Vulvar diseases are common in the general population and have a negative impact on the quality of life.To describe our experience as dermatologists in the management of vulvar dermatosis consultations.A retrospective observational study was conducted with patients who attended monographic vulvar consultations over a 5-year period. Clinical information was obtained from the patient’s charts.148 women were studied. Their mean age was 43.24 years (standard deviation: 15.15 years), with ages ranging from 4 months to 80 years. 53.4% of patients took between 2 and 5 years to seek medical attention for the first time. The most frequent diagnosis was lichen sclerosus (41.9%), irritative eczema of the vulva (14.9%), and lichen simplex chronicus (10.1%). 83.8% reported anogenital itching, 66.2% pain, and 45.9% dyspareunia. The most frequently prescribed treatment was ultra-potent topical corticosteroids . Patients with lichen sclerosus were significantly older than those who presented with any of the other diseases. No differences were found in terms of either the time of disease evolution or in symptom presentation.Retrospective study. Vulvar diseases with an infectious cause are usually managed in primary care, therefore, were not included. All patients were recruited from a single private hospital which limits the comparisons with the public health system.Vulvar diseases frequently occur and are associated with high morbidity. It is essential to promote the development of specific vulvar consultations in hospitals. Specialties such as dermatology, gynecology, urology, or physiotherapy must be part of these units. Vulvar diseases are common in the general population, although their true importance and frequency are often underestimated.Even though gynecologists are specialists who are generally the first to see patients with vulvovaginal symptoms, they generally receive little training in the management of dermatological diseases of the vulva.Although there has been a growing interest among dermatologists in the study of the vulva in recent yearsA retrospective observational study was carried out over a 5-year period in Viamed Santa Angela de la Cruz hospital in Seville, southern Spain. Between May 2015 and May 2020, all patients who visited our monographic vulvar unit were included in the study. Data collection was carried out by a specialist in dermatology. The data were obtained from the clinical history of each patient. The following variables were collected for analysis: patients’ age, symptoms, time of evolution, main and secondary diagnoses, complementary tests, and treatments used. The study was approved by the ethics committee of the hospital, and a study information document was provided to patients who were interested in participating in the study.U test was used to compare the quantitative variables. The level of statistical significance was established at α = 0.05. Statistical analyses were performed with SPSS version 25.0 for Apple macOS .A descriptive analysis was performed using measures of central tendency and dispersion for quantitative variables, and frequency distribution for qualitative variables. For the statistical analysis, the authors used the statistical Chi-Squared test, or Fisher’s exact test if the expected frequencies were <5, in order to compare the qualitative variables. The Mann–Whitney A total of 148 women were studied at our monographic vulva clinic over a 5-year period. The mean ± Standard Deviation age (SD) was 43.24 ± 15.15 years, with patients’ ages ranging from 4 months of age to 80 years. Patients were divided by age with the following distribution: <18 years , between 18 and 40 years , between 40 and 60 years , and >60 years .The most frequent primary diagnosis was lichen sclerosus , followed by irritative eczema of the vulva , and lichen simplex chronicus . A total of 14 (9.5%) patients also had another concomitant dermatosis at the time of the visit. The evolution of the different primary diseases was as follows: <1 year , between 2 and 5 years , and >5 years . A total of 124 patients (83.8%) reported anogenital itching, 98 (66.2%) pain, and 68 (45.9%) dyspareunia. Some complementary tests were performed in 36 (22.3%) cases, of which 14 (9.5%) had microbiological samples taken, and 22 (14.9%) had a skin biopsy performed.The most frequently prescribed treatment was ultra-potent topical corticosteroids  and the most commonly prescribed adjuvant treatment was topical ketoconazole gel . In 34 (23%) women, pelvic floor physiotherapy was recommended for vulvar discomfort, in 23 (15.5%) antihistamines, and in 15 (10.1%) a formula with 0.5% triamcinolone. In 8 (5.4%), calcineurin inhibitors were prescribed. Other prescribed treatments were cryotherapy , topical antifungals , topical and/or oral antibiotics , vaginal dilators , topical imiquimod , topical gabapentin , topical diltiazem , antivirals , and surgery .A detailed analysis of the different diagnoses collected is represented in The authors described the patients’ characteristics based on the most relevant diagnoses. The authors performed a comparative analysis between those patients who presented with lichen sclerosus sclerosis versus those who presented with other vulvar dermatoses.In all, 62 patients with lichen sclerosus were studied; patients had a mean ± SD age of 46.33 ± 18.35 years. The evolution was <1 year in 13 (21%) patients, between 2–5 years in 34 (54.8%), and >5 years in 15 (24.2%). A second concomitant dermatosis was recorded in 7 patients, with vitiligo being the most frequent . Overall, 55 (88.7%) patients had itching, 38 (61.3%) pain, and 27 (43.5%) dyspareunia. A skin biopsy was taken in 9 (14.5%) of the cases and microbiological samples were obtained in 4 (6.5%). Skin biopsies were taken to confirm lichen sclerosus diagnosis in clinically doubtful cases, in steroids-resistant cases  and in uThe most frequent treatment was ultra-potent topical corticosteroids , with 2% ketoconazole gel serving as adjunctive therapy in 25 (40.3%) cases. In 8 (12.95%) patients, a formula with 0.5% triamcinolone in the gel base was used. In 9 (14.5%) women, antihistamines were also indicated for itching.A comparative analysis was performed between the patients with lichen sclerosus, and the rest of the patients included in the study. Statistically significant differences were found in terms of age and some of the prescribed treatments . No differences were found either in terms of the time of evolution of the disease or in the symptoms. Twenty-two patients with irritative vulvar eczema were studied; they had a mean ± SD age of 38.19 ± 15.41 years being the younger one a 4-month-old girl. The evolution was <1 year in 5 (22.7%) patients, from 2–5 years in 15 (68.2%), and >5 years in 2 (9.1%). In a single patient  patients had itching, 19 (86.4%) pain, and 12 (54.5%) dyspareunia. A skin biopsy was taken in only 2 (9.1%) cases, and microbiological samples in 3 (13.6%). An ultra-potent topical corticosteroid was indicated in 4 (18.2) patients, pelvic floor physiotherapy in 5 (22.7%), and a formulation with 0.5% triamcinolone in 1 (4.5%). As adjunctive therapy, antihistamines were indicated in 5 (22.7%) cases, and ketoconazole 2% topical gel in 5 (22.7%).Among the products related to dermatitis, a wide variety of creams for intimate and general use were collected, the most frequent of which were blastostimulin and the use of intimate wipes for hygiene. In one case, treatment was related to the use of hair dye in a patient previously diagnosed with an allergy to p-phenylenediamine; this represents the only case of allergic contact dermatitis in our entire series.Fifteen patients with lichen simplex chronicus were studied; they had a mean ± SD age of 41.51 ± 7.00 years. The most frequent evolution was <1 year in 7 (46.7%) patients. A concomitant dermatosis, candidal intertrigo, was recorded in a single patient. All patients had itching (100.0%), pain , and dyspareunia . In no cases was a skin biopsy taken, and microbiological samples were obtained in a single case. An ultra-potent topical corticosteroid was indicated in 7 (46.7%) patients, pelvic floor physiotherapy in 2 (13.3%), and a formula featuring 0.5% triamcinolone in 2 (13.3%). As adjunctive therapy, antihistamines were indicated in 6 (40%) cases, and topical ketoconazole in 6 (40%).Six women with hidradenitis suppurativa were observed, with a mean ± SD age of 45.03 ± 7.69 years. The evolution was <1 year in 1 (16.7%) patient, between 2–5 years in 3 (50%), and >5 years in 2 (33.3%). Four (66.7%) patients had itching, 5 (83.3%) pain, and 7 dyspareunia (50%). In no cases were skin biopsies or microbiological samples taken. Topical and/or oral antibiotics were prescribed in three patients. Pelvic floor physiotherapy was indicated in one patient. As adjunctive therapy, 2% topical ketoconazole gel was indicated in one case.Six patients with vulvar lichen planus were evaluated, with a mean ± SD age of 56.41 ± 13.22 years. The most frequent evolution time was 2–5 years in 5 (83.3%) patients. Five (83.3%) patients had itching, 5 (83.3%) had pain, and 4 (66.7%) had dyspareunia. A skin biopsy was taken in 5 (83.3%) cases, and microbiological samples were obtained from a single patient. An ultra-potent topical corticosteroid was indicated in 4 (66.7%) patients; 0.5% triamcinolone was prescribed for 4 (66.7%) patients, and pelvic floor physiotherapy was indicated in 3 patients (50%). As adjunctive therapy, topical 2% ketoconazole gel was indicated in a single patient.Eight patients attended our consultations for nonspecific vulvar pain, 6 of which were diagnosed with provoked secondary vestibulodynia, with a mean ± SD age of 44.06 ± 10.48 years. The evolution was <1 year in 1 (16.7%) patient, between 2–5 years in 3 (50%), and >5 years in 2 (33.3%). A concomitant dermatosis, vulvovaginal candidiasis, was recorded in a single patient. Five (83.3%) patients had itching, 5 (83.3%) pain, and 4 dyspareunia (66.7%); the other 2 patients did not have sexual intercourse, so the presence or absence of dyspareunia could not be assessed. In no case was a skin biopsy taken, and microbiological samples were obtained in only one case. Among the treatments, pelvic floor physiotherapy was indicated in 5 cases, topical gabapentin in one case, and surgery in one case.Two patients were consulted for vulvodynia with a mean ± SD age of 30.66 ± 6.5 years. Both patients had a disease evolution time of >5 years. In no cases were skin biopsies or microbiological samples taken. In terms of treatment, pelvic floor physiotherapy was indicated in one patient, and psychotherapy in another patient.This study shows the authors’ 5-year experiences as dermatologists managing specific consultations related to diseases of the vulva. At all times, these consultations were organized in close collaboration and with constant communication between the various team members at the gynecology service of our hospital. In all, 148 women were evaluated; those who attended the consultation were most likely to be between 40 and 60 years, and the most frequent diagnosis was lichen sclerosus. This was followed by irritative eczema and lichen simplex chronicus, like other series.Patients with vulvar diseases often take a long time to seek medical attention, especially because of anxiety and embarrassment. In addition, this delay in going to the doctor causes patients to frequently use home remedies as a treatment, which is frequently associated with the worsening of symptoms.The most frequently identified disease process in our series was lichen sclerosus, a chronic inflammatory disease that mainly affects the anogenital area. It most frequently affects prepubertal and postmenopausal women, and its etiology is influenced by genetic and autoimmune factors.Taken together, inflammatory diseases, including lichen sclerosus, vulvar eczema, lichen simplex chronicus, and lichen planus, accounted for 71% of the total series. On the other hand, 8 patients in the series (5.4%) sought consultation for vulvar pain syndromes, including vulvodynia and vestibulodynia. Currently, the