Most patients with cancer lack the prognostic understanding necessary to make informed decisions. We tested the feasibility and acceptability of the Oncolo‐GIST  intervention and explored its associations with patients' improved prognostic understanding.n = 31) were recruited from October 2020 through November 2022. We compared patients who discussed their progressive scans with an oncologist trained in the GIST technique or not . A primary outcome was prognostic understanding  assessed within a week of the scan discussion visit.The Oncolo‐GIST intervention distills prognostic discussions into easy‐to‐understand talking points. Patients with metastatic cancers that progressed on ≥1 line of chemotherapy and not expected to survive 12 months (n = 4) appeared receptive to the Oncolo‐GIST intervention and scored nearly perfectly on post‐training tests of material mastery after a < 2‐h tutorial. Post‐scan discussion visit, 100% of patients who met with an Oncolo‐GIST‐trained clinician understood that their cancer was considered incurable (a 31% improvement from pre‐visit) compared with 91% of patients meeting with usual care oncologists (an 18% improvement); 33% of patients who met with an Oncolo‐GIST‐trained oncologist understood that they likely had months, not years, compared to 18% in the usual care group. No statistically significant differences emerged for these changes, nor for therapeutic alliance, anxiety, or depression scores between groups.Oncologists (Oncolo‐GIST appears to be an easily learned approach to improve prognostic understanding that neither undermines therapeutic alliances nor increases patients' anxiety or depressive symptoms. Efficacy testing in a larger trial is warranted. Most patients with advanced cancer do not realize how close to death they are. The Oncolo‐GIST communication intervention is easy for physicians to learn and appears to promote patient prognostic understanding while not harming the doctor‐patient relationship nor patient mental health. We have shown that oncologists can accurately predict when patients have a life expectancy of 12 months or less,Patients who grasp that they are dying, ,To address this need we developed the “Giving Information Simply and Transparently” (GIST) communication technique for oncologists, which we call the Oncolo‐GIST intervention.The present study reports on a trial of Oncolo‐GIST for patients with metastatic cancers that progressed on at least 1 line of chemotherapy and whom oncologists did not expect to survive 12 months. Patient assessments occurred after enrollment and again within 1 week after the clinic visit in which progressive scan results were discussed. We sought to determine if patients who met with an oncologist trained in Oncolo‐GIST were more likely than patients who received usual care to report (a) that their cancer was considered by oncologists to be incurable; (b) that they likely have “months to live,” and (c) are at a late‐/end‐stage of their illness; that is, that they “got the gist” of their poor prognosis.2This trial was funded by NIH/NINR (NR018693: MPIs: Prigerson/Epstein) to determine if the Oncolo‐GIST intervention could improve patients' prognostic understanding. Enrollment of the first trial participant occurred on October 25, 2020, and the study primary completion date was November 8, 2022. This study was approved by the Weill Cornell Medicine Institutional Review Board.2.1G) the scan result using simple language such as “the scan showed the cancer is growing, which means that treatment is not stopping the spread of cancer. This means that your condition is worsening, and now more serious.”Step #1: GIVING (I) prognosis by using language such as “I wish it were not the case, but for people with your prognosis, when the cancer progresses on treatment, the average life‐expectancy is months, not years, to live. This means that for almost all patients in your situation, I expect survival from now to be months, but not years.”Step #2: INFORMING (S) next steps using language such as “hoping for the best and preparing for the worst,” and then making a medical recommendation such as “Given what I know about your cancer, the benefits and harms of various treatments, and what's important to you, I recommend we…”.Step #3: STRATEGIZING (T) asking the patient what was heard by using language such as “Help me to understand what you've taken away from our discussion. Please tell me in your own words what the scan results mean… and I will fill in any gaps.”Step #4: TRANSPARENTLY  led the training, which included a < 2‐h session in which the material for communicating key prognostic talking points was presented, brief video demonstrations were reviewed, and a role‐play undertaken. Questions regarding the technique were answered at that time and following training, the oncologist trainees were tested with a brief survey of the four Oncolo‐GIST talking points and communication recommendations in the Oncolo‐GIST manual.One of the three trained oncologists was removed from study participation prior to patient enrollment due to non‐adherence to the Oncolo‐GIST manual guidelines . This left two trained and two untrained oncologists participating in this trial. The two trained oncologists completed a posttraining test and were found to have nearly perfect mastery of the material , suggesting that it was easy to learn. We then proceeded to pilot test Oncolo‐GIST 2.0.2.32.3.1Patients were included if they were 18 years of age or older, receiving care including regular scans and ≥2 visits with the referring oncologist, had a radiologist scan impression revealing progressive disease on ≥1 line of systemic cancer therapy, had a life‐expectancy of ≤12 months based on their oncologists' opinion, and who were fluent in English . Patients who scored <6 on the short portable mental status questionnaireEligible patients were randomly assigned to meet with either a GIST‐trained oncologist or an oncologist who did not receive such training. Patients were assessed by trained research staff at a baseline evaluation, which occurred after consent, and then again at follow‐up within 1 week of the clinic visit in which progressive scan results were discussed. When a patient's first scan on the study did not show disease progression, study staff instead contacted them for follow‐up at a subsequent scan (within 1 year) that did show progression.2.42.4.1Patients' age, sex, race/ethnicity, level of educational attainment, religion, spirituality, and primary cancer diagnosis  were assessed at baseline via self‐report and verified against information found in their medical record.2.4.2Patient prognostic understanding was assessed with our validated measure of prognostic understanding2.4.3Therapeutic alliance was assessed using our validated Human Connection scale.Depression and anxiety were assessed with the depression and anxiety subscales of the validated hospital anxiety and depression scale (HADS), which measures depression and anxiety symptom severity.2.5t‐tests were used to determine if the Oncolo‐GIST and usual care groups differed to a significant degree (p < 0.05) from each other on mean overall prognostic understanding scores. Likelihood ratio tests were used to determine if the Oncolo‐GIST and usual care groups differed to a significant degree (p < 0.05) from each other with respect to baseline and post‐scan assessment changes in categorical outcomes .Descriptive statistics were used to characterize oncologists' mastery of the training material and participating patients' baseline characteristics. Two‐sample 3Screening and recruitment for this study are detailed in the CONSORT diagram below Figure . 73 patiN = 31) was comprised of 18 patients with cancer who met with an Oncolo‐GIST‐trained oncologist and 13 patients with cancer who met with an oncologist without this training. The average age was 66 years; 65% of the patients self‐identified as male, 71% White, 13% African American/Black, 10% Hispanic, and 3% Asian; 61% were Christian; nearly 70% reported being moderately to very spiritual; and over 70% were diagnosed with a GI cancer. Oncolo‐GIST and usual care patient trial participants did not differ significantly (p < 0.05) on these characteristics.As displayed in Table The results in Table The overall change in prognostic understanding based on a summary score from these three items was positive for both groups, but the mean improvement was slightly higher  for the Oncolo‐GIST group compared to the usual care group ; changes in overall prognostic understanding are displayed in Figure To display these results another way, Figure p = 0.588).In Table 4Results of this pilot of the Oncolo‐GIST technique demonstrated receptivity to the approach and improvement in patient prognostic understanding without significant harm to the patient‐oncologist relationship or to the patient's mental health. Specifically, we found that oncologists approached for this study agreed to participate, though 1 declined to adhere to its guidelines. Those who participated in the Oncolo‐GIST training demonstrated nearly perfect mastery of the Oncolo‐GIST material. Retention of patients was also good (>75%) with most participating in the follow‐up assessment. Patients who met with Oncolo‐GIST‐trained oncologists scored higher on measures of understanding that their cancer was incurable, that they were at a late/end stage of their illness, and that they likely had months, not years, left to live. Though these differences were not statistically significant, the feasibility and acceptability data along with these promising patterns suggest that testing the intervention in a larger, well‐powered trial is warranted. The approach did not appear to adversely affect the patients' relationships with their oncologists, nor did it significantly increase their symptoms of depression or anxiety. These findings suggest that the Oncolo‐GIST communication intervention is feasible and acceptable to implement in a clinical setting. Results also suggest that Oncolo‐GIST may improve patient prognostic understanding, while not appearing to harm the doctor‐patient relationship or patient mental health.We found that at baseline, roughly 30% of enrolled patients did not realize that their oncologists considered their cancer to be incurable. This finding is consistent with what Weeks et al.Over half of enrolled patients understood that their cancer was at a late/end stage at baseline. While 25% of patients who met with an Oncolo‐GIST‐trained oncologist improved in their understanding of this information after discussing progressive scan results with their oncologist, 18% of patients improved in this understanding in the usual care group. Conversely, 17% of patients in the Oncolo‐GIST arm decreased in understanding that they were at a late‐ or end‐ stage of their illness, compared to 27% in the usual care group. These results suggest