A Clinical Reasoning-Encoded Case Library Developed through Natural Language Processing.

IMPORTANCE: Case reports that externalize expert diagnostic reasoning are utilized for clinical reasoning instruction but are difficult to search based on symptoms, final diagnosis, or differential diagnosis construction. Computational approaches that uncover how experienced diagnosticians analyze the medical information in a case as they formulate a differential diagnosis can guide educational uses of case reports. OBJECTIVE: To develop a "reasoning-encoded" case database for advanced clinical reasoning instruction by applying natural language processing (NLP), a sub-field of artificial intelligence, to a large case report library. DESIGN: We collected 2525 cases from the New England Journal of Medicine (NEJM) Clinical Pathological Conference (CPC) from 1965 to 2020 and used NLP to analyze the medical terminology in each case to derive unbiased (not prespecified) categories of analysis used by the clinical discussant. We then analyzed and mapped the degree of category overlap between cases. RESULTS: Our NLP algorithms identified clinically relevant categories that reflected the relationships between medical terms (which included symptoms, signs, test results, pathophysiology, and diagnoses). NLP extracted 43,291 symptoms across 2525 cases and physician-annotated 6532 diagnoses (both primary and related diagnoses). Our unsupervised learning computational approach identified 12 categories of medical terms that characterized the differential diagnosis discussions within individual cases. We used these categories to derive a measure of differential diagnosis similarity between cases and developed a website ( universeofcpc.com ) to allow visualization and exploration of 55 years of NEJM CPC case series. CONCLUSIONS: Applying NLP to curated instances of diagnostic reasoning can provide insight into how expert clinicians correlate and coordinate disease categories and processes when creating a differential diagnosis. Our reasoning-encoded CPC case database can be used by clinician-educators to design a case-based curriculum and by physicians to direct their lifelong learning efforts.

Feasibility and cost analysis of day 4 granulocyte colony-stimulating factor mobilized peripheral blood progenitor cell collection from HLA-matched sibling donors.

BACKGROUND: Guidelines recommend treatment with 4-5 days of granulocyte colony-stimulating factor (G-CSF) for optimal donor peripheral blood progenitor cell (PBPC) mobilization followed by day 5 collection. Given that some autologous transplant recipients achieve adequate collection by day 4 and the possibility that some allogeneic donors may maximally mobilize PBPC before day 5, a feasibility study was performed evaluating day 4 allogeneic PBPC collection. METHODS: HLA-matched sibling donors underwent collection on day 4 of G-CSF for peripheral blood (PB) CD34+ counts ≥0.04 × 106/mL, otherwise they underwent collection on day 5. Those with inadequate collected CD34+ cells/kg recipient weight underwent repeat collection over 2 days. Transplant and PBPC characteristics and cost analysis were compared with a historical cohort collected on day 5 per our prior institutional algorithm. RESULTS: Of the 101 patient/donor pairs, 50 (49.5%) had adequate PBPC collection on day 4, with a median PB CD34+ cell count of 0.06 × 106/mL. Day 4 donors were more likely to develop bone pain and require analgesics. Median collected CD34+ count was significantly greater, whereas total nucleated, mononuclear and CD3+ cell counts were significantly lower, at time of transplant infusion for day 4 versus other collection cohorts. There were no significant differences in engraftment or graft-versus-host disease. Cost analysis revealed 6.7% direct cost savings for day 4 versus historical day 5 collection. DISCUSSION: Day 4 PB CD34+ threshold of ≥0.04 × 106/mL identified donors with high likelihood of adequate PBPC collection. Day 4 may be the optimal day of collection for healthy donors, without adverse effect on recipient transplant outcomes and with expected cost savings.

Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4+ T Cells in Peripheral Blood of Subjects with Type 1 Diabetes.

