Hypophosphatasia (HPP) manifests in adults as fractures/pseudofractures, pain, muscle weakness, and other functional impairments. Better phenotypic disease characterization is needed to help recognize disability and treat patients with HPP.Baseline/pretreatment demographic, clinical characteristic, and patient-reported disability/health-related quality-of-life (HRQoL) data from adults (≥18 y) in the Global HPP Registry (NCT02306720) were stratified by presence of overt skeletal manifestations  versus muscular/pain manifestations without skeletal manifestations (muscular/pain group) and summarized descriptively. Disability was measured using the Health Assessment Questionnaire–Disability Index (HAQ-DI), and HRQoL using the 36-item Short Form Health Survey (SF-36v2).P=0.047) but a lower median age at first HPP manifestation , with more signs and symptoms  and involved body systems  than the muscular/pain group. More patients in the skeletal group required any use of mobility aids . Six-Minute Walk test distances walked were similar between groups. SF-36v2 and HAQ-DI scores were similar between groups for physical component summary , mental component summary , and HAQ-DI .Of 468 adults, 300 were classified into the skeletal group and 73 into the muscular/pain group. The skeletal group had a higher median age at baseline (50.1 vs 44.4 y; Adults with HPP experience similar QoL impairment regardless of skeletal involvement.https://clinicaltrials.gov/ct2/show/NCT02306720 and https://www.encepp.eu/encepp/viewResource.htm?id=47907, identifier NCT02306720; EUPAS13514. Hypophosphatasia is a rare, inherited disorder that can affect the bones and teeth and can also cause muscular symptoms and/or pain in different patients. Data from many patients with hypophosphatasia have been entered into the Global HPP Registry. To learn more about the effects of bone symptoms and pain on quality of life, disability, and mobility in patients with HPP, registry data from 300 adults with bone symptoms were compared with data from 73 adults with muscular symptoms and/or pain but no bone symptoms. Results of this analysis suggest that hypophosphatasia caused considerable disability and lower quality of life, even in patients with no overt bone manifestations. In addition, patients with bone symptoms had experienced symptoms earlier in life than patients with muscular symptoms and/or pain and, therefore, had more severe symptoms possibly because of the longer time they had the disease. Some patients had experienced other complications of hypophosphatasia, including worsening in organ function and body systems, by the time their data were entered into the registry. These patients also more commonly relied on mobility aids, such as walkers, canes, crutches, wheelchairs, or scooters. Overall, patients with hypophosphatasia had more disability and lower quality of life than the general population. Because the complications of hypophosphatasia can change and progress over time, adults with this disease should meet regularly with their physicians and other health care providers to discuss the complications and how hypophosphatasia affects their lives.1Hypophosphatasia  is a rare, inborn, inherited metabolic disease caused by deficient activity of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP) , 3. BecaBecause HPP has a heterogeneous clinical presentation, misdiagnosis and delays in diagnosis often occur . In addiWhile skeletal manifestations and muscular/pain disease manifestations of HPP likely both contribute to poor function, disability, and reduced HRQoL in adult patients, the relevance of muscular pain/weakness in the absence of skeletal signs remains uncertain. Currently, only small case series and cross-sectional studies focused on the “bone phenotype” describe the impact of muscle pain/weakness among patients with HPP, and none discriminate between patients with and without overt skeletal signs –14. The 22.1The Global HPP Registry is an observational, prospective, multinational study that was initiated in 2014   or time of initiation of treatment with asfotase alfa.Baseline medical history data of eligible patients were analyzed. Baseline refers to the time of registry enrollment for patients who were never treated with asfotase alfa (Strensiq2.2ALPL (HGNC ID 438) variant (including only pathogenic/likely pathogenic variants and variants of unknown significance) were eligible for participation in the Registry regardless of age, age of HPP onset, or prior or current asfotase alfa treatment status.Patients with a diagnosis of HPP confirmed by serum alkaline phosphatase (ALP) activity that was under the age- and sex-adjusted reference ranges and/or had an Because HPP affects primarily the musculoskeletal system, patients were grouped into 2 phenotypic categories based on the expert opinion of the Registry Advisory Committee: patients whose phenotype included specific skeletal manifestations regardless of muscular and/or pain manifestations  and those with muscular and/or pain manifestations without skeletal manifestations (muscular/pain group). Skeletal manifestations were defined as medical history of rickets, osteomalacia (if a bone biopsy was performed), recurrent or poorly healing fractures/pseudofractures, any fracture, chronic bone inflammation, bone marrow edema, calcific periarthritis, pseudogout, chondrocalcinosis, ectopic calcifications, abnormally shaped chest, abnormally shaped skull, bowing of long bones in legs or arms, scoliosis, and/or club foot deformity. Muscular/pain manifestations were defined as the absence of any of the skeletal manifestations described above and with a medical history of chronic muscle or generalized body pain, weakness, abnormal gait, fatigue, fibromyalgia, bone pain severe enough to limit activities, and/or bone pain severe enough to require pain medication. Patients who had skeletal manifestations in addition to muscular issues/pain were assigned to the skeletal group. Patients who did not have skeletal or muscular/pain manifestations were excluded from this analysis.2.3via scores in 8 domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, social role functioning, emotional role functioning, and mental health  and HRQoL . The SF-36v2  is a generic 36-item questionnaire that measures HRQoL l health , 16. EacMobility was assessed by quantifying the use of mobility aids as well as through the 6-Minute Walk Test (6MWT). The 6MWT assesses ambulatory capacity by measuring the distance a person can walk on a hard, flat surface over a period of 6 minutes . The 6MW2.4Data are summarized using descriptive statistics. The n values with available data on respective measures may be different than the study population N values based on sign and symptom manifestations. Continuous variables are reported as median  and mean (standard deviation [SD]). Prevalence ratios and 95% confidence interval (CI) were calculated for HPP signs and symptoms by body system for patients with any skeletal symptoms compared with patients with only muscular and/or pain symptoms. Age of onset, number of signs and symptoms per patient, need for aid devices, and number of body systems affected per patient were compared between groups using the nonparametric Wilcoxon rank-sum test.33.1P=0.160) but a lower median age at earliest HPP manifestation (P=0.0473) than those in the muscular/pain group. At baseline, the median number of signs and symptoms per patient was higher in the skeletal group than in the muscular/pain group (P<0.0001). Similarly, patients in the skeletal group also had more body systems affected per patient at baseline (P<0.0001). The number of patients with dental signs and symptoms at baseline was higher in the skeletal group than in the muscular/pain group, particularly early loss of primary teeth . Most  patients in the skeletal group had muscle or pain symptoms.Of 468 adults in the Global HPP Registry with a confirmed HPP diagnosis, 300 had a phenotype that included skeletal manifestations , and 73 had muscular/pain without skeletal manifestations (muscular/pain group). A total of 95 patients were excluded: 37 had signs and symptoms that were not skeletal or muscular/pain in nature, and 58 had signs and symptoms that were skeletal or muscular/pain in nature but did not occur prior to baseline. Demographics and baseline characteristics are shown in 3.2HRQoL assessment, performed using the SF-36v2, was available for 238 patients . SF-36v2 summary scores are shown in 3.3P=0.22).Disability assessment data captured from the HAQ-DI questionnaire were available for 239 patients . Details are shown in 3.4P=0.001). Specifically, a larger proportion of patients in the skeletal group had used a walker, a cane, or crutches , and part-time or periodic use of a wheelchair or scooter was infrequent and exclusive to the skeletal group (1.4%). A minority of patients were wheelchair dependent at baseline in both groups .A comparative analysis of the use of assistive devices or mobility aids among skeletal and muscular/pain groups is shown in P=0.855). Overall, of patients who completed the 6MWT, 9 out of 41 (22%) in the skeletal group and 2 out of 5 (40%) patients in the muscular/pain group walked less than 400 m.Results from the 6MWT are shown in 4This analysis of adult patients in the Global HPP Registry suggests that patients with HPP can experience considerable disability and compromised QoL regardless of whether they have any overt skeletal manifestations of the disease. Because this analysis was cross-sectional, it is conceivable that, given the evolving and progressive nature of HPP, the muscular/pain group also may manifest overt skeletal signs over time , 5. CompBoth the skeletal group and muscular/pain group had similar 6MWT performances, disability factors other than physical functioning, and QoL measures. This comparable degree of disability and general QoL highlights the importance of including muscular issues and pain in the diagnostic workup of patients with suspected HPP. This approach has the potential to prevent a missed diagnosis or a misdiagnosis in patients with relevant disease burden devoid of overt bone manifestations and to promote better disease recognition in the clinical setting.Patients with HPP have been reported to have poor HRQoL resulting from heavy disease burden, including pain and disease manifestation in multiple body systems . This poIn the present study, the degrees of disability, as indicated by HAQ-DI scores, were similar between patients with and without skeletal HPP manifestations. These data suggest that the presence of skeletal manifestations is not the main or only determinant of poor function, disability, and reduced HRQoL in adults with HPP and that muscular/pain manifestations also play a role.The 6MWT is a reliable and valid measurement of functional capacity in children, adolescents, and adults with HPP . In patiThere was a preponderance of female patients in the study population assessed, so the proportion of female participants was slightly larger than in previous reports on other adult HPP cohorts. Considering the autosomal inheritance and largely balanced gender distribution in pediatric HPP cohorts, there is no reasonable pathophysiologic explanation for this preponderance. Potential reasons for this finding may include an enhanced health awareness and readiness among female patients to seek professional evaluation for nonspecific symptoms such as those frequently observed in adults with HPP. The larger proportion of females may also represent ascertainment bias because the data may reflect