1. Introduction

Oral lichen planus (OLP) is a chronic mucocutaneous, autoimmune and inflammatory disease affecting oral mucosa, skin and genitalia which is T-cell mediated [1,2]. It involves 0.1-2% of general population. It has malignant potential between 0.07% and 5.8%. It commonly affects females in their 4th decade of life and clinically appears as white striations, erosions and desquamative gingivae [3]. Various forms are reticular, erosive, erythematous, popular, plaque, bullous, annular and ulcerative [4]. Main pathogenesis of OLP is antigen specific cell mediated immune response, which includes accumulation of activated CD8+lymphocytes on basal keratinocytes causing apoptosis. Genetic, psychological factors initiate autoimmune mediated response [5].

Corticosteroids are the mainstay treatment modality and effective in controlling the symptoms of the disease; but side effects such as secondary candidiasis, telangiectasia, hypothalamic-pituitary-adrenal suppression, muco-cutaneous atrophy and increased potential of systemic absorption are also common with its prolonged use [6]. Curcuma longa is a perennial plant belonging to Zingiberaceae family possessing anti-inflammatory effects. Its main constituents include three curcuminoids including curcumin (the primary ingredient and the one responsible for its yellow color and anti-inflammatory effect), demethoxycurcumin and bisdemethoxycurcumin [7]. It has anti-oxidant, anti-carcinogenic, anti-microbial, anti-proliferative and wound healing properties. Studies show that curcumin reduces multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel disease in human and animal models [8]. These properties have prompted investigators to check its efficacy on oral diseases namely, lichen planus, oral submucous fibrosis (OSMF), leukoplakia, recurrent aphthous stomatitis, etc. Previous studies have indicated that use of topical curcumin has a chemopreventive effect in oral potentially malignant disorders such as OSMF and leukoplakia [9,10]. Considering this, we attempted this study to compare curcumin and clobetasol propionate in management of patients with oral lichen planus.

2. Methodology

We included sixty- four patients of OLP in our prospective observational study with the informed verbal consent of all participants. Institutional ethical review committee's approval for the present study was obtained. Our study followed declaration of Helsinki. All cases were confirmed clinically as well as histopathologically and only atrophic and ulcerative variety was taken. The exclusion criteria were pregnant lactating mothers, patients on anticoagulants or antiplatelet agents, history of gastric ulcers, duodenal ulcers.

A simple stratified random sampling was performed where 32 patients were put in group I in which patients received 0.1% triamcinolone and in group 2, 32 patients received 5% curcumin paste for 4 weeks and were asked to apply it TDS per day after eating and brushing. All patients were refrain from eating for 20 minutes. Measurement of the appearance score and severity of pain was done at baseline and at the end of 2 and 4 weeks and recorded in the patients' questionnaires. In our study we used the criteria by Thongprasom et al. for determining the appearance score as: 0: No lesion, normal mucosa, 1: Mild white striae, no erythematous area, 2: White striae with atrophic area less than \(1cm^{2}\),3: White striae with atrophic area more than \(1cm^{2}\) , 4: White striae with ulcerative area less than \(1cm^{2}\) and 5: White striae with ulcerative area more than \(1cm^{2}\). Response rate was measured as complete remission-100% reduction in signs and symptoms, good response- 50% or more reduction in signs and symptoms and poor response- < 50% reduction in signs and symptoms. Results were compared in two groups using Mann Whitney U test where p value less than 0.05 considered significant.

3. Results

The mean age was 45.2 years in group 1 and 43.7 years in group 2. Males: Females ratio of 10:22 and 11:21 was seen in group 1 and 2 respectively. Pain at baseline (VAS) was 5.48 in group 1 and 5.12 in group 2. At baseline, lesion size was 3.85 cm2 in group 1 and 3.72 \(cm^{2}\) in group 2, see Table 1.

Table 1. Baseline characteristics.

Characteristics	Group 1	Group 2
Mean age (years)	45.2	43.7
M:F	10:22	11:21
Pain at baseline (VAS)	5.48	5.12
Lesion size at baseline (cm2)	3.85	3.72

Mann Whitney U test

Common site was buccal mucosa in both groups (group 1- 15, group 2- 17), maxillary gingiva (group 1- 6, group 2- 5), labial mucosa (group 1- 4, group 2- 6), mandibular gingiva (group 1- 3, group 2- 2), tongue (group 1- 2, group 2- 1), floor of mouth (group 1- 1, group 2- 1) and palate (group 1- 1, group 2- 0). A non- significant difference among site distribution was seen (P> 0.05), see Table 2 and Figure 1.

Table 2. Common site involved in both groups.

Site	Group 1	Group 2	P value
Buccal mucosa	15	17	>0.05
Labial mucosa	4	6
Tongue	2	1
Palate	1	0
Maxillary gingiva	6	5
Mandibular gingiva	3	2
Mouth floor	1	1

Mann Whitney U test

Complete remission in pain was seen in 30% in group 1 and 35% in group 2, good response in 28% in group 1 and 17% in group 2, poor response in 24% in group 1 and 25% in group 2 and no response in 18% in group 1 and 33% in group 2. A non- significant difference among good and no response was seen (P< .05), see Table 3 and 2.

Table 3. Comparison of pain reduction.