The significance of islet Ag-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects is unclear, partly because similar cells are also found in healthy control (HC) subjects. We hypothesized that key disease-associated cells would show evidence of prior Ag exposure, inferred from expanded TCR clonotypes, and essential phenotypic properties in their transcriptomes. To test this, we developed single-cell RNA sequencing procedures for identifying TCR clonotypes and transcript phenotypes in individual T cells. We applied these procedures to analysis of islet Ag-reactive CD4+ memory T cells from the blood of T1D and HC individuals after activation with pooled immunodominant islet peptides. We found extensive TCR clonotype sharing in Ag-activated cells, especially from individual T1D subjects, consistent with in vivo T cell expansion during disease progression. The expanded clonotype from one T1D subject was detected at repeat visits spanning >15 mo, demonstrating clonotype stability. Notably, we found no clonotype sharing between subjects, indicating a predominance of "private" TCR specificities. Expanded clones from two T1D subjects recognized distinct IGRP peptides, implicating this molecule as a trigger for CD4+ T cell expansion. Although overall transcript profiles of cells from HC and T1D subjects were similar, profiles from the most expanded clones were distinctive. Our findings demonstrate that islet Ag-reactive CD4+ memory T cells with unique Ag specificities and phenotypes are expanded during disease progression and can be detected by single-cell analysis of peripheral blood.

Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state.

The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes. Comparing basal IL-2 responses in resting versus activated cells, memory Teff displayed lower, but more sustained, responses to IL-2 overtime. These results suggest that T1D-associated defects in the Teff compartment are due to intrinsic factors related to activation. Evaluation of both Teff and Treg IL-2R signaling defects in T1D subjects may inform selection of therapies.

An Atypical Withdrawal Syndrome in Neonates Prenatally Exposed to Gabapentin and Opioids.

We report a retrospective case series of 19 infants exposed to both opioids and gabapentin prenatally. We describe a unique behavioral phenotype in 15 of these infants and report a treatment strategy.

CD40 is required for protective immunity against liver stage Plasmodium infection.

The costimulatory molecule CD40 enhances immunity through several distinct roles in T cell activation and T cell interaction with other immune cells. In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite. Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves. Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice. Thus, protective immunity generated during immunization with fabb/f(-) was largely dependent on effective APC licensing via CD40 signaling.

Improvement of sleep disturbance and insomnia following parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: The aim of the present study was to investigate the incidence of sleep disturbance and insomnia in patients with primary hyperparathyroidism (PHPT), and to evaluate the effect of parathyroidectomy. METHODS: A questionnaire was prospectively administered to adult patients with PHPT who underwent curative parathyroidectomy over an 11-month period. The questionnaire, administered preoperatively and 6 months postoperatively, included the Insomnia Severity Index (ISI) and eight additional questions regarding sleep pattern. Total ISI scores range from 0 to 28, with >7 signifying sleep difficulties and scores >14 indicating clinical insomnia. RESULTS: Of 197 eligible patients undergoing parathyroidectomy for PHPT, 115 (58.3 %) completed the preoperative and postoperative questionnaires. The mean age was 60.0 ± 1.2 years and 80.0 % were women. Preoperatively, 72 patients (62.6 %) had sleep difficulties, and 29 patients (25.2 %) met the criteria for clinical insomnia. Clinicopathologic variables were not predictive of clinical insomnia. There was a significant reduction in mean ISI score after parathyroidectomy (10.3 ± 0.6 vs 6.2 ± 0.5, p < 0.0001). Postoperatively, 79 patients (68.7 %) had an improved ISI score. Of the 29 patients with preoperative clinical insomnia, 21 (72.4 %) had resolution after parathyroidectomy. Preoperative insomnia patients had an increase in total hours slept after parathyroidectomy (5.4 ± 0.3 vs 6.1 ± 0.3 h, p = 0.02), whereas both insomnia patients and non-insomnia patients had a decrease in the number of awakenings (3.7 ± 0.4 vs 1.9 ± 0.2 times, p = 0.0001). CONCLUSIONS: Sleep disturbances and insomnia are common in patients with PHPT, and the majority of patients will improve after curative parathyroidectomy.

Establishing priorities for implementation of large language models in pathology and laboratory medicine.