diagnosis in osteoporosis clinics; females undergo screening for osteoporosis and other medical check-ups more regularly than males, during which a low ALP level may be a coincidental finding. Another factor that may have contributed to the exceptionally larger proportion of females in this study, even when compared with retrospective adult HPP cohorts, may be an increased preparedness of females to participate in health-related scientific projects.There were a few limitations to this study. Because the Global HPP Registry is purely observational, with data collected from medical records during standard medical practice, there may be variations in the availability of data due to differences in standard of care from site to site and for different patients based on severity of disease. To mitigate issues due to data variation, all attempts were made to obtain missing data (including patient data at baseline) in the Global HPP Registry and to verify the accuracy of key parameters. Small numbers in some patient groups, particularly those in the muscular/pain group with the 6MWT data available, also may limit our ability to draw conclusions from these data. Registry data do not explicitly indicate whether patients were unable to complete the 6MWT, so data were available only for those who completed the assessment. In addition, the history of clinical manifestations, while obtained from medical records, may be influenced by recall bias if events were reported to the clinician by the patient. Long recall intervals may have reduced the accuracy of the data, particularly for those with less severe manifestations. Assessments used in this analysis focused on general disability and QoL, may not accurately capture the burden of disease for patients with predominantly dental manifestations, and may be affected by assessment not including all patients being assessed. Additionally, muscle or pain symptoms in the patients in the skeletal group could have impacted HRQoL and disability scores.5The results of this analysis show that adults with HPP, regardless of age of onset or overt skeletal involvement, experience serious disease burden. Patients with skeletal involvement appear to have a greater number of body systems affected than those with muscular/pain manifestations but no skeletal manifestations. Overall, these data add to the emerging understanding of HPP manifestation in adults, indicating that assessment of adults with HPP should regularly include assessment of muscular symptoms and pain in addition to skeletal evaluation.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.This study involved human participants and was reviewed and approved by the institutional review board  of participating study sites and is being conducted in accordance with International Conference on Harmonisation Good Clinical Practice Guidelines and the Declaration of Helsinki. All patients and/or their parent/legal guardians provided written informed consent and approval to release medical records before participation. The patients/participants provided their written informed consent to participate in this study.Conceptualization and methodology: KD, LS, PK, AP, WH, AL, GM-M, KO, SM, and CR-G. Data curation: KD, LS, PK, WH, AL, GM-M, KO, and CR-G. Formal analysis: SM. Writing – original draft, review, and editing: KD, LS, PK, AP, WH, AL, GM-M, KO, SM, and CR-G. All authors contributed to the article and approved the submitted version.


Rotator Cuff Related Shoulder Pain (RCRSP) is the most common type of shoulder pain and the most disabling common symptom in people with Rotator Cuff Tear (RCT). The patient’s point of view concerning health status has become important in decision-making procedures and has therefore been considered a possible criterion standard for assessing treatment efficacy. The study aims to explore patients’ experiences and perceptions during pre-admission for Rotator Cuff Repair surgery.A qualitative descriptive study was conducted using a phenomenological approach based on Husserl’s philosophical perspective. A consecutive sample of twenty RCT patients awaiting repair surgery agreed to participate and was interviewed until the information was saturated. None of the patients enrolled was lost during the data collection phases. Data were collected through open-ended interviews between December 2021 and January 2022. The credibility, reliability, confirmability, and transferability criteria of Lincoln and Guba have been adopted to guarantee the trustworthiness of the results. The data analysis was conducted according to inductive content analysis.Four main themes and sub-themes related to each have been identified from the phenomenological analysis. The major themes were: (1) Pain changes lifestyle habits, (2) Pain control requires specific strategies, (3) Suffering turns time into waiting, (4) Waiting for Surgery between trust and fear.Investigating patients’ experiences and the emotional impact of Rotator Cuff Tear facilitates the development of specific educational and therapeutic strategies to improve care and post-intervention outcomes. Rotator Cuff Tear (RCT) is one of the most common shoulder disorders in people between 60 and 80 years , 2. RotaIn orthopaedic patients, pain is usually assessed as current pain severity on a Likert-style scale or Visual Analog Scale (VAS). However, these scales have limitations since they do not consider the complexity of the individual’s pain experience . TherefoScientific evidence also focuses on evaluating preoperative psycho-social factors as they could influence functionality, disability and perceived pain in patients with RCT . BesidesCurrently, the literature investigating patients’ experiences, perceptions and points of view with RCT is poor, and many aspects of the disease are analysed only by quantitative scores. However, the inter variability of the pain perception could alter the results.Qualitative research could represent the best choice for understanding patients’ needs and could improve the use of targeted and personalised therapeutic strategies , 13, 14.Therefore, it is necessary to conduct studies that assess the qualitative perception of pain and functionality in RCT, obtaining a different point of view on the topic as it could allow for more personalised therapies.The study aims to explore patients’ experiences in pre-admission for Rotator Cuff Repair surgery.A qualitative descriptive study  was condThis phenomenological approach was chosen as it allows for the acquisition of content-rich experiences, perceptions, emotions, judgments, perspectives and visions of the world of the patients involved in the study . PhenomeA consecutive sample of twenty RCT patients awaiting repair surgery agreed to participate and was interviewed until the information was retrieved. None of the patients in the sample was lost during the data collection phases, and all twenty enrolled patients completed the interview. After each day of interviews, a saturation grid was used to define data saturation, hence the term of enrolment, indicated by the absence of meaningful information provided by new respondents .To ensure the adequacy and quality of the sampling strategy  patientsData were collected through open-ended interviews between December 2021 and January 2022 at the Department of Orthopedic and Traumatological Surgery of the Campus Bio-Medico University Hospital of Rome, Italy. The interviews were scheduled according to the pre-admission list for surgery. All interviews were conducted in hospitals . The interviews lasted 5 to 15 min and were digitally audio-recorded and transcribed verbatim.Before starting the interview, the main themes of the study were explored, the researcher encouraged the interviewees to narrate freely in response to the questions, and the consent was signed.The questions were designed to allow respondents the flexibility to direct the flow of the conversation and structure it to ensure critical topics were addressed.The following questions were asked: Can you tell me about your health problem? What changes  did it bring about in your life? What are your fears (emotions/thoughts) about the future of your illness? How do you sleep? How is the quality of sleep? Would you like to add more?All twenty participants answered the abovementioned questions in a free-form response mode.The data analysis followed the steps outlined by Giorgi’s descriptive phenomenological method  and was For the first step, the researcher who conducted the interviews performed the collection of verbal data, while a second researcher transcribed the verbatim, noting pauses, gestures and emotions (pointed out in the field during the interview) to reflect the meaning of words and preserve the accuracy of verbal data collection. During the second step: reading the textual data in its entirety, the researchers kept an open mind to get a general sense of the information gathered rather than trying to thematise any aspect of the descriptions. In the third step: splitting the data into parts, once each researcher gathered a general sense of the material, the data was divided into two parts, and the text was carefully reread line by line to identify the “units of meaning”, defined as distinct units that express an autonomous meaning . In the A senior researcher experienced in qualitative research oversaw all phases of the analysis, and the research team discussed all discrepancies until a unanimous agreement was reached.For this study, the researchers did not use specific qualitative data analysis software, preferring the transcripts on grids and tables built for group analysis and discussion of each step.To guarantee the trustworthiness of the results, credibility, reliability, confirmability and transferability, the Lincoln and Guba criteria were adopted . To ensuThe study was conducted according to the Declaration of Helsinki . It was Eligible patients were contacted by telephone during their pre-admission day. They received verbal information on the study’s purpose, the interview modality and the need for a digital audio recording. They were also informed that their contribution to the study would be voluntary and free and that the data collected would be analysed and reported in a way that ensures confidentiality. All participants then signed informed consent for this study’s adherence before data collection. Anonymity was guaranteed through an identification code during the transcription of the interviews and the entire data analysis process, ensuring that no single participant could be traced in the reporting study. Participants were also told they could withdraw from the study at any time.A sample of twenty patients, 12 male and 8 female, with a mean age of 58.4 years, in the pre-admission phase for RCR surgery, agreed to participate and were interviewed.The participants’ clinical and demographic characteristics are described in Table Four main themes and sub-themes related to each have been identified from the phenomenological analysis , 26. TabPain is undoubtedly the dominant symptom with pain in the shoulder and arm, common to all patients from the onset of the disease and is responsible for the most significant changes that patients experience. The beginning of the disease can be acute and traumatic following falls on the ground, loss of balance, direct trauma on the affected arm, or secondary to other pathologies such as osteoporosis or repetitive work activities. According to this distinction, the pain can be perceived as very acute and excruciating, like a stab or a sensation of continuous discomfort.In any case, it is a persistent pain at a precise point that necessarily affects normal daily activities, has a negative impact even in activities during work, and upsets the hours of sleep.