset to emergency room presentation (ERT) and emergency room to operation room time (ORT). Results Overall, 80 patients were included in the study. The 12 (15%) patients who expired were significantly older (57 ± 17.7 years of age), had a higher Charlson Comorbidity Index and had longer ORT [median ORT in hours-discharged vs expired: 8.2 (IQR 5-15) vs 16 (IQR 12-28) p=0.02]. ERT was also longer but lacked statistical significance [median ERT in hours-discharged vs expired: 24 (IQR 22-72) vs 48 (IQR 24-120) p=0.19]. Multivariable logistic regression analysis revealed ORT to be significantly associated with mortality [odds ratio (OR): 1.02, 95% confidence interval (CI): 1.003-1.041; p=0.02]. Adjusted Cox regression analysis showed that each hour of ORT increased the risk of mortality by 1.5% [hazard ratio (HR) 1.015, 95% CI 1.001-1.030]. Conclusion Inpatient delays increased the risk of mortality for patients undergoing emergency laparotomy for alimentary tract perforation. Larger sample sizes and prospective studies are needed to better understand this relationship and the impact pre-hospital delays have on outcomes.

Mild Hyperthermia Responsive Liposomes for Enhanced In Vitro and In Vivo Anticancer Efficacy of Doxorubicin against Hepatocellular Carcinoma.

The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81-187.13 ± 4.15 nm), colloidal stability (-13.27 ± 0.04 to -32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01-79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E(AL)) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E(AL) (T100% ≈ 1 h) by Korsmeyer-Peppas model based Fickian diffusion (n < 0.45). Likewise, an in vitro cytotoxicity study and lower IC50 values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E(AL) in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E(AL) at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E(AL). In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.

Phytochemical profiling, in vitro and in vivo anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides (Fenzl) Verdc. (Aizoaceae).

Sesuvium sesuvioides (Fenzl) Verdc is traditionally used in the treatment of inflammatory diseases such as arthritis and gout The aim of present study was to assess the possible anti-inflammatory, analgesic and antipyretic potential of the methanol extract of Sesuvium sesuvioides (SsCr) to prove scientifically its folklore use in the inflammatory diseases and to screen its total antioxidant capacity by multiple methods and phytocompounds by GC-MS. The preliminary phytochemical studies showed the presence of phenols, flavonoids, glycosides, coumarin, terpenoids, saponins, fats and carbohydrates in crude extract. The total phenolic contents (27.31 ± 0.28 mg GAE/g) and total flavonoids (3.58 ± 0.12 mgRE/g) values were observed. The antioxidant capacity of SsCr showed significant DPPH, ABTS, CUPRAC, FRAP, PBD and metal chelating results. GC-MS analysis displayed the phytoconstituents with anti-inflammatory potentials such as 2-methoxy-4-vinylphenol, vanillin, umbelliferone, methyl ferulate, palmitoleic acid, methyl palmitate and phytol. SsCr presented noteworthy HRBC membrane stability with maximum inhibition of cell hemolysis (47.79%). In carrageenan-induced hind paw edema assay result showed dose-dependent anti-inflammatory action. SsCr presented significant (p < 0.05) analgesic activity in hot-plate and tail flicking tests similarly it also showed the noteworthy inhibition in pain latency against formalin induced analgesia at 1st and 2nd phases. SsCr reduced the acetic acid-induced writhes at different doses (250, 500 and 750 mg). Results of antipyretic activity of SsCr extract were significant at 500 and 750 mg. The results of in vitro and in vivo experimental studies verified the anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides and supported the folklore uses of this plant.

Comparing the utility of 30- and 60-minute cortisol levels after the standard short synacthen test to determine adrenal insufficiency: A retrospective cross-sectional study.

Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 µg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level.Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value.Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ±â€Š286.58, 722 ±â€Š327.11, and 827 ±â€Š369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST (P-value < .0001).Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226 nmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.

Association of Body Mass Index and Diet with Symptomatic Gall Stone Disease: A Case-Control Study.