Artificial intelligence and machine learning have numerous applications in pathology and laboratory medicine. The release of ChatGPT prompted speculation regarding the potentially transformative role of large-language models (LLMs) in academic pathology, laboratory medicine, and pathology education. Because of the potential to improve LLMs over the upcoming years, pathology and laboratory medicine clinicians are encouraged to embrace this technology, identify pathways by which LLMs may support our missions in education, clinical practice, and research, participate in the refinement of AI modalities, and design user-friendly interfaces that integrate these tools into our most important workflows. Challenges regarding the use of LLMs, which have already received considerable attention in a general sense, are also reviewed herein within the context of the pathology field and are important to consider as LLM applications are identified and operationalized.

Development and preliminary testing of Health Equity Across the AI Lifecycle (HEAAL): A framework for healthcare delivery organizations to mitigate the risk of AI solutions worsening health inequities.

The use of data-driven technologies such as Artificial Intelligence (AI) and Machine Learning (ML) is growing in healthcare. However, the proliferation of healthcare AI tools has outpaced regulatory frameworks, accountability measures, and governance standards to ensure safe, effective, and equitable use. To address these gaps and tackle a common challenge faced by healthcare delivery organizations, a case-based workshop was organized, and a framework was developed to evaluate the potential impact of implementing an AI solution on health equity. The Health Equity Across the AI Lifecycle (HEAAL) is co-designed with extensive engagement of clinical, operational, technical, and regulatory leaders across healthcare delivery organizations and ecosystem partners in the US. It assesses 5 equity assessment domains-accountability, fairness, fitness for purpose, reliability and validity, and transparency-across the span of eight key decision points in the AI adoption lifecycle. It is a process-oriented framework containing 37 step-by-step procedures for evaluating an existing AI solution and 34 procedures for evaluating a new AI solution in total. Within each procedure, it identifies relevant key stakeholders and data sources used to conduct the procedure. HEAAL guides how healthcare delivery organizations may mitigate the potential risk of AI solutions worsening health inequities. It also informs how much resources and support are required to assess the potential impact of AI solutions on health inequities.

Clinicopathologic characteristics of colonic carcinoid tumors.

BACKGROUND: Extra-appendiceal colonic carcinoids are uncommon neuroendocrine tumors with a poor prognosis compared with carcinoids of other gastrointestinal origins. Few studies have examined the clinicopathologic profile and behavior of this rare tumor. MATERIALS AND METHODS: A retrospective analysis was performed on patients with colonic carcinoid tumors evaluated at a single tertiary care center between 1996 and 2012. Collected data included patient and tumor characteristics, presentation, treatment, recurrence, and survival. Results were integrated into a comprehensive review of the colonic carcinoid literature. RESULTS: In total, 114 patients with colorectal carcinoid tumors were identified, and 15 patients with extra-appendiceal tumors were analyzed. The mean age was 58.6 ± 3.0 y, and subjects were predominantly male (73.3%). The most common presenting problem was abdominal pain (33.3%), although 26.7% of patients were asymptomatic. Cecal tumors were the most prevalent (73.3%), and most patients underwent right hemicolectomy. Three patients with lesions < 1 cm were treated endoscopically. The mean tumor diameter was 2.9 ± 0.5 cm, with lymph node or distant metastasis present in 53.3% and 26.7%, respectively. All but two patients underwent a presumed curative resection. During a mean follow-up of 4.2 ± 1.0 y, there was only one death (non-carcinoid specific). Eleven patients were alive without evidence of disease at last follow-up and three patients were alive with disease, one of whom initially had a presumed curative resection that recurred. CONCLUSIONS: This case series further elucidates the clinicopathologic characteristics of colonic carcinoid tumors, which aids physicians in guiding the diagnosis and management of these rare tumors.

Unilateral thyroidectomy for the treatment of benign multinodular goiter.