that progressive scan visits do not necessarily promote patient acknowledgment of disease stage. While the Oncolo‐GIST intervention appeared to encourage greater understanding among some patients, further honing of this message may be needed to improve other patients' recognition that they are likely in the final stage of their illness.That said, the message in greatest need of improvement appeared to be that of life expectancy. Consistent with prior research,While efficacy testing in a larger trial is needed to draw conclusions about the significance of the effects observed in this pilot study, these preliminary findings suggest that the Oncolo‐GIST intervention may improve patient prognostic understanding and harm neither the therapeutic bond between oncologist and patient nor patient mental health. Although patients in the Oncolo‐GIST group responded more than twice as frequently than those in the usual care group that their doctor asked how their family was coping with their illness, they also reported being less comfortable asking questions of their physician (possibly because they did not want to hear more bad news). Still, overall, these results suggest that this approach appears to be a net positive for promoting informed end‐of‐life decision‐making among patients with advanced cancer.4.1n = 24) of the patients originally recruited to the study had died within a year of their enrollment–a rate similar to the 75% accurate year‐long survival prediction among oncologists that we found in a prior observational Study.This trial was conducted at a single site and included data from only 4 oncologist participants and 31 patients with advanced cancers in their clinics. Results should, therefore, be considered cautiously and warrant confirmation in larger, multi‐site, and adequately powered studies. Recruitment coincided with the COVID‐19 pandemic, which posed several challenges to study implementation. Among these challenges were difficulties with patient recruitment and evaluation of oncologist adherence to the Oncolo‐GIST protocol. Oncologists also shared that it was difficult for them to identify eligible patients, with many dying or opting for hospice before referral. This suggests another potential target for interventions to improve prognostic understanding; that is, an identified need to improve oncologists' acknowledgment and acceptance of their patients' impending deaths. In an examination of follow‐up data we found that 73% ; data curation (lead); formal analysis ; funding acquisition (lead); investigation (lead); methodology (lead); resources (lead); software (supporting); supervision (lead); validation (lead); visualization (supporting); writing – original draft (lead); writing – review and editing (lead). David Russell: Conceptualization (supporting); data curation (supporting); formal analysis (lead); funding acquisition (supporting); investigation (supporting); methodology ; project administration (supporting); resources (supporting); software (lead); supervision (supporting); validation ; visualization ; writing – original draft (supporting); writing – review and editing (supporting). Sophia E. Kakarala: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (lead); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Heather M. DerryVick: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Manish A. Shah: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Ashish Saxena: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Valerie F. Reyna: Conceptualization ; data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration ; resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Allyson Ocean: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Ronald Scheff: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Paul K. Maciejewski: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Andrew S Epstein: Conceptualization ; data curation ; formal analysis (supporting); funding acquisition ; investigation ; methodology ; project administration ; resources (supporting); software (supporting); supervision ; validation ; visualization ; writing – original draft (supporting); writing – review and editing (supporting).This work was supported in part by a grant from the National Institute of Health/National Institute of Nursing Research (NIH/NINR) to Dr. Prigerson and Dr. Epstein (NR018693), a grant to Dr. Prigerson from the National Institute of Minority Health and Health Disparities (MD017704) and a grant from the National Cancer Institute (NCI) to Dr. Prigerson (CA197730).Dr. Epstein discloses royalties from Up‐To‐Date for peer reviewing GI medical oncology and palliative care topic reviews; Dr. Ocean discloses royalties from Guardant Health and Natera, Dr. Shah discloses research funding from Merck Inc., Bristol Meyers Squibb, and Oncoloys Biopharma; Dr. Derry‐Vick discloses an unrelated financial relationship with Dechra through her spouse's employment, Dr. Saxena discloses relationships to AstraZeneca Advisory Boards and G1 Therapeutics. All the remaining authors report nothing to disclose.NCT04179305.


BackgroundMulticystic dysplastic kidney (MCDK) is a type of kidney dysplasia consisting of many irregular, various-sized cysts divided by dysplastic renal tissue, which negatively impacts kidney function. MCDK is one of the most common renal congenital disorders seen in antenatal ultrasounds. The typical prognosis of MCDK is complete or partial involution that starts antenatally and continues postnatally. The aim of the study was to shed light on the overall outcome of patients with MCDK.MethodsWe retrospectively collected data on MCDK patients from 2016 until 2022 at King Abdulaziz Medical City, Ministry of National Guard Health Affairs in Saudi Arabia, Riyadh. The data included the recording of epidemiological data, radiological and laboratory reports, and the presence of urological or non-urologically associated anomalies.ResultsA total of 57 patients with MCDK were reviewed. Seven of them were excluded due to the diagnosis of bilateral MCDK, which was incompatible with life. Of the remaining 50 patients, the right kidney was affected in 52% of them. Most patients were diagnosed antenatally (98%). The mean duration of follow-up for the study was 48 months. Vesicoureteral reflux (VUR) was detected in 22% of the total sample. Overall, 90% of the patients underwent kidney involution. A small percentage had genitourinary anomalies (20%), while a larger percentage (48%) had extrarenal abnormalities.ConclusionMulticystic dysplastic kidney disease is relatively common in children. The prognosis is affected by the presence of genitourinary and non-genitourinary anomalies. Patients have an overall good prognosis with conservative management. Antenatal screening, diagnosis, and long-term nephrological follow-up are essential for the optimal management of patients. Renal cystic diseases are multiple heterogeneous conditions characterized by the existence of multiple cysts that develop in the kidneys. These conditions are one of the primary causes of chronic kidney disease (CKD). Renal cystic diseases are categorized in numerous different ways. However, it is clinically beneficial to classify them as genetic disorders, such as autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease, and non-genetic disorders, such as multicystic dysplastic kidney (MCDK), as this method is helpful in assessing and managing the patients .Multicystic dysplastic kidney (MCDK) is a type of kidney dysplasia consisting of many irregular, variously sized, non-communicating cysts divided by dysplastic renal tissue, which has harmful effects on kidney function. Therefore, kidney function relies on the normal contralateral kidney. MCDK is one of the most common renal congenital disorders seen in antenatal ultrasound, with an incidence of one out of every 4300-4500 live deliveries , 3.The majority of MCDK cases are unilateral and isolated. The typical prognosis of MCDK is complete or partial involution that starts antenatally and continues postnatally . In a mePrevious studies have shown that most MCDK kidneys eventually involute within the first five years of life. ,7,8 A coThe nephrological follow-up of MCDK patients is essential. In our study, we retrospectively reviewed and analyzed the records of children with MCDK to assess the outcome, clinical course, parameters, and related renal and urological anomalies.We retrospectively collected data on multicystic dysplastic kidney disease (MCDK) patients at King Abdulaziz Medical City, Ministry of National Guard Health Affairs in Saudi Arabia, Riyadh. The population of the study included pediatric patients with multicystic dysplastic kidney disease diagnosed from 2016 until 2022. Patients’ data were obtained by reviewing their electronic medical files. We included all patients diagnosed with MCDK, both antenatally and postnatally. All cases of MCDK that were incompatible with life were excluded, as were patients who were followed up for less than a year.The collection of data included the recording of demographic data, history of consanguinity, blood pressure, electrolytes, urine analysis, ultrasound, dimercaptosuccinic acid (DMSA) radionuclide scan, micturating cystogram (MCUG), creatinine, and blood urea nitrogen (BUN) at presentation and on the last follow-up. Additionally, the presence of a urinary tract infection history, kidney involution, urological abnormalities, and non-urological anomalies was noted. We calculated the estimated glomerular filtration rate (e-GFR) using the Schwartz formula. Hypertension was defined as blood pressure (BP) above the 95 percentile for age, height, and sex.Our aim is to evaluate the outcome of children with antenatally or postnatally detected MCDK by documenting complications, the size of the affected kidney, and renal function. Furthermore, documentation of compensatory changes in the contralateral kidney was taken into consideration, which involved changes in size, function, and the presence of vesicoureteral reflux (VUR) or any other abnormalities.This research is integrated with human individuals, so ethical issues were considered. We maintained complete confidentiality during the collection and analysis of the patient’s data. Moreover, to avoid harm and ensure privacy, patients’ medical information was kept anonymous. No medical record numbers or names were taken. Informed consent was not needed as the study was conducted through a chart review. Ethical approval was obtained for this study by the Institutional Review Board of King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia (IRB/2435/22).Statistical analysisThe data were recorded using Microsoft Excel and presented in the form of tables. R Studio software  was used for data analysis. The normality of the data distribution was checked using the Kolmogorov-Smirnov test. Continuous normally distributed variables were