prevalence of this condition is unknown in our environment, both due to the lack of patient consultations and the lack of training for those specialists who care for them. Vulvodynia is a frequently occurring, but seldom recognized, the disorder of vulvar pain and is defined as spontaneous or provoked pain in the vulvar area with a duration of >3 months of evolution without an established cause.Eleven patients (7.4%) sought consultation for an infectious cause. Contrary to the present study, other authors have stated that the most frequently occurring vulvar diseases in medical consultations are fungal and bacterial infections.Due to their particular anatomical characteristics, vulvar diseases are treated differently from other areas of the skin. In inflammatory diseases, the use of ultra-potent topical corticosteroids is essential.The authors must highlight the multidisciplinary work in our practice, as we not only work with gynecology, but we integrate a specific pelvic floor unit, as well as specialists in psychology and sexology into our team. Almost 100% of the patients seen reported vulvar pain in relation to the outbreaks of their specific disease, or even in the periods between outbreaks, representing part of the secondary vulvar pain syndromes. In general, vulvar pain can affect up to 20% of women at some point in their lives, and it is known that most cases are associated with pelvic floor disorders.Pelvic floor physiotherapy is a relatively new discipline that has been gaining relevance in the last decade, not only due to its effectiveness as a treatment for women with primary or secondary vulvar pain, but also given that it aids in the prevention and maintenance of pelvic floor health during pregnancy, postpartum, and climacteric.20The great majority of patients attended in our department referred to vulvar pain or discomfort. Pelvic floor physiotherapy allows an assessment of these processes and early diagnosis and treatment of possible secondary vulvodynia and muscle pelvic dysfunctions.Unfortunately, in our environment, neither the public health system nor insurance companies typically cover this type of assistance; so, although the authors recommend a large percentage of patients come in for an assessment, the economic limitations and lack of information on this specialty mean that only a small percentage attend , with clear improvements in all of them. Something similar has occurred with psychotherapy and sexology. A large percentage of women (45.9%) reported pain or discomfort with sexual intercourse, but only two patients consulted with a specialist in psychology and sexology. Financial reasons, shame, and the fact that consultation with a psychologist/sexologist is considered socially taboo were the main cited reasons why patients abstained from consulting. In future studies, the authors consider starting from baseline studies like this one to assess how pelvic floor physiotherapy and psychotherapy influence the quality of life of patients with vulvar diseases.The present study has several limitations. On the one hand, this study featured the various limitations associated with retrospective studies. On the other, the limited number of patients, as well as the presence of certain entities, such as vulvar diseases with an infectious cause, are usually managed in primary care without monographic consultations; therefore, these cases were not included in this study. Furthermore, no data were collected on the response and/or satisfaction of patients with the different treatments. Finally, the fact that all patients came from a single private hospital limited the possibility with which relevant conclusions could be drawn as, when compared with the public health system, is remarkably easier to get a consultation with a Dermatologist and other medical specialties and health-related services. On the other hand, there are different socioeconomic limitations associated with access to private health care and the different insurance coverages.In conclusion, the authors present their experience after 5 years of carrying out specific vulva consultations. Vulvar diseases are frequently occurring and often associated with high morbidity. It is thus essential that these patients are evaluated in specific units that guarantee comprehensive care. It is also necessary for these units to include other specialists with experience in the field, such as gynecologists, urologists, physiotherapists, or psychologists, who can ensure a multidisciplinary approach to providing care to patients with vulvovaginal symptoms.None declared.Fernando García-Souto: Preparation and writing of the manuscript; data collection, analysis and interpretation; statistical analysis; critical literature review.Ana Isabel Lorente-Lavirgen: Study conception and planning; preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic management of studied cases; approval of the final version of the manuscript.Francisco Manuel Ildefonso Mendonça: Intellectual participation in propaedeutic and/or therapeutic management of studied cases; critical literature review; approval of the final version of the manuscript.Manuel García-de-Lomas: Intellectual participation in propaedeutic and/or therapeutic management of studied cases; critical literature review.Mariana Viktoria Hoffner-Zuchelli: Intellectual participation in propaedeutic and/or therapeutic management of studied cases; critical literature review.Desiree Rodriguez-Ojeda: Intellectual participation in propaedeutic and/or therapeutic management of studied cases.Elena Pozo: Intellectual participation in propaedeutic and/or therapeutic management of studied cases; Critical literature review.José Bernabéu-Wittel: Intellectual participation in propaedeutic and/or therapeutic management of studied cases; Approval of the final version of the manuscript.None declared.


A total of 295 patients (63.4%) were predicted to cease HPN based on gastrointestinal anatomy but only 162/295 (54.9%) achieved this; those unable to do so were older with a higher comorbidity index. There were no differences in long-term nutritional and survival outcomes or surgical decisions between patients with SBS and fistulas, or between enterocutaneous and enteroatmospheric fistulas. This study represents one of the largest datasets describing the ability of HPN-dependent patients with SBS or fistulas to achieve nutritional autonomy. While reconstructive surgery facilitates HPN cessation, approximately one-fifth of patients declined surgery despite HPN dependency. These data will better inform patient expectation and help plan alternative therapies.Short bowel syndrome (SBS) and enterocutaneous or enteroatmospheric fistulas are common indications for home parenteral nutrition (HPN). However, there are few data describing factors influencing surgical decision-making or outcomes particularly following fistula development. We aimed to compare outcomes between patients with SBS and fistulas and explore surgical decision-making. HPN-dependent adults from 2001–2018 at a national reference centre were included in this study. HPN cessation was analysed using death as competing risk. In total, 465 patients (SBS (62%), fistula (38%)) were included, with median HPN dependency of 2.6 years. In total, 203 patients underwent reconstructive surgery; while frailty was the commonest reason for not undergoing surgery (49.2%), 22.7% declined surgery. Overall, 170 ceased HPN, with a probability of 13.8%, 34.1% and 38.3% at 1, 5 and 10 years, respectively. Patients undergoing surgery had higher nutritional autonomy rates (109.8 incidences/1000 patient years) compared to those not undergoing surgery (18.1 incidences/1000 patient years;  Short bowel syndrome (SBS) following massive intestinal resection, and enterocutaneous fistula (ECF) or enteroatmospheric fistula (EAF) are common causes of intestinal failure (IF) and commonly result in the need for parenteral nutrition (PN) . There aIn patients with SBS and intestinal fistulas, the need for permanent PN is determined by the clinical condition, length of remnant small bowel and the type of the digestive circuit after anastomosis . There aThe aims of this study were therefore to evaluate the likelihood of, and predictors of the restoration of nutritional autonomy in HPN-dependent patients with SBS and intestinal fistulas, to identify the predictors influencing the decision to perform reconstructive surgery and to describe the long-term outcomes of patients with SBS, compared to those with EAFs or ECFs.Clinical records of adult patients receiving HPN between 2001 and 2018 cared for at a UK national IF reference centre were reviewed. All consecutive adult patients with SBS defined as a remnant small bowel length of ≤200 cm [Data were collected on patient demographics and clinical characteristics including: start date of HPN, total time requiring HPN, mechanism and severity of IF at the point of discharge as defined by the European Society of Clinical Nutrition and Metabolism (ESPEN) , diseasep-value < 0.05 was considered statistically significant. The statistical software used was R Version 4.0.3 , packages: cmprsk ver. 2.2-10, ComplexHeatmap ver. 2.7.11, UpSetR ver. 1.4.0.Categorical variables are described as proportions and continuous variables are described as median . Analyses were performed using Chi square for categorical variables and Mann–Whitney U or Kruskal–Wallis for non-parametric continuous variables to compare different groups of subjects. Achieving nutritional autonomy was analysed using death as a competing risk, and cumulative incidence was estimated using the Aalen-Johansen (Aa-J) estimator. This method prevents bias associated with the more commonly used Kaplan–Meier analysis where deaths are censored, which ultimately leads to providing estimates of “probability of HPN dependence in immortal patients” . Fine anIn total, 465 patients were included in the analysis. Median follow-up time was 4.5 years (range 16 days–19.7 years), and the total observation time was 2566.5 patient years. The mechanism of IF at the time of HPN initiation was classified as SBS group 1 in 261 (56.1%) cases, SBS group 2 in 19 (4.1%) cases, SBS group 3 in 5 (1.1%) cases and intestinal fistulas in 180 (38.7%) cases. More patients had ECFs  than entero-atmospheric fistulas . The most common diagnosis leading to IF was surgical complications in 198 (42.6%) cases, followed by Crohn’s disease in 118 (25.4%) and mesenteric ischaemia in 107 (23.0%) cases. Patient demographics and clinical characteristics at HPN initiation are summarised in p < 0.001), as did the median Charlson Comorbidity Index .The number of new patients increased per study period from 92 in years 2001–2006 to 148 in years 2007–2012 and 225 in years 2013–2018. Median age at inclusion also increased over the study period  and an increase in those with surgical complications from other underlying conditions  over the study period  9.1–14.2). This duration was longer in the later study period (8.3 months vs. 11.4 months vs. 15.6 months), but was similar between SBS and fistulas (11.3 months vs. 11.2 months) and between ECF and EAF (11.2 months vs. 11.2 months). The type of reconstructive surgery involved fistula repair in 70 (34.5%) cases, restoration of continuity in 124 (61.1%) cases and small bowel transplant in 9 (4.4%) cases.p < 0.001. On the other hand, colon was brought back into continuity in a higher proportion of patients with SBS in comparison to those with fistulas . Of patients with SBS who underwent surgery, 21.0% had Crohn’s disease, 38.0% mesenteric ischaemia, 31.0% surgical complications and 10% other diagnosis leading to IF. In comparison, of the patients with fistulas undergoing surgery, 30.9% had Crohn’s disease, 2.1% mesenteric ischaemia, 63.8% surgical complications and 3.2% other diagnosis leading to IF.Patients who underwent transplant surgery were excluded from the analysis of the changes in intestinal anatomy. Median gain in small bowel length after surgery was 60 cm (IQR 0–140 cm). Following surgery, 144/194 (74.2%) patients