BACKGROUND: Benign multinodular goiter (MNG) is one of the most commonly treated thyroid disorders. Although bilateral resection is the accepted surgical treatment for bilateral MNG, the appropriate surgical resection for unilateral MNG continues to be debated. Bilateral resection generally has lower recurrence rates but higher complication rates than unilateral resection. Therefore, the purpose of this study was to define the recurrence and complication rates of unilateral and bilateral resections to determine the appropriate intervention for patients with unilateral, benign MNG. METHODS: We reviewed a prospectively maintained database of all patients who underwent a thyroidectomy for treatment of benign MNG at a single institution between May 1994 and December 2011. All patients with bilateral MNG were treated with bilateral resection. Surgical treatment for unilateral MNG was determined by surgeon preference, with all but one surgeon opting for unilateral resection to treat unilateral MNG. Data were reported as means ± standard error of the mean. Chi-squared analysis was used to determine statistical significance at a level of P < 0.05. RESULTS: A total of 683 patients underwent thyroidectomy for MNG. Of these patients, 420 (61%) underwent unilateral resection and 263 patients (39%) underwent total thyroidectomy. The mean age was 52 ± 17 y, and 542 patients (79%) were female. The mean follow-up time was 46.1 ± 1.9 mo. The rate of recurrent disease was similar between unilateral (2%, n = 10) and bilateral (1%, n = 3) resections (P = 0.248). Unilateral resection patients had a lower total complication rate than patients with bilateral resections (8% versus 26%, P < 0.001); however, there was no difference in the rate of permanent complications (0.2% versus 1%, P = 0.133). Thyroid hormone replacement was rare in unilateral resection patients but necessary in all patients with bilateral resection (19% versus 100%, P < 0.001). CONCLUSIONS: Patients that had unilateral resections endured less overall morbidities than those who had bilateral resections, and their risk of recurrent disease was similar. They were also significantly less likely to require lifelong hormone replacement therapy postoperatively. Although bilateral resection remains the recommended treatment for bilateral MNG, these data strongly support the use of unilateral thyroidectomy for the treatment of unilateral, benign MNG.

Large Language Models and Medical Education: Preparing for a Rapid Transformation in How Trainees Will Learn to Be Doctors.

Artificial intelligence has the potential to revolutionize health care but has yet to be widely implemented. In part, this may be because, to date, we have focused on easily predicted rather than easily actionable problems. Large language models (LLMs) represent a paradigm shift in our approach to artificial intelligence because they are easily accessible and already being tested by frontline clinicians, who are rapidly identifying possible use cases. LLMs in health care have the potential to reduce clerical work, bridge gaps in patient education, and more. As we enter this era of healthcare delivery, LLMs will present both opportunities and challenges in medical education. Future models should be developed to support trainees to develop skills in clinical reasoning, encourage evidence-based medicine, and offer case-based training opportunities. LLMs may also change what we continue teaching trainees with regard to clinical documentation. Finally, trainees can help us train and develop the LLMs of the future as we consider the best ways to incorporate LLMs into medical education. Ready or not, LLMs will soon be integrated into various aspects of clinical practice, and we must work closely with students and educators to make sure these models are also built with trainees in mind to responsibly chaperone medical education into the next era.

Gender Disparities in Critical Care Procedure Training of Internal Medicine Residents.