presented as mean (± SD) and compared using an independent t-test. Continuous non-normally distributed variables were presented as medians  and compared using the Wilcoxon test.Categorical variables were presented as frequencies (%) and compared using Pearson’s Chi-squared test or Fisher’s exact test. Univariate logistic regression was done for all variables, and the odds ratio  was reported.A multivariate logistic regression analysis was used to correlate various factors with the risk of readmission. Factors reaching or approaching statistical significance (p ≤ 0.1) in the univariate analysis were included in the multivariate model. For all analyses, p < 0.05 was considered statistically significant.A total of 57 patients with MCDK were reviewed. Seven of them were antenatally diagnosed with bilateral MCDK that was incompatible with life and died due to hypoplastic lungs, thus being excluded from the study. Of the remaining 50 patients, the right kidney was affected in 26 (52%), and the left kidney in 24 (48%) patients. The majority of cases were diagnosed antenatally . All of the samples were from Saudi patients. The median gestational age was 38 weeks. The mean duration of follow-up for the study was 48 months. Table Out of 50 participants, VUR was detected in 11 patients 22%). Three of them didn’t have associated hydronephrosis. Two of the hydronephrosis-free patients had low-grade VUR reflux, which resolved spontaneously. Most of the VUR cases were in the contralateral kidney. Three VUR cases affected the dysplastic kidney, all of which were grade I. In the contralateral VUR, five out of seven cases were low-grade, while the remaining two patients had grade III and IV VUR. None of the patients with VUR in this study required surgery. Overall, 45 (90%) patients underwent kidney involution, while five patients (10%) had no kidney involution, which might be due to the short period of follow-up. All the patients had abnormal dimercaptosuccinic acid (DMSA) results for the affected kidney and normal results for the contralateral kidney. Table 2%. ThreeAmong the 50 patients included, only eight developed a urinary tract infection (UTI). Additionally, 17 patients were prescribed prophylactic antibiotics. Thirteen of them were given antibiotics due to a reflex detected by micturating cystourethrogram (MCUG), while the remaining four patients were on antibiotics due to one or more previous UTIs. The median glomerular filtration rate (GFR) was 83  mL/min/1.73 m2. The systolic and diastolic blood pressure readings were within the normal range in all the samples. Table A small percentage of the studied sample had genitourinary anomalies (20%). Three (6%) patients had pelvi-ureteric junction obstruction, all of whom underwent pyeloplasty surgeries. Likewise, undescended testes were present in a total of three patients (6%). On the other hand, a larger percentage had extrarenal abnormalities 48%). Cardiac disease was found to be the most common extrarenal abnormality in a total of 12 patients (24%); half of the cases were septal defects; three cases were coarctation of the aorta; two were patent ductus arteriosus; and only one was tetralogy of fallout. Table 8%. CardiThe size of the affected kidney decreased from a median of 4.90 cm at the initial assessment to a median of 2.70 cm at five years. In contrast, the size of the contralateral kidney increased from a median of 4.90 cm at the initial assessment to a median of 9.30 cm at five years. The corticomedullary differentiation of the affected kidney was preserved in 7.6% of the cases at the initial assessment, and the percentage decreased to 3.8% at two years and was 0% at five years. The corticomedullary differentiation of the contralateral kidney was preserved in 93.62% of the cases at the initial assessment, 97.87% at one year, and 100% at two and five years. The echogenicity of the affected kidney was normal in 23% of the cases at the initial assessment, 17.3% at one year, 9.6% at two years, and 0% at five years. The echogenicity of the contralateral kidney was normal in 95.74% of the cases at the initial assessment, 97.78% at one year, and 100% at two and five years. Table In our study, we assessed the outcomes of 50 MCDK patients. We observed a degree of kidney involution in the vast majority of the patients in a relatively short period of follow-up. Additionally, associated renal and extrarenal abnormalities were present in a considerable number of the patients. A previous local study reported that MCDK is the most common renal cystic disease at King Abdulaziz University Hospital . Most ofMost of our patients were investigated consistently, with a mean follow-up of 48 months. However, discontinuity of follow-up was noted in some of the MCDK patients. This could be attributed to the reassuring prognosis of the disease. As one study suggests, urological follow-up is unnecessary in such patients . During Contralateral kidney hypertrophy as a compensatory mechanism was reported in half of our sample, which is considered a low percentage when compared to a previous study where 77% of the patients developed compensatory hypertrophy . FurtherHypertension does not usually develop in MCDK patients; previous articles have shown that among 1115 patients, only six had hypertension . If hypeThe micturating cytogram (MCUG) was previously considered a standard diagnostic test performed postnatally in patients suspected of having MCDK. MCUG was performed in our study sample, showing that 22% of patients had vesicoureteral reflux. Some studies showed a similar incidence of vesicoureteral reflux (VUR), with percentages ranging from 4.5% to 28% of the patients ,20,21. MProteinuria was not reported in any of our patients. Patients had a normal electrolyte level with an overall reassuring outcome. Laboratory tests showed the median creatinine and blood urea nitrogen (BUN) values were 52  µmol/L and 2.8  mmol/L at presentation, respectively, and 43  µmol/L and 3.75  mmol/L at the last visit, respectively. A recent study conducted in 2019 documented that the maximum BUN  and creatinine  were significantly higher in infants with complex MCDK .The main strength of our study is that it describes the outcome of MCDK in one of the largest tertiary care centers in Saudi Arabia. In addition, the presentation and outcomes of MCDK among our population are consistent with the local and international literature. In our study, we emphasize the importance of antenatal screening and the necessity of follow-up. Our study has a few limitations, including the observational nature of the study and being limited to a single center. Additional limitations include the relatively small sample size and the short period of follow-up.Multicystic dysplastic kidney disease is relatively common in children. The prognosis is affected by the presence of genitourinary and non-genitourinary anomalies, but patients have an overall good prognosis with conservative management. Antenatal screening and diagnosis are beneficial for optimal patient management. Patients should be followed up for long periods of time. In this study, the period of follow-up was longer among simple cases in view of the higher mortality among complex cases. Though MCUG is helpful in most cases, studies advocate against routine imaging due to its low clinical significance.


As today’s society ages, age-related diseases become more frequent. One very common but yet preventable disease is the development of pressure ulcers (PUs). PUs can occur if tissue is exposed to a long-lasting pressure load, e.g., lying on tissue without turning. The cure of PUs requires intensive care, especially for the elderly or people with preexisting conditions whose tissue needs longer healing times. The consequences are heavy suffering for the patient and extreme costs for the health care system. To avoid these consequences, our objective is to develop a pressure ulcer prophylaxis device. For that, we built a new sensor system able to monitor the pressure load and tissue vital signs in immediate local proximity at patient’s predilection sites. In the clinical study, we found several indicators showing correlations between tissue perfusion and the risk of PU development, including strongly reduced SpO In an aging society, the prevalence of age-related diseases rises. Pressure ulcers, also known as bedsores, pressure injury, or decubitus, are one of these illnesses that already have a significant negative impact on the healthcare system. To increase readability, the acronym for pressure ulcers “PU” will be used throughout this work. A PU is defined as a local tissue or skin damage that occurs as a consequence of applied pressure with or without additional shear stress. Mainly, PUs emerge at predilection sites such as bony prominences or during long-term exposure to hard materials. The consequences can reach from minor skin or tissue damages to large and very painful wounds. PUs rarely occur in patients with normal sensory function and mobility, since conscious and unconscious feedback leads to position shifts before irreversible tissue damage occurs. Many risk factors of PU development are known and tend to arise with age. Major risk factors include age, sensory impairment  or immobility, for example after surgery .The main goals of this study are (1) to lower the pain experienced by patients and 2) to reduce healthcare costs. For that, prophylaxis tools are the most efficient way since they reduce the need for extensive care. Within the KIPRODE (German acronym for “AI for the prophylaxis of decubitus”) project  to reduc providesAccording to official statistics , there wAdditionally, pressure ulcers also lead to a significant economic burden. Even though only a small amount of data about actual prevention costs exists, Demarre et al.  comparedAnthony et al.  estimatePressure ulcers (PUs) are one of the most critical diseases that bedridden individuals and those with limited mobility can suffer from. The most common predilection sites for PUs are body areas with little soft tissue between the bone and the skin. Applying pressure to these areas over an extended period can lead to the formation of a pressure ulcer. Some of these sites include the skin over the sacrum, coccyx, hips, and shoulder blades, as well as the skin on the heels, elbows, knees, ankles, and the back of the skull . The basThe risk of developing a pressure ulcer depends on numerous factors that can affect the skin’s resistance to pressure. Some of these factors are a humid microclimate, atherosclerosis, paralysis, neuropathy , malnutrition, increased age, BMI > 23, and hypertension ,12,13,14PUs have a high risk for recurrence. Patients who already had a PU with or without surgery show a recurrence risk of up to 80% within the first years after treatment . Very seThe classification of pressure ulcers is commonly guided by the