changed their digestive circuit from end-ostomy or fistula to small bowel in continuity with colon. Anatomy at initiation of HPN, as well as the final anatomy, are summarised in There were 128 patients who could have potentially undergone surgery to facilitate HPN cessation based on their predicted anatomy  [p = 0.03) and decrease in the proportion of patients who died prior to intended surgery . For patients who declined surgery, the median age was 60 years (IQR 53–73) and Charlson Comorbidity Index was 3 (IQR 1–4), which was not statistically different to patients who did not undergo surgery for other reasons, median age 64 years (IQR 53–72), p = 0.87 and median Charlson Comorbidity Index 3 (IQR 2–4), p = 0.69, respectively. There was no difference in the proportion of patients with predicted favourable anatomy declining surgery based on the mechanism of IF  or disease leading to IF . Patients with EAF were more likely to decline surgery in comparison to patients with ECF although the result was not statistically significant .The proportion of patients who did not undergo surgery despite potentially suitable intestinal anatomy increased over the study period with 13/92 (14.1%) in years 2001–2006, 37/148 (25.0%) in 2007–2012 and 78/225 (34.7%) in 2013–2018. The reasons for patients not to undergo surgery also changed over the time periods, with an increase in the proportion of patients with comorbidities preventing surgery , with a total time on HPN of 1704.8 patient years. Overall, 170 patients achieved nutritional autonomy. The probability of achieving nutritional autonomy was 13.8% at 1 year, 24.5% at 2 years, 34.1% at 5 years and 38.3% at 10 years .The relationship between the mechanism of IF at HPN initiation, surgery and nutritional autonomy is shown in A further Fine and Gray regression was performed to identify predictors of achieving nutritional autonomy. Younger age, greater small bowel length and presence of colon in continuity were all associated with an increased likelihood of achieving nutritional autonomy .p < 0.001). The median time of achieving nutritional autonomy after surgery was 5.2 months (95% CI 4.4–7.1), which was significantly affected by the final bowel length (p < 0.001) (p = 0.50).The rate of achieving nutritional autonomy was higher in patients who underwent reconstructive surgery (109.8 incidences per 1000 patient years) in comparison to patients who did not undergo surgery  . There wp < 0.001). Of note, 8 (4.7%) patients who were not predicted to achieve autonomy based on their anatomy were successful in ceasing HPN. The most common reason for not achieving autonomy was high volume output , followed by renal impairment and weight loss. Each patient could have had one or more reasons for not achieving autonomy, which are presented in A sub-analysis of patients who were “predicted” to achieve nutritional autonomy based on their final intestinal anatomy was performed. Of the 295 patients predicted to achieve autonomy only 162 (54.9%) achieved it. There was a significant difference in achieving nutritional autonomy for different anatomy groups, with only 29.1% of patients with ≥115 cm of small bowel to end-ostomy or fistula (SBS group 1) achieving nutritional autonomy in comparison to 73.1% of patients with small bowel length of ≥60 cm anastomosed to >50% or <50% colon (SBS group 2) and 78.9% of patients with small bowel length of ≥35 cm anastomosed to intact colon (SBS group 3), (p < 0.001), had higher Charlson Comorbidity Index , were less likely to undergo reconstructive surgery  and received HPN for a longer period of time prior to surgery   .Overall, by the censoring date, 215 out of 465 (46.2%) patients died. There was no difference in the mortality rates between patient with SBS in comparison to patients with fistulas  and between ECF and EAF . The cause of death was IF related in 23 out of 215 (10.7%) patients, underlying disease in 43 (20.0%), other in 130 (60.5%) and unknown in 19 (8.8%) patients. Regarding IF-related causes, 6 patients died due to catheter-related bloodstream infection, 15 due to IFALD and 2 after IF surgery .In total, 62/203 (30.5%) of the patients who underwent surgery died. The 30-day survival post-surgery was 99.0% and 1-year survival was 94.4%. The cause of death after surgery was IF related in 7 (11.3%) patients (IFALD in 5 patients and following surgery in 2 patients as above), underlying disease in 12 (19.4%), other in 29 (46.7%) and unknown in 14 (22.6%). The median time of death after surgery in patients with unknown causes of death was 9 years with earliest death occurring 3.7 years after surgery.This is one of the largest and longest single-centre series reporting outcomes in patients with SBS, ECFs or EAFs associated with intestinal failure and the first one to specifically compare outcomes of SBS to intestinal fistulas. The probabilities of achieving nutritional autonomy in our cohort were 13.8% at 1 year, 24.5% at 2 years, 34.1% at 5 years and 38.3% at 10 years, which is similar to previous studies focusing on outcomes in SBS ,15,16. YOnce IF has developed, a structured, multidisciplinary approach is essential for reducing morbidity and mortality as well as restoring nutritional autonomy. In the acute setting of type 2 IF, this includes resolving sepsis, optimising nutritional status, defining intestinal anatomy and then formulating a definitive management plan, which may include reconstructive surgery if appropriate after a period of recuperation at home on parenteral nutrition ,18. It hAlthough recommendations regarding optimal clinical characteristics for any surgery have been evaluated in the past ,4,22,23,Another novel finding of our study was that 45.1% of patients predicted to achieve autonomy based on their final gastrointestinal anatomy failed to do so. This is substantially more than described in previous studies with rates around 12% in a study by Nightingale et al.  and 17% The main limitation of the study is that medical records were used as a data collection source. However, the patient database was maintained prospectively and all the patient records were accessible electronically, such that the only missing data involved gastro-intestinal anatomy for 16 (3.4%) cases. In addition, the single-centre nature of the study may limit generalisability. However, this clearly allowed for consistent data collection from a very large cohort over a long period in a national referral centre that may be difficult to replicate elsewhere; this may also have reduced variation in clinical practice affecting outcomes since the data derive from care delivered by an experienced multi-disciplinary team. In addition, due to irretrievable pharmacy prescription data for patients before 2011, we have not collected specific data on patient medications in this study. Lastly, frailty was included as a reason preventing surgical procedure if it was specifically stated in clinical records; however, we did not utilise a specific tool to define its severity, which would be an important next step in future studies.In conclusion, we demonstrate one of the largest single-centre experiences describing the long-term ability of HPN-dependent patients with SBS or intestinal fistula to achieve nutritional autonomy. Reconstructive surgery facilitates HPN cessation but the reasons for patients not undergoing surgery are complex. Our data can inform the development of models aimed at predicting nutritional autonomy that will better inform patient expectation and help the planning of alternative therapies.


However, in both groups, stage IIB patients had a significantly higher 5-year OS rate, despite the presence of nodal metastases in group 2. In the first group it was 75.1% in IIB vs. 54.8% in IIIB (p = 0.040) 5-year OS and 77.5% vs. 55.8% (p = 0.034) in the second group. Important was also a significant association between the dose of BT and survival in group 2: 45.7% vs. 69.2% for dose <28 Gy and 28 Gy (p = 0.018). Evolution in the diagnosis and treatment of patients with cervical cancer had led to improvement in the survival of patients and precise treatment with an appropriate stage assessment. However local advance of the tumour is still the most important prognostic factor.Concurrent radiochemotherapy (RCHT) has been the standard treatment for locally advanced cervical cancer since 1999. During this 20-year period, both diagnostic and radiotherapy techniques have developed, such as positron emission tomography (PET) or brachytherapy (BT) planning. The aim of the study was to assess the relationships between prognostic factors and the results of treatment in patients with advanced cervical cancer independent of these changes. The analysis included 266 patients with stage IIB or IIIB FIGO 2009 cervical cancer divided into two groups: one including 147 patients diagnosed with physical examination and ultrasonography (USG) and treated with RCHT with 2D BT from 2001 to 2005; another including 119 patients with metastatic pelvic lymph node diagnosed with PET and treated from 2010 to 2016 with RCHT and 3D BT. The mean five-year overall survival (OS) rate was 59.2% in the first vs. 65.5% in the second group ( Cervical cancer is one of the most common cancers worldwide. According to GLOBCAN data, there were 604,000 new cases and 342,000 deaths due to cervical cancer in 2020 . Over thn = 32) or IIIB (n = 115) disease treated from 2001 to 2005 with follow-up through the end of 2010. Group 2 consisted of 119 patients with stage IIB (n = 55) or stage IIIB (n = 64) disease treated from 2010 to 2016 and followed until the end of 2021. In both groups, the tumour stage was determined according to FIGO 2009 criteria. We analyzed these two groups independent according to clinical and treatment prognostic factors. We retrospectively evaluated 266 patients diagnosed and treated for stage IIB or IIIB cervical cancer at our centre  from 2001 to 2021. Follow-up was performed through the end of 2021. The patients were divided into two groups according to the period during which they were diagnosed and treated (2001–2005 vs. 2010–2016). Group 1 consisted of 147 patients with stage IIB (p = 0.000). The mean (standard deviation [SD]) age was 51 (8.7) years. Mean body mass index was 25.7 ± 5.1. We observed comorbidities such as hypertension, diabetes and varicose veins of the lower legs in 28.6% of patients.A total of 147 patients diagnosed between 2001 and 2005 with cervical cancer in stage II or III were included in group 1. There were 32 patients in stage IIB and 115 in stage IIIB according to FIGO 2009. Disease progression was determined according to physical examination consisting of per vaginam and per rectum examination, chest X-ray, and ultrasound. Tumour size and the presence of invasion to adjacent structures were assessed. Routine lymph node assessment was not performed. The mean (SD) size of the primary cervical tumour was 4.98 (1.56) cm. For stage IIB, it was 3.96 (1.42), and for IIIB, it was 5.26 (1.48), respectively)  was squamous cell carcinoma (SCC). In five cases (3.4%), the histological type was adenocarcinoma. The tumours were graded according to the degree of differentiation: well differentiation—Grade 1 (G1), moderate differentiation—Grade 2 (G2) or poor differentiation—Grade 3 (G3); most of the tumours were classified as G2 (77.5%), followed by G3 (12.3% of cases), and G1 (10.2% of cases). p = 0.125).All patients were treated with external beam radiotherapy (EBRT) plus brachytherapy and weekly chemotherapy. Conformal EBRT was performed using four photon radiation cross beams (“box” technique), with a dose of 1.8 Gy per fraction. The 4 × 10 cm sheaths from a multi-leaf collimator were used with a dose of 30 Gy to the clinical target volume (CTV). The arrangement was verified on the basis of kilovolt photons. The mean EBRT dose to the tumour was 32.2 (±5.6) Gy, with no significant differences between patients with stage IIB or IIIB disease (p = 0.115).All of the patients in group 1 underwent intracavitary low-dose rate (LDR) brachytherapy, administered with cesium 137 radioisotope and