“(…) the world changed overnight.(…) I cannot do daily activities, and consequently, problems arise” .Therefore, this theme has brought out three sub-themes described below: restriction or inability to move, poor sleep quality, and dependence on others for basic needs.Most interviewees reported that pain generates severe limitations in arm movements (such as lifting or holding things) which they consider a very penalising event. To overcome the limitation, some claim to physically exert themselves and perform calibrated and studied movements to limit the pain.“I can’t do many things anymore” .Interviews show the strong negative impact of RCT and related pain on sleep. Patients cannot sleep well at night; they sleep very little, suffering through the night. Sleep problems are different; some complaint of repeatedly waking up every time they move in bed. Others complain of not being able to fall asleep because of the pain. Conversely, some do not find an “analgesic” or comfortable position that relieves shoulder pain. In any case, the quality of sleep is impaired, it is judged to be just sufficient, and sleep is not regenerating, negatively impacting waking hours.“It is awful [the quality of sleep], I usually sleep on one side and change sides often at night, and therefore the right side is penalised, and it is difficult to find the position to fall asleep at night, then naturally I collapse from fatigue, but often I wake up, or I wake up at night with shoulder pain” .The condition of pain and severe functional limitation implies the dependence on other people for assistance even in simple, everyday life. It highlights the need for help that these patients express. If carried out independently, daily activities require physical effort and sacrifice and are not carried out as they should be. The activities that need someone’s help are the simplest: getting dressed, washing, eating, simply fastening the bra, driving, cleaning the house, washing clothes, and putting your hair behind your ear.Due to the condition described, patients perceive a state of incompleteness, insufficiency, incapacity, and suffering, and their desire is exclusively to regain all functionality.“Lots of difficulties because when the pain becomes acute, I can’t even get my panties up, button up my bra, normal life things, take a plate from the dish drainer. So be addicted to so many things. It was awful” .All interviewees stated the need to adopt appropriate behaviour and pay attention to controlling pain. This allows them to continue to carry out their daily or work activities, albeit with limitations.Patients’ strategies are the most varied and sometimes very personal, including adopting certain antalgic positions. They also resort to drugs or physical therapies depending on the doctor’s prescription.“I find some relief even if the pain is always in the background” .Each patient interviewed mentioned having adopted personal and autonomous interventions to cope with pain in the various phases of the day and to try to lead an everyday life.The most adopted strategy is undoubtedly to help the sore arm with the other healthy one, particularly those affected by the dominant arm, help with the contralateral, or replace the use of the affected arm with the healthy one, learning new skills.Some adopt positions that relieve pain during the day, such as extending their arms from the sofa and sleeping on the side of the painful shoulder at night.Other strategies are inherent in the specific case. For example, one patient said she found relief in sandblasting; another interviewee bought special pyjamas to keep the affected shoulder warm, and another changed pillows until she found relief during the night.“At the beginning, when I had the first symptoms. I even had to accompany the right arm with my left arm” .Before deciding in favour of surgery, some patients also adopted different strategies following the prescriptions of the doctor they contacted. These prescriptions covered infiltrative therapy, pain-relieving drugs, and anti-inflammatory physiotherapy.“I tried palliatives, anti-inflammatories, and physiotherapy” .This theme contains the thoughts, emotions, and feelings that accompany patients from the moment they are affected and discover the first difficulties related to pain but underestimate the problem believing that they can continue to move on with life until the waiting is filled with hope and impatience of the surgery, the only solution to the problem.Plight and suffering are the factors that increase daily and project all hopes in RCR.“I find the situation dramatic” .Generally, patients in an initial phase tend to need to pay more attention to the extent of the problem. They try to continue to carry out all their usual activities while neglecting the initial pain. This happens especially when the injury does not manifest in an acute and traumatic way, and the discomfort can be endured for months.This initial underestimation also leads to postponing the intervention several times, believing it can be resolved without it.“It started with small pains (…) at first they were very mild and then slowly they began to increase. Then they went in periods, that is, a month I had it, and a month they disappeared, and in winter, I noticed that this was when I felt it the most. And now the pain has become more intense “ .As mentioned, pain and functional limitations are common to most patients and are the manifestations that cause the most discomfort. In particular, the patients interviewed described pain from an emotional and psychological point of view, generating negative feelings and is described as suffering, a disaster, a mortification that creates nervousness and fatigue.“Psychologically, it knocked me down” .Most interviewees say of arriving when it becomes inevitable to find a solution, to decide to face surgery: to make a choice. The decision to act is often postponed for fear of post-operative recovery, for personal accident causes, or hoping that everything will be resolved without any external intervention. In the moment of choice, their perception of time changes. You realise that time passes, and you must take action to improve your health. Underestimation turns into expectation.“I can’t wait to be operated on” .RCR is regarded by all respondents as a lifeline and generates mixed feelings. Common to most interviewees is the total trust placed in surgeons, their teams and the hospital. All the hopes of the patients are poured into the intervention: the success of the surgery, which will prevent the recurrence of this episode in the future and take them back to their previous life and the disappearance of pain.“I hope everything is fine and the arm is fine again, as it was before.“ .All the patients interviewed showed that they understood the need for surgery. The session with the orthopaedic surgeon during the pre-admission phase is crucial, as patients are informed about the type of arthroscopic surgery. This news brings positive feelings and much confidence. Despite their living conditions, patients perceive arthroscopy as low-impact and minimally invasive. This perception generates positive feelings about the surgery, and the patients are calm. The only fear shown on the subject relates to the fear of anaesthesia.“I’m going calmly. I’m calm; it’s not an important operation” .Despite the expressed optimism about the type of surgery, patients show post-surgery fear.The biggest fear is that of not resolving, not being able to return to everyday life and not improving the limitations from which they are suffering. This thought generates profound uncertainty. Most interviewees give significant importance to postoperative rehabilitation and plan how to deal with that period: wearing the brace for a month, taking a month of almost complete rest and paying close attention to movements.“Rehabilitation is important because if I don’t do the rehabilitation well, the surgery will not be as good as it should be” .Our themes and sub-themes of the phenomenological analysis show that most patients undergoing to RCR described acute pain, severely disturbed sleep, limitation or inability to move, dependence on others for basic needs, and fear of not being solved. The negative impact of an RCT on the activities of daily life, work and adaptation strategies put in place to continue activities as normally as possible were analysed. Optimism and confidence for arthroscopic surgery were emphasised.To our knowledge, the current study explores a topic that does not have extensive supporting literature. Minns Lowe CJ et al. described people’s experiences with symptomatic RCT, their symptoms, the impact on their daily life, and the coping strategies used by patients . HoweverThe present study’s first main and most relevant theme is “Pain changes lifestyle habits”. Pain is the most common and disabling symptom in all patients with symptomatic shoulder disease –5, 13. TThe second theme is “Dependence on basic needs”. Care dependence can be related to suffering and humiliation . The patThe third main theme is “Suffering turns time into waiting”. Not all patients have an acute and traumatic history of the disease. Sometimes the pain is described as a nuisance because it derives from chronic conditions. Therefore, with some effort, patients manage to carry out most of their daily activities, even work and underestimate the problem, believing that they can carry on with life, and they end up exhausted. Due to the pressing limitations they suffer daily, physically and mentally, they do not realise that surgery is the only solution. In this phase, patients experience a climate of anticipation and profound uncertainty.The final central theme that emerged is “Optimism and confidence for arthroscopic surgery”. Evidence shows that arthroscopic RCRs improve patients’ quality of life and related disorders such as sleep , 29, 30.The limitations of this study could be due to the generalisation of the results. As the study was conducted in Italy with Italian participants, countries with other cultures and habits could present differences. Therefore, future research should explore whether and how patients’ experiences change after RCR, even retrospectively, to gain a broader view. This knowledge could support the development of specific educational and therapeutic strategies to improve care.The study showed, through the experiential analysis of the experiences of the patients interviewed, the negative impact of RCT on different aspects of daily life. The topics most discussed in the interviews are acute pain, severely disturbed sleep, limitation or inability to move, dependence on others for basic needs, and fear of not resolving the problem. Arthroscopic surgery appears to significantly impact the uncertainty experienced by patients waiting for surgery. Patients who become aware of this type of intervention tend to be calmer and more confident about a faster recovery.The experiences described in the study could offer helpful insights for patient preoperative assessment and help healthcare professionals analyse and understand the power of the emotional, personal and social impacts of symptoms on RCT patients. This would ensure that patients needing help for emotional conditions such as fear, depression or extreme addiction are identified early and appropriate support, education and treatment are ensured.