severity of tissue damage and categorized into four stages following the guidelines set by the European Pressure Ulcer Advisory Panel , the NatFor the finger test according to Phillips, a professional presses a finger to compress the red (hyperemic) skin of a patient and examines the spot where the finger is pressed. If there is no visual indication for a reduction of the hyperemia after the finger is removed, the Phillips finger test is considered positive, indicating a stage one PU. A stage two pressure ulcer is described as partial destruction of the skin in the pressure-exposed area that can reach down to the dermis. Commonly a flat, light red sore bed without scabs or layering is visible through these lesions. To be classified as a stage three PU, the lesion must be deep enough to clearly expose subcutaneous fat, while not revealing any visible bone, tendons, or muscle. A stage four pressure ulcer is only diagnosed when the affected area has severe tissue damage, showing the underlying bone, muscle, and tendon structures. Scabs and plaque are often present in these wounds as well.Regular inspection of predilection sites and turning or repositioning of the patient are clinical standards for preventing pressure injuries in hospitals. The literature frequently mentions turning intervals of two hours, but this guideline appears to be based more on economical considerations than on scientific findings ,20. To iLechner et al.  summarizAccording to Roaf , the preThe advantage of wearable prophylaxis systems is their potential usage in the ambulatory setting and the ability to individually monitor patients during the whole day. Cicceri et al.  present The authors could not find any preventive tools that focus on the actual PU development. As presented in The pressure ulcer risk factor discussed above, tissue perfusion, correlates with tissue blood oxygenation  with the goal to predict their early occurrence. Therefore, the following section introduces the developed electronics for data acquisition as well as the study population for the human trials . The acquired data presents an entirely new set of vital sign trends combined with pressure load measurements taken directly on the skin and is published on request . The resSince we want to record vital signs and pressure measurements in local proximity to the PU predilection sites of a human body, we had to develop a new sensor system. Usually, vital sign trends of interest are only recorded with a finger pulse oximeter, in a smartwatch or an ear thermometer  in a periodic interval  and saves the data onto an SD card. In a next development stage, the data should be sent via Bluetooth to a connected device. For ease of engineering and due to the absence of compatible smartphones during the trials, we opted to use SD storage.For manufacturing, first the circuit boards are assembled and tested. That comprises the main board (1) with most electronic components and the sensor node (3) holding the skin temperature sensor and pulse oximeter. The pressure sensor foil (2) has a pin header to easily connect it with the electronics. All wire connections are implemented with adjusted cords and protected against impacts of touch as well as humidity with heat shrink tubing of different sizes. To enable the exchange of broken wires or damaged sensors, the wires are plugged into the main electronics that reside in a plastic housing white in a. The grThe pulse oximeter is the MAX30102 chip from Analog Devices  and reprData streams from our KIPRODE system for around six hours are presented in Additionally, we calculate a validity factor for each reading that analyzes the raw values of each light sensor and only gives a validity statement if the values appear reasonable. The positive outcome is that we can read tissue blood oxygenation at predilection sites (here: the trochanter) with acceptable quality and reliability as shown in Within the project, we collected time continuous sensor data as well as corresponding medical data from the physicians. The medical data contains physical data, relevant preexisting conditions, vital sign data recorded by the medical staff as well as dates and results of the Phillips finger tests see .All recorded data needs safe and privacy-ensuring transfer and storage. Therefore, we utilize the so-called “Pflegekonsil” which is an online database for medical data in the German healthcare system and is provided by our partner Monks . It holdThe study was carried out by the clinic and polyclinic for plastic surgery and hand surgery at the Rechts der Isar clinic in Munich (MRI). The study was designed to primarily include bedridden patients that are likely to stay in the stationary clinical setting for up to two weeks. Because these patients are bedridden, they have an increased risk of developing pressure ulcers during their stay, compared to mobile patients. Eligible patients are selected and invited to participate by medical doctors working in the plastic surgery team at the clinic. Participating patients got a profile including physical data and preexisting conditions. During the study, we documented their daily vitals obtained with gold-standard measurements  together with corresponding timestamps.To identify the best position for the sensor placement, every patient was individually examined and asked about their preferred lying position. Based on those results we attached the two sensing devices  on the predilection site experiencing the highest pressure, meaning that the patient was lying on that site for a large majority of the time. The chosen sites were most commonly the sacrum or spina iliaca superior posterior when the patient’s main resting position was on their back. If patients had to lie on their side, we typically placed the sensory devices on the trochanter major facing the bed. The sensory devices were attached with a Mepilex plaster with a gap of 1–2 cm between each device. We paid special attention to to ensure consistent sensor placement for each patient.To maximize the battery run-time and still have quasi-continuous measurements by the sensor, we had to compromise on the measurement intervals. Given that pressure measurements require more energy than the other sensors, we used a five-minute sampling frequency, while the other sensors were read every minute. This was not considered problematic because pressure changes are less frequent than HR or SpObove see  and the The observation of patients in this study was time consuming and required commitment from the patients. Due to discomfort with the sensor system, a number of patients withdrew from the study. We tried to use as much of their collected data as possible. Every long-term patient at the MRI was considered a potential participant if their health status was stable and they where able to contribute. Most of them had to stay for up to two weeks and were in care because of a wound or operation, hence they have had preexisting conditions already. An ideal control group would exhibit physical data very similar to that of the patients group only without the risk-influencing preexisting conditions. However, creating such a group would involve elderly individuals who might not be accustomed to electronic devices and could be challenging to recruit outside the hospital. Therefore, we opted to work with a healthier group of individuals who responded to our notice in the hospital. This notice was positioned in the MRI asking for people to join the control group study. Nevertheless, the control measurements allow for the verification of the system functionality  as well The study population can be described by their physical data such as age, height and weight as well as preexisting conditions. Pulse oximeters measure optically which means that light scattering can influence the recorded results. This can also occur with higher pigmented skin types and potentially distort SpOterature ,47. The A more detailed analysis of preexisting conditions within the patient group is presented in The following section introduces the data processing steps used to format the data for machine learning methods. Further insight into these methods can be gained by reviewing the publicly available software .First, all data files are uniformly formatted. Then the data of every tested person is aggregated, missing timestamps are filled up with blank values, and out-of-range sensor data is deleted. Missing sensor values of the skin temperature, the heart rate, and the SpONext, the data is split into relevant sections. This is performed by introducing a data quality factor that calculates the fraction of valid sensor data per timestamp. Sections of data with a data quality factor higher than a preset threshold are marked as relevant. The distribution of the lengths of relevant sections can be seen in The high data quality of the skin temperature measurements allows us to further investigate how the skin temperature changes in response to varying pressure loads of different duration. Therefore, we adopt the following approach: first, we locate notable events in the pressure time series using peak detection algorithms. Subsequently, we group these events based on their duration using clustering techniques. To examine the skin temperature reaction to pressure events of different duration, we employ spike-triggered averaging (STA). This process allows to gain insights into how skin temperature responds to variations in pressure over varying duration periods; a comprehensive description follows hereafter.First, the time series data are smoothed using a Butterworth filter to enhance its resemblance to a plausible physiological process and to eliminate noise. Clustering is sensitive to data scales, therefore we standardize the data through z-score normalization and transform it to have zero mean and unit variance.After that, we used the popular scipy library  to identTo distinguish the temperature reaction to pressure load events of different duration, we used machine learning-based clustering. There are a multitude of different clustering techniques for different purposes. We evaluated several time series clustering algorithms on an annotated subset of our detected pressure events. The best overall performance was achieved using time series k-means with input scaling and with Euclidean distance as distance metric. Time series k-means is based on the popular k-means algorithm . It is sTo analyze the impact of the detected pressure events on the skin temperature, we needed a technique that summarizes the temperature measurements after the pressure events over all the segments in each cluster. More precisely, we wanted to compare how the skin temperature changes after a pressure event relative to a reference point right before the pressure event. A suitable approach is spike-triggered averaging (STA) . Our modFirst, we verify the sensor validity by comparing