the “afterloading” technique on a Selectron device . Treatment was delivered in two fractions. The dose rate at the reference point was 1.0–1.2 Gy. Planning of the dose distribution in the applicators was based on x-rays and virtual planning in accordance with International Committee for Radiological Units 38 (ICRU 38) recommendations —Figure 1p = 0.164). The total dose for the combined treatments in group 1 was 87.1 (±10) Gy, with no significant differences between patients with stage IIB or IIIB disease .All patients also received adjuvant chemotherapy with Cisplatin with a dose of 40 mg/mp = 0.616). The mean (SD) size of the primary cervical tumour in the PET was 5.34 (1.48) cm. For stage IIB, it was 4.89 (1.51) and for IIIB it was 5.56 (1.22), respectively (p = 0.002).Group 2 included 119 patients treated from 2010 to 2016. There were 55 patients in stage IIB and 64 in stage IIIB according to FIGO 2009. The diagnostic work-up was similar to that applied in group 1 , but with the addition of fluorine-18 deoxyglucose (18FDG) PET imaging to check for the presence of nodal invasion (pelvic and/or para-aortic lymph nodes) and/or distant metastases. As a result of the analysis, we included only patients with pelvic lymph node metastases, obtaining a relatively homogeneous group. According to FIGO 2009 criteria, all of these patients were classified as stage IIB or IIIB, despite the presence of pelvic node disease. If the revised 2018 FIGO criteria had been in place at the time of diagnosis, these patients would have been considered stage IIIC1. The mean (SD) number of metastatic lymph nodes in group 2 (based on PET imaging) was 2.42 (±1.59). In patients with IIB, the mean number of involved nodes was 2.44 (±1.49) and 2.42 (±1.59) in the IIIB stage, respectively (The mean (SD) age of these patients was 52.7 ± 10.7 years. The mean body mass index was 26.9 ± 4.9. We observed comorbidities such as hypertension, diabetes and varicose veins of the lower legs in 14.2% of patients.The histopathologic classification for most of these tumours (85.7%) was SCC, with the remaining 14.3% classified as adenocarcinoma. The differentiation status was as follows: well differentiation (G1) in 3.4% of patients, moderate differentiation (G2) in 74% of patients and poor differentiation (G3) in 22.6%. n = 112, 94.1%) underwent three-dimensional conformal radiotherapy (3D-CRT) delivered through a linear accelerator equipped with a multileaf collimator (MLC) which enabled mapping of the irradiation field in accordance with the recommendations of ICRU reports 50 and 62. The total dose was 50.4 Gy (whole pelvis plus the tumour) with 1.8 Gy per fraction. In the remaining seven patients (5.9%), the radiation modality was IMRT, due to anatomy that requires a change in the arrangement of radiation beams. Patient positioning on the treatment table was regularly verified through kilovolt and megavolt imaging.All patients in group 2 received the same treatment as in group 1 (EBRT plus brachytherapy and weekly chemotherapy). Most patients , depending on received a boost to the metastatic lymph nodes diagnosed in the PET. A 10 Gy boost (IMRT) was delivered in 66 patients (55.5%). In this subgroup, 28 patients were stage IIB (50.9%) and 38 were stage IIIB (59.4%).In the second group, patients were treated with high-dose-rate (HDR) intracavitary brachytherapy with the use of Fletcher or Ring applicators. The brachytherapy dose (>12 Gy/h) was delivered with the Nucletron device. Computed tomography (CT) or magnetic resonance imaging (MRI) were used to determine the gross tumour volume (GTV). MRI was also used to check for the presence of invasive disease and to determine the high-risk clinical target volume (HR-CTV), including the cervix, vaginal vaults, and part of the uterine body. A total dose of 28 Gy was prescribed to cover 90% of the HR-CTV administered in four fractions based on 3D imaging (CT or MRI) according to The Groupe Européen de Curiethérapie (GEC) and the European Society for Radiotherapy and Oncology (GEC-ESTRO) working group protocol —Figure 22 administered once weekly for the entire duration of EBRT. The mean (SD) number of chemotherapy courses was 3.67 ± 1.96, with no differences between the two stages (stage IIB and IIIB).The patients also received chemotherapy—Cisplatin with 40 mg/mp = 0.05. The Pearson Chi-square test, the Fisher test, and the Mann–Whitney test were applied as appropriate. The Kaplan–Meier algorithm was used to construct the survival curves. Kaplan–Meier curves were compared using the log-rank test.All calculations were performed with the statistical package STATISTICA v.10  . The cutp = 0.048). The results are presented in The mean five-year overall survival (OS) rate was 59.2% in group 1 versus 65.5% in group 2, a statistically significant difference of 6.3 percentage points (The mean (SD) survival time of the patients who died during follow-up was 1.9 ± 0.9 in the first group and 2.6 ± 1.3 years in the second group, respectively.p = 0.040). In the second group, the corresponding 5-year OS rates were observed in 77.5% of patients with IIB stage and in 55.8% of patients with IIIB, respectively (p = 0.034). The results are presented in In both groups, stage IIB patients had a significantly higher 5-year OS rate, despite the presence of nodal metastases in group 2. In the first group, the 5-year OS rate was observed in 75.1% of patients in stage IIB and in 54.8% of patients in stage IIIB with statistical significance (p = 0.015). In group 2, the mean (SD) tumour size of patients alive after 5 years of follow-up was 4.9 (±1.2) vs. 5.4 (±1.4) cm in those who died during this time period (p = 0.003).The variable most strongly correlated with 5-year survival outcomes was the clinical stage. Tumour size (measured by ultrasound in the first group and PET in the second one) was also correlated with survival. In group 1, the mean (SD) tumour size of patients alive after 5 years of follow-up was 4.7 (±1.5) vs. 5.3 (±1.6) cm in those who died during this time period  nor the differentiation grade was significantly associated with 5-year OS rates in either group, with p = 0.677). The results are presented in In group 2, in which all patients had metastases to pelvic lymph nodes, we found no statistically significant association between the number of metastatic nodes and survival outcomes. We observed that the 5-year survival rate was similar in patients with one metastatic lymph node and three and five or more metastatic lymph nodes (p = 0.317 and in the second one: p = 0.281.The EBRT dose to the pelvis had no significant effect on 5-year OS in either group. In the first group: p = 0.711). There was, however, a significant association in the second group. In patients who received a dose lower than 28 Gy, the 5-year OS was observed in 45.7% of them. In patients who received doses of 28 Gy, we observed 5-year OS in 69.2% of them (p = 0.018). The results are presented in Analysis of the brachytherapy dose shows that there was no association with OS in the first group 1 . All patients received a total dose >85 Gy.There was no correlation between the total tumour dose and OS, regardless of the clinical stage in either group (p = 0.903). There were also no significant differences in 5-year OS observed in patients who received a boost versus no boost, regardless of disease stage. In patients with stage IIB, it was 78.6% vs. 77.4% (p = 0.96) and in stage IIIB patients: 57.5% vs. 53.1% (p = 0.708). The results are presented in All patients included in group 2 had metastatic lymph nodes. Of the 119 patients in this group, 66 patients (55%) received a 10 Gy boost by IMRT to the metastatic nodes. OS at 5 years in the boosted group was observed in 64.9% of patients versus 65.4% in the non-boost group of patients, named as the control subgroup (p = 0.419 and p = 0.821 in groups 1 and 2).Finally, the number of courses of chemotherapy had no significant influence on OS rates in either group  treated at our institution during two distinct time periods (2001–2005 and 2006–2010) over the past 20 years of changes in diagnostic and treatment methods. The mean five-year OS rate was significantly higher in group 2 (65.5%% vs. 59.2%) , despite criteriaChemoradiotherapy has been the standard of care for patients with advanced cervical cancer from 1999 until now ,14. SincIn our study, we were looking for prognostic factors mostly correlated with survival in these two groups of patients  independent of changes in diagnostic and treatment methods mentioned in the first place as associated with better survival in the modern group. In our analysis, the variable that had the greatest impact on survival was the clinical stage (2009 FIGO criteria), in line with previous reports ,18,19,20The size of the primary tumour is also associated with the clinical stage and treatment outcomes ,22,23,24p = 0.677)  .In our study, all patients in group 2 underwent PET-CT imaging, which allowed for the assessment not only of local tumour progression but also the determination of the presence of metastases to the lymph nodes and neighbouring organs. The introduction of the new FIGO classification in 2018 , in whicThe radiotherapy dose depends on tumour size and local advancement. Other studies also have demonstrated the prognostic significance of the radiation dose ,30. BothThe diagnosis and treatment of advanced cervical cancer have improved substantially in the last 20 years, leading to better survival outcomes. The introduction of PET-CT imaging as part of the diagnostic process allows clinicians to better assess local disease extension and to identify metastases to the lymph nodes and distant organs.Radiotherapy techniques have also improved substantially during this time period, and HDR brachytherapy is increasingly used in 3D planning, thus allowing for full radiation coverage of the whole tumour volume with better protection of healthy organs and highly precise dose delivery.However, the results of the present study, which involved patients with advanced cervical cancer treated in two distinct time periods (2001–2005 and 2006–2010), show that local tumour advancement remains the most important parameter for survival at 5 years. This finding underscores the importance of cancer prevention and early detection to ensure the best outcomes in patients with cervical cancer.


Schizoaffective disorder remains relatively unknown today compared to other psychiatric disorders. This disorder is however recognized by the international medical classifications DSM 5 and mainly affects many people.Describe the socio-demographic and contextual clinical characteristics of patients with schizoaffective disorderWe conducted a descriptive retrospective study including patients with schizoaffective disorder (DSM 5) in the psychiatric department G at Razi hospital and who were hospitalized for a period of 1 year from 1 January to 21 December 2020. We collected 57 patients.The average age of our sample is 40.16 years. The majority of patients (75.4%) were single and the school level did not exceed secondary studies in 64.9% of cases. Most of these patients were unemployed previously working as a day laborer in 47.4%. In addition, the type of schizoaffective disorder was dominated by the bipolar type (94.7%). These patients had a personality disorder in 26.3% mainly schizoid. The psychiatric interview of these patients revealed irritable mood in 47.4%, inappropriate affects in 59.6%, speech of a maniac in 52.6%, delusions of persecution and grandeur in 70.2% with intuitive mechanism (47.4%) and hallucinatory (auditory 45.6%). Disorganized behavior in 50% and catatonic behavior in 5.3% Mental automatism and morbid rationalism in 29.8% Insomnia: 94.7% and concentration disorder: 56.1% Type of treatment was the combination of atypical antipsychotics, mood stabilizers and benzodiazepines 33.3% with regular follow-up in 49.1%Schizoaffective disorder is one of the most misdiagnosed psychiatric disorders in clinical practice and the need to know its characteristics is a necessity.No significant relationships.