BACKGROUND: Gall stone disease (GSD) is one of the commonest gastrointestinal disorders. Causative factors can be non-modifiable as genetics and modifiable like dietary habits. High-fat diet and high BMI are well known contributing factors world-over. Local and regional data is deficient about these factors. Moreover, Indo-Pakistani dietary patterns are very different from the western population. This study was conducted to see the association of high BMI and diet with GSD in our population. MATERIALS AND METHODS: This case-control study was conducted in Shifa International Hospital, Islamabad, from 2012 to 2017. We included all female patients above 25 years of age with symptomatic gall stones on ultrasonography as cases and all females above 25 years of age with no gall stones on ultrasonography (done for any reason) as controls. The patients with gall stones having some other clear predisposing cause for gallstone formation, e.g., stoma, sudden weight loss, etc. were excluded. BMI, demographic details, dietary habits, and clinical profile of cases and controls were recorded. Data were analyzed by SPSS v 21. p-values were calculated. RESULTS: A total of 396 patients were included in this study, with 103 cases and 293 controls. The mean BMI of GSD cases was 27.576±5.753, while controls had a mean BMI of 25.638±7.008 (p=0.08). About 26.4% of cases had an average fat consumption greater than 100g/day as compared to 11.9% controls (p=0.035). The average red meat intake per week was 222g among cases while 210g among controls (p=0.001). The average intake of fried food per week was 270g among controls and 250g among cases (p=0.012). The average intake of bakery items per week was 240g among cases and 210g among controls (p=0.038). CONCLUSION: Gall stone disease is significantly related to high BMI and high dietary fat and meat intake in our population.

Seasonal Variation in Acute Cholecystitis: An Analysis of Cholecystectomies Spanning Three Decades.

BACKGROUND: Seasonal variation in the occurrence of medical illnesses reflects the effect of the environment, provides insight into pathogenesis, and can assist health care administrators in allocating resources accordingly. Seasonal variation has been reported in various infectious and surgical diseases, but has been rarely studied in acute cholecystitis. Our objective was to study seasonal variation in acute cholecystitis at our institution. METHODS: We performed a retrospective analysis of patients who underwent cholecystectomy for acute cholecystitis from January 1988 to December 2018. Chi-square goodness-of-fit test was used to analyze seasonality of acute cholecystitis adjusting for variation in number of days between seasons. The number of days for seasons were taken as 92, 92, 91, and 90.25 for spring, summer, fall, and winter, respectively. RESULTS: Overall, 3924 patients underwent cholecystectomy for acute cholecystitis during the study period. The frequency of cholecystectomies performed varied between months (minimum February n = 259, maximum July n = 372, P < 0.001) and seasons (minimum winter n = 789, maximum summer n = 1101 P < 0.001). Age and gender distribution across months and seasons was similar (P > 0.05). CONCLUSIONS: Our findings confirm seasonal variation in occurrence of acute cholecystitis with summer season witnessing the most and the winter season encountering the least patients with acute cholecystitis. Validation of our findings through prospectively collected data at national level is the way forward.

Are Rural Hospitals in Pakistan Responding to the Global Surgery Movement? An Analysis of the Gaps, Challenges and Opportunities.

BACKGROUND: Access to essential surgical care is vital for reduction in mortality and morbidity as a result of surgical conditions. These account for 28-32% of the overall global burden of disease, yet billions of people lack access to safe, affordable surgical and anesthesia care when needed. The purpose of this study was to assess the capacity for surgical care in rural hospitals across four provinces of Pakistan. METHODS: This was a cross-sectional study undertaken in 10 rural hospitals across four provinces of the country. Of these, six were district and four sub-district hospitals that were purposively selected in consultation with the government. Data were gathered using the WHO-PGSSC Surgical Assessment Tool. RESULTS: This study estimated 3 of the 6 indicators proposed by the Lancet Commission on Global Surgery. While most hospitals had basic provisions of infrastructure and equipment, severe shortage of specialists was observed with 0.56 specialists (surgeons, gynecologists and anesthetists) present per 100,000 population. Two-hour access was possible for the catchment population of 7 out of the 10 hospitals. Of the 43 essential surgical procedures assessed, 13 or 30% procedures were available per hospital. The three Bellwether procedures were provided by only 1 hospital. Mean number of surgeries performed was 753 ± 979 per 100,000 population. CONCLUSIONS: Our study has demonstrated major gaps in the provision of surgical care in rural hospitals in Pakistan. While developing a strategy and national action plan is necessary, implementation can immediately begin at the local level to address the gaps that need urgent attention.

The Characteristics of Appendicoliths Associated with Acute Appendicitis.