Introduction: Transplanting a tooth from one area of the mouth to another is known as autogenous tooth transplantation. It is a great choice for restoring young patients' teeth with developing alveolar bone because it uses the patient's own tooth as the replacement rather than a false one. This study aims to evaluate pain, infection, mobility, resorption, ankylosis, and success rate in the replacement of mandibular non-restorable molars through an immediate autotransplantation of the nonfunctional impacted mandibular third molar.Materials and methods: In this in vivo study, 20 patients between the ages of 22 and 50 were selected. The cases in which the first or second mandibular molar was nonrestorable and had an impacted third molar for transplantation were selected. In all the cases, the nonrestorable molar was extracted and replaced with a nonfunctional, impacted third molar. All the cases were evaluated for pain, infection, mobility, ankylosis, and resorption at the postoperative second week, one month, third month, and six months. The pain was assessed on the visual analog scale (VAS), infection was assessed by the presence of purulent discharges, mobility was assessed on a clinical examination of tooth movements, ankylosis was seen radiographically as the obliteration of the periodontal ligament space, and the absence of the lamina dura and resorption were seen radiographically as radiolucency on the root surface. All the readings were tabulated and statistically analyzed.Results: Pain was seen to be maximal at two weeks and minimum at six months. Infection was not seen at all time intervals. Mobility was reduced with time. There was no significant ankylosis or resorption. Out of the 20 cases, four patients required extractions due to resorption and grade 3 mobility. One patient showed ankylosis. The success rate of the autotransplantation was 75%. Fifteen patients showed well-defined lamina dura without ankylosis or resorption.Conclusion: Autotransplantation is a valuable tooth replacement option and more economical, especially when provided with proper case selection. Abulcasis was the first to report autotransplantation in 1050; nevertheless, the first recorded operation describing tooth bud transplantation did not occur until 1564, when it was conducted by a French dentist named Ambroise Paré. John Hunter, a pioneer in the field of dental transplantation and reimplantation, first demonstrated the tooth-to-tissue bonding properties of a human tooth hetero-transplanted into a cock's crest in 1771 [There are three categories that may be used to describe tooth transplantation: autogenous, homogeneous, and heterogeneous. A tooth or tooth bud can be transplanted in three different ways: autogenously, when one person's tooth or bud is placed into another person's socket; homogeneously, when one species' tooth or bud is placed into another species' socket; and heterogeneously, when one species' tooth or bud is placed into another species' socket . When itTooth agenesis, especially of the premolars and lateral incisors, traumatic tooth loss, atopic eruption of canines, root resorption, extensive endodontic lesions, cervical root fractures, and localized juvenile periodontitis are some of the other disorders for which transplantation may be a possibility -12. RegiThere are very few studies that have studied the success rate of impacted mandibular molar autotransplantation . Hence, This research is a cross-sectional analysis of real-life samples. Twenty cases were chosen from those reported to the Division of Oral and Maxillofacial Surgery. The patients' ages ranged from 22 to 50, with a mean of 36 years old, seven men (35%) and 13 women (65%). The research was conducted over the course of 112 years (from September 2016 to March 2018) at Bharati Vidyapeeth Dental College and Hospital in Sangli, India. Ethical clearance was obtained to carry out the study (BVDCMC&H/Sangli/IEC/Dissertation 2015-16/160).The inclusion criteria include patients with an age group of 22-50 years, male and female individuals; patients having an impacted mandibular third molar that can be extracted without sectioning; non-restorable mandibular first or second molars having approximately the same or more size; the size of donor and recipient molars being approximately the same; donor tooth having complete root formation; and physically and mentally fit patients without any known source of infection in the oral cavity. Simple mesioangular impacted molars that can be removed without splitting are selected. The exclusion criteria included patients with systemic diseases , donor teeth with incomplete root formation, and unwillingness or inability to be followed up for radiographic and clinical examination.Twenty individuals were chosen for this in vivo cross-sectional investigation, It was a time-bound study done for 1.5 years. The cases reported in this tenure were selected and randomly divided, all of whom had impacted third mandibular molars and were missing either their first or second permanent molars. The patient's medical history was well documented, and their informed consent was obtained prior to any surgical procedures. Regular blood tests were required for the patients. All procedures were performed by the same operational surgeon using the same equipment and local anesthetic . Before the surgery, panoramic X-rays were taken to ensure that all third molars were in the correct position and had fully developed roots. All patients were set up for surgery in accordance with standard operating procedures. A 2% lignocaine hydrochloride solution with a 1:80,000 adrenaline solution was used to provide a pterygomandibular block. A tooth that could not be saved was removed. In all the cases, the inter-radicular bone had to be removed from the recipient site, and more bone had to be removed from beyond the apex to provide a tension-free apical cushion. To prevent early occlusal interactions, the transplant was placed at or slightly below the occlusal plane owing to the apical preparation.A full-thickness mucoperiosteal flap was mirrored via a Ward's incision. The incision started below the buccal sulcus. An incision was performed at the gingival border of the upper right second molar, starting at the distobuccal line angle. The incision was then made from the cervical region behind the second molar to the distal midpoint of the tooth. From there, a rearward buccal incision was made along the exterior oblique ridge. The mucoperiosteal flap's full thickness was mirrored using a periosteal elevator Figure .Using a straight elevator, the impacted third molar was loosened before being removed using molar forceps and very little pressure. To flush out the incision and eliminate any remaining debris, a sterile saline solution was gently injected into the area. The tissue edges were given a new lease on life. After the impacted tooth was extracted using the routing minor surgical kit, the prepared socket of the non-restorable tooth was used to place the extracted tooth. If the recipient site needed to be further prepared after the third molar was transferred from the donor site, a bone trimmer was used to prepare the socket for reimplantation. It was placed between two gauze pads saturated with a normal saline solution. It was mandated that you take extra care not to touch the root sheath or any of the surgical tools. In cases where the transplanted molar was at risk of making a premature occlusal contact, the recipient site was further prepared. Positions 1-2 mm below the occlusal plane were regarded as optimal, but no occlusal modifications were made. No. 3 silk sutures or composite strips were used to stabilize the transplanted third molar and prevent it from moving vertically. The reimplanted tooth was splinted to an adjacent tooth with an 18-gauge wire and composite. The donor's tooth had its gingival flap securely closed over it. Sutures were used to seal the extraction socket of the donated tooth. When initial stability was not attained, only then did we resort to wire fixing  and antibiotics (amoxicillin 500 mg t.i.d. (three times a day), Metrogyl 400 mg t.i.d.) were administered orally to all patients. Advice on maintaining good dental hygiene and a liquid-only diet was advised for the first two weeks. After a week, the sutures and wire were taken out. After the third molars were transplanted, they were held in place with a wire splint or silk suture for two to three weeks. Closed apex molars were treated regularly with root canal therapy after one month. All the cases were evaluated for pain, infection, mobility, ankylosis, and resorption at postoperative two weeks, one month, three months, and six months. The 47 tooth was extracted in the figure given below and replaced with the 48 tooth Figure .The severity of the pain was measured using a visual analog scale (VAS) with ratings of 0 (no pain), 1 (very little pain), 2 (some discomfort), 3 (moderate pain), and 4 (intense pain). The presence of infection was assessed based on the presence of purulent discharge and recorded as present-p or absent-a. The degree of tooth mobility was clinically assessed by holding the tooth firmly between the handles of two metallic instruments or by using one metallic instrument and one finger. The radiographs of a patient with ankylosis revealed a lack of the lamina dura and a closure of the PDL gap. Both present-p and absent-a notations were made. A radiographic examination of the root surface revealed radiolucency, indicative of resorption. Both present-p and absent-a notations were made. Success evaluation criteria are commonly utilized in published works -12. At tStatistical analysisThe readings were tabulated and statistically analyzed by IBM SPSS Statistics for Windows, Version 22 . The pain was assessed by Friedman and Wilcoxon signed-rank tests. Mobility, ankylosis, and resorption were assessed by the chi-square test.The descriptive statistics for pain are shown in Table The average pain score was 2.72 at two weeks and 0 at six months, with pain being at its highest and lowest points during those times  . In thisThe study has certain limitations, such as the limited sample size, and further research over a longer period of time is required to fully understand the findings.A dependable method of replacing missing teeth is the third molar autotransplant technique. The surgical procedure must be as painless as possible in order to protect the PDL of the tooth that will be transplanted. The root's level of development is also related to the likelihood of success, with a fully grown root having a worse prognosis. In India, immediate third molar autotransplantation is a feasible and effective treatment option to replace a tooth that cannot be saved.