N = 906, application of eligibility criteria yielded N = 46. Upon analysis of risk of bias N = 41 demonstrated high risk. Studies found a positive association between elevated PM2.5, PM10 and SARS-related outcomes. A geographic and temporal variation in both PM and C19’s role was observed. Conclusion: C19 is a high mortality and resource intensive disease which devastated the globe. PM exposure is also a global health crisis. Our systematic review focuses on the intersection of this impactful disease-exposure dyad and understanding the role of PM is important in the development of interventions to prevent future spread of viral infections.Background: Particulate matter (PM) exposure is responsible for seven million deaths annually and has been implicated in the pathogenesis of respiratory infections such as severe acute respiratory syndrome (SARS). Understanding modifiable risk factors of high mortality, resource burdensome C19 and exposure risks such as PM is key to mitigating their devastating effects. This systematic review focuses on the literature available, identifying the spatial and temporal variation in the role of quantified PM exposure in SARS disease outcome and planning our future experimental studies. Methods: The systematic review utilized keywords adhered to the PRISMA guidelines. We included original human research studies in English. Results: Initial search yielded  Coronaviruses (CoV) are a common cause of respiratory disease. However, at least two novel CoVs have plagued humanity ,2. In 202.5 is known to activate tumor-associated signaling pathways by microRNA dysregulation, DNA methylation and by increasing the levels of inflammatory cells, cytokines. Altered macrophage-mediated inflammatory response to viral infections due to PM exposure has been hypothesized to play a role in these adverse outcomes ..28]. We Studies that performed Nucleic Acid Amplification Test (NAAT) using reverse-transcription polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 RNA from the upper respiratory tract, physician diagnosis or other clinical tests, were categorized as low risk for detection bias. For studies with unknown methods of diagnosis, we categorized them as unclear risk of detection bias.Studies that adjusted for age, gender, individual levels of exposure or any other relevant covariates were categorized as low risk for this domain. Studies that did not adjust results for at least one covariate were categorized as high risk.Studies that included a control group were categorized as low risk for this domain, whereas those that did not were categorized as high risk. The three key domains were assessed for overall risk of bias judgment. Studies were categorized as low overall risk of bias if it was at low risk for all key domains, and high if any of the domains were high. For the time series studies only two domains, i.e., assessment of outcomes and adjustment for confounding were considered to analyze the risk of bias.Based on the inclusion and exclusion criteria, we screened and selected manuscripts (EndNote™ 20.1). Each article was screened for study design, patient characteristics, sample size, tools used, incidence, severity and mortality of SARS in association with quantifiable PM exposure. Results from each database search were filtered for human subjects, English language, publication date (after November 2002) and imported into EndNote. The references were then screened for duplicates. Only original research papers were then reviewed for title, abstract and full text to ascertain eligibility. The references cited in the relevant articles were also examined. All results were screened by SP and MSF and further independently evaluated by AN. Disagreements were resolved by consensus see .Data was generated from sources using our review PEO question and summarized into tables and plots . QualitaN = 732 were assessed for inclusion (abstract and title review). Finally, 46 original research articles were considered eligible [A total of 906 studies (334 PubMed and 572 Embase) were identified after filtering for relevant studies . After religible ,72,73,74N = 2 studies were high risk for outcome assessment, N = 24 were high risk due to lack of adjustment for confounders and N = 39 were high risk due to lack of a control group in their studies. Overall, N = 3 studies had low risk of bias, whereas N = 40 had high risk of bias Risk of bias assessment was performed for outcome, confounders and control group assessment. Of the three domains assessed for cohort studies, N = 3 were low risk for outcome assessment and N= 1 was considered high risk for due to lack of adjustment for confounders. Overall, N = 2 were low risk for bias and N = 1 had high risk of bias.For the time series studies of the two domains assessed (outcome and confounders), N = 43), while N = 3 were time-series studies [2.5 and PM10 have played a role in SARS severity and spread.As the C19 pandemic swept the globe from 31 December 2019, understanding the phenotype of both the disease and associated risk factors of disease severity has been challenging. Cohort studies were the predominant type  of daily SARS mortality was 1.06 (1.00–1.12) [SARS-1 originated in Guangdong, China in 2003, and in six months had spread to more than two dozen countries resulting in at least 774 deaths . Due to 00–1.12) . There w00–1.12) . In cont00–1.12) .2.5 through a risks study using days with the highest and lowest incidence numbers in February [3 increase in PM2.5 and PM10 resulted in 2.21% (95% CI:1.13–3.29), 2.67% (95% CI: 0.33–5.01), increase in daily counts of C19 infected cases, respectively [N = 6); prevalence (N = 2); morbidity (N = 1) and mortality (N = 6). Negative association was observed with mortality (N = 1) and incidence (N = 1), and equivocal results were reported by N = 1 [N = 17); prevalence (N = 4); morbidity (N = 6) and mortality (N = 18). Negative association with incidence was observed in N = 2. Equivocal results reported by N = 4 [A decline in the incidence, mortality, and hospitalization was observed during the later pandemic period, from approximately late April–June 2020. A temporal analysis in Beijing from 25 April–31 May 2020 showed a declining trend in daily mortality count . While tby N = 1 ,52,63. Oby N = 4 .Few, if any, areas of the globe have been left unaffected by the C19 pandemic. Meo et al. studied 17 countries across the globe and noted a significant positive association between PM and C19 incidence . CertainN = 16) studies [2.5 and C19 cases was observed in Lombardy, Italy by Rovetta et al. [2.5 levels, the number of SARS-CoV-2 infections significantly increased by 0.1% in London [2.5 levels recorded in 2010 were significantly associated with an increased SARS-CoV-2 positive testing likelihood  [N = 9); incidence (N = 6); prevalence (N = 4); morbidity (N = 2). Equivocal results were reported by (N = 2) [Europe was the setting of  . Overall2.5 and C19 cases in Wuhan  and Xiagan  [3 rise in levels of PM2.5 (lag 0–14 was positively associated with RR of 1.050 (95% CI: 1.028–1.073) daily newly confirmed cases [N = 4); mortality (N = 3); prevalence (N = 1).Similarly, of the nine studies dedicated to Asia ,36,37,38 < 0.01) . In Hubeed cases . Overall10 positively correlated to daily cases of C19  [2.5 for several days showed significant association to confirmed cases [2.5 due to a sandstorm in Saudi Arabia was associated with a significant increase in the number of SARS-CoV-2 cases (Spearman’s correlation coefficient ρ = 0.944 (<0.0001)) [Six studies with a focus on the Middle East were identified ,69,70,71ctively) . Similared cases . Increas2.5 was associated with an increased risk of mortality  and ICU admission  per 1-µg/m3 increase in PM2.5 [2.5 . PM was positively associated with C19: incidence rate (N = 7); mortality (N = 4) and prevalence (N = 1). A negative association with mortality was observed by N = 2 [In the U.S, data from seven New York City (NYC) hospitals concluded that higher and long-term exposure to PMin PM2.5 . Similarby N = 2 ,64.3 in PM2.5 increased the mortality risk by approximately 7.4% in Mexico City metropolitan area in October 2020 [Similarly, as in 2/3 Latin American countries, PM and C19 incidence and mortality had a positive association. In contrast, one study reported equivocal results . Specifiber 2020 .2.5 (<2.5 mm) and coarse PM10 (<10 mm). PM2.5 is more likely to travel and deposit deeper in the lungs like the alveolus, whereas PM10 can deposit on the surfaces of larger airways inducing inflammation. Ambient air pollutants are risk factors for cardiopulmonary diseases and responsible for over 6 million annual deaths.PM is a heterogeneous mixture of solid particles and liquid droplets found in the air. It is commonly grouped by diameter into fine PM2.5 was assessed by 19/46 studies. PM2.5 was positively associated with C19: incidence (N = 11); mortality (N = 6); morbidity (N = 5); and prevalence (N = 1). Negative association with prevalence was seen in only one study [The role of PMne study .10 was evaluated in eight studies, and it was positively associated with C19 incidence (N = 5); prevalence (N = 1); and mortality (N = 1). Finally, PM10 and PM2.5 were evaluated by N = 19 studies. A positive association with C19 incidence (N = 9); mortality (N = 5) was seen. Negative association was seen in N = 2 and equivocal results were identified in N = 1.PMOur systematic review identified the role of PM to be important in the incidence, mortality and morbidity due to SARS infection. These studies had significant differences in the populations, methods, and outcomes that were studied . We idenLonger durations and higher levels of PM increased the risk of ICU admissions and deaths due to C19. Several mechanisms have been hypothesized. Oxidative stress and disruptive immune and/or neuroendocrine function can result in increased severity of viral pulmonary infections ,82.3 increase in PM2.5 was associated with increased measles incidence. A similar observation was also noted with respiratory syncytial virus, which causes bronchiolitis and pneumonia [2.5 in four study sites and found the highest levels of SARS-CoV-2 RNA on PM2.5 [PM has been associated with enhanced infection with RNA viruses such as SARS . PM concneumonia . A studyon PM2.5 . PM expoon PM2.5 ,86. Expoon PM2.5 ,88. Theron PM2.5 ,72.2.5. Spatial variation in the concentration of PM2.5 in some areas such as California’s central valley and Italy’s Po Valley can be contributed to geographical features with climate inversion events that trap these pollutants. The air trapping in these regions can also lead to chronic exposure to these particulates increasing the risk for respiratory and cardiovascular diseases which further enhances the risk [Variation in C19 outcomes in different regions could be attributed to social determinants of health such as poverty, access to health care facilities and health literacy. Populations with limited resources also have a high prevalence of chronic health conditions ,90. Urbathe risk .10 [2.5 is known to increase the risk of COPD, a known risk factor for severe C19 infection [Worsening asthma and COPD leading to hospitalization has been noted with short-term (up to 24 h) exposures to PM10 . Long-tenfection .An NYC hospital-based study noted that mortality rates dropped from 25.6% in March to 7.6% in August 2020 . This reStrengths of Systematic Review. This review focuses on the environmental inducers of infectious diseases, a global health issue. It incorporates the variation in PM and the risk of Coronaviruses geographically. Manuscripts from across the globe were reviewed, which made this study more generalizable. Each article was screened for study design and was further subcategorized to understand temporal, spatial variability.N = 6 studies analyzed the spatial variation [Our systematic review has several limitations. Since assessing the risk of bias inherently has some level of subjectivity, we categorized high- vs. low-risk studies using a determined set of criteria. While many of the studies that we assessed had a high risk of bias, future studies would benefit from assessing their data in the context of potential confounders including age, gender, and comorbidities. Several variants have been identified since the 2019; however, our manuscript does not discuss the disparity in disease outcomes for different variants . The manariation ,55,62,65In conclusion, these studies have expanded our knowledge of PM exposure and its association with SARS infection. The review highlights the clinical impact of PM and the need for implementing measures to combat climate change and dangerous levels of environmental toxin. There was a spatial and temporal variation in the characteristics of the disease. Overall, it was seen that exposure to quantified PM was associated with increased incidence, mortality and morbidity to C19. Measures can be taken on both global and a personal level, such as improving air ventilation design and systems in enclosed spaces and buildings, restricting wildlife trading and deforestation, and training our healthcare professionals to educate masses on taking personal steps to ensure less production and exposure to pollution, such as using facemasks, and walking/cycling instead of motorized transport.Future experimental studies will include developing our understanding of the role of PM in accentuating the response to pathogens such as C19, understanding the effects estimate for chronic vs. short-term exposure to PM, and in furthering our management of PM exposure to limit severity of viral infections. These projects will focus on quantifying the association of PM concentrations (by zip code and/or geocoding) and the incidence of C19 related morbidity and mortality.