Response	Group 1	Group 2	P value
Complete remission	30%	35%	>0.05
Good response	28%	17%	< 0.05
Poor response	24%	25%	>0.05
No response	18%	33%	< 0.05

Mann Whitney U test

Complete remission in clinical response was seen in 5% in group 1 and 6% in group 2, good response in 8% in group 1 and 22% in group 2, poor response in 42% in group 1 and in group 2 and no response in 45% in group 1 and 30% in group 2. A non- significant difference among good and no response was seen (P< .05), see Table 4 and Figure 3.

Table 4. Comparison of clinical response.

Response	Group 1	Group 2	P value
Complete remission	5%	6%	>0.05
Good response	8%	22%	< 0.05
Poor response	42%	42%	>0.05
No response	45%	30%	< 0.05

4. Discussion

We selected this study on 64 OLP patients of either gender which were randomized to received either 0.1% triamcinolone and 5% curcumin. As there is dysregulation of T-cell mediated immunity, blocking the activity of IL-12, TNF-\(\alpha\), IFN-\(\gamma\), MMP-9, RANTES and up-regulating TGF-\(\beta\)1 will benefit the treatment aspects of OLP [11]. No radical therapy for OLP is present, inspite of increased focus on pathogenesis and treatment options [12,13]. Main objective of treatment is to control and reduce the symptoms, eliminate lesions, decrease malignant transformation. Calcineurin inhibitors, retinoids, dapsone, hydroxychloroquine, steroid sparing agents like azathioprine are applied for OLP, still proper treatment regime till now is not available [14]. Systemic/topical corticosteroid is a mainstay drug but has many side-effects such as high blood pressure, adrenal suppression, secondary candidiasis and high recurrence rate. The trend towards the drugs of natural or herbal origin with antioxidant, anti-inflammatory, anti-cancer properties have been considered [15].

Our study showed that the mean age was 45.2 years in group 1 and 43.7 years in group 2. There were10 males and 22 females in group 1 and 11 males and 21 females in group 2. Dharman et al., [14] study comprised of 315 OLP patients, wherein four studies revealed that topical curcumin had no statistically significant difference when compared to corticosteroids in treating pain, burning sensation, erythema and ulceration. In three clinical trials compared with placebo, one study showed statistical significance with increased oral dosage (6000 mg) of curcumin, two were not significant due to its reduced oral dosage (2000 mg). Two studies showed that curcumin was effective with increased concentration. Three studies with no controls were statistically significant in reducing burning sensation and clinical appearance of OLP.

Our study demonstrated that pain at baseline (VAS) was 5.48in group 1 and 5.12 in group 2. At baseline, lesion size was 3.85 cm2 in group 1 and 3.72 \(cm^{2}\) in group 2. Keshari et al., [16] assessed the efficacy and safety of topical curcumin in the management of OLP. 27 adult OLP patients, who were randomly divided into two groups. The control group (n = 12) was treated with triamcinolone acetonide 0.1% and the study group (n = 15) with commercially available topical curcumin ointment each to be applied thrice daily for 2 weeks. The patients were reviewed every week. The research groups showed a significant reduction in all the parameters measured. The comparison showed significant improvement in the erythema (P = 0.002), but non-significant reduction in pain (P = 0.697), and ulceration (P = 0.291) in the study group as compared to the control group.

Our findings were common site was buccal mucosa in group 1- 15 and group 2- 17, maxillary gingiva in group 1- 6 and group 2- 5, labial mucosa in group 1- 4, group 2- 6, mandibular gingiva in group 1- 3, group 2- 2, tongue in group 1- 2, group 2- 1, floor of mouth in group 1- 1, group 2- 1 and palate in group 1- 1, group 2- 0.

Thomas AE et al., [17] assessed increased reduction of burning sensation measured by NRS, observed in triamcinolone acetonide group, followed by curcumin 6 times daily application. Curcumin oral gel, applied 3 times a day, was insignificant compared to TA. Application of curcumin oral gel six times daily was considered equally effective compared to triamcinolone acetonide. There was comparable effect in pain reduction score in both triamcinolone and curcumin groups with non- statistical significant difference between two groups. Effects were similar to those of topical corticosteroids, and thus, it can be a suitable alternative to corticosteroids.

Chainani-Wu et al., [18] administered a primary dose of systemic prednisone (60 mg/day for the first week) in both groups, which was not done in our study and could have affected their final results. Long periods of observation not only can interfere with patient compliance and cooperation. Curcumin, a phytochemical has been used as a dietary supplement as well as a therapeutic agent. Curcumin displays a wide range of pharmacological properties against various human disorders. Curcumin exhibits strong anti-inflammatory, analgesic, antioxidant, anti-aging, chemopreventive, antitumoral, anti-angiogenic, anti-metastatic, radio sensitizing, and chemosensitizing effects in cancer. Of therapeutic interest, studies have indicated that curcumin as a lone therapeutic agent is safe and exhibits no major toxicity [19].

5. Conclusion

Oral lichen planus is common inflammatory autoimmune disease. Curcumin in our study showed slightly better results than triamcinolone, hence suggesting that it can be used in patients with oral lichen planus.

Author Contributions

All authors contributed equally to the writing of this paper. All authors read and approved the final manuscript.

Conflicts of Interest

"The authors declare no conflict of interest.''