The patient reported a positive experience with cryoneurolysis for toe clawing and dorsal foot pain.Toe clawing in patients with upper motor neuron disorders is often attributed to the flexor digitorum longus (FDL) and is a common presentation among patients with multiple sclerosis (MS). This movement may be painful because of the altered pressure distribution and may increase the risk of falls, heighten energy expenditure during gait, and lower gait speed. Cryoneurolysis is a minimally invasive treatment that may be beneficial for pain and focal muscle hypertonicity. An ambulatory patient with MS was treated bilaterally with cryoneurolysis to the superficial fibular nerves for pain on the dorsum of the foot, and to the intramuscular tibial nerve motor branch to FDL for toe clawing. The patient felt that toe clawing was immediately reduced during gait and noted the ability to voluntarily spread their toes. The patient stated that the neuropathic pain on the dorsum of the foot was fully eliminated immediately post procedure. The patient reported improved confidence in their gait, maintained independence, and reduced toe clawing during a structured interview 12 weeks after treatment. The effects lasted for 5.5 months before symptoms returned. Retreatment at 6 months reproduced the benefits Patients with multiple sclerosis (MS) are prone to both altered movement patterns and pain.,Cryoneurolysis is a minimally invasive procedure that involves the generation of an ice ball at temperatures ranging from -60 to -88 °C depending on the freezing agent. Under ultrasound guidance, a specialized probe used for cryoneurolysis (cryoprobe) is used to create an ice ball from interstitial fluid near a peripheral nerve causing secondary axonotmesis.A 50-year-old woman with MS of more than 20 years had long standing pain on the dorsal aspect of both feet and dystonic toe clawing with associated cramping on standing and walking. There was no appreciable spasticity in the toes with a passive range of motion assessment in the resting position. She has a 10-year history of bilateral botulinum toxin (BoNT) injections to the FDL (50 units of incobotulinum toxin per side). For her neuropathic pain, she used 150 mg of pregabalin 3 times a day, nortriptyline 10 mg every night, and 60 mg of duloxetine daily. The medications assisted with pain in other areas of her body as well. She reported partial relief from toe clawing for up to 10 weeks after BoNT injections, but no change in foot pain. She had reduced vision and used a visual impairment cane at times.This study follows the Case Reports (CARE) guidelines and reports the required information accordingly. Institutional research ethics board approval was not required. Informed consent was obtained for the procedures and for the preparation of this manuscript.On clinical examination, the FDL was determined to be implicated in the toe clawing and was therefore identified as a potential target for cryoneurolysis. The flexor hallucis longus was determined not to be a significant contributor. The tibial nerve intramuscular branch to FDL was visualized on ultrasound; electrical stimulation was used to confirm the target refer to , Fig 2. Sensory innervation to the dorsum of the foot is provided by the superficial fibular nerve. This pain generator was chosen as the target to address the patient's primary pain. The superficial fibular nerve was visualized on ultrasound and a DNB was performed to hydro dissect the nerve 15 cm distal to the fibular head refer to .Fig 3PerThere was no undesirable loss of sensation or function because of the DNBs; no adverse events were reported during or immediately after the treatment.a This is a free-standing unit that uses liquid nitrous oxide capsules. After the effects of the lidocaine waned, the skin around the injection site was prepared with chlorhexidine swabs to lower the risk of infection. The entry point was anesthetized with a local infiltration of 1% lidocaine. A 16-gauge angiocatheter was inserted to guide the cryoprobe, to increase ultrasound echogenicity, and to protect the skin from potential cold-related adverse events. The cryoprobe was inserted through the catheter and the target nerve was located using known anatomy, as established during the DNB. For the intramuscular motor branch to the FDL, the target was confirmed prior to each cycle using electrical stimulation of less than 1 mA at 1 Hz. Two lesions were created along the intramuscular FDL branches  allows for extremely precise localization and treatment that further reduces the risk of undesirable weakness or sensory loss from poor localization. Finally, the use of a DNB prior to cryoneurolysis likely reduces the risk of adverse events from poor specificity by informing treatment decisions before any long-lasting intervention is applied. This process complements the clinical evaluation to ensure that only nerves innervating muscles that are directly implicated in the pathology are treated.Cryoneurolysis has been well tolerated by most patients with adverse events being described as mild in severity.The described case reports on the experience of a single patient and is not generalizable to the entire population of patients with MS with toe clawing and neuropathic pain; MS is a progressive and diverse illness that is unique to each patient, leading to varying responses to treatment. Further research should validate objective measures of treatment efficacy for dystonic toe clawing. Future studies should include well-designed randomized controlled trials to understand the efficacy of this treatment compared with other options.Bilateral cryoneurolysis of the tibial nerve intramuscular branch to FDL, and of the superficial fibular nerve were performed for toe clawing and dorsal foot pain in a patient with MS. The patient reported a positive experience with cryoneurolysis when interviewed 12 weeks after treatment, which lasted to five and half months before retreatment was required. Further studies are required to understand the efficacy of this treatment.a. Iovera 190 Smart Tip; Pacira Bioscicences


Shoulder pain is a common clinical problem after laparoscopic surgeries. The use of non-pharmacological massage and transcutaneous electrical nerve stimulation (TENS) as an adjunct to routine treatment is increasing to provide optimal pain relief. Therefore, we aimed to determine the effect of TENS and massage therapy on post laparoscopic shoulder pain (PLSP).This study was conducted on 138 patients who underwent laparoscopic cholecystectomy. Patients were randomly divided into three groups: massage plus conventional pharmacological treatment (n = 46), TENS plus conventional pharmacological treatment (n = 46), and conventional pharmacological treatment (n = 46). Massage and TENS were performed three consecutive times after the patients regained consciousness in the inpatient wards. The intensity of Shoulder pain was evaluated using a visual analog scale before and 20 min after each treatment.Both massage therapy and TENS led to a significant reduction in the intensity of PLPS compared to the control group in all three measured times (p < 0.001). However, no significant difference was observed between TENS and massage at any of the three-time points.This study’s findings demonstrated that massage and TENS techniques could reduce PLSP.www.irct.ir) in 05/02/2022 with the following code: IRCT20200206046395N1.Registered in the Iranian registry of clinical trials ( Laparoscopic cholecystectomy is the standard procedure in gallbladder surgery . AlthougVarious approaches have been investigated to relieve PLSP following laparoscopic cholecystectomy. In some studies, different surgical techniques, drainage, respiratory approaches , drugs sMultifaceted methods for pain relief are essential due to the complex pain mechanism after laparoscopic cholecystectomy . Non-pha“Therapeutic massage is the manipulation of the soft tissue of whole body areas to bring about generalized improvements in health, such as relaxation or improved sleep, or specific physical benefits, such as relief of muscular aches and pains” . It is aIn addition, transcutaneous electrical nerve stimulation (TENS) as an essential strategy in interventions and clinical approaches for analgesia and its side effects due to unique benefits such as ease of use, efficiency, inexpensiveness, and low risk is increasing. TENS uses batteries and electrodes on the skin based on the adjusted frequency and pulse width by providing alternating current for various therapeutic purposes . TENS haAlthough various techniques have significant effects in reducing PLSP, to our knowledge, no previous research compared these two interventions, massage therapy and TENS, for the relief of shoulder pain after laparoscopic cholecystectomy. Considering the prevalence of 63% of shoulder pain after laparoscopic cholecystectomy and the increase of patients who complain of PLSP , it is nThis study is a prospective, randomized, single-blind, parallel controlled, and triple-arm clinical trial. It was conducted on 138 patients with gallstones treated with laparoscopic cholecystectomy at Imam Reza Hospital, affiliated with Kermanshah University of Medical Sciences, Iran. Eligible patients were selected from February 2022 to August 2022. They were randomly divided into three groups, including massage (A), TENS (B), and control (C). The ethics committee of the Vice-Chancellor of Research approved the study at Kermanshah University of Medical Sciences (Code: IR.KUMS.REC.1400.757). It was registered on the Iranian Clinical trial Registry with identification number IRCT IRCT20200206046395N1 (registration date: 05/02/2022).The inclusion criteria for patients were:Undergoing laparoscopic