BackgroundThe prevalence of dyslipidemia is higher in type 2 diabetes mellitus (T2DM) and hypolipidemic drugs like statins are effective for the primary and secondary prevention of cardiovascular events. Most of the patients with type 2 diabetes have a mixed type of dyslipidemia. This study aimed to evaluate the utilization of hypolipidemic drugs, patterns, and factors affecting dyslipidemia in T2DM participants.MethodsThis cross-sectional observational study was approved by the institutional ethics committee (IEC) of the Vydehi Institute of Medical Sciences and Research Center. It was conducted for a period of one year from July 2021 to June 2022. Participants with T2DM visiting the Department of General Medicine and Endocrinology were enrolled after obtaining informed consent. Demographic details, medication history, and laboratory data were recorded in case report form and statistical measures were applied.ResultsOut of 237 participants enrolled in the study, the predominance  was males. The mean age of the study population was 47.92±9.17 years, and the mean duration of diabetes was 6.8±5.3 years. Out of the total participants, 164 (69%) had deranged lipid profiles. Out of them, 129 (78.65%) were on hypolipidemic drugs. Regarding drug utilization, 122 (94.6%) received statins either rosuvastatin (54%) or atorvastatin (40%). In the deranged lipid profiles pattern, 24% (58) participants had one abnormal lipid parameter and the majority 70% (166) had combined lipid profile abnormality. Factors like increased BMI were significantly associated with dyslipidemia (p=0.004). Utilization of hypolipidemic drugs was also significantly associated with the control of dyslipidemia (p<0.001). It was observed that participants who were not on lipid-lowering drugs had 5.38 times more chance of dyslipidemia .ConclusionA high prevalence of dyslipidemia was observed among diabetic patients. Statins were the most prescribed drug in the study. BMI and lack of pharmacotherapy were found to have a statistically significant association with dyslipidemia in diabetic patients. Diabetic dyslipidemia is characterized by elevated plasma triglyceride levels, low high-density lipoprotein cholesterol (HDL-C) levels, and an increase in several small dense forms of low-density lipoprotein (LDL) particles which are highly atherogenic . AccordiBesides antidiabetic drugs, lifestyle modification and hypolipidemic drugs are effective ,4. StatiPrevious studies on diabetic dyslipidemia in India found that dyslipidemia was more in females and the age group 45-54 years. They also concluded that the majority 44.2% of participants suffer from a mixed type of dyslipidemia ,8. They The present study was a cross-sectional observational study. The study was conducted by the Department of Pharmacology in collaboration with the Department of Endocrinology and the Department of General Medicine at Vydehi Institute of Medical Sciences and Research Center, Bengaluru. The duration of the study was one year from July 2021 to June 2022. The study was conducted after receiving approval from the institutional ethics committee, under the registration number VIEC/PG/APP/015/2020-21. Participants were screened for inclusion and exclusion criteria. Both male and female patients with type 2 diabetes irrespective of lipid-lowering therapy between 18 and 60 years attending the OPD and consenting to the study were included. The exclusion criteria included type 1 diabetes mellitus patients, gestational diabetes mellitus, and inpatients. The study objectives and process were explained to the participants or their relatives in their language. Participants were asked to read and sign an informed consent form. The demographic details, medical history, personal history, medication history, and laboratory data of all participants included in the study were recorded on Case Report Form (CRF). Participants were divided into two groups based on lipid profile level. Group one was participants with high lipid levels than the normal range, and group two was participants with low lipid levels than the normal range. Drug utilization was evaluated. Several factors like age, gender, body mass index (BMI), duration of disease, comorbidities, drug utilization of hypolipidemic drugs, family history, and HbA1c were compared between the two groups. Finally, all details from the CRF form were recorded on an excel sheet and statistical measures were applied. The following biological references were considered low lipid levels. Total cholesterol less than 200 mg/dL, triglycerides less than 150 mg/dL, HDL cholesterol more than 40 mg/dL, LDL cholesterol less than 100 mg/dL, VLDL between 2 and 30 mg/dL. Any one or more than one lipid parameter higher than the normal lipid range was considered high lipid levels. The sample size was calculated considering a confidence interval of 95%, precision of 5%, and power of study at 80%.Data collected were entered into a Microsoft office excel sheet. Demographic details were subjected to descriptive statistical analysis and were expressed as mean SD and percentages. Drug utilization patterns were analyzed and expressed in frequencies and percentages. The categorical variable was compared using the chi-square test and odds ratio. Association between all categorical variables and lipid profile was observed and a P-value of less than or equal to 0.05 was considered statistically significant.Demographic details2. Most participants had a family history of T2DM. The mean duration (± SD) of the disease was 6.8 ± 5.3 years. Most participants had a duration of disease of less than six years. And in the same category, 75% (91) were found to have dyslipidemia. The mean HbA1c (± SD) was 8.9 ± 2.35%. The results are presented in Table The total number of participants in the study was 237. Out of 237 participants, 56% 133) were males. Out of the males, 72% (96) were found to have high lipid levels. The mean age (± SD) of the participants was 47.91 ± 9.17 years. Most participants were in the age group of more than 30 years. The mean BMI (± SD) was 25.27 ± 4.08 kg/m33 were mHypolipidemic drugs utilizationOut of 237 participants, 69% 164) participants were found to have high lipid levels. Out of them, 78.65% (129) received hypolipidemic drugs. A total of 129 generic drugs were prescribed. Most of the participants 94.6% (122) received HMG-CoA reductase inhibitors, statins. In fixed dose combination (FDC), rosuvastatin and fenofibrate was the common prescription. The drug utilization pattern is presented in Figure 64 particPatterns of dyslipidemiaRegarding dyslipidemia, high lipid level was observed in 69% (164) participants, isolated in 24% (58) of participants and combined abnormality in 70% (166). After analyzing dyslipidemia components low level of HDL-C was found in 35% (82), hypertriglyceridemia in 44% (104), elevated level of LDL in 60% (142), and hypercholesterolemia in 26% (61) participants, respectively. The details are presented in Table Factors affecting dyslipidemiaThe factors like gender, age, occupation, hypertension, family history of diabetes, and duration of disease, HbA1c had no statistically significant association with dyslipidemia. The participants with hypertension had 1.2 times more chance of having dyslipidemia . The participants with a family history of T2DM had 1.17 times more chance of having dyslipidemia . Regarding BMI and dyslipidemia statistical significance was seen p=0.004). It was seen that participants in the overweight and obese category had 1.07 times more chance of having dyslipidemia than those in the normal weight category . Regarding drug utilization and dyslipidemia statistical significance was observed (p<0.001). It was observed that participants who were not on lipid-lowering medication had 5.38 times more chance of having a derranged lipid profile . The results are presented in Tables . It was 2 and 58% (62) of them had high lipid levels. Equivalent results were observed by Bekele et al. where 58% (130) participants were in a normal BMI category and 29.5% (66) had dyslipidemia [The purpose of this study was to evaluate the prevalence of dyslipidemia and the utilization of hypolipidemic drugs use among participants suffering from T2DM. In this study, 56% (133) of the participants were males, and high lipid levels were present in 72% 96) of males. Comparable results were observed in a prior study by Bekele et al. where 53.6% 120) participants were males and 70% (84) had high lipid levels 6 of male. The meaipidemia . This ma0 particiIn the present study, 54% (129) of participants received hypolipidemic medications. Out of which 94.6% (122) of participants received statins, and atorvastatin accounted for 40% (52) prescriptions. Like Jayaram's study , Gupta eIn this study, 69% (164) of the individuals had elevated lipid levels. Among them, 24% 58) of participants had one abnormal lipid parameter and 70% (166) had several abnormal lipid parameters. Borle et al. discovered that 28% (14) of participants exhibited isolated lipid profile abnormalities, while 58% (29) had combined and mixed lipid profile abnormalities  of parti. A studyGender, age, occupation, hypertension, family history of diabetes, and disease duration exhibited no statistically significant association with the incidence of dyslipidemia in the present study. Also, no statistical significance was found between hypertension and abnormal lipid profiles (p=0.60). Participants with hypertension had a 1.2 times greater likelihood of having high lipid levels . In contrast to a study conducted by Bekele et al. where hypertension had 1.3 times more chance of having dyslipidemia , and Haile et al. found that participants with hypertension had 2.65 times more chance of having dyslipidemia  .A family history of type 2 diabetes in this study did not statistically significantly correlate with abnormal lipid profiles (p=0.42). The odds of having abnormal lipid profiles were also 1.17 times higher in persons with a family history . Bekele et al. reported similar findings, finding that participants with a family history had a 2.1 times greater likelihood of having high lipid levels  .BMI was shown to be strongly linked with abnormal lipid profiles in this study (p=0.004). It was also observed that those who were overweight or obese had 1.07 times greater likelihood of having high lipid levels . A similar substantial correlation was observed by Kebede et al., where obese participants had 3.5 times the risk of having disordered lipid profiles . Ahmmed et al. found that participants who were overweight or obese had a 2.08 times greater likelihood of having high lipid levels  ,19.In the present study, drug use was found to have a statistically significant relationship with dyslipidemia (p 0.001). Participants who were not using cholesterol-lowering medication had a 5.38 times greater likelihood of having abnormal lipid profiles than those who were . There is insufficient evidence or previous research to support the findings.Limitations of the studyIn this study the sample size was small. Participants in this study belonged to a small geographical area and were from a single centre. High-risk participants from the cardiology department were not included. Confounding factors such as poor glycemic control and concurrent primary hyperlipidemias that act independently of T2DM were not evaluated. In this study, a high prevalence of increased lipid levels was observed among diabetic patients. Also, poor T2DM control was found to contribute significantly to high lipid levels, with other confounders such as primary hyperlipaemias playing a role in the overall process. This study has highlighted the need for a collaborative approach between healthcare providers and patients toward the holistic goal of the management of T2DM and associated comorbidities.