the measured values with the clinical reference and common sense in To verify the KIPRODE sensor system and ensure proper sensor operation, all recorded data files are compared to gold standard measurements of today’s medicine whenever available. Basically, two different ways of sensor verification are used: first is the comparison with medical reference data that is recorded twice a day during the study by medical personnel . The second way is to compare the measured data of patients with the control group and set it into relation with expected values (common sense).The primary values that we measure and analyze within this research are SpOA practical way to assess the functionality of the sensor system involves comparing it with the medical screening data that the personnel documented daily. Not all values can be directly compared as no standard reference measurement exists. We evaluate the sensor system by comparing the distributions of sensor data and reference data. The biggest challenge is that we measure at patients’ hips or back  but standard reference measurements are performed at finger tips : This research investigates the correlation between tissue blood oxygenation, skin health and PU development risk. Here, we looked at the influence of preexisting conditions on the body vital signs in the patient group. Preexisting conditions that are commonly associated with a high PU risk are, among others, paraplegia, immobility, diabetes, or if a patient already had a PU or even a PU-related surgery. All of them affect the body tissue SpO surgery b,c: bothThe skin temperature is affected by underlying tissue perfusion as high blood circulation leads to increased skin temperature. The methods to analyze the relationship between skin temperature and pressure loading were elaborated in more detail in the master’s thesis of Schillinger .The assumption that changes in skin temperature are linked to the risk of pressure ulcer development has been demonstrated in prior studies ,56. In mThe approach within the study is to investigate skin temperature values directly after a notable pressure change is detected. The latter would probably occur due to a patient changing their position from one body site to another; hence relieving the previous body site from pressure load. By utilizing machine learning methods .As described in In 2016, about 18.6 million people worldwide were affected by DFUs alone and 6.8 million had to live with an amputation of lower extremities . This coIn the KIPRODE study, we modified our system to also investigate those PUs, considering their medical proximity. In this study, we did not monitor the development of any PU. Hence, the investigation focuses on the prophylaxis of the main risk factor for DFUs: pressure peaks at patients’ feet. It is widely assumed that individually adjusted orthopedic shoes offer the most effective protection against these risk factors. We investigate this hypothesis by continuous feet pressure load monitoring.To prevent the severe consequences of feet ulcers, we have to adjust our KIPRODE system as described in Neuropathy leads to a reduced or diminished sense for pressure load at patients’ feet. That can lead to unnoticed developments of pressure ulcers at their feet. Hence, a reasonable approach to reduce the risk for foot ulcers is the reduction in pressure peaks. This has already been tried through the use of orthopedic shoes that are precisely fitted to the patient.The main research question is whether an individually adjusted orthopedic shoe can reduce the risk for the generation of foot ulcers. As the study does not expect the actual formation of foot ulcers, the parameter under investigation is the pressure load on the feet during the daily activities of ambulatory patients. The goal is to determine abnormal pressure load patterns by machine learning algorithms and warn a patient if such is detected.During the study conducted at Fußnetz Bayern (FNB) , half ofThe whole patient group comprises ambulant patients that are already regularly visiting the doctor because of a previous ulcer. In this study, the KIPRODE sensor system is applied to the opposite foot, where no ulcer has occurred previously. Those patients are at a high risk of developing further ulcers and are therefore motivated to mitigate the risk as far as possible. For the adapted study, we included 13 ambulant patients for a period of more than two weeks and nine healthy control subjects for a period of more than one week. The duration of the patient study varied strongly (ranging from a few days to more than three weeks), depending on patients’ commitment and comfort.To evaluate the pressure load on patients’ feet, we measure the pressure load inside a shoe continuously over the observation period. Therefore, every minute a pressure scan is performed across the whole sole, including 48 elements (4 by 12 rows) and saved with the vital signs at their legs. Since obtaining high-quality vital sign measurements proved to be challenging with ambulatory patients, meaningful interpretation is not feasible, and we focus exclusively on pressure load data. As we want to compare the pressure load between patients wearing orthopedic shoes and those without, we split the group accordingly, as shown in the graphs in In order to obtain the necessary data for the intended design of a PU prediction and prophylaxis system, we needed to develop a new sensor system. The authors are unaware of any comparable sensor system that allows the recording of body vital signs and pressure loads in humans. We focused on bedridden patients with an increased risk of PU development, hence, the system is optimized for placement at the hip or back . Nevertheless, it could be adjusted for other body sites as well. The introduction of a new and highly integrated electronic device invariably brings along certain vulnerabilities and requires multiple rounds of improvement. For this reason, the sensor was constantly refined and optimized for clinical use. Although the method of measuring data remained consistent throughout the entire study to ensure data reproducibility, the hardware box was modified for ease of use. Examples of these optimizations include the implementation of double coverings and the extension of individual cables, along with the installation of strain relief at the connection points between the cables and the box. These changes have made the daily maintenance of the sensors much easier and increased their mechanical stability. Numerous code adjustments were required, which led to data loss at the beginning of the study. However, after some iterations, the KIPRODE sensor system was operating reliably and could be used for our purposes. The main findings include that patients with severe preexisting conditions require even simpler-to-use devices than the healthy control group. After a successful control group study, we encountered several system failures, for example due to removed cables, humidity or other mechanical stress. That resulted in some data loss until we increased the mechanical stability. For future developments, this should be taken into account from the beginning.The long-term goal is to provide those prophylaxis tools to at-risk patients at home. As evident from the study, the system still requires a high level of monitoring and supervision by trained individuals. Some patients quit the study because the sensor system was not comfortable enough. This indicates that following the completion of functional development, a few additional comfort-related optimizations are required.A major challenge when building a prophylaxis tool lies in the conflict between the necessity to monitor the disease and the simultaneous attempt to prevent its occurrence. In this case, it has resulted in only one well-documented and diagnosed PU in our study. Consequently, no statistically significant analysis is possible for our observations and we have to rely on qualitative analysis by comparing our findings with medically expected conditions. For future studies, we recommend to include hospital stations with an even higher risk for PU development, such as intensive care units.The patient who developed a PU exhibited a noticeable decline in the mean SpOOn average, the control group is younger and lighter than the patient group. Ideally, the only distinction between the control group and patients would be their preexisting conditions. However, recruiting healthy individuals with comparable physical characteristics to the patients is challenging. We publicly searched for volunteers on the MRI website and on the hospital’s white board and received the control group as presented above. The significance of certain findings is constrained by these differences between the two groups. However, since we validated our measurements as described in z et al. , who shoOur interpretation, the inverse relationship between SpOi et al. , who fouNevertheless, there remain certain overarching challenges associated with mobile pulse oximetry measurements (photoplethysmography), which we want to highlight. We cannot exclude all external disturbances in a real-life study. Kim et al.  provide 2 levels ,47. Howe2 levels  that cou2 levels , present2 levels , who alsThe investigation on how preexisting conditions impact the body vital signs reveals another finding: As a result of the KIPRODE study, we propose a PU predictor that continuously analyzes SpOs et al. , who detThe presented KIPRODE study reveals several interesting findings about tissue blood perfusion, skin health and the risk for developing a pressure ulcer (PU). We designed, built and thoroughly tested a new wearable sensor system: the KIPRODE sensor system. It enables the recording of vital signs at the hip or back  of patients and combines them with the corresponding pressure load measurements in local proximity. We observed a significant decrease in tissue blood oxygenation (SpOFurthermore, we explored additional hypotheses regarding pressure ulcers at patients feet: how does the distribution of pressure loads on patients’ feet during their daily life influence the risk of PU development? Additionally, how can orthopedic shoes aid in foot ulcer prophylaxis by mitigating pressure spikes? Individually adjusted shoes or insoles have been found to significantly decrease both the average pressure load and the occurrence of pressure spikes. Therefore, they offer valuable support for preventing foot ulcers.The KIPRODE study provides a further step towards understanding the development of PUs and, consequently, their possible prevention. The sensor systems are ready for further studies with larger patient groups to verify the PU predictor and optimize its machine learning algorithms. Establishing a reliable PU prophylaxis would be a critical step in addressing a severe and preventable disease that affects numerous patients.