1. Introduction

The novel corona virus (COVID-19) outbreak declared as a global pandemic [1] on March 11, 2020, which Impact a large number of people worldwide. A significant increase in number of COVID-19 cases was observed leading to collapse of local health-care systems [2]. COVID-19 has already claimed more than one million lives worldwide. The severity of the disease ranges from asymptomatic infection to respiratory failure and death [3]. Glucocorticoids are the only drugs proven to be beneficial in COVID-19. Glucocorticoids are inexpensive, widely available, and have been shown to reduce mortality in hypoxemic patients with COVID-19. Nevertheless, glucocorticoids can Increase the risk of secondary fungal and bacterial infections. With increasing risk of new strains of covid virus infections and now the latest dreadful fungal infection Mucormycosis, the situation is becoming more and more devastating [4].

Mucormycosis is an opportunistic infection caused by organisms in the order Mucorales [5]. These organisms are ubiquitous in nature but can cause devastating rhino-orbito-cerebral infection in susceptible patients [6]. Mucormycosis is often associated with rapid progression to Orbital apex syndrome with brain infarction in a patient with ketotic diabetes and COVID-19. Early diagnosis and treatment are essential to prevent further end organ damage.

Mucormycosis is usually seen in immunocompromised individuals with diabetes being an independent risk factor. Diabetes has also been identified as an independent variable associated with severity of COVID-19 infection and hospitalization. SARS-CoV-2 virus itself has been implicated in causing an impaired cell mediated immune response with drop in CD4 + T and CD8 + T cell counts [7]. A combination of these factors makes the hospitalized COVID-19 patients a high-risk Group for fungal infections like aspergillosis and mucormycosis. Whereas aspergillosis is associated with Fungus balls of the sinuses without tissue invasion, mucormycosis is an angioinvasive fungal infection which causes ischemic necrosis of the areas involved. The clinical course is rapid with case fatality rate of 46% [8].

With patients on ongoing Covid treatment, it's very essential to take thorough history of any prior drug use especially steroids and other comorbidities like diabetes mellitus. A complete head and neck examination and neurological examination are required.

2. Discussion

Acute invasive rhino- orbital Mucormycosis is rare and life threatening infection with high mortality. It is characterized by direct invasion and necrosis of local structures followed by rapid progression and angioinvasion from the nasal and sinus mucosa into the orbit and brain. While many Fungal species can cause this, it most commonly involves Aspergillus, Rhizopus, Mucor, and Rhizomucor [9]. Mortality is high, ranging between 50% and 80%, with factors including Intracranial or orbital involvement, irreversible immune suppression, and mucormycosis leading to poorer outcomes [10].

A complex interplay of factors, including preexisting diseases, such as diabetes mellitus, previous respiratory pathology, use of immunosuppressive therapy, the risk of hospital-acquired infections, and systemic immune alterations of COVID-19 infection itself may lead to secondary infections, which are increasingly being recognized in view of their impact on morbidity and mortality [11].

The symptoms presenting in rhino-orbito-cerebral Mucormycosis are facial pain and paresthesia, headache, periorbital and nasal swelling, inflammation, eyelid drooping, Proptosis, external and internal ophthalmoplegia, visual Loss, and blackish necrosis of palate and nasal mucosa [12]. The Disease usually initiates on the nasal and oral mucosa and spreads to paranasal sinuses. It propagates into the orbital space through the lamina papyracea. Vision loss is due to the involvement of optic nerve or retinal supplying vessels. Intracranial space can be involved directly through the Orbital orifices and sinus walls, or through the bloodstream. Cavernous sinus thrombosis as another complication results In damage to the cranial nerves III, IV, V1, V2, and VI [13]. Regular examination and imaging (CT and MRI) are crucial to detect the propagation of the mucormycosis. Based on the infected region, the imaging findings may include opacifications of involved paranasal sinuses, bone destruction of Sinus walls, alterations of intraorbital tissue signal with or Without focal mass, cavernous sinus filling defect, intracranial focal mass, and/or alteration of the meningeal signal.Mucormycosis is confirmed by the detection of blackish necrotic tissues in the involved region and histopathology. The histological stains that identify the mucor structures include hematoxylin and eosin, Periodic acid-Schiff (PAS), and Gomori methenamine silver (GMS). Histopathologic examinations disclose relatively broad non-septate hyphae with right angle branches, necrotizing granulomatous inflammation, and vasculitis together with the presence of mucor hyphae within the vascular wall and lumen.

Rhinoorbitocerebral mucormycosis is a relatively fatal infection. Survival in mucormycosis depends on early diagnosis, alleviation of basic predisposing factors, aggressive debridement of necrotic tissues, and appropriate systemic antifungal agents [12]. Predisposing factors such as corticosteroid therapy should be discontinued, and blood sugar should be controlled restrictively. Systemic amphotericin B and its liposomal formulation is the first drug of choice for the treatment of mucormycosis and significantly improve the survival rate [15].