Reliable markers to predict or diagnose anastomotic leakage (AL) of stapled circular anastomoses following colorectal resections are an important clinical need. Here, we aim to quantitatively investigate the morphology of anastomotic rings as an early available prognostic marker for AL and compare them to established inflammatory markers. We perform a prospective single-center cohort study, including patients undergoing stapled circular anastomosis between August 2020 and August 2021. The predictive value of the anastomotic ring configuration and the neutrophil-to-lymphocyte ratio (NLR) regarding anastomotic leakage is examined by ROC analyses and compared to the C-reactive protein (CRP) as an established marker. We included 204 patients, of which 19 suffered from anastomotic leakage (LEAK group), while in 185 patients the anastomoses healed well (HEAL group). The minimal height of the anastomotic rings as a binary classifier had a good ROC-AUC of 0.81 but was inferior to the NLR at postoperative day (POD) 5, with an excellent ROC-AUC of 0.93. Still, it was superior to the NLR at POD 3 (0.74) and the CRP at POD 3 (ROC-AUC 0.54) and 5 (ROC-AUC 0.70). The minimal height of the anastomotic rings as indicator for technically insufficient anastomoses is a good predictor of AL, while postoperatively the NLR was superior to the CRP in prediction of AL. Anastomotic leakage (AL) is currently the most common serious complication after colorectal surgery ,2. AlthoAlthough patients with AL often present with non-specific clinical symptoms such as a fever, leukocytosis, dyspnea or abdominal distension, these symptoms often occur after the manifestation of AL and cannot be used for prediction of AL after colorectal surgery ,7. ThereHowever, heterogeneous patient cohorts in previous studies, as well as inconsistent diagnostic criteria for AL and cut-off values of postoperative CRP have affected the application value of CRP as an early predictor of AL. Therefore, finding reliable and easily detectable predictors in the prevention of AL still has a high clinical significance.In recent years, intraluminal stapling techniques have been widely used, especially in laparoscopic surgery . So far,In this study, we aim to investigate the morphological configuration of anastomotic rings as an early available prognostic marker for AL and compare the prognostic value to the NLR and CRP as classifiers of AL occurrence.This study was approved by the Ethics Committee of Tongren Municipal People’s Hospital of Guizhou Medical University [(2020)47-4] at 31 July 2020. Informed consent was obtained from all patients included in the study. Patients were included during the study period from 10 August 2020 to 12 August 2021. Patient data were collected during the study period, including gender, age, ASA score, Body Mass Index (BMI), operation time, intraoperative blood loss, CRP and NLR at the Tongren Municipal People’s Hospital of Guizhou Medical University.Patients undergoing surgical resection of pathologically confirmed CRC with subsequent stapled circular anastomosis were included in the study. Patients with the following confounders were excluded: preoperative signs of infection, concomitant hematological diseases, additional diagnoses of malignant diseases, preoperative radio-/chemotherapy or preventive ileostomy.min), maximal height (Hmax), minimal width (Wmin) and maximal width (Wmax) of the fresh rings  Proof of anastomotic defect by digital rectal exam, colonoscopy or rectoscopy; (2) Purulent or stool-like secretion of the pelvic drainage; (3) Radiologically confirmed perianastomotic abscess formation or anastomotic defect; (4) Rectovaginal or rectovesicular fistula.p < 0.05 were considered statistically significant.SPSS 28.0  software was used for statistical analyses. Ratio data were presented as mean ± standard deviation (mean ± SD) in tables and box plots in diagrams, categorical data were presented as frequencies (in %). Chi-square test was used for the comparison of categorical data. Two-sided unpaired T-test was used for the comparison of ratio scaled, Gaussian distributed data. Receiver Operating Characteristics (ROC) as well as Area-Under-the-Curve (AUC) analyses were used to evaluate the ring measures and the NLR and the CRP as binary classifier to predict AL postoperatively. Optimized cut-off values were determined by maximizing the Youden index. Values of In total, 247 patients underwent resection for colorectal cancer followed by circular stapler anastomosis in Tongren Municipal People’s Hospital of Guizhou Medical University during the period from 10 August 2020 to 12 August 2021. Among these 247 patients, 43 cases were excluded for meeting the exclusion criteria. The resulting 204 patients had a mean age of 63.2 ± 11.6 years and a mean BMI of 22.8 ± 2.1. The collective consisted of 83 females and 121 males. The patients included were staged for stage II or III according to the UICC/AJCC classification (8th Edition) and underwent an anterior resection of the proximal rectum and the distal sigmoid colon with a sigmoidorectostomy. All operations were performed by a single surgeon (S. Q.) and were completed laparoscopically with his surgical group. All procedures were carried out without conversion to conventional laparotomy. The specimens were removed through left lower quadrant incision. The mean operation time was 161.4 ± 31.1 min and the mean intraoperative blood loss was 175.8 ± 38.1 mL .To perform the anastomosis, two different stapler sizes were used: CDH25A and CDH29A . Although the diameters of the rings differed between the stapler types, there were no statistical differences between the two stapler types regarding all other measurements of anastomotic rings .min value was statistically lower in the LEAK group than that of the HEAL group . Hmax, Wmin and Wmax did not show statistical differences between the LEAK group and the HEAL group (The measurement results of the rings in 204 patients were as follows: the ring HAL group .Anastomotic leakage occurred in 19 of 204 patients (9.3%) after a mean of 5.8 ± 1.4 days. Compared with the 185 cases in HEAL group, there was no statistical difference in terms of gender, age, ASA score, BMI, operating time, intraoperative blood loss and tumor stage .min as a potential binary classifier for anastomotic leakage, the optimal cut-off value of 4.95 mm was determined by maximizing the Youden index. At this value, the sensitivity for predicting AL following colorectal surgery was 56.8% with a specificity of 84.2% , as shown in min above 4.95 mm) and the latter group (Hmin below 4.95 mm)  developed AL. In 96 cases, minimal anastomotic ring heights were below 4.95 mm, of which 16 (16.7%) developed AL. Between the two groups separated by an H4.95 mm) .min to established inflammatory markers, the NLR and the CRP values were monitored and analyzed perioperatively. Compared to the preoperative measurements (2.8 ± 0.5), the NLR markedly increased at POD 1 (12.7 ± 1.0), and then stabilized  in the LEAK group. Patients in the HEAL group had NLR values of 2.6 ± 0.4 preoperatively. A postoperative increase to 12.6 ± 1.4 was followed by a gradual decrease to 8.4 ± 1.1 and 6.7 ± 1.5 postoperatively. The values between the groups were statistically different at POD 3 (p < 0.002) and POD 5 (p < 0.001) (In order to compare H< 0.001) A.p < 0.001) , the CRP kept increasing postoperatively in the LEAK group . Patients in the HEAL group had CRP values of 5.1 ± 0.8 mg/L, followed by a less pronounced postoperative increase of 26.3 ± 11.0 mg/L, 52.0 ± 13.3 mg/L, 55.2 ± 12.6 mg/L. The values between the groups were statistically different at POD 5 (< 0.001) B.min outperformed all values except the NLR at POD 5 with a good ROC-AUC value of 0.81  studies will be needed. The loss to follow-up cannot be excluded for patients suffering from late AL after being discharged from the hospital. Still, the risk should be low, as AL usually occurs early and within the postoperative in-house treatment. Although gender, age, ASA score, BMI, operation time, blood loss and tumor stage did not differ between the groups, we cannot exclude other confounders to affect the occurrence of AL in our analysis.In summary, our study confirms that proper configuration of the anastomotic rings is essential to prevent leakage. A low minimal height represents a technical flaw and can indicate the risk to develop leakage with a high specificity, and thus should be evaluated intraoperatively. In the postoperative period, the NLR is superior to the established CRP to identify AL and should be preferred.


Psychological and social factors related to work activity can improve or deteriorate the physical and mental health of employees. Since the COVID-19 pandemic, the psychological well-being of workers has been strongly affected. Particularly, jobs with isostrain characterized by high work demands and low work control, coupled with low social support, place employees at highest risk for poor mental health. We aimed to assess the factors associated with isostrain among employees in the tourism sector in Sousse.A cross-sectional study was conducted between September and November 2020 among tourism workers belonging to 12 hotels and restaurants in Sousse, Tunisia, using a self-administered questionnaire. ‘Isostrain’ was assessed using the Karasek questionnaire. ‘Isostrain’ is a situation where there is a combination of ‘jobstrain’ (‘tension at work') and low social support (score below the median of the group). SPSS 20 software was used to analyze the data.A total of 226 workers were included. The mean age was 38.2 ± 9.6 years. The sex ratio was 2.7. The majority of employees (64.8%) were working at workplace during COVID-19 lockdown. The prevalence of isostrain was 5.4%. Isostrain was reported by 5.7% of women (p = 1). All workers older than 50 years did not have isostrain (p = 0.6). Moreover, isostrain was found among 6.6% of workers with less than 5 years of work experience (p = 0.4), 4.8% of married employees (p = 0.7), and 7.6% of employees with a university education (p = 0.53).Isostrain can affect employees in the tourism sector. Social support should be promoted among workers to ensure good mental health.• Prevalence of isostrain in tourism sector of Sousse during COVID-19 pandemic is quite high.• Preventive strategies of mental health should be promoted at workplace in Tunisia.