cholecystectomy surgery.Visual Analogue Scale (VAS) shoulder pain score at baseline (within 3 h after surgery) ≥ to 3.Class I or II physical conditions based on the American Society of Anesthesiology (ASA).No history of mental, motor ,or cognitive disorders according to medical records.Lack of shoulder pain before surgery.The exclusion criteria were:Age under 18 years and over 60 years.Addiction to painkillers and sedatives.Ulcers, phlebitis, trauma ,and arthritis in the massage area.Contraindications to TENS such as pregnancy and internal pacemaker.After a pilot study on 30 participants (10 in each group), the minimum number of samples based on a 10-point pain scale 4 h after cholecystectomy using the mean and standard deviation (3.83 ± 1.94 in the control group and 5 ± 1.67 in the intervention group) was identified. By accepting α = 0.05 and a power of 80%, the standard sample size for each group was calculated as 38 patients . Considering a 20% drop rate, 46 participants were included in each group   was prescribed 15 mg/kg/dose every 8 h according to our standard organizational protocol to relieve postoperative pain. In addition, patients received intramuscular Pethidine 25 mg/mL at regular intervals in case of more severe pain.Both massage therapy techniques and TENS were performed at regular intervals of 4, 8, and 12 h after surgery by a trained individual and under the supervision of a physiotherapist. The interventions lasted 30 min in a quiet environment away from noise .In addition, to avoid bias, in all groups, the researcher attended during the study at the mentioned times, and asked the participants to lie on the bed for 30 min in a supine position with their head at a height of 30 Degree headrest.The massage was performed in the first intervention group using this protocol:The masseur washed his hands thoroughly and dried them with a towel. He applied massage on the patient’s dominant hand using kneading-friction-petrissage techniques. The wrist was held in one hand, and with the other hand, the massage started with direct pressure from the base of each finger and circularly continued to the tip. The palm was kneaded with C-like movements and firm pressure in alternating directions, then the back of the hand was stretched with forward movements from the wrist to the base of each finger. Around the wrist bones, the massage continued with circular movements of the thumbs clockwise and then counterclockwise. While the patient’s arm was lying flat on the bed, the therapist’s palm was used for upward movements from the wrist to below the elbow and downward movements from the elbow to the wrist. Finally, the massage ended with gentle twisting movements of the forearm Fig. . PatientPetrissage Massage: Apply direct pressure slowly and rhythmically with the fingertips.Friction Massage: Rubbing in small areas in a circle where the masseur presses the area with the front of the fingertips or the front of the palm.Kneading Massage: It is similar to twisting and changes the compression direction in succession .Patients in the second intervention group received TENS. Initially, the researcher watched the skin of the scapula and shoulders to ensure that no foreign objects obstructed the attachment of four electrodes (5 cm x 10 cm). Then the electrodes were placed on the skin in the area of trapezius muscle and scapula, in both sides of the shoulders, parallel to the spine Fig. . After pParticipants’ data, including demographic and clinical characteristics, were collected using two parts form and multiple-choice questions.In Its first part, age, sex, education and previous history of abdominal surgery were recorded one day before the operation.1: 20 min before the start of the first intervention, T2: 20 min after the first intervention, T3: 20 min before the start of the second intervention, T4: 20 min after the second intervention, T5: 20 min before the start of the third intervention, T6: 20 min after the third intervention.In the second part, duration of surgery, duration of anesthesia, amount of analgesia used during the intervention and severity of PLSP were assessed by the outcome assessor, unaware of the type of interventions and randomization. According to the beginning of the first, second and third interventions at 4, 8 and 12 h after cholecystectomy, pain was recorded six times. TData analysis was conducted using the SPSS 25.0 software. In the present study, Data normality was confirmed using the Kolmogorov-Smirnov. ANOVA analysis of variance compared quantitative variables in three groups. Also, the variables of gender, education, and history of previous abdominal surgery were evaluated with the Chi-square test. In each group, ANOVA with repeated measures was used to compare the trend of changes in the severity of PLSP at 4, 8, and 12 h after surgery. P-value < 0.05 was considered significant.This study was conducted on 138 patients with a mean age of 43.19 ± 11.3 years after laparoscopic cholecystectomy  Table .Comparing the two groups regarding changes in PLSP intensity showed that the effect of massage therapy and TENS was more significant than the control group (p < 0.001). However, there was no significant difference between the two interventions of massage therapy and TENS at any time Table .In addition, Mauchly test confirmed the assumption of sphericity of the data. ANOVA with repeated measurements showed a significant difference between the three groups in the average intensity of PLSP after the intervention. Hence, the relief of pain in the intervention groups was more than the control group (p < 0.001) Table .The present study evaluated the effectiveness of classical hand massage in reducing PLSP compared to TENS. To our knowledge, no previous research compared these two interventions to relieve PLSP. Therefore, the current randomized trial was the first study following laparoscopic cholecystectomy. Based on our findings, TENS significantly reduced PLSP when added to multimodal treatment methods. In other studies on different types of surgery, the effect of active TENS has been compared to placebo , 20, 25,In a previous study, Asgari et al.  comparedIn line with our study, Borges et al.  evaluateAlso, Platon et al.  reportedIn another study, 52 patients undergoing inguinal hernia surgery were divided into two active TENS and control groups (26 people in each group) to investigate the effects of TENS on postoperative pain. The duration of the intervention was 24 h and applied five times after the operation for 30 min. In the experimental group, TENS was used with a frequency of 100 Hz and a pulse width of 100 microseconds. In the other group, TENS was applied without electrical stimulation. Similarly, the results indicated a significant reduction in pain in the Active TENS group .However, in some studies, no evidence confirmed the effect of TENS on pain. In this regard, Kurata et al.  investigAlso, in these three studies, no effect of TENS on pain at rest (static pain) after abdominal surgery , hystereWe also found that classic hand massage significantly reduced PLSP. The present finding can improve our understanding of the value of massage therapy techniques on pain.In a systematic review and meta-analysis, an evidence was presented that short-term or long-term massage is an effective method for reducing shoulder pain . ConsistIn another study, 105 patients with rheumatoid arthritis were divided into three massage, reiki, and control groups to investigate the effects of hand massage and reiki on pain. The interventions were repeated six times and each time for 30 min. Similar to the current study, the results indicated a significant reduction in pain in both groups .Rasooli et al.  used 15-In two clinical trials on patients undergoing heart surgery, the effect of hand massage on postoperative pain showed that in both studies, massage significantly reduced patients’ pain compared to those who received only routine care , 36.In the present study, there was no significant difference in the dose of pethidine used between the three groups. Contrary to the current findings, some studies reported that massage and TENS reduced analgesic use compared to control or placebo groups , 37. TheSeveral mechanisms have been proposed for massage therapy and TENS to relieve pain , 39. AccDespite the strengths of the present study, our research has the following limitations:Although the surgical procedure and anesthesia were the same for all patients, the patients underwent surgery under the supervision of different anesthesiologists and surgeons.There was insufficient evidence on the best time for TENS and massage to start interventions to improve shoulder pain which may affect the results to somewhat.Shoulder pain was assessed in all patients only at rest, and no separate pain measurement was performed at rest and in motion.The primary source of patients’ pain (incision and shoulder pain) was not assessed when they requested analgesia.The effect of interventions on patients’ shoulder pain was not assessed for a long time and was limited to the initial hours after surgery.At the end, the sample size was small, and it was unclear whether the findings would be different if used in multiple centers in different environments and with larger sample sizes.It seems that massage therapy and TENS can be effective in PLSP relief. Considering that the shoulder pain is often expected after laparoscopy, and the large number of this clinical problem, specifies the need to pay more attention to this matter. It is recommended to use frequent massage therapy and TENS with a longer duration on patients’ having shoulder pain after other laparoscopic surgeries so that their effect on the amount of analgesia used by patients can be seen.