Treatment of Mucormycosis requires a multimodal approach involving antifungal therapy, surgical debridement, and reversal of immunosuppression to the degree possible. Hyperglycemia, Diabetic ketoacidosis, and metabolic disturbances provide a favorable environment for fungal growth and should be aggressively addressed with glycemic control and electrolyte repletion [16]. Concurrently, surgical debridement of necrotic tissue and antifungal therapy with liposomal amphotericin B or combination Therapy with amphotericin B and posaconazole or caspofungin has been shown to improve survival. Posaconazole is an oral antifungal agent that has been used as step-down therapy after initial control of the mucormycosis by amphotericin. Regular daily debridement of necrotic tissues from Paranasal sinuses is necessary to prevent the propagation of mucormycosis. Also, irrigation of the sinuses and the involved regions with diluted amphotericin B is recommended. Orbital exenteration in the presence of focal mass or extensive necrotic tissues has been suggested in most studies.

3. Conclusion

COVID-19 patients treated with corticosteroid therapy due to hypoxia have a risk of rhino-orbital and/or rhino-orbitocerebral Mucormycosis, particularly when another risk factor such as Diabetes mellitus is present. In these patients, vision changes, orbital Pain, and orbital inflammation should be promptly evaluated; otherwise, the propagation of the infection into the intracranial space may be fatal. This early the diagnosis is made, early the intervention and treatment, the better will be the result.

Author Contributions

All authors contributed equally to the writing of this paper. All authors read and approved the final manuscript.

Conflicts of Interest

"The authors declare no conflict of interest.''

1. Introduction

Propofol has attained unmatched popularity as an agent for intravenous (i.v.) induction. It is also used for short duration surgery, day care surgery, sedation and ambulatory surgery [1]. But very often, it has the disadvantage of causing pain or discomfort on injection, especially when given in small veins on the dorsum of hand [2,3]. This pain may be distressing to the patients and can reduce the acceptability of an otherwise useful agent [4]. Among 33 clinical problems, propofol-induced pain ranked seventh when both clinical importance and frequency were considered [5].

Propofol, a widely used drug for induction, often causes local pain when administered into a peripheral vein [6]. Many patients experience mild to moderate pain or even excruciating pain during propofol injection. Several methods have been described to reduce this pain, of which most effective and common are the use of a larger vein and mixing with lignocaine [7].

Numerous studies have been conducted to know the better among them for prevention of post-operative nausea and vomiting (PONV) but less for reducing propofol-induced pain. Ondansetron has been proved to have a local anaesthetic effect, other than antiemetic property [8]. There is no direct evidence for the increased local anaesthetic effect of ramosetron as compared to ondansetron [9]. However, ramosetron is benzimidazole derivative structurally independent of the previously developed 5-HT3 receptor antagonists such as ondansetron, granisetron and tropisetron [10]. Ramosetron is one of the potent 5-HT3 antagonist commonly used as an antiemetic and has been found to be effective in prevention of early PONV compared to ondansetron [11]. Considering this, we attempted present study with the aim to compare effect of ondansetron and ramosetron in attenuation of propofol-induced pain during induction of anaesthesia.

2. Methodology

A total of sixty subjects with American Society of Anesthesiologists (ASA) physical status (PS) 1 and 2, age ranging 18-60 years scheduled for various elective surgical procedures under general anaesthesia were included in this randomized control trial. Institutional ethical review committee approved our study and after this, written consent from all subjects was sought.

Patients were randomly divided into 2 groups based on computer-generated randomization. Group 1 received 4 mg of ondansetron and Group II received 0.3 mg of ramosetron. All the pre-treatment drugs were made into 2 ml volume with normal saline. After intravenous (IV) pre-treatment of study drug, manual occlusion of venous drainage was done at mid-arm with the help of an assistant for 1 min. This was followed by administration of propofol (1%) after release of venous occlusion. Pain was assessed with a four-point scale. Results were clubbed together entered in Excel sheet and statistically analyzed using Chi- square test. The level of significance was set below 0.05.

3. Results

Mean age of patients in group 1 was 36.2 years and in group 2 was 36.0 years. There were 16 males and 14 females in group 1 and 17 males and 13 females in group 2. ASA grade I was seen in 20 in group 1 and 24 in group 2 and ASA grade II was seen in 10 in group 1 and 6 in group 2. A non- significant difference between both groups was seen (P> 0.05), see Table 1.

Table 1. Demographic characteristics.

Characteristics	Group 1	Group 2	P value
Mean age (Years)	36.2	36.0	>0.05
Male: Female	16:14	17:13	>0.05
ASA I	20	24	>0.05
ASA II	10	6	< 0.05

Pain score 0 was observed in 14 in group 1 and 20 in group 2, score 1 in 9 in group 1 and 6 in group 2, score 2 in 4 in group 1 and 3 in group 2 and score 3 seen in 3 in group 1 and 1 in group 2. A significant difference between both groups was seen (P< 0.05), see Table 2 and Figure 1.

Table 2. Comparison of pain score between both groups.

Pain score	Group 1	Group 2	P value
0	14	20	< 0.05
1	9	6	< 0.05
2	4	3	>0.05
3	3	1	< 0.05

4. Discussion

In present study we compared effect of ondansetron and ramosetron in attenuation of propofol-induced pain during induction of anaesthesia. Incidence of pain with i.v. propofol varies between 28% and 90% in adults and 28% and 85% in children[12]. The younger the child, the higher is the incidence and intensity of pain on propofol [13]. Many factors like site of injection, size of vein, speed of injection, buffering effect of blood, temperature of propofol and concomitant use of drugs such as local anesthetics, opiates, etc., appear to affect the incidence of pain. A number of both pharmacological (e.g., pre-treatment with lignocaine, ondansetron, ketorolac, nafamostat, ketamine or topical nitroglycerine application with propofol, diluting propofol with 5% dextrose or 10% intralipid and using medium- and small-chain triglycerides) and non-pharmacological methods have been used with variable results and the research for the ideal agent to decrease pain on propofol injection is still going on [14].