Background: Procedural training is a required competency in internal medicine (IM) residency, yet limited data exist on residents' experience of procedural training. Objectives: We sought to understand how gender impacts access to procedural training among IM residents. Methods: A mixed-methods, explanatory sequential study was performed. Procedure volume for IM residents between 2016 and 2020 was assessed at two large academic residencies (Program A and Program B: 399 residents and 4,020 procedures). Procedural rates and actual versus expected procedure volume by gender were compared, with separate analyses by clinical environment (intensive care unit [ICU] or structured procedural service). Semistructured gender-congruent focus groups were conducted. Topics included identity formation as a proceduralist and the resident procedural learning experience, including perceived gender bias in procedure allocation. Results: Compared with men, women residents performed disproportionately fewer ICU procedures per month at Program A (1.4 vs. 2.7; P < 0.05) but not at Program B (0.36 vs. 0.54; P = 0.23). At Program A, women performed only 47% of ICU procedures, significantly fewer than the 54% they were expected to perform on the basis of their time on ICU rotations (P < 0.001). For equal gender distribution of procedural volume at Program A, 11% of the procedures performed by men would have needed to have been performed by women instead. Gender was not associated with differences in the Program A structured procedural service (53% observed vs. 52% expected; P = 0.935), Program B structured procedural service (40% observed vs. 43% expected; P = 0.174), or in Program B ICUs (33% observed vs. 34% expected; P = 0.656). Focus group analysis identified that women from both residencies perceived that assertiveness was required for procedural training in unstructured learning environments. Residents felt that gender influenced access to procedural opportunities, ability to self-advocate for procedural experience, identity formation as a proceduralist, and confidence in acquiring procedural skills. Conclusion: Gender disparities in access to procedural training during ICU rotations were seen at one institution but not another. There were ubiquitous perceptions that assertiveness was important to access procedural opportunities. We hypothesize that structured allocation of procedures would mitigate disparities by allowing all residents to access procedural training regardless of self-advocacy. Residency programs should adopt structured procedural training programs to counteract inequities.

Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins.

Microproteins (MPs) are a potentially rich source of uncharacterized metabolic regulators. Here, we use ribosome profiling (Ribo-seq) to curate 3,877 unannotated MP-encoding small ORFs (smORFs) in primary brown, white, and beige mouse adipocytes. Of these, we validated 85 MPs by proteomics, including 33 circulating MPs in mouse plasma. Analyses of MP-encoding mRNAs under different physiological conditions (high-fat diet) revealed that numerous MPs are regulated in adipose tissue in vivo and are co-expressed with established metabolic genes. Furthermore, Ribo-seq provided evidence for the translation of Gm8773, which encodes a secreted MP that is homologous to human and chicken FAM237B. Gm8773 is highly expressed in the arcuate nucleus of the hypothalamus, and intracerebroventricular administration of recombinant mFAM237B showed orexigenic activity in obese mice. Together, these data highlight the value of this adipocyte MP database in identifying MPs with roles in fundamental metabolic and physiological processes such as feeding.

Surveillance of small rectal carcinoid tumors in the absence of metastatic disease.

BACKGROUND: The incidence of rectal carcinoids is rapidly increasing, typically presenting as small (<1.0 cm), localized tumors. Although the evaluation of rectal carcinoids on presentation is well standardized, surveillance after resection has not been well established. METHODS: A prospective database documented patients with rectal carcinoids at our institution between January 1995 and September 2011. Information collected included patient and tumor characteristics, treatment method, surveillance schedule, recurrence, and survival. RESULTS: Twenty-eight patients with rectal carcinoid were identified. Ten patients were excluded for tumors >1 cm, known metastases at presentation, <6 months follow-up, or previous resections. The mean age of the remaining patients was 56 ± 3 years, and 61% of the patients were female. All patients were diagnosed at endoscopy, with 50% diagnosed incidentally on screening endoscopy. Treatment methods included endoscopic therapy (n = 13, 72%), transanal excision (n = 3, 17%), and transanal endoscopic microsurgery (n = 1, 5.5%). One patient (5.5%) received no additional invasive therapy after diagnostic endoscopy. The mean tumor diameter was 4.6 ± 0.5 mm. The average length of follow-up was 5.4 ± 0.9 years, with a median number of 2 follow-up endoscopies (range 0-6). Two patients (11%) died within the follow-up period from noncarcinoid causes. Importantly, no surviving patients developed local or distant recurrence with up to 12.3 years of follow-up. CONCLUSIONS: On the basis of this experience, patients presenting with small (≤1.0 cm), nonmetastatic rectal carcinoids are unlikely to develop local or distant recurrence after resection. Aggressive surveillance with repeat endoscopies or other imaging studies after resection may be unnecessary in this patient population.

Incidence of concomitant hyperparathyroidism in patients with thyroid disease requiring surgery.