Correction: BMC Anesthesiol 21, 152 (2021)https://doi.org/10.1186/s12871-021-01374-xFollowing publication of the original article , we provThe methods for obtaining invasive blood pressure measurements from the radial artery (INV) and non-invasive measurements from the ClearSight™ finger cuff (FC) have been published previously . AccordiSystolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded digitally at 5-minute intervals from the initial blood pressure measurement for each patient for up to one hour, or until cessation of anesthesia, whichever occurred first.Data from 29 participants were analysed. The correct cuff was allocated in two (7%) patients, according to the manufacturer’s recommendations and based on the measured mid-arm circumference. Of the incorrectly allocated cuffs, all were too small. In two participants, the arm circumference was outside the range provided for by the manufacturer. Eight (28%) patients had ipsilateral NIBP and INV arm measurements. Patients had complete data until 35 minutes of general anesthesia. Thereafter it ranged between 24 and 28 readings per method, as the length of surgery differed between patients.We firstly present here the output of the analysis comparing the measurements obtained from the ClearSight™ finger cuff and the NIBP upper arm cuffs. Table We also present the output of the analysis comparing the measurements obtained from the invasive arterial monitoring with the measurements obtained from the NIBP arm cuffs. Table In a methods comparison analysis, each technique should be undertaken according to manufacturer’s recommendations. For this reason we urge caution in drawing any conclusions from interpretation of these results.In the original paper we stated: “Comparison of the FC with automated oscillotonometric NIBP cuff readings would have added to our study.” This statement would have been better expressed “Comparison of the FC with accurately measured automated oscillotonometric NIBP cuff readings would have added to our study.” Our intention was to comply with recommendations of the European Society of Hypertension  and the


To evaluate the precipitating factors and symptoms of primary spontaneous pneumomediastinum (PSPM) and to assess the factors related with recurrent spontaneous pneumomediastinum (RSPM).From 2010 to 2021, 237 PSPM patients were included in this retrospective study. Clinical information including in-hospital periods, morbidity, mortality, presenting symptoms, precipitating events, smoking, and asthma history was obtained. The patients with smoking history were subdivided into “ex-smoker” or “current smoker”. The severity of asthma was categorized into “mild intermittent”, “mild persistent”, “moderate persistent”, or “severe persistent”. During follow-up, patients with RSPM were classified into “recurrence” group and the others were into “no recurrence” group. Multivariate regression analysis was used to elucidate the associated factors with RSPM.p = 0.010) or asthma  was significantly higher in “recurrence” group than “no recurrence” group. On multivariate analysis, asthma was the only factor associated with RSPM .The mean age of study patients (men: women = 222: 15) was 23.4 years and mean period of hospital stay was 7.5 days. There was no mortality and morbidity. Most frequent symptom and precipitating factor were acute chest pain  and cough , respectively. RSPM occurred in 11 patients (4.6%). The proportion of patients with smoking (72.8% vs. 37.1%, PSPM is a benign disease with no morbidity and mortality. Asthma may be the associated factor with RSPM; thus, despite the low rate of recurrence, patients with asthma should be informed about the chance of RSPM. Pneumomediastinum, defined as the presence of free-air within the mediastinum, can be divided into two types: spontaneous or secondary. Secondary pneumomediastinum may commonly occur in situations which can damage the esophagus or airway such as trauma, surgery, and other interventions, or by gas-forming mediastinal infections. In contrast, primary spontaneous pneumomediastinum (PSPM) is a diagnosis of exclusion and is rare, but mainly benign disease .Although occasionally obvious precipitating factors cannot be identified in patients with PSPM, previous studies reported that there were benign precipitating factors including asthma, smoking, coughing, vomiting, training, or etc. for PSPM . HoweverTherefore, the aim of this study was 1) to evaluate the precipitating factors and symptoms of PSPM in a relatively large sample size at a single-center with over a 10-year period and 2) to assess the factors related with RSPM.This single-center retrospective study was approved by our institutional review board, which waived the requirement for informed consent.From January 2010 to December 2021, 237 patients with their first diagnosed PSPM were eligible for inclusion in this study. All the study patients underwent unenhanced or contrast-enhanced chest computed tomography (CT)  and undeClinical information including age, sex, period of hospital stays, morbidity and mortality, presenting symptoms, combined thoracic abnormality , presence of precipitating events, smoking history, and asthma history was obtained from the electronic medical charts. Then, the patients with smoking history were subdivided into “ex-smoker” or “current smoker”. In patients with asthma, the severity of asthma was categorized into “mild intermittent”, “mild persistent”, “moderate persistent”, or “severe persistent”, based on daytime symptoms, nighttime symptoms and lung function . During p < 0.1) in the univariate analysis were included in the multivariate analysis. Outcomes are expressed as odds ratio (OR) and 95% confidence intervals (CIs). All statistical analyses were performed with SPSS 27.0 for Windows  and P < 0.05 were considered as statistically significant.Continuous variables are expressed as mean ± standard deviation (SD) or as median with interquartile range (IQR). Continuous variables were compared by using one-way analysis of variance, while categorical variables were compared by using Fisher exact or Chi-square tests. Univariate and multivariate logistic regression analyses were used to identify the risk factors for recurrent pneumomediastinum. Factors significantly associated with recurrence , respectively. The mean period of hospital stay was 7.5 ± 2.6 days . There was no mortality and morbidity, and any treatment such as oxygen inhalation or antibiotics did not affect hospital course.st precipitating factor was cough , followed by upper respiratory infection , physical exertion , and retching/vomiting . There was no precipitating factor in 29 of 237 patients (12.2%). Of the 92 patients with smoking history (38.8%), 66 patients were ex-smokers and 26 patients were current smokers. In 99 patients with asthma history (41.8%), 88 patients had mild intermittent or mild persistent asthma, and 11 patients had moderate persistent asthma. There was no patient with severe persistent asthma. Subcutaneous emphysema and pneumothorax was combined in 6 patients (2.5%) and 9 patients (3.8%), respectively (Most of study population was men (93.7%) (men: women = 222: 15). Most frequent symptom was acute chest pain , followed by acute neck pain , and dyspnea . The 1ectively . In casep = 0.010). Furthermore, not only the proportion of patients with asthma (81.8% vs. 39.8%), but that of patients with moderate persistent asthma (27.3% vs. 3.5%) was also significantly higher in “recurrence” group than “no recurrence” group (p < 0.001). There was no significant difference in age, sex, presenting symptoms, precipitating events, and combined thoracic disease between two groups . The proportion of smokers (72.8% vs. 37.1%) and current smokers (36.4% vs. 9.7%) was significantly higher in “recurrence” group than “no recurrence” group (o groups . One patp = 0.060) and asthma  were the related factors to recurrence. However, multivariate analysis showed that asthma was the only factor associated with a higher risk of RSPM .st precipitating factor was cough (30.4%), followed by upper respiratory infection (27.8%), physical exertion (23.6%), and retching/vomiting (14.3%). During the mean follow-up period of 48.6 ± 30.9 months, RSPM occurred in 11 patients (4.6%). On multivariate regression analysis, asthma was the only associated factor with RSPM .In the present study, all the 237 patients with PSPM showed benign clinical course without morbidity nor mortality. Most frequent symptom was acute chest pain (89.0%), followed by acute neck pain (51.9%), and dyspnea (32.9%). The 1Though there have been previous studies regarding PSPM, the present study with relatively large sample size was conducted to improve the understanding of PSPM and RSPM, since research on over 100 patients with pneumomediastinum is scarce. The results of our single-center study are in many ways consistent with previous reports. First, our result shows that PSPM is a self-limited and benign disease; thus, specific treatment may not be required in PSPM patients without concurrent pneumothorax. Second, the mean age was 23.4 ± 3.4 years  and the proportion of men was overwhelmingly high 222/237, 93.7%), concordant with the existing knowledge that PSPM generally affected young adult males , 12. Thi, 93.7%, p = 0.010) or asthma  was significantly higher in “recurrence” group than “no recurrence” group. However, on multivariate analysis, asthma was the only associated factor with recurrence . Asthma exacerbation has been known as one of the most prominent risk factors for PSPM and PSPM has been reported both as a sign of a first asthma attack and as a consequence of an asthma exacerbation. Furthermore, PSPM may be associated with poorly-controlled asthma [In this study, the recurrence rate of spontaneous pneumomediastinum was 4.6%, comparable to the reported PSPM recurrence rates of 0–4.5% in previous case series studies –16. Howed asthma , 18. TheThere are some limitations in this study. The main limitation is the small sample size. There were only 11 patients included in the recurrent group. To validate the results that asthma and smoking are significantly associated factors with RSPM, studies involving more RSPM patients are needed. Second, the present study was conducted based on retrospective design, and selection bias could affect the results. Third, since poorly-controlled asthma is known to be associated with spontaneous pneumomediastinum, it may be necessary to check whether asthma is well controlled by medication or not; however, it is difficult to confirm because this clinical information was not accurately recorded in the electronic medical charts. Further research is needed on these areas, and an improved understanding of associated factors with PSPM and RSPM can lead to more efficient management of patients with spontaneous pneumomediastinum.In conclusion, PSPM is a self-limited and benign disease and specific treatment may not be required if there is not concurrent pneumothorax. Furthermore, patients with asthma should be informed about the chance of recurrence despite the low rate of recurrence, since the asthma may be the associated factor with RSPM.