Our study comprised of 60 patients scheduled for various elective surgical procedures under general anaesthesia. Sumalatha et al., [15] in their study 150 adult patients posted for various elective surgical procedures under general anaesthesia were randomly assigned to three groups of 50 each. Group R received 0.3 mg of ramosetron, Group L received 0.5 mg/kg of 2% lignocaine and Group O received 4 mg of ondansetron. After intravenous (IV) pre-treatment of study drug, manual occlusion of venous drainage was done at mid-arm with the help of an assistant for 1 min. This was followed by administration of propofol (1%) after release of venous occlusion. Pain was assessed with a four-point scale. The overall incidence and intensity of pain were significantly less in Groups L and R compared to Group O (P = 0.001). The incidence of mild to moderate pain in Groups O, R and L was 56%, 26% and 20%, respectively. The incidence of score '0' (no pain) was significantly higher in Group L (76%) and Group R (72%) than Group O (34%) (P < 0.001).

We observed that mean age of patients in group 1 was 36.2 years and in group 2 was 36.0 years. There were 16 males and 14 females in group 1 and 17 males and 13 females in group 2. ASA grade I was seen in 20 in group 1 and 24 in group 2 and ASA grade II was seen in 10 in group 1 and 6 in group 2. Lee et al., [16] in their study found that the incidence of pain was reported to be 60% and 38% respectively with pre-treatment by ramosetron 0.3 mg or combination with ramosetron and lignocaine 20 mg. In a study by Piper SN [17], severity but not the incidence of pain on injection was significantly reduced by dolasetron (50%) compared with placebo, and there was no significant difference between dolasetron and lignocaine. These results show effective reduction in propofol injection pain.

Our results showed that pain score 0 was observed in 14 in group 1 and 20 in group 2, score 1 in 9 in group 1 and 6 in group 2, score 2 in 4 in group 1 and 3 in group 2 and score 3 seen in 3 in group 1 and 1 in group 2. Ahmed et al., [18], the incidence of propofol injection pain was reduced from 60% to 15% after granisetron pre-treatment. The effect of pre- treatment by palonosetron (0.075 mg) on propofol-induced pain. 72.5% of patients experienced a decrease in the occurrence of propofol-induced pain. A study done by Swarika et al., [19] reported that ramosetron 0.3 mg IV was more effective than palonosetron 0.075 mg and ondansetron 8 mg in the early post-operative period.

Singh et al., [20] assessed the efficacy of pretreatment with various drugs to alleviate the propofol injection pain. One hundred American Society of Anesthesiology (ASA) I and II adults, scheduled for various elective surgical procedures under general anesthesia (GA), were included in the study. They were randomly divided into four groups having 25 patients in each group. Group A received pre-treatment with intravenous (i.v.) magnesium sulfate, group B received i.v. granisetron, group C received i.v. nitroglycerine and group D was the control group. One-fourth of the total calculated induction dose of propofol was administered over a period of 5 seconds. The patients were asked about the pain on injection. The intensity of pain was assessed using verbal response. A score of 0-3 which corresponds to no, mild, moderate and severe pain was recorded. All the three drugs reduced the incidence and intensity of pain on propofol injection but the order of efficacy in attenuation of pain on the propofol injection was granisetron > nitroglycerine > magnesium sulfate > control.

5. Conclusion

Results of our study showed that ramosetron alone can be used to reduce the propofol-induced pain. Pre-treatment with IV ramosetron found to be effective as compared to ondansetron in preventing propofol-induced pain.

Author Contributions

All authors contributed equally to the writing of this paper. All authors read and approved the final manuscript.

Conflicts of Interest

"The authors declare no conflict of interest.''

1. Introduction

Gallstone disease is considered a benign disease affecting large amount of population. The number of patients with gall bladder diseases is on rise. It demands major abdominal surgery. Among various diseases [1]. Cholelithiasis, or gallstones is most common one. It is evident in literature that the occurrence of gallstones increases with age [2]. Risk factors includes obesity, diabetes mellitus (DM), women gender, rapid weight cyclers, and patients on hormone therapy or taking oral contraceptives. Until and unless, gall stones pose pain, they remain asymptomatic [3]. Most of the symptomatic patients shows symptoms of biliary colic due to the intermittent obstruction of the cystic duct by a stone. Patient experience moderate to severe pain which lasts one to five hours. Pain is usually localized to the epigastrium or right upper quadrant of the abdomen [4].

The occurrence of fever along with colic pain with high white blood cell count (WBCs) raises the suspicion of complications such as acute cholecystitis, gallstone pancreatitis, and ascending cholangitis [5]. The diagnosis of gall stones is by ultrasonography (USG). USG is useful in detection of gall stones [6].

The management of cases of gall stones includes laparoscopic cholecystectomy. It is gold standard treatment options for symptomatic and complicated gallstones [7]. Advantages of this modality is shorter convalescence period and short hospital stay comparing to open cholecystectomy [8]. Percutaneous cholecystostomy is an alternative for patients who are critically ill with gallbladder empyema and sepsis. It is found that adhesions are amongst the common reasons for open conversion of laparoscopic cholecystectomy [9]. We attempted this study to compare single versus multiple gall stone disease in patients undergoing laparoscopic cholecystectomy.