Introduction Differences between appendicoliths associated with appendicitis and those found incidentally have not been studied. The objective of this study was to determine the characteristics of appendicoliths that are associated with acute appendicitis. Methods A cross-sectional study of patients with appendicoliths identified on computed tomographic (CT) scan from January 2008 till December 2014 was conducted. Patients were divided into two group: appendicitis and appendicoliths (AA) and incidentally discovered appendicoliths (IA). Results Overall, 321 patients were included in the study. Of these, 103 (32%) patients were in the AA group while 218 (68%) patients were in the IA group. Both groups were similar in age and gender distribution. Significantly greater proportion of patients in the AA group had more than one appendicolith [AA vs. IA: 63 (62%) vs. 82 (38%), p < 0.001], appendicolith location at the base [AA vs. IA: 34 (33%) vs. 33 (15%), p < 0.001] and appendicolith diameter of 5 mm or more [AA vs. IA: 71 (69%) vs. 28 (13%), p < 0.001]. On multivariate analysis, more than one appendicolith [Odds ratio (OR): 1.9, 95% CI: 1.1-3.4; p = 0.02] and diameter of 5 mm or more (OR: 13, 95% CI: 7.1-23.6; p < 0.001) were independently associated with acute appendicitis. Conclusion Multiple appendicoliths and appendicoliths larger than 5 mm are associated with acute appendicitis.

Preoperative and Operative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Cholecystectomy in Pakistan.

Introduction The currently available literature suggests a wide range of conversion (4.9-20%) from laparoscopic cholecystectomy (LC) to open cholecystectomy (OC) despite the increase in surgical expertise. Open cholecystectomy is important as the last resort for safe surgical practice in complicated cases. Increased number of pre-operative and perioperative risk factors need to be identified to pre-empt conversion. However, there has been a significant decrease in conversion rates over the past few decades. This study was conducted to determine conversion rates in our population and to identify any significant risks for conversion. Methods This prospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, including 1081 cholecystectomies, performed over a two-year period from January 2017 to January 2019. Comparison of risk factors between the two groups; laparoscopic cholecystectomy (LC) group and conversion to open cholecystectomy (OC) group was done. Statistical analysis was done using SPSS 24.0.1. P<0.05 were considered significant. Results In our study, the overall conversion rate was 7.78%. Factors of conversion to open cholecystectomy (OC) included age ≥65, morbid obesity, diabetes mellitus, and previous abdominal surgery. Deranged alkaline phosphatase (ALP), increased total bilirubin, increased common bile duct (CBD) diameter, and multiple stones in ultrasonography showed a statistically significant association with the conversion. Per-operative findings of increased adhesions >50%, empyema gallbladder (GB), perforated GB, and scleroatrophic GB showed a higher risk of conversion too (p <0.05). However, there was no statistical association with preoperative endoscopic retrograde cholangiopancreatography (ERCP) to OC in our population. Conclusion An open cholecystectomy is a safe approach for patients with complicated gallbladder disease. No doubt laparoscopic cholecystectomy is the gold standard having its outstanding benefits. This study identifies predictors of choice for OC in addition to the decision to convert to OC. In view of the raised morbidity and mortality associated with open cholecystectomy, distinguishing these predictors will serve to decrease the rate of OC and to address these factors preoperatively.

Factors Associated with Complicated Appendicitis: View from a Low-middle Income Country.

Introduction Factors associated with complicated appendicitis have been inconsistently identified. Moreover, studies are lacking from low and low-middle countries where access to surgical care is limited. Our objective was to identify factors predicting complicated appendicitis as diagnosed intraoperatively in a low-middle income country hospital. Methodology Retrospective case-control study of patients who underwent laparoscopic appendectomy from 01/2008 to 12/2015 was completed. Based on intraoperative diagnosis of complicated appendicitis, patients were divided into two groups; those with complicated appendicitis (CA) and those who had non-complicated appendicitis (NCA). CT scans were further reviewed to identify presence of appendicolith. Result Of the 442 patients included, 88 (20%) patients were in the CA group while 354 (80%) patients were in the NCA group. Patients in the CA group were older [CA vs. NCA: 34.6 ± 14 vs. 30.4 ± 11.5; p-value < 0.001], had symptoms for longer duration [CA vs. NCA: 2 ± 1.2 vs. 1.5 ± 0.8; p-value: 0.001] and had a greater proportion of patients with appendicoliths [CA vs. NCA: 37 (42%) vs. 84 (23.7%); p-value: 0.001]. On multivariable regression analysis, patients with complicated appendicitis had greater odds of having appendicoliths (OR: 2.4, 95% CI: 1.4-4.07; p-value < 0.001) and symptoms for a longer duration (OR: 1.57, 95% CI: 1.25-1.97; p-value < 0.001). Conclusion Patients with complicated appendicitis had greater odds of having appendicoliths and symptoms for a longer duration. Further studies are warranted in low and low-middle income countries to gauge the impact delay in presentation and intervention has on appendicitis and its outcomes.