Platelet-rich plasma (PRP) is a rising therapy treating locomotor system lesions such as knee osteoarthritis. The objective of this study was to evaluate patients’ satisfaction 6 to 12 months after a PRP injection for cartilage lesions of their knee under real-life conditions. Patients’ satisfaction was assessed by a specific questionnaire named SATMED-Q©, which explores six different dimensions of a given treatment. In addition, pain and function were assessed thanks to VAS pain, WOMAC, and IKDC scores. Responders were identified through the OMERACT-OARSI criteria. We observed excellent satisfaction after a PRP injection with a SATMED-Q© score of 80.81% 6 to 12 months after the procedure. Even when there was no significant improvement in pain and function scores, 52% of the evaluated population fulfilled the OMERACT-OARSI criteria and were considered responders. According to the sub-group analysis, patients with less osteoarthritis damage  and older study subjects  with focal chondropathy had benefited most from their PRP injection. Thus, platelet-rich plasma seems to be a well-tolerated and efficient therapy for cartilage lesions of the knee. The latest discoveries concerning platelet-rich plasma (PRP) revealed its consequent complexity in its composition and mechanisms of action. Probably underestimated or entirely unknown in early stages ,2,3, theThis therapy currently suffers from a substantial methodologic heterogeneity in the scientific literature. We also observe a lack of standardization in PRP preparation protocols and a fluctuant terminology. These variations lead to very different final injected products and clinical results ,14,15,16In spite of the numerous studies existing in the literature, none specifically focused on the patient’s experience. This is why we wanted to provide an insight on this point: are patients undergoing PRP concretely satisfied with this treatment or not?Our study aimed to evaluate patient satisfaction after a PRP injection for cartilage lesions of the knee in real-life conditions thanks to a specific score named SATMED-Q©.The secondary endpoints consisted of the description of the population who received this product as well as the cellular composition of the final product that was administered. To put the satisfaction study into perspective with clinical outcomes, patients’ pain and function were also assessed.The protocol of this study was validated by the Research and Innovation Department of the French Military Health Service and the Hospital Clinical Research Program unit. It was registered under the following number: 54-2020 HIA-CS. Our protocol completed the reference method MR004 with a declaration made at the CNIL , the French national data protection agency.Sas-PRP is a retrospective routine care study. It is an observational and evaluative work that was retrospectively conducted in the Physical and Rehabilitation Service of the French Instruction Military Hospital Percy of Clamart, Ile-de-France. We included all patients presenting a cartilage lesion of the knee who received at least one PRP injection for 16 consecutive months, between November 2019 and February 2021. “Cartilage lesions” was here used as a generic term to refer to knee osteoarthritis and focal cartilage lesions . All participants were affiliated with the French social security system. Patients who refused to participate and those who could not read or understand French were not included in the study.®. This sampling kit is commercialized by Fidia Farmaceutici s.p.a. Both the sampling and injection kits were paid for by the patient. The Fidia society also provided the cellular centrifugation system named DUOGRAFTER II® and the automatic blood analysis system Bio-QControl®. The blood analysis system was used for collecting cellular data on both whole blood samples and platelet-rich plasma. No option was added to the initial system.The sampling kit used for PRP preparation was the Hy-Tissue PRP 50Peripheral blood was first collected in a 50 mL syringe containing 5 mL of a 3.8% sodium citrate solution. During the blood sample, the syringe was softly shaken every 5 mL in order to homogenize the anticoagulation. The blood sample ended when the 50 mL syringe was completed. The citrated blood was transferred into a tube of a similar volume to be centrifuged. The centrifugation lasted 8 min at 1800 rpm creating a 360 G centrifuge force. Only one centrifugation cycle was achieved. The platelet-poor supernatant was then removed from the tube. The PRP final volume was adjusted according to the whole blood platelet concentration. A cellular analysis was realized with three drops of PRP. The aim was to provide between 3 and 4 billion platelets to the knee. This dose was collectively determined, taking into account the manufacturer’s instructions as well as the compromise of achieving a high platelet dose within a limited volume. No activation factor was added to the PRP. The injection was immediately performed in an aseptic condition.To preserve platelets and their activity, patients were informed to not use NSAIDs  or oral corticosteroids 7 days before and after the procedure. Intra-articular corticosteroid injections should not have been performed for the last 6 weeks. It was not asked to stop an antiplatelet treatment.No premedication or local analgesia was given before or during the infiltration. We could use MEOPA (Nitrogen Monoxide–Oxygen Mixture) that was delivered by a facial mask during the procedure according to the patient’s pain.All patients were put under observation for 15 min after the injection before leaving.Evaluation of patients’ satisfaction was performed with the Scaling and Scoring of the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q©) . This quIn addition to this satisfaction survey, we combined two adapted pain and function scores: the Western Ontario and McMaster University index (WOMAC) and the subjective questionnaire of the International Knee Documentation Committee (IKDC) ,22.Improvement in pain or in function ≥ 50% and absolute change ≥ 20;Improvement in pain VAS score ≥ 20% and absolute change ≥ 10;Improvement in function ≥ 20% and absolute change ≥ 10;Improvement in patient’s global assessment ≥ 20% and absolute change ≥ 10.Or improvement in at least two of the following:We finally used the OMERACT-OARSI criteria  to identThe function assessment was performed by the WOMAC total score.These different questionnaires were part of the current care proposed in our service. They are submitted before and between the sixth and twelfth month following a PRP infiltration.Discrete variables are described as numbers and percentages. Quantitative variables are presented as mean ± standard deviation (SD) or median and interquartiles .t tests. For ordinal variables, the Kruskal–Wallis test was used.Concerning quantitative variables, comparisons between groups were performed using the Wilcoxon Mann–Whitney and Student’s For the pain and function sub-group analysis, we decided not to perform statistical analysis if the results did not reach the MCII  threshold or if the population was too tiny (≤5 subjects).p-value < 0.05 was considered statistically significant.All tests were two-sided and a Between November 2019 and February 2021, 81 patients received at least one PRP intra-articular injection of their knee. The population is described in According to the DEPA classification , the injA total of 58 questionnaire replies were collected between M6 and M12. The mean response delay was 8.7 months .The mean SATMED-Q score was 80.8/100. This result appeared similar to the one obtained by direct rating which was 7.89/10. Scores of the different SATMED-Q dimensions are delivered in The sub-groups analysis  did not Results concerning patients’ pain and function showed an improvement in every score. None reached a significant difference .The OMERACT-OARSI criteria were analyzed for 37 patients thanks to the collected data. A total of 19 of them were considered as responders according to the pre-defined criteria.The sub-group analysis of pain and function scores revealed significant differences between baseline and the last response (M6 to M12) in the population with focal cartilage lesions (chondropathy) and particularly those ≥40 years old .Patients declared a mean onset of action of 6.02 weeks  and deemed it appropriate.Later monitoring data were available for 67 patients. A total of 28 of them were re-injected with PRP. The mean re-injection delay was 18.6 months ± 7.8 . Four patients were operated on: three total knee prostheses and one tibial valgus osteotomy.Our study population was relatively young compared to recent papers ,11,24. WPatients’ satisfaction after a PRP injection for a cartilage lesion of the knee seemed to be especially good in our real-life study with a mean SATMED-Q score of 80.8/100. Meanwhile, we observed a global improvement in pain and function scores notably in patients with early osteoarthritis lesions or older ones with focal chondropathy. In the global population, platelet-rich plasma appears to be both efficient and well tolerated. All in all, this product turns out to be a highly convincing therapeutic option for the management of knee lesions. Even if randomized controlled trials are the scientific studies’ gold standard, routine care studies also seemed especially relevant to assess this kind of therapeutic. Future research may lie in establishing databases or wide registers.