2. Methodology

The approval for this prospective, comparative study was obtained from Ethical and review authority of the institute. A total of one hundred and thirty patients (males- 52, females- 78) within age group 20-65 years presented with colic pain to general surgery department. All were diagnosed with cholelithiasis using USG.

All were those who gave their consent for the part of this study. Randomization of them into 2 groups was performed. Group 1 comprised of single stone patients and group II had multiple stones. A routine laboratory investigation comprised of Hemoglobin % (Hb), total leucocyte count (TLC), differential leucocyte count (DLC), random blood sugar (RBS), serum urea and creatinine was carried out. Apart from this, Assessment of serum bilirubin, serum amylase, alkaline phosphate, bilirubin total, renal and liver function test was determined. Before operating the patients, electrocardiography (ECG) and chest X-ray (CXR) were performed.

Advanced imaging such as ultrasonography of abdomen (USG) was done to study the nature, number, size of the gall stones, gall bladder wall thickness, CBD, intra hepatic biliary radicals status, any other relevant findings. Computed tomography (CT) scan and magnetic resonance imaging (MRI) was carried as and when required. Results after recording all relevant data were subjected for statistical inferences using chi- square test. The level of significance was significant if p value is below 0.05.

3. Results

Maximum cases were seen in age group 40-50 years in both groups (group 1- males- 16, females- 20, group 2- males- 15, females- 20). Minimum cases were seen in age group 20-30 years (group 1- males- 5, females- 6, group 2- males- 2, females- 5). A non- significant in gender was observed \((P> 0.05)\), see Table 1.

Table 1. Age and gender distribution of cases used in study.

Age group (Years)	Group 1 (M:F)	Group 2 (M:F)	P value
20-30	5:6	2:5	>0.05
30-40	2:10	5:6
40-50	16:20	15:20
50-65	4:8	3:3

Most common clinical symptoms found to be fever in both groups (87%- group 1, 90%- group 2). Other symptoms were dyspepsia seen in 25% and 30%, nausea/ vomiting in 45% and 38% in group 1 and 2 patients respectively. A non- significant in gender was observed \((P> 0.05)\). (Table 2, Figure 1).

Table 2. Comparison of clinical features in groups.

Clinical findings	Group 1	Group 2	P value
Fever	87%	90%	>0.05
Dyspepsia	25%	30%
Nausea/ vomiting	45%	38%
Icterus	6%	8%
Mass	12%	11%

Group 1 patients showed gall bladder distention in 56 and group 2 in 62 patients, gall bladder contraction was seen in 6 patients in group 1 and 3 in group 2, adhesions were exhibited by 11 patients in group 1 and 20 in group 2. 4 patients in group 2 converted to open surgery. Gangrenous gall bladder was seen in 1 in group 1 and 5 in group 2. A significant difference was observed \((P< 0.05)\), see Table 3.

Table 1. Operative findings.

Operative findings	Group 1	Group 2	P value
Gall bladder distension	56	62	< 0.05, Significant
Gall bladder contraction	6	3
Adhesion	11	20
Gangrenous gall bladder	1	5
Conversion to open surgery	0	4

4. Discussion

Gallstone disease (cholelithiasis) is one of the most common gastrointestinal disorders in today's life. The prevalence of gallstones is found to be approximately 10%-15% [10]. Women exhibits higher prevalence compared to males over the age of 40 years [11]. In most people, gallstones are asymptomatic. About 20% of people with gallstones experience pain and complications [12]. There is always debate regarding which method is better for the management of gall bladder stones [13]. Laparoscopic cholecystectomy is recent treatment modality which overcome the limitation of open surgery [14]. The most common complications associated with cholelithiasis are severe acute cholecystitis, which may lead to complications such as empyema, obstructive jaundice due to the obstruction of the common bile duct, acute cholangitis and acute pancreatitis [15]. In this study we compared single versus multiple gall stone disease in patients undergoing laparoscopic cholecystectomy.

Our study comprised of 130 patients divided into 2 groups of 65 each based on the presence of single or multiple stones. It was found in our study that maximum cases were seen in age group 40-50 years in both groups (group 1- males- 16, females- 20, group 2- males- 15, females- 20). Minimum cases were seen in age group 20-30 years (group 1- males- 5, females- 6, group 2- males- 2, females- 5). Mofti et al., [16] evaluate 692 consecutive patients undergoing cholecystectomy of whom 80 had single stone. Only about 30% asymptomatic patients need surgery in their life-time.

It was observed that most common clinical symptoms were fever in both groups seen among 87% in group 1 and 90% in group 2 patients. Other symptoms were dyspepsia seen in 25% and 30%, nausea/ vomiting in 45% and 38% in group 1 and 2 patients respectively. A study by Zhang et al., [17] suggested that LC is the gold standard in the treatment for cholelithiasis. Prophylactic cholecystectomy is justified only high suspicion of life. They found that developing mucocele, empyema gall bladder perforation and post-operative complication were more common in patients with solitary stone. Gabriel et al., [18] in their study observed that 61 (26.1%) LC required conversion.