Salmonella spp. are a major threat to public health. Bacteriophages offer a unique method for the treatment of these multidrug resistant bacteria. We studied the infection dynamics of a potential mono-phage therapy of Salmonella typhimurium under various pathophysiological conditions. Furthermore, we determined the resistance dynamics of Salmonella typhimurium against P22 phage treatment. We also determined synergy with antibiotics such as ampicillin and kanamycin. This research helps to further define and show the versatility of bacteriophages as potential novel treatment methods.The prevalence of multidrug resistant bacterial diseases is a major global health risk. Multidrug resistant bacterial diseases are prevalent, and the need for novel methods of treatment is essential to the preservation of public health. Annually foodborne pathogens cause 1.35 million infections and 26,500 hospitalizations in the United States alone. Foodborne pathogens such as  The massive and sometimes inappropriate use of antibiotics has led to the increased prevalence of multidrug-resistant bacterial strains that present treatment challenges in the clinical setting [The discovery of antibiotics revolutionized modern medicine; however, as we progress into the mid-21 setting . Antibio setting . A major setting , 7.Salmonella, which can be found in numerous food products such as poultry, seafood, and other fresh and processed meats [Salmonella spp. accounts for 1.35 million infections, 26,500 hospitalizations, and 420 deaths in the United States alone. An increased prevalence of antibiotic-resistant Salmonella strains could potentially result in an increase rate of mortality making it critical to develop new novel treatment strategies. Salmonella typhimurium has been of significant relevance due to the reported prevalence of antibiotic-resistance in this species [Salmonella typhimurium accounted for 59% of ampicillin-resistant infections [S. typhimurium as well as other Salmonella species [One of the most prevalent foodborne pathogens is ed meats –11. Annu species , 13. The species .A potential alternative to antibiotic treatment is the utilization of phage therapy as a novel therapeutic treatment –18. BactSalmonella typhimurium. The lytic Salmonella phage P22 has been widely studied but requires further study to be utilized as a standard treatment against Salmonella typhimurium [Salmonella typhimurium. Salmonella typhimurium typically colonizes within the small or large intestines after the pathogen is consumed [Salmonella typhimurium would also require further understanding of phage-host interactions in disease-mimicking conditions.Phage therapy is a strong potential candidate for the treatment of foodborne pathogens such as himurium , 26, 11.consumed . The varconsumed , 30. DetSalmonella typhimurium infections. These pathophysiological conditions include acidic pH and stationary phase. We utilized Salmonella typhimurium (referred to as BV4012) as the model organism for this study. This strain has a generation time of 30 minutes, allowing for kinetics under pathophysiological conditions to be examined rapidly. We show the ability of the phage P22 as an effective antibacterial agent against Salmonella typhimurium under low pH and stationary conditions. Additionally, we showed synergy with ampicillin and kanamycin. Most importantly, we showed that P22 could prevent the growth of Salmonella typhimurium under pathophysiological conditions, encouraging further study of P22 and other similar phages as potential antibacterial agents.In this study, we have performed phage-bacteria kinetic studies under several pathophysiological conditions related to 2.2.1To detect and quantify the phage P22, the soft agar overlay technique was utilized. Soft Agar was prepared by adding agar (0.8%) to Luria-Bertani (LB) media.  This suspension was autoclaved and allowed to cool to 45 °C in a water bath. 1 mL of late log phase BV4012 bacterial culture (OD > 1) and 100 μL of P22 phage dilutions were added to 5 mL of the soft agar and was poured onto a Luria agar plate. The soft agar was allowed to cool to room temperature and solidify. These plates were then incubated at 37 °C overnight.Salmonella typhimurium BV4012 (OD > 1). These cultures were plated on a LB agar plate to form a bacterial lawn. P22 phage samples were serially diluted and spotted onto the bacterial lawn. Plates were incubated at 37 °C for 24 h, and the number of plaques formed at various dilutions was quantifiedFor verification of phage titers, spot assays were conducted using late log phase 2.2S. typhimurium host. Liquid amplification was carried out by the addition of a P22 sample at 10 MOI to a log phase culture (OD between 1 and 2) and incubated for 12–24 h at 37 °C with rotary shaking at 180 rpm. Following incubation cultures were then centrifuged at 4,000 g for 10 minutes, and the supernatant was collected. For plate amplification, a soft agar overlay containing log phage S. typhimurium (OD 1–2) was prepared, and the P22 phage sample (10 MOI) was spotted on top of the soft agar. The plates were incubated for 12–24 h at 37 °C. The soft agar overlay was used to determine phage titers [P22 phage was amplified on e titers .2.3To study bacterial growth kinetics, LB media was prepared and inoculated with 50 μL of lag-phase secondary bacterial culture (OD<1) per 10 mL of the media. The cultures were then incubated at 37 °C with rotary shaking at 180 rpm. Measurements of bacterial density (OD) were taken periodically over the span of 48 h .2.4To study how pathophysiological conditions affect infection dynamics, phage kinetics assays were performed to observe phage kinetics at acidic pH and stationary phase. To study the effects of pH on phage infection dynamics, a phage kinetics assay was performed at varied media pH. The pH of the media was reduced from 6.8 utilizing Hydrochloric acid to either 6.0 or 5.5. Bacteria was inoculated into the media at pH 6.8, 6.0, and 5.5. Phage treated samples were inoculated with P22 phage at a MOI of 10 at the beginning of the experiment (lag phase).To examine phage kinetics in the stationary phase, BV4012  was grown in LB media until the OD was 10. The stationary phase cultures were then either treated with the phage P22 at 10 MOI or left untreated. OD values were obtained periodically over the span of 48 h.2.52O were made for these sets of experiments. Stocks were stored in a −20 °C refrigerator until usage. Several dilutions were prepared in serial fashion . A 96 well plate with 100 μL of Salmonella typhimurium culture with an OD of 0.1 in each well was inoculated with either one of the antibiotic dilutions or left untreated. The plate was incubated for 48 h at 37 °C and growth was measured through absorbance at 600 nm. The lowest concentration of antibiotic without bacterial growth was termed as the minimum inhibitory concentration (MIC) [The MICs of ampicillin and kanamycin were determined to establish the antibacterial activity of the respective antibiotics against Salmonella typhimurium strains (BV4012). Antibiotic stock solutions of 50 ug/mL in sterile ddHon (MIC) .2.6To study the effects of the antibiotic ampicillin or kanamycin on Salmonella typhimurium growth. LB media was prepared and inoculated with 50 μL of log phase secondary bacterial culture per 10 mL of the media. The cultures were then incubated at 37 °C with rotary shaking at 180 rpm. The OD of the bacteria was periodically measured against a media blank. The final concentrations of antibiotics in treated samples were either 50 μg/mL or 5 μg/mL were added at the beginning of the experiment (lag phase). To study the possible synergetic relationship between P22 phage and the antibiotics used, cultures were co-treated with an antibiotic and the P22 phage at MOIs of 10, 1, and 0.1 .2.7To determine the susceptibility of bacterial populations and developed resistance after exposure to the phage P22, BV4012 cultures were seeded into a 96 well plate  and inoculated initially with P22, ampicillin, or kanamycin. The OD600 was recorded over a period of 48 h. Bacterial cultures that showed developed resistance following 48 h of exposure to phage or antibiotic treatment were treated again with P22. The OD600 was recorded following rechallenge for 24 h.2.8AB and MICp22 are representative of the MIC values of the antibiotic used and the MIC value of P22. Values <0.5 were defined as synergistic, values between 0.5 and 4 as no interaction or additive, and values over four as antagonism.To study the potential synergy between ampicillin or kanamycin and the phage P22, the checkerboard assay was utilized. Salmonella typhimurium strain (BV4012) was seeded into a 96 well plate at an OD of 0.01 (50 μL/10 mL of media). Plate cultures were then inoculated with antibiotic and phage at respective concentrations and incubated at 37 °C while shaking at 180 rpm for 24 h. OD readings were taken at 600 nm using a plate reader (Biotek Cytation 3 Cell Imaging System). Fractional Inhibitory Concentrations (FIC) values were calculated using the formula ∑FIC = FICAB + FICP22 = (CAB/MICAB) + (CP22/MICP22) , 32. In 2.98 solution of P22 phage at pH 6.8, 6.0, and 5.5 were incubated at 37 °C. Samples of the solutions were collected and titrated against S. typhimurium.To study the stability of the phage P22 at varying pH, a 102.10BV4012 samples were treated with P22 phage, and the morphology and surface microstructure of the bacteria observed using scanning electron microscopy. Untreated BV4012 served as control. Prior to microscopy, the specimens were dried in a vacuum, and sprayed with gold using EMS Quorum (EMS 150R ES) ion-sputtering instrument and observed through Analytical Scanning Electron Microscope (SEM)  installed with IntouchScope software.Sample preparation for SEM was carried out as described by Li et al., 2021  with few2.11All experiments were performed on independent biological replicates. Statistical significance was determined for control and experimental groups using paired sample t-test. Data points were excluded if contamination was identified.3.3.19 pfu/mL. To determine the effect of P22 phage on Salmonella typhimurium culture (BV4012), cultures were infected with P22 phage at the MOI of 10 either in the lag-phase or in the mid-log-phase. The optical density (OD) was recorded using a spectrometer (Molecular Devices SpectraMax® ABS Plus) at various time intervals. S. typhimurium cultures treated with P22 phage showed a significant reduction in OD in the mid-log phase as well as an inhibition of growth at the lag phase within the initial 8 h following infection  cultures were then seeded into media at pH 5.5, 6.0, or 6.8 and then treated with P22 phage at 10 MOI. Optical densities recorded over 5 h determined that there was no functional loss of the phage in the acidic conditions and remained effective in reducing the growth of S. typhimurium  were treated with antibiotics at concentrations of 50 μg/mL, 5 μg/mL, 0.5 μg/mL, or 0.05 μg/mL and P22 phage at MOIs of 10, 1, 0.1, or 0.01 during the lag phase. The optical density of the samples was recorded over 24 h. In comparison to ampicillin treated S. typhimurium cultures, cultures treated with ampicillin and P22 at MOIs of 0.1 and 1 resulted in greater inhibition of growth than ampicillin alone over the span of 24 h . While this strain is ideal for our study, it may not translate to naturally occurring S. typhimurium infections with variations in growth rate. It was demonstrated that P22 is effective against S. typhimurium, however after extended exposure, the development of resistance raises concerns about the use of P22 phage and the threat of infection resurgence. Further study of the resistance mechanisms possessed by S. typhimurium against P22 phage is essential to gaining a full understanding of this interaction. While we showed that P22 is effective in vitro against S. typhimurium cells, we did not explore phage delivery methods in vivo. The delivery of P22 phage to the location of infection is essential to the success of therapy, and an area that requires further study. Another major challenge of phage therapy is the human immunological response. Studies show that there is an immunological response to phage treatments and that this response can be in ways synergistic in the elimination of acute and chronic bacterial infections [A limitation of our study is the use of fast-growing laboratory use fections –63.5.S. typhimurium. These conditions included lag-phase, log-phase, and stationary phase of S. typhimurium as well under various pH ranges (4–8). Additionally, we showed that P22 phage is effective killing S. typhimurium, and the phage seemed to perform comparably to standard antibiotic’s such as ampicillin and kanamycin in killing S. typhimurium. We examined the synergistic potential of P22 phage at MOIs of 10, 1, 0.1 and 0.01 with ampicillin or kanamycin at concentrations of 50 μg/mL, 5 μg/mL, 0.5 μg/mL, 0.05 μg/mL against S. typhimurium cultures. The best synergistic effect was observed at phage MOI of 0.1 and kanamycin concentrations of 0.5 and 0.05 μg/mL. Whereas the best synergistic effect was observed at MOI of 1 of P22 phage and 0.5 μg/mL of ampicillin co-treatment.In summary, we demonstrated the efficacy of the phage P22 under pathophysiological conditions associated with