Background and objective: Essential hypertension is a leading cause of cardiovascular morbidity worldwide, but its precise etiology remains unclear. Although its prevalence is high, there is no established predictor for the condition at an early age. Recent research has suggested that olfactory function may be associated with blood pressure regulation. This study sought to explore the association between olfactory function and essential hypertension.Methods: Thirty middle-aged volunteers of both sexes with essential hypertension were recruited for the study along with 30 healthy control subjects matched for age and demographic characteristics. Participants completed a demographic questionnaire and then underwent olfactory function tests to assess odor threshold and identification using the Indian Smell Identification Test (InSIT). The researchers calculated a combined threshold-identification score for both groups and performed the statistical analysis.Results: The study group showed significant olfactory scores in comparison to the control group participants. Control group showed a significantly higher mean combined olfactory score than the study population (p = 0.03). Significant negative correlation between systolic blood pressure and olfactory function  and a similar significant negative correlation between diastolic blood pressure and olfactory function  were the other observations. Gender differences did not account for any difference in the smell sense.Conclusions: There may be a connection between olfactory function and blood pressure regulation in individuals with essential hypertension. However, further research is needed to better understand this association and to determine whether olfactory function could be used as a predictor or marker for hypertension. Hypertension is one of the most common cardiovascular conditions with global prevalence affecting around 1.39 billion adults in the age group of 30-79 years, mostly (two-thirds) from low- and middle-income countries  classifiThe physiology of blood pressure control mechanisms is complex, and changes in blood pressure are compensated for by feedback mechanisms. However, when the balance between these mechanisms is disturbed, essential hypertension can develop . This coOlfaction is the sense of smell, and it involves the perception of chemical odors by the olfactory system. The olfactory transduction process begins with the contact of odorants with primary olfactory neurons, which then send signals to the secondary olfactory structures in the brain . The impRecent attention has been drawn to olfactory changes as a potential diagnostic tool for COVID-19. Anosmia, or loss of smell, is a common symptom in COVID-19 patients and is caused by the virus's impact on olfactory epithelial cells that express angiotensin-converting enzyme 2 (ACE-2) receptors. These receptors are also present in renal olfactory receptors which release renin and play a crucial role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS) mechanism -8.This study aims to provide a crucial first step in understanding the relationship between olfaction and hypertension. By exploring the neural olfactory mechanism's link to cardiovascular pathology, further research can identify early indicators of hypertension and develop novel treatments. This study's results suggest that olfactory function may be a potential early indicator of hypertension, providing a new avenue for hypertension diagnosis and treatment.It is an analytical cross-sectional study conceived to investigate the association of olfactory dysfunction with essential hypertension in the adult population of the region. Thirty newly diagnosed hypertensive volunteers in the age group of 30 to 50 years including both male and female have been recruited for the study after written informed consent. Thirty age and sex-matched healthy normotensive volunteers have been recruited as control group participants after due consent. It was a quasi-purposive sampling with the recruitment of volunteers visiting the Institute Medicine OPD within the reference period (two months) and consenting to the study. A prior ethical clearance has been taken from the Institutional Ethical Committee of the All India Institutes of Medical Sciences, Patna (AIIMS/Pat/IEC/2022/913).Participants diagnosed with essential hypertension as per JNC 7 recommendations were included in the study group. Participants with systolic blood pressure less than 140 mmHg and diastolic blood pressure less than 90 mm Hg (as per JNC 7 recommendations) have been included in the control group. The participants with a history of major acute or chronic illness, a history of major neurological diseases like Alzheimer’s, and Parkinson’s, etc, those suffering from any disorder known to cause alternation in the sense of smell, having a recent history of COVID-19 positivity (in the last six months), or those with any known causes for hypertension (secondary hypertension) like chronic kidney disease, obstructive sleep apnoea, hormonal abnormality history of long term medications like NSAIDs, antidepressants or birth control pills, or chronic alcoholic participants were excluded from the study.MethodologyAfter the recruitment, demographic information was collected using a pre-designed questionnaire. The questionnaire was used to gather participant data such as age, smoking status, alcohol intake, history of hypertension, any smell-related disorder along with current medications, etc. Further two types of olfactory tests have been performed using the olfactory threshold test (OTT) and Indian smell identification test (InSIT). The olfactory function tests were performed to evaluate the odor threshold of the participant in which the minimum concentration of the odorant necessary for a smell to be perceived by a person was determined; olfactory discrimination test was performed to assess a person's ability to differentiate one smell from another. A combined threshold-identification score was calculated for both test and control groups to understand the overall status of the olfactory function of the participant.OTTTest odorant 1-butanol was employed as the material for the OTT. 1-butanol is commonly used as it is low in toxicity, colourless, water-soluble, readily available in high purity, and has a neutral odor quality . BecauseInSITInSIT  was emplData analysisFor the purpose of analysis , a P value of less than 0.05 was taken as significance level. Data analysis was done using SPSS version 22 . The data has been tested for the normality of distribution using Shapiro-Wilk test, Q-Q plot, and box plot methods. The normally distributed interval data has been expressed as a mean with 95% CI and analysed using parametric tests. The non-normally distributed observations have been expressed as median with interquartile range and have been analysed using non-parametric tests. Pearson’s correlation analyses were performed to evaluate the relationship between combined threshold-identification score and systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure.The demographic and blood pressure findings of the control and study group population is summarized in Table The variables were tested for the normality of distribution using box plots, Q-Q plots, and Kolmogorov- Smirnov test with Lilliefors significance correction and were found normally distributed for most of the measured variables except for the mean BP Figure .The mean combined olfactory scores, computed by combining the composite OTT and composite InSIT, for the test and control group were 9.13 ± 2.21 and 10.7± 1.62, respectively. The result of the olfactory function test is presented in Table The Independent sample t-tests showed that the study group had lower mean OTT, InSIT, and combined olfactory scores in comparison to the control group participants though the difference was not statistically significant for the olfactory threshold test. Participants with lower blood pressure scored more in the combined odor threshold test in comparison to those with higher blood pressure Figure .The correlation study between various cardiovascular and demographic parameters recorded in the study using Pearson’s correlation test shows that both InSIT and OTT scores have a negative correlation with systolic blood pressure, diastolic blood pressure, and mean BP. The age of the participants has shown a statistically significant negative relationship with InSIT score but not with OTT. BMI appears to be positively correlated with the OTT score Table .The chi-square test showed that out of 10 items used in the InSIT, the essence of rose could be perceived less efficiently by hypertensive individuals in comparison to non-hypertensive participants  Table .This study found a statistically significant association between olfactory function and hypertension. The subjects with hypertension showed a higher olfactory threshold for the serial dilutions of 1-butanol used for the purpose, in comparison to those with normal blood pressure, though the difference was not statistically significant (p=0.09). Both systolic as well diastolic pressure values showed a negative correlation with the odor threshold scores. A similar finding was also observed in InSIT. InSIT scores showed a better correlation with systolic blood pressure than diastolic or mean blood pressure. The combined olfactory score showed significantly higher values for normotensive individuals in comparison to hypertensive individuals. In this study, age was found to have a negative correlation with InSIT score but it did not show any correlation with OTT. The findings agree with many previous studies -14.Blood pressure has a well-established relationship with cardiovascular morbidity including ischemic heart disease, heart failure, cardiac remodelling, etc. Besides, it is also implicated in the pathogenesis of stroke, reno-vascular pathophysiology, and many other systemic disorders with hypertensive angiopathies.The altered smell perception in hypertension may be associated with some pathogenic mechanism, commonly associated with both the olfactory as well as blood pressure control pathways. One possible mechanism could be the shared olfactory receptor 78 (Olfr78) present in both the olfactory apparatus and various extra nasal sites including the kidneys. Another mechanism linking smell and taste sensation with hypertensive disorders has been proposed by Pluznick et al. (2013) suggesting that the short-chain fatty acids produced by the gut flora play an important role in the upregulation of renin causing raised blood pressure [A study utilizing RNA sequencing on human tissues discovered that olfactory receptors exist in various locations outside the nasal region such as sperm, muscle, skin, adipose tissue, and the gastrointestinal tract, etc. These receptors serve diverse functions ranging from facilitating cell migration and motility to the release of hormones. Interestingly, the kidneys  also exhibit sensory characteristics. Within the kidney, the renal vasculature and tubular epithelial cells assume the role of monitoring the blood and ultrafiltrate composition, regulating processes such as filtration, reabsorption, and secretion. Notably, the human kidney contains some 13 distinct olfactory receptors, believed to contribute significantly to maintaining renal homeostasis . The olfPrevious studies have shown that cardiovascular disorders are intimately associated with olfaction . A longiThe sample size was one of the limitations of the study, Further research may be needed with a bigger sample size to conclusively establish or refute the olfactory dysfunction as a marker for essential hypertension. Despite its limitations, the present work attempts to highlight the importance of olfactory function in the pathophysiology of conditions like hypertension.The study demonstrates that subjects with hypertension had lower smell perception as measured by the combined olfactory score and InSIT. The subjects with hypertension showed a lower mean olfactory threshold in comparison to the normotensive individuals but the difference was not statistically significant. Further, systolic blood pressure, diastolic blood pressure, and mean BP of the participants showed a negative correlation with the olfactory function but the strength of association appears to be weak. Out of the common substances of the InSIT, the smell of rose showed some association with the trait of essential hypertension which may require further studies in the area for a conclusive remark.


Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes.We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities.n = 14; median age 76.5 years [71.9–83]) developed a kidney disease 6 months [1.6–25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25–3.4], and median serum creatinine was 2.26 mg/dl [1.46–2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9–34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978).Sixteen patients (males, In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.  Kidney diseases in patients with hematological malignancies are common, with various etiologies.CMML is an overlap syndrome that has characteristics of a myelodysplastic syndrome, whereas other findings are more consistent with the diagnosis of myeloproliferative neoplasm.,CMML can be associated with systemic inflammatory and autoimmune diseases in 10% to 30% of patients, mostly neutrophilic diseases, connective tissue disorders, arthritis, and vasculitis.The objective of this work was to study the clinical and histological presentation of patients with renal impairment during CMML, as well as their therapeutic management in a multicenter cohort. Then, we compared the hematological phenotype of patients with a kidney injury occurring during CMML with CMML patients’ controls without kidney disease.Patients with an established diagnosis of CMML and diagnosed with AKI, CKD, or urine abnormalities were retrospectively included. We collected data of patients from 3 different sources . The firDiagnoses criteria for CMML were based on the World Health Organization classification revised in 2016. CMML were classified as CMML-0 , CMML-1 , and CMML-2 . Cytogenetic analysis and molecular findings were collected when available in the center.2), or markers of kidney damage: albuminuria with albumin-to-creatinine ratio ≥30mg/g, urine sediment abnormalities, electrolyte and other abnormalities due to tubular disorders, and abnormalities detected by histology among other things.We included adult patients (>18 years old) diagnosed with CMML, and a kidney disease less than 10 years apart. According to the National Kidney Foundation’s Kidney Disease Outcome and Quality Initiative guidelines, CKD is defined as either a decreased glomerular filtration rate  for the binary variables, and in median (interquartile range) for the continuous variables. Given the size of the numbers and the lack of a normal distribution of values, we used nonparametric tests. Comparisons of continuous variables between 2 groups were made using the Mann-Whitney test, and those of binary variables were made using the Chi-square test. A Kaplan-Meier method was used to estimate overall survival. The significance level was Statistical analyses were performed using GraphPad Prism v8.00 for MacOS , and R v4.0.3 for MacOS .This study was conducted according to the Declaration of Helsinki and fulfilled the recommendations of the French “Commission Nationale Informatique & Libertés” CNIL. According to its policy, this study was approved by the Institutional Review Board of the Brigham and Women’s Hospital (protocol number 2019P003787), who validated a waiver of consent.n = 14, aged 76.5 years [71.9–83]) with a kidney disease associated with CMML were included in this study. CMML disease subtypes were as following: type 0 in 5 patients (25%), type 1 in 10 patients (66.7%), and type 2 in 1 patient (8.3%) , PTPN1, NRAS in patient FRA-02; JAK2 in patient FRA-04; NRAS, KRAS, ASXLI1 in patient FRA-11; EVI1 duplication in patient FRA-28; and BCORL1, NRAS, PHF6, SRSF2, TET2, ZRSR2 in patient FRA-32.Overall, 16 patients  . Median 2. Median proteinuria was 2 g/g (1.25–3.4), with a microscopic hematuria present in 6 of the 10 patients with an evaluation of the urine sediment. Leukocyturia was available in 8 patients with a positivity in 25% of the cases.Time between the hematologic and kidney disease was 6 months [1.6–25.6] . The dian = 9; 64%), then nephrotic syndrome , rapidly progressive glomerulonephritis , and a progressive CKD . A preexisting CKD of unknown cause with an eGFR of 33 and 44 ml/min per 1.73 m2 was present in 2 patients. Hypertension was present in 82% of the patients, whereas diabetes represented 18%. Few patients had systemic symptoms  with 2 organs preferentially incriminated: skin and lungs . Four patients had a monoclonal immunoglobulin (3 IgG kappa and 1 IgG lambda) with a median peak of 3 g/l [1.6–9]. Median C-reactive protein was 56 mg/l [9.6–100]. Auto-immunity was detected in 5 of the 10 tested patients . One patient had a detectable cryoglobulinemia associated with a diagnosis of lysozyme nephropathy. Regarding the serum complement analyses, 25% had a low C3 and 12.5% a low C4.The first indication of the kidney biopsy was AKI associated to a tubular proteinuria , and an interstitial infiltrate compatible with a CMML infiltration in the kidney   underwent a kidney biopsy. The 2 most frequent diagnoses were lysozyme nephropathy  . Among tn = 4), and a vacuolization of the epithelial cells of the proximal tubules (n = 7). Lysozyme staining was positive in 5 (n = 62.5%) patients (4 immunohistochemistry and 1 immunofluorescence). Four patients with lysozyme nephropathy had also lysozymuria. Interstitial fibrosis ranged from 10% to 30%. Inflammatory infiltrate with mostly mononuclear myeloid cells was described in 9 patients. For the patients who had a characterization of the infiltrate by immunohistochemistry, MPO and CD68 staining were positive  for 5 (45.5%) patients and got improved in 5 (45.5%) patients (4 missing data). One patient refused to be treated by azacitidine, and his kidney function remained stable after 68 months.After a median follow-up of 15 months (9.9–34.9), hematologic malignancy worsened in 6 patients , with 5 deaths at last follow-up . After treatment, kidney function worsened in 1 (9%) patient. It was stable (eGFR change ± 5 ml/min per 1.73 mP < 0.001) (P = 0.005). Even if there was no difference in terms of prognostics, with an International Prognosis Scoring System-Revised above 3.5 in 28.4% of CMML control group against 20% (P = 1), patients with CMML with a kidney injury were more susceptible to develop an AML: 30.8% versus 6.9% in the control group (P = 0.02). Patients with CMML who had a kidney injury were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents . The median follow-up from CMML diagnosis was 21 months [7–39.5] in patients without a kidney injury, and 34.9 months [13.9–46.5] in patients with a kidney injury (P = 0.174). The median survival was 59 months, and not reached for the follow-up period in CMML with and without a kidney injury, respectively   . Moreove3–3.28]) .Table 3CCMML is a myeloid neoplasm characterized as a myelodysplastic syndrome/ myeloproliferative neoplasm overlap syndrome. CMML is associated with significant monocytosis, which is correlated with AKI and CKD.et al.et al.et al.,In our study, the time between the diagnosis of CMML and the development of a kidney injury was 6 months, which is close to the delay reported by Grignano Lysozyme is a small cationic protein produced by monocytes, that is freely filtered by the glomerular filtration barrier, and reabsorbed by proximal tubules.,,,Kidney infiltration by CMML is mostly seen in the tubulointerstitial compartment, even if it has already been described in the glomerulus.et al.et al.At last follow-up, kidney function evolution was heterogenous, with 4 patients evolving to CKD 3, 4 patients to CKD 4, and 1 patient to end-stage kidney disease, which was comparable to Belliere Limitations of this work are mainly due to its retrospective design, and the small sample size of the cohort. To push further the analysis, the next objectives will be to collect kidney biopsy samples to further characterize the pathological features of the kidney injuries (infiltrate and lysozyme staining) associated with CMML. One of our perspectives will be to realize next-generation sequencing on the kidney biopsies of patients with an infiltrate, to see if we can find a significant renal clonal infiltrate of CMML cells.In conclusion, a regular screening for blood pressure, proteinuria, and kidney function should be proposed to all patients with CMML. In case of kidney dysfunction, kidney biopsy seems important to confirm the diagnosis in patients with CMML or to rule out differential diagnoses. Dosage of lysozymuria can also be informative, although not easily accessible in routine. In this cohort of patients with CMML with a kidney injury, the 2 most frequent kidney complications were lysozyme-induced nephropathy, and kidney infiltration by the CMML. The occurrence of a kidney injury in the course of a CMML seems to worsen the prognosis of these patients.List of the MINHEMON group: Marie-Camille Lafargue, Mickaël Bobot, Thibault Comont, Nathalie Cambier, Kamel Laribi, Olivier Fain,Lionel Adès, Pierre Fenaux, Arsène MekinianList of GFM group: Thibault Comont, Nathalie Cambier, Kamel Laribi, Olivier Fain, Lionel Adès, Pierre Fenaux, Arsène MekinianList of French VEXAS group: Thibault Comont, Olivier Fain, Lionel Adès, Pierre Fenaux, Arsène MekinianAM is investigator of CELGENE, ROCHE, CHUGAI founded trials with APHP and Hopital 15-20 promotion; AM received several fees for congress travels and experts’ use from LFB, SANOFI, SHIRE, and CELGENE. All other authors have declared no conflicting interest.