It was seen in our study that 56 patients in group 1 and 62 in group 2 showed gall bladder distention, gall bladder contraction was seen in 6 patients in group 1 and 3 in group 2, adhesions were exhibited by 11 patients in group 1 and 20 in group 2. 4 patients in group 2 converted to open surgery. Gangrenous gall bladder was seen in 1 in group 1 and 5 in group 2. A study conducted by Raja et al., [19] in year 2020 where patients of gall bladder stones were divided into 2 groups as single or multiple stones. In both groups, female incidence, 41-50 years age group is more common. Both groups presented with abdominal tenderness (RUQ), fever more in group-1, dyspepsia more in group-2 and icterus more in group-2. Complications of gall stones as suggested by USG of abdomen like cholecystitis, gangrenous cholecystitis, gallbladder perforation, empyema of gallbladder were more in multiple than single stone patients. Group II had difficult cholecystectomies based on the above timings noted intraoperatively.

The natural course of gallstone disease is benign, with relatively low progression from asymptomatic disease to symptomatic disease. Natural history studies have shown low mortality from gallstone disease with typically less than 1% of people dying from gallbladder-related causes. Festi et al., study (2010) [20] revealed that the overall frequency of symptom development in asymptomatic people was around 20% over a long follow-up period (mean 8.7 years). In people with symptomatic uncomplicated gallstone disease, the annual rates of developing complications have been reported to be as low as 1%-3%. The Italian Group for the Epidemiology and Prevention of Cholelithiasis Study reported an annual incidence of complications of 0.7% for symptomatic people.

5. Conclusion

Results of our study showed that females were commonly affected and maximum case were observed in age group 40-50 years. Multiple gall stones patients had more symptoms and prevalence of conversion to open surgery was more in these patients.

Author Contributions

All authors contributed equally to the writing of this paper. All authors read and approved the final manuscript.

Conflicts of Interest

"The authors declare no conflict of interest.''

1. Introduction

The plantar fascia is a broad band of fibrous tissue forming the medial longitudinal arch of the foot [1]. Plantar Fasciitis is an inflammatory condition which results in pain at the inferior aspect of the heel, affecting 10-15% of the general population [2]. Plantar fasciitis, a self-limiting condition, is a common cause of heel pain in adults [3]. It affects more than 1 million persons per year, and two-thirds of patients with plantar fasciitis will seek care from their family physician. Plantar fasciitis affects sedentary and athletic populations [4]. It is the most common cause of heel pain in the population aged above 40 years. Obesity, excessive foot pronation, excessive running, and prolonged standing are risk factors for developing plantar fasciitis [5].

It accounts for 10% of injuries in runners and is seen in both sedentary and athletic individuals. Patients with plantar fasciitis experience sharp or knife-like pain in the morning which subsides with a few initial steps [6]. However, the symptoms may also arise with prolonged standing which is sometimes accompanied by stiffness and in chronic case, the pain worsens by the end of the day limiting patient's daily activities [7].

Diagnosis is primarily based on history and physical examination. Patients may present with heel pain with their first steps in the morning or after prolonged sitting, and sharp pain with palpation of the medial plantar calcaneal region [8]. Discomfort in the proximal plantar fascia can be elicited by passive ankle/first toe dorsiflexion. Diagnostic imaging is rarely needed for the initial diagnosis of plantar fasciitis [9]. Use of ultrasonography and magnetic resonance imaging is reserved for recalcitrant cases or to rule out other heel pathology; findings of increased plantar fascia thickness and abnormal tissue signal the diagnosis of plantar fasciitis [10]. The use of oral non-steroidal anti-inflammatory drugs (NSAIDs) in reducing inflammation and providing pain relief has been tried. Silicone insole is a non-invasive modality that works by providing cushioning and add comfort to the sole as it absorbs 42% of shock while walking [11]. Considering this, we compared different treatment modalities in management of plantar fasciitis.

2. Methodology

Our study comprised of forty- five patients with plantar fasciitis (males- 25- females- 20). The study was approved from Ethical review committee. All patients within age limit 18-50 years were enrolled whereas patients with history of steroid injection, history of any surgery in the affected lower limb were not taken. Written consent was obtained.

After recording demographic data of patients, randomization was performed based on computer. Group 1 patients received conventional treatment, group 2 patients received heat treatment with silicone heel pad and group 3 patients received active plantar fascia stretching with sham calf stretching. Patient was evaluated using foot function index (FFI) and the foot and ankle disability index (FADI) to know the baseline scores of pain, disability and restrictions in activities of daily living. 3 sub-scales such as pain, disability, and activity restriction, each item evaluated on a scale of 0-10. Results of the present study after recording all relevant data were subjected for statistical inferences using One-way ANOVA test. The level of significance was significant if p value was below 0.05.

3. Results

One-way ANOVA test

In group 1, foot function pre-intervention index score and post-intervention score was 68.2 and 43.5, in group 2 was 64.8 and 6.9 and in group 3 was 70.5 and 1.6 respectively. A significant difference was observed (P< 0.05) (Table 1, Figure 1).

Table 1. Comparison of foot function index score.

Groups	Pre-intervention score	Post-intervention score	P value
Group 1	68.2	43.5	< 0.05
Group 2	64.8	6.9	< 0.05
Group 3	70.5	1.6	< 0.05

One-way ANOVA test

In group 1, pre-intervention foot and ankle disability score and post-intervention score was 61.5 and 76.4, in group 2 was 66.5 and 95.2 and in group 3 was 61.3 and 97.6 respectively. A significant difference was observed (P< 0.05) (Table 2, Figure 2).