BACKGROUND: Thyroid disease and hyperparathyroidism (HPT) are among the most common endocrine disorders, however, their association has not been well established. The aim of the present study was to determine the incidence of concomitant HPT in patients with thyroid disease requiring surgery, because a single definitive surgery should ideally be performed. METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent thyroidectomy at a single institution. Data collected included the patients' initial indication for surgery, preoperative workup, and operative findings. RESULTS: Of the 1,049 patients who underwent thyroidectomy, 56 (5%) had concomitant HPT and underwent simultaneous parathyroidectomy. Of these 56 patients, 36 initially presented with thyroid disease and 20 with HPT. The mean age was 59 ± 2 years, and 79% were women. The mean preoperative calcium and parathyroid hormone levels were elevated at 10.4 ± 0.1 mg/dL and 87 ± 7 pg/mL, respectively. Most of these patients had primary HPT (n = 54, 96%). Of the 36 patients presenting initially with thyroid disease, 26 had an elevated calcium or parathyroid hormone value and were preoperatively diagnosed with HPT. The remaining 10 patients had normal laboratory findings; however, a pathologically enlarged parathyroid gland was found at thyroidectomy. The overall cure rate for HPT within our series was 96%. CONCLUSION: The incidence of concomitant HPT in patients with thyroid disease requiring surgery is significant at 5%. Recognition of concurrent disease is important, because it allows for a single definitive surgery to treat both pathologies.

Protecting reproductive health information in the post-Roe era: interoperability strategies for healthcare institutions.

On June 24, 2022, the US Supreme Court ended constitutional protections for abortion, resulting in wide variability in access from severe restrictions in many states and fewer restrictions in others. Healthcare institutions capture information about patients' pregnancy and abortion care and, due to interoperability, may share it in ways that expose their providers and patients to social stigma and potential legal jeopardy in states with severe restrictions. In this article, we describe sources of risk to patients and providers that arise from interoperability and specify actions that institutions can take to reduce that risk. Institutions have significant power to define their practices for how and where care is documented, how patients are identified, where data are sent or hosted, and how patients are counseled, and thus should protect patients' privacy and ability to receive medical care that is safe and legal where it is performed.

Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: oxaliplatin versus mitomycin C.

BACKGROUND: Oxaliplatin (OX) is increasingly used for hyperthermic intraperitoneal chemotherapy (HIPC) for patients with peritoneal metastases. Our aim was to review electrolyte disturbances and complications after HIPC with oxaliplatin (OX) versus mitomycin C (MMC). MATERIALS AND METHODS: We included patients enrolled in single-institution prospective clinical trials who underwent cytoreductive surgery and HIPC with MMC or OX. We reviewed patient demographics, pathology, perioperative course, HIPC administration, and postoperative electrolyte disturbances. Measured postoperative sodium values were corrected for systemic hyperglycemia using the formula: (measured Na(+)) × [(glucose - 100/100) × 1.6]. RESULTS: From January 2002 to April 2009 we performed 80 HIPC procedures. A total of 60 patients (75%) received MMC (dose range 12.5-50 mg/m(2)) carried in lactated ringers solution. There were 20 patients (25%) who received OX (dose range 300 × 400 mg/m(2)) carried in 5% dextrose solution. For patients receiving HIPC with OX, electrolyte disturbances were the most common complication. Compared with MMC, patients receiving OX had significant 24-h postoperative uncorrected hyponatremia (P < 0.001), corrected hyponatremia (P < 0.001), hyperglycemia (P < 0.001), and metabolic acidosis (P < 0.001). In the OX group, corrected (mean 130.5) and uncorrected (mean 127.4) sodium levels were significantly lower than preoperatively (mean 139.9, P < 0.001). The overall nonelectrolyte complication rate was 56.2%. (MMC n = 33, 55.0%; OX n = 12, 60%); the 30-day mortality rate was 0% in both groups. CONCLUSIONS: Compared with MMC, HIPC with OX was associated with significant but predictable electrolyte disturbances; however, these electrolyte disturbances were not associated with higher overall complication rates. Close monitoring with early correction is imperative to maximize perioperative care. Further studies are needed to provide mechanistic insight.