The purpose of this study was to explore the resting-state functional connectivity (FC) changes among the pain matrix and other brain regions in herpes zoster (HZ) and postherpetic neuralgia (PHN) patients. Fifty-four PHN patients, 52 HZ patients, and 54 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We used a seed-based FC approach to investigate whether HZ and PHN patients exhibited abnormal FC between the pain matrix and other brain regions compared to HCs. A random forest (RF) model was constructed to explore the feasibility of potential neuroimaging indicators to distinguish the two groups of patients. We found that PHN patients exhibited decreased FCs between the pain matrix and the putamen, superior temporal gyrus, middle frontal gyrus, middle cingulate gyrus, amygdala, precuneus, and supplementary motor area compared with HCs. Similar results were observed in HZ patients. The disease durations of PHN patients were negatively correlated with those aforementioned impaired FCs. The results of machine learning experiments showed that the RF model combined with FC features achieved a classification accuracy of 75%. Disrupted FC among the pain matrix and other regions in HZ and PHN patients may affect multiple dimensions of pain processing. Herpes zoster (HZ) is caused by the reactivation of varicella-zoster virus (VZV) latent in the dorsal root or cranial nerve ganglia and is characterized by a shingles rash on the skin corresponding to the affected nerve, often with severe pain at the site of the rash . PostherIn recent decades, with the rapid development of neuroimaging technology, rs-fMRI has been widely used to explore the central mechanisms associated with pain-related diseases as a rapid, noninvasive technique to study brain functional activity . StudiesChanges in the functional connection of the pain matrix during spontaneous pain in patients with HZ and PHN may be related to pain perception and processing, and the FC in the core pain matrix requires further study. Therefore, this study used pain matrix-related brain regions as core regions of pain processing. To evaluate the conversion mechanism of HZ and PHN, brain regions closely related to pain in PHN were selected as regions of interest (ROIs), including the bilateral thalamus, insula, anterior cingulate gyrus (ACC), inferior parietal lobule (IPL), precentral gyrus , and postcentral gyrus . Furthermore, we systematically estimated differences in seed-based FC in the upper brain regions in patients with HZ and PHN compared to HCs and assessed the associations between altered brain connectivities and pain intensity, duration of disease, and emotion scores. In addition, the random forest (RF) machine learning algorithm was applied to explore the potential FC differences between the HZ and PHN. Therefore, we hypothesized that abnormal connection patterns may be present in the pain matrix and other regions. These findings might serve as neuroimaging markers for the transition from HZ to PHN patients.We used G*Power (version 3.1) and selected the F test to calculate the prior sample size of three groups at an alpha level of 0.05, a statistical power of 0.80, and an effect size of 0.43. The total number of samples needs to be at least 57 per group. All research procedures were reviewed and approved by the Medical Research Ethics Committee of the First Affiliated Hospital of Nanchang University and conducted in accordance with the ethical principles of the Helsinki Declaration. Subjects were recruited in the Department of Pain at the First Affiliated Hospital of Nanchang University. Before taking part in the study, all subjects obtained a complete explanation and completed written informed consent forms.The clinical diagnoses of HZ and PHN were made by two consultant physicians from the Pain Department according to the standards of the International Association for Pain Research . The parThe clinical information of participants was collected before MRI scanning, and the patient’s pain intensity was assessed with the visual analog scale (VAS). The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to evaluate the anxiety and depression status of all participants.MRI data were collected by a 3.0T Siemens Trio TIM Scanner  and an 8-channel phased array head orthogonal coil in the Radiology Department of the First Affiliated Hospital of Nanchang University. fMRI data were acquired using an echo-planar imaging sequence. There were the following parameters: repetition time (TR) = 2000 ms, echo time (TE) = 30 ms, flip angle = 90°, field of view (FOV) = 220 × 220 mm, matrix = 64 × 64, 30 interleaved axial slices, slice thickness = 4.0 mm, and scanned time points = 240. Three-dimensional high-resolution T1-weighted structural images with TR = 1900 ms, TE = 2.26 ms, flip angle = 9°, FOV = 215 × 230 mm, matrix = 240 × 256, 176 sagittal slices, and 1 mm slice thickness. During the rs-MRI scan, participants should close their eyes, try not to think, and avoid falling asleep.http://rfmri.org/DPARSF (accessed on 26 October 2022) and SPM12 (http://www.fl.ion.ucl.ac.uk/spm (accessed on 11 October 2022)) software based on MATLAB R2018a . The following steps were included in the process: (1) DICOM format conversion; (2) removal of the first 10 time points to achieve magnetic field stabilization; (3) slice timing; (4) head motion correction ; and (5) segmentation and registration. The T1-weighted structural images and functional images of the participants were registered through linear transformation, and the transformed T1-weighted structural images were divided into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) and normalized to the Montreal Neurological Institute (MNI) space. Then, the DARTEL [Preprocessing was performed using the Data Processing Assistant for rs-fMRI ), a binary-based RF classifier model was created. By retaining the sample percentage of each class, the data set was randomly divided into 70% data for training and the remaining 30% for testing. The model parameters were optimized by using the grid search method. Evaluated classification performance on test sets with the best parameter models. To quantify the performance, the accuracy, sensitivity, and specificity of the model classification were calculated and evaluated using receiver operating characteristic (ROC) curves. To further evaluate the performance of the classifier, we performed a permutation test in which we randomized the class labels of the data before training and repeated the above process 10,000 times. A classifier is considered to perform well if the accuracy of the classifier trained with true class labels exceeds the 95% confidence interval of the accuracy of the classifier trained with random class labels [Based on all the brain regions that differed among the three groups in the functional connectivity analysis described above, FC Z values from the corresponding brain regions were extracted and used to find potential FC differences that existed between HZ and PHN. In the scikit-learn-python library  was used for statistical descriptive analysis of demographic and clinical data. The Shapiro–Wilk test was used to test the normality of all the data. Measurement data conforming to a normal distribution were expressed as the mean ± standard deviation; otherwise, the median (interquartile spacing) was used for statistical description. ANOVA was used for comparisons between the three groups, and the least significant difference method (LSD) p value of <0.001, and a cluster-level p value of <0.05. Gaussian random fields (GRF) were applied to correct thresholds for post hoc comparisons.Differences in FC z values between the three groups were assessed using one-way ANCOVA, and multiple comparisons were adjusted using Bonferroni’s method, with covariates including age and sex. Post hoc analyses were performed to further explore the differences in FC, with a two-tailed voxel-level p < 0.05.The FC z values with statistically significant differences were extracted for correlation analysis with the clinical data. Age and sex were used as covariates. Pearson correlation coefficients were calculated to determine the relationships among the continuous variables conforming to normality; otherwise, Spearman rank correlation coefficients were calculated, and the significance threshold was set as p = 0.100) or sex  among HZ, PHN patients, or HCs. There were no significant differences in patients’ VAS scores  or skin lesions . HAMA and HAMD scores were significantly higher in HZ and PHN patients than in HCs, and HAMD scores were higher in PHN patients than in HZ patients. Demographic and clinical data for all subjects are shown in There were no statistically significant differences in age , AUC = 0.69 , right insula and left precuneus , left M1 and left insula , left IPL and right inferior temporal gyrus , left IPL and left M1 , right IPL and right middle frontal gyrus , and right S1 and left insula   B–H.Previous studies have found that PHN patients had structural and functional abnormalities that were closely associated with brain regions located in the pain matrix . In this study, we systematically investigated the FCs between brain regions within the pain matrix and other brain regions. The results showed that compared with HCs, the FCs between those aforementioned regions were decreased in PHN patients. Similar results were observed in HZ patients. In addition, we applied the RF classifier to distinguish PHN from HZ and found that the model achieved an accuracy of 75%.The interaction of higher brain centers, including thalamocortical pathways, may be involved in the perception of pain and emotion . PreviouThe insula and ACC, which are components of the limbic areas of the brain, play important roles in encoding pain-related emotions and motivation, and patients with abnormalities in these areas often show altered emotional responses to pain . The insWe found that the FCs between the ACC and the putamen and middle cingulate gyrus were disrupted in PHN patients. The ACC is involved in pain regulation and the evaluation and expression of negative emotions. The putamen is a component of the striatum. Anatomically, the cingulate gyrus is connected to the striatum and is involved in the formation of cortical striatal thalamocortical circuits . Our resIn this study, we found that, compared to HCs, PHN patients had disrupted FCs between the IPL and the inferior temporal gyrus, amygdala, precentral gyrus, middle frontal gyrus, and fusiform gyrus. The IPL is involved in spatial discrimination and attention to pain , and itsWe found that the M1 and S1 in PHN patients had decreased FCs in many other brain regions, including the right amygdala, left insula, left superior temporal gyrus, left inferior temporal gyrus, right inferior frontal gyrus, and right putamen. Interestingly, all of these brain regions are mentioned in the above neuropathology involving PHN patients. In addition, we also found FC disruptions within the sensorimotor cortex, where the FC of the bilateral S1 was lower in PHN patients than in HCs, which is consistent with previous studies . FC of tp < 0.001, cluster level: p < 0.05). In recent years, machine learning combined with diverse neuroimaging features to identify previously unknown key factors or interactions has been increasingly applied to study different types of pain disorders [p = 0.0035; sensitivity: 78.6%, specificity: 61.1%). Previous studies have found increased brain activity in the M1 and inferior frontal gyrus, increased thalamic GMV, and decreased temporal lobe GMV in PHN patients when HZ progresses to PHN, suggesting that functional and structural changes in these brain regions may be correlated with HZ-PHN chronification [We found no significant difference in FC between the two groups of patients, possibly due to the relatively short disease duration of the included PHN patients or the stringent correction method for GRF (voxel level: isorders ,47. RF ification . Our finThere are some limitations to this study. First, this is a cross-sectional study, and our results need to be further validated and refined by longitudinal studies. Second, our small sample size influenced the analysis of changes in other neuroimaging measurements. Third, we assessed pain matrix internetwork changes, and further studies are needed to investigate pain matrix intranetwork changes. Fourth, we did not delve into pain transmission pathways in PHN patients. Fifth, there are few investigations on brain network graph theory in HZ and PHN patients. Sixth, this study lacks clinical evidence to support potential abnormalities in some network functions. Seventh, we did not collect PHN patients with paresthesias for analysis. In the future, we will make more scientific contributions in these aspects.HZ and PHN patients had disrupted FCs among the pain matrix and putamen, superior temporal gyrus, middle frontal gyrus, middle cingulate gyrus, amygdala, precuneus, and supplementary motor area. In addition, those aforementioned abnormal FCs were correlated with disease duration. The RF classifier was 75% accurate in distinguishing between HZ and PHN patients. The feature of functional connectivity between the left primary motor cortex and the right inferior frontal gyrus had the greatest weight. These findings suggest that the pain matrix plays a key role in the complex pathophysiology of HZ and PHN patients.