Table 2. Foot and ankle disability index.

Groups	Pre-intervention score	Post-intervention score	P value
Group 1	61.5	76.4	< 0.05
Group 2	66.5	95.2	<0.05
Group 3	61.3	97.6	< 0.05

4. Discussion

We compared different treatment modalities in management of plantar fasciitis. We created 3 groups of 15 each. Group 1 patients received conventional treatment, group 2 patients received heat treatment with silicone heel pad and group 3 patients received active plantar fascia stretching with sham calf stretching.

Plantar fasciitis is a common cause of heel pain in adults [12]. It is estimated that more than 1 million patients seek treatment annually for this condition, with two-thirds going to their family physician [13]. Plantar fasciitis is thought to be caused by biomechanical overuse from prolonged standing or running, thus creating microtears at the calcaneal enthesis [14]. Some experts have deemed this condition "plantar fasciosis," implying that its etiology is a more chronic degenerative process versus acute inflammation [15].

Our results demonstrated that in group 1, foot function pre-intervention index score and post-intervention score was 68.2 and 43.5, in group 2 was 64.8 and 6.9 and in group 3 was 70.5 and 1.6 respectively. Gupta et al., [16] in their study on 140 patients of plantar fasciitis were divided into four groups with 35 patients each. Patients in four groups received analgesics, hot water fomentation and silicon heel pads, plantar fascia stretching and calf stretching exercises, respectively. Heel pain was evaluated using foot function index (FFI) and disability using foot and ankle disability index (FADI). Clinical evaluation was done weekly up to a period of 4 months and then at 6 months, 8 months, 10 months and 12 months. Mean age of patients was \(43.4 \pm 10.6\) years with average duration of symptoms being 27.26 weeks (range 4-200 weeks). Both FFI and FADI showed statistically significant improvement at 12 months in all the four groups (p value < 0.0001 for all groups). However, groups 2, 3 and 4 were observed to show statistically better results in terms of heel pain reduction (FFI) as compared to group 1 (ANOVA, p value < 0.0001 for group 1 vs. 2, group 1 vs. 3 and group 1 vs. 4). In terms of disability (FADI), best results were observed in group 3.

Our results showed that in group 1, pre-intervention foot and ankle disability score and post-intervention score was 61.5 and 76.4, in group 2 was 66.5 and 95.2 and in group 3 was 61.3 and 97.6 respectively. In a randomized controlled trial by Pfeffer et al., [17] on 236 patients, the comparison was made between three prefabricated shoe inserts (a rubber heel cup, a felt insert and a silicone heel pad) along with Achilles tendon and plantar fascia stretching and stretching alone. Only 190 patients completed the 8 weeks follow-up, the response rates were found to be better in the silicone insert group than in the stretching-only group \((p=0.019)\). Although, the silicone insert group was shown to improve more on FFI as compared to stretching alone, but there was no significant difference \((p=0.54)\).

Donley et al., [18] in their study twenty-nine patients with the diagnosis of plantar fasciitis were treated with a conservative regimen that included heel-cord stretching, viscoelastic heel cups, and night splinting. They were randomly assigned to either a placebo group or an NSAID group. In the NSAID group, celecoxib was added to the treatment regimen. Pain and disability mean scores improved significantly over time in both groups, although there was no statistical significance between the placebo and NSAID groups at 1, 2, or 6 months. There was a trend towards improved pain relief and disability in the NSAID group, especially in the interval between the 2 and 6-month follow up. Pain improved from baseline to 6 months by a factor of 5.2 and disability by 3.8 in the NSAID group compared to 3.6 and 3.5, respectively, in the placebo group. Even though at baseline the pain and disability scores were higher in the NSAID group, the final pain and disability scores were subjectively lower in the NSAID group than in the placebo group (1.43 for pain and 1.16 for disability in the NSAID group, compared to 1.86 and 1.49, respectively, in the placebo group).

Radford et al., [19] in their study ninety-two participants with plantar heel pain were recruited and were randomly allocated to an intervention group that were prescribed calf muscle stretches and sham ultrasound (n = 46) or a control group who received sham ultrasound alone (n = 46). Primary outcome measures were 'first-step' pain (measured on a 100 mm Visual Analogue Scale) and the Foot Health Status Questionnaire domains of foot pain, foot function and general foot health. Both treatment groups improved over the two weeks period of follow-up but there were no statistically significant differences in improvement between groups for any of the measured outcomes. For example, the mean improvement for 'first-step' pain (0-100 mm) was -19.8 mm in the stretching group and -13.2 mm in the control group. For foot function (0-100 scale), the stretching group improved 16.2 points and the control group improved 8.3 points. Ten participants in the stretching group experienced an adverse event, however most events were mild to moderate and short-lived.

5. Conclusion

Results of our study showed that active plantar fascia stretching with sham calf stretching exercise resulted in most significant improvement in FFI and FADI score followed by treatment with heat and silicone heel pad and conventional treatment.

Author Contributions

All authors contributed equally to the writing of this paper. All authors read and approved the final manuscript.

Conflicts of Interest

"The authors